thesis renal disease

• Open access
• Published: 10 January 2022

Chronic kidney disease and its health-related factors: a case-control study

• Mousa Ghelichi-Ghojogh 1 ,
• Mohammad Fararouei 2 ,
• Mozhgan Seif 3 &
• Maryam Pakfetrat 4  

BMC Nephrology volume  23 , Article number:  24 ( 2022 ) Cite this article

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Chronic kidney disease (CKD) is a non-communicable disease that includes a range of different physiological disorders that are associated with abnormal renal function and progressive decline in glomerular filtration rate (GFR). This study aimed to investigate the associations of several behavioral and health-related factors with CKD in Iranian patients.

A hospital-based case-control study was conducted on 700 participants (350 cases and 350 controls). Logistic regression was applied to measure the association between the selected factors and CKD.

The mean age of cases and controls were 59.6 ± 12.4 and 58.9 ± 12.2 respectively ( p  = 0.827). The results of multiple logistic regression suggested that many factors including low birth weight (OR yes/no  = 4.07, 95%CI: 1.76–9.37, P  = 0.001), history of diabetes (OR yes/no  = 3.57, 95%CI: 2.36–5.40, P  = 0.001), history of kidney diseases (OR yes/no  = 3.35, 95%CI: 2.21–5.00, P  = 0.001) and history of chemotherapy (OR yes/no  = 2.18, 95%CI: 1.12–4.23, P  = 0.02) are associated with the risk of CKD.

Conclusions

The present study covered a large number of potential risk/ preventive factors altogether. The results highlighted the importance of collaborative monitoring of kidney function among patients with the above conditions.

Peer Review reports

Chronic kidney disease (CKD) is a non-communicable disease that includes a range of different physiological disorders that are associated with an abnormal renal function and progressive decline in glomerular filtration rate (GFR) [ 1 , 2 , 3 ]. Chronic kidney disease includes five stages of kidney damage, from mild kidney dysfunction to complete failure [ 4 ]. Generally, a person with stage 3 or 4 of CKD is considered as having moderate to severe kidney damage. Stage 3 is broken up into two levels of kidney damage: 3A) a level of GFR between 45 to 59 ml/min/1.73 m 2 , and 3B) a level of GFR between 30 and 44 ml/min/1.73 m 2 . In addition, GFR for stage 4 is 15–29 ml/min/1.73 m 2 [ 4 , 5 ]. It is reported that both the prevalence and burden of CKD are increasing worldwide, especially in developing countries [ 6 ]. The worldwide prevalence of CKD (all stages) is estimated to be between 8 to 16%, a figure that may indicate millions of deaths annually [ 7 ]. According to a meta-analysis, the prevalence of stage 3 to 5 CKD in South Africa, Senegal, and Congo is about 7.6%. In China, Taiwan, and Mongolia the rate of CKD is about 10.06% and in Japan, South Korea, and Oceania the rate is about 11.73%. In Europe the prevalence of CKD is about 11.86% [ 8 ], and finally, about 14.44% in the United States and Canada. The prevalence of CKD is estimated to be about 11.68% among the Iranian adult population and about 2.9% of Iranian women and 1.3% of Iranian men are expected to develop CKD annually [ 9 ]. Patients with stages 3 or 4 CKD are at much higher risk of progressing to either end-stage renal disease (ESRD) or death even prior to the development of ESRD [ 10 , 11 ].

In general, a large number of risk factors including age, sex, family history of kidney disease, primary kidney disease, urinary tract infections, cardiovascular disease, diabetes mellitus, and nephrotoxins (non-steroidal anti-inflammatory drugs, antibiotics) are known as predisposing and initiating factors of CKD [ 12 , 13 , 14 ]. However, the existing studies are suffering from a small sample size of individuals with kidney disease, particularly those with ESRD [ 15 ].

Despite the fact that the prevalence of CKD in the world, including Iran, is increasing, the factors associated with CKD are explored very little. The present case-control study aimed to investigate the association of several behavioral and health-related factors with CKD in the Iranian population.

Materials and methods

In this study, participants were selected among individuals who were registered or were visiting Faghihi and Motahari hospitals (two largest referral centers in the South of Iran located in Shiraz (the capital of Fars province). Cases and controls were frequency-matched by sex and age. The GFR values were calculated using the CKD-EPI formula [ 16 , 17 ].

Data collection

An interview-administered questionnaire and the participant’s medical records were used to obtain the required data. The questionnaire and interview procedure were designed, evaluated, and revised by three experts via conducting a pilot study including 50 cases and 50 controls. The reliability of the questionnaire was measured using the test-retest method (Cronbach’s alpha was 0.75). The interview was conducted by a trained public health‌ nurse at the time of visiting the clinics.

Avoiding concurrent conditions that their association may interpreted as reverse causation; the questionnaire was designed to define factors preceding at least a year before experiencing CKD first symptoms. Accordingly participants reported their social and demographic characteristics (age, sex, marital status, educational level, place of residency), history of chronic diseases (diabetes, cardiovascular diseases, hypertension, kidney diseases, family history of kidney diseases, autoimmune diseases and thyroid diseases [ 18 ]). Also history of other conditions namely (smoking, urinary tract infection (UTI), surgery due to illness or accident, low birth weight, burns, kidney pain (flank pain), chemotherapy, taking drugs for weight loss or obesity, taking non-steroidal anti-inflammatory drugs, and taking antibiotic) before their current condition was started. Many researchers reported recalling birth weight to be reliable for research purposes [ 19 ]. Moreover, we asked the participants to report their birth weight as a categorical variable (< 2500 g or low, 2500- < 3500 g or normal, and > 3500 g or overweight). Medical records of the participants were used to confirm/complete the reported data. In the case of contradiction between the self-reported and recorded data, we used the recorded information for our study.

Verbal informed consent was obtained from patients because the majority of the participants were illiterate. The study protocol was reviewed and approved by the ethical committee of Shiraz University of Medical Sciences (approval number: 1399.865).

Sample size

The sample size was calculated to detect an association‌ between the history of using antibiotics (one of our main study variables) and CKD as small as OR = 1.5 [ 20 ]. With an alpha value of 0.05 (2-sided) and a power of 80%, the required sample size was estimated as large as n  = 312 participants for each group.

Selection of cases

The selected clinics deliver medical care to patients from the southern part of the country. In this study, patients with CKD who were registered with the above centers from June to December 2020 were studied. A case was a patient with a GFR < 60 (ml/min/1.73 m 2 ) at least twice in 3 months. According to the latest version of the International Classification of Diseases (2010), Codes N18.3 and N18.4 are assigned to patients who have (GFR = 30–59 (ml/min/1.73 m 2 ) and GFR = 15–29 (ml/min/1.73 m 2 ) respectively [ 21 ]. In total, 350 patients who were diagnosed with CKD by a nephrologist during the study period.

Selection of the controls

We used hospital controls to avoid recall-bias. The control participants were selected from patients who were admitted to the general surgery (due to hernia, appendicitis, intestinal obstruction, hemorrhoids, and varicose veins), and orthopedic wards‌ from June to December 2020. Using the level of creatinine in the participants’ serum samples, GFR was calculated and the individuals with normal GFR (ml/min/1.73 m 2 ) GFR > 60) and those who reported no history of CKD were included ( n  = 350).

Inclusion criteria

Patients were included if they were ≥ 20 years old and had a definitive diagnosis of CKD by a nephrologist.

Exclusion criteria

Participants were excluded if they were critically ill, had acute kidney injury, those undergone renal transplantation, and those with cognitive impairment.

Statistical analysis

The Chi-square test was used to measure the unadjusted associations between categorical variables and CKD. Multiple logistic regression was applied to measure the adjusted associations for the study variables and CKD. The backward variable selection strategy was used to include variables in the regression model. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. All p -values were two-sided and the results were considered statistically significant at p  < 0.05. All analyses were conducted using Stata version 14.0 (Stata Corporation, College Station, TX, USA).

In total, 350 cases and 350 age and sex-matched controls were included in the analysis. The mean age of cases and controls were 59.6 ± 12.4 and 58.9 ± 12.2 respectively ( p  = 0.83). Overall, 208 patients (59.4%) and 200 controls (57.1%) were male ( p  = 0.54). Also, 149 patients (42.6%) and 133 controls (38.0%) were illiterate or had elementary education ( p  = 0.001). Most cases (96.9%) and controls (95.7%) were married ( p  = 0.42). The mean GFR for CKD and control groups were 38.6 ± 11.4 and 78.3 ± 10.2 (ml/min/1.73 m2) respectively.

Result of univariate analysis

Table  1 illustrates the unadjusted associations of demographic and health-related variables with CKD. Accordingly, significant (unadjusted) associations were found between the risk of CKD and several study variables including education, history of chronic diseases (diabetes, cardiovascular, hypertension, kidney diseases, autoimmune diseases, and hypothyroidism), family history of kidney diseases, smoking, UTI, surgery due to illness or accident, low birth weight, burns, kidney pain, chemotherapy, taking non-steroidal anti-inflammatory drugs, and taking antibiotics) ( P  < 0.05 for all).

Results of multivariable analysis

Table  2 illustrates the adjusted associations between the study variables and the risk of CKD. Most noticeably, low birth weight (OR yes/no  = 4.07, 95%CI: 1.76–9.37, P  = 0.001), history of surgery (OR yes/no  = 1.74, 95%CI: 1.18–2.54, P  = 0.004), family history of kidney diseases (OR yes/no  = 1.97, 95%CI: 1.20–3.23, P  = 0.007), and history of chemotherapy (OR yes/no  = 2.18, 95%CI: 1.12–4.23, P  = 0.02) were significantly associated with a higher risk of CKD. On the other hand, education (OR college/illiterate or primary  = 0.54, 95%CI: 0.31–0.92, P  = 0.025) was found to be inversely associated with CKD.

The results of the present study suggested that several variables including, education, history of diabetes, history of hypertension, history of kidney diseases or a family history of kidney diseases, history of surgery due to illness or accident, low birth weight, history of chemotherapy, history of taking non-steroidal anti-inflammatory drugs, and history of taking antibiotics may affect the risk of CKD.

In our study, the level of education was inversely associated with the risk of CKD. This finding is in accordance with the results of a study conducted by K Lambert et.al, who suggested that illiteracy or elementary education may raise the risk of CKD [ 22 ]. The fact that education level is associated with health literacy, may partly explain our results that lower education and inadequate health literacy in individuals with CKD is associated with worse health outcomes including poorer control of biochemical parameters, higher risk of cardiovascular diseases (CVDs); a higher rate of hospitalization, and a higher rate of infections [ 23 ].

In the current study, the history of diabetes was associated with a higher risk of CKD. This finding is consistent with the results of other studies on the same subject [ 20 , 21 , 24 , 25 , 26 , 27 ]. It is not surprising that people with diabetes have an increased risk of CKD as diabetes is an important detrimental factor for kidney functioning as approximately, 40% of patients with diabetes develop CKD [ 27 ].

The other variable that was associated with an increased risk of CKD was a history of hypertension. Our result is consistent with the results of several other studies [ 20 , 24 , 25 , 28 ]. It is reported that hypertension is both a cause and effect of CKD and accelerates the progression of the CKD to ESRD [ 29 ].

After controlling for other variables, a significant association was observed between family history of kidney diseases and risk of CKD. Published studies suggested the same pattern [ 24 ]. Inherited kidney diseases (IKDs) are considered as the foremost reasons for the initiation of CKD and are accounted for about 10–15% of kidney replacement therapies (KRT) in adults [ 30 ].

The importance of the history of surgery due to illness or accident in this study is rarely investigated by other researchers who reported the effect of surgery in patients with acute kidney injury (AKI), and major abdominal and cardiac surgeries [ 31 , 32 ] on the risk of CKD. Also, AKI is associated with an increased risk of CKD with progression in various clinical settings [ 33 , 34 , 35 ]. In a study by Mizota et.al, although most AKI cases recovered completely within 7 days after major abdominal surgery, they were at higher risk of 1-year mortality and chronic kidney disease compared to those without AKI [ 31 ].

The present study also showed that low birth weight is a significant risk factor for CKD. This finding is consistent with the results of some other studies. However, the results of very few studies on the association between birth weight and risk of CKD are controversial as some suggested a significant association [ 19 , 36 , 37 ] whereas others suggested otherwise [ 36 ]. This may be explained by the relatively smaller size and volume of kidneys in LBW infants compared to infants that are normally grown [ 38 ]. This can lead to long-term complications in adolescence and adulthood including hypertension, decreased glomerular filtration, albuminuria, and cardiovascular diseases. Eventually, these long-term complications can also cause CKD [ 39 ].

Another important result of the current study is the association between chemotherapy for treating cancers and the risk of CKD. According to a study on chemotherapy for testicular cancer by Inai et al., 1 year after chemotherapy 23% of the patients showed CKD [ 40 ]. Another study suggested that the prevalence of stage 3 CKD among patients with cancer was 12, and < 1% of patients had stage 4 CKD [ 41 , 42 ]. Other studies have shown an even higher prevalence of CKD among cancer patients. For instance, only 38.6% of patients with breast cancer, 38.9% of patients with lung cancer, 38.3% of patients with prostate cancer, 27.5% of patients with gynecologic cancer, and 27.2% of patients with colorectal cancer had a GFR ≥90 (ml/min/1.73 m 2 ) at the time of therapy initiation [ 43 , 44 ]. The overall prevalence of CKD ranges from 12 to 25% across many cancer patients [ 45 , 46 , 47 ]. These results clearly demonstrate that, when patients with cancer develop acute or chronic kidney disease, outcomes are inferior, and the promise of curative therapeutic regimens is lessened.

In our study, the history of taking nephrotoxic agents (antibiotics or NSAIDs drugs) was associated with a higher risk of CKD. Our result is following the results reported by other studies [ 48 , 49 ]. Common agents that are associated with AKI include NSAIDs are different drugs including antibiotics, iodinated contrast media, and chemotherapeutic drugs [ 50 ].

Strengths and limitations of our study

Our study used a reasonably large sample size. In addition, a considerably large number of study variables was included in the study. With a very high participation rate, trained nurses conducted the interviews with the case and control participants in the same setting. However, histories of exposures are prone to recall error (bias), a common issue in the case-control studies. It is to be mentioned that the method of selecting controls (hospital controls) should have reduced the risk of recall bias when reporting the required information. In addition, we used the participants’ medical records to complete/ confirm the reported data. Although the design of the present study was not able to confirm a causal association between the associated variables and CKD, the potential importance and modifiable nature of the associated factors makes the results potentially valuable and easily applicable in the prevention of CKD.

Given that, chemotherapy is an important risk factor for CKD, we suggest the imperative for collaborative care between oncologists and nephrologists in the early diagnosis and treatment of kidney diseases in patients with cancer. Training clinicians and patients are important to reduce the risk of nephrotoxicity. Electronic medical records can simultaneously be used to monitor prescription practices, responsiveness to alerts and prompts, the incidence of CKD, and detecting barriers to the effective implementation of preventive measures [ 51 ]. Routine follow-up and management of diabetic patients is also important for the prevention of CKD. We suggest a tight collaboration between endocrinologists and nephrologists to take care of diabetic patients with kidney problems. In addition, surgeons in major operations should refer patients, especially patients with AKI, to a nephrologist for proper care related to their kidney function. Treatment of hypertension is among the most important interventions to slow down the progression of CKD [ 12 ]. Moreover, all patients with newly diagnosed hypertension should be screened for CKD. We suggest all patients with diabetes have their GFR and urine albumin-to-creatinine ratio (UACR) checked annually. Finally, the aging population and obesity cause the absolute numbers of people with diabetes and kidney diseases to raise significantly. This will require a more integrated approach between dialectologists/nephrologists and the primary care teams (55).

Availability of data and materials

The datasets generated and/or analyzed during the current study are not publicly available due to their being the intellectual property of Shiraz University of Medical Sciences but are available from the corresponding author on reasonable request.

Abbreviations

• Chronic kidney disease

End-stage renal disease

Glomerular filtration rate

Renal replacement treatment

Urinary tract infection

Odds ratios

Confidence intervals

Hypertension

Acute kidney injury

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Acknowledgments

This paper is part of a thesis conducted by Mousa Ghelichi-Ghojogh, Ph.D. student of epidemiology, and a research project conducted at the Shiraz University of Medical sciences (99-01-04-22719). We would like to thank Dr. Bahram Shahryari and all nephrologists of Shiraz‌ University of medical sciences, interviewers, and CKD patients in Shiraz for their voluntary participation in the study and for providing data for the study.

Shiraz University of Medical Sciences financially supported this study. (Grant number: 99–01–04-22719).

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Candidate in Epidemiology, Student Research Committee, Shiraz University of Medical Sciences, Shiraz, Iran

Mousa Ghelichi-Ghojogh

HIV/AIDS research center, School of Health, Shiraz University of Medical Sciences, P.O.Box: 71645-111, Shiraz, Iran

Mohammad Fararouei

Department of Epidemiology, School of Health, Shiraz University of Medical Sciences, Shiraz, Iran

Mozhgan Seif

Nephrologist, Shiraz Nephro-Urology Research Center, Department of Internal Medicine, Emergency Medicine Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

Maryam Pakfetrat

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Contributions

MGG: Conceptualization, Methodology, Statistical analysis, Investigation, and writing the draft of the manuscript. MP: were involved in methodology, writing the draft of the manuscript, and clinical consultation. MS: was involved in the methodology and statistical analysis. MF: was involved in conceptualization, methodology, supervision, writing, and reviewing the manuscript. The authors read and approved the final manuscript.

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Correspondence to Mohammad Fararouei .

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The study protocol was reviewed and approved by the ethical committee of Shiraz University of Medical Sciences (approval number: 1399.865). All methods were performed in accordance with the relevant guidelines and regulations of the Declaration of Helsinki. The participants were assured that their information is used for research purposes only. Because of the illiteracy of a considerable number of the patients, verbal informed consent was obtained from the participants. Using verbal informed consent was also granted by the ethical committee of Shiraz University of Medical Sciences.

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Ghelichi-Ghojogh, M., Fararouei, M., Seif, M. et al. Chronic kidney disease and its health-related factors: a case-control study. BMC Nephrol 23 , 24 (2022). https://doi.org/10.1186/s12882-021-02655-w

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DOI : https://doi.org/10.1186/s12882-021-02655-w

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The effects of social determinants on renal care among eskd patients in the philippines: rural vs. urban areas.

Melanie Rojas , Dominican University of California Follow

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Bachelor of Science in Nursing

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Patricia Harris, PhD, RN, CNS

From a Public Health Nursing (PHN) perspective, populations who are diagnosed with chronic disease or illness are the most vulnerable to end-stage kidney disease (ESKD) or end-stage renal disease (ESRD). The International Society of Nephrology (ISN) states that the mortality rate for ESKD amounts to roughly 7 million individuals worldwide. In examining causes of ESKD throughout both history and the lifespan, high mortality rates are attributed to the lack of access to life-sustaining therapies such as dialysis or transplantation. The lack of access to therapy or healthcare services has been an immense Public Health crisis in the last few decades. Accessibility to various resources such as healthcare, transportation, food, and other basic needs, are defined as social determinants . Typically, a lack of accessibility equates to poor health, and an abundance of accessibility equates to optimal health. In rural countries such as the Philippines, accessibility is questionable, and populations suffer from a lack of research addressing the relationship between social determinants and quality of health.

A comprehensive literature review was performed, and a gap was observed in the current research literature that focuses on Philippine populations and renal therapies. Dialysis or other life-sustaining treatments are less available for individuals in low-research settings. The root of the issue is systemic, indicating that intervention must be done at the governmental or authoritative forefront. A research study is proposed to address this gap.

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Kidney disease intervention outcomes encouraging, despite null result

by University of Pittsburgh

Manisha Jhamb, M.D., launched the Kidney-CHAMP study five years ago because she saw a looming tsunami of chronic kidney disease cases. She was pulled to find a way to assist the primary care physicians (PCPs) upon whom this burden would fall.

The results of her study are published in JAMA Internal Medicine . And, even though the study didn't prove that Kidney-CHAMP staves off disease progression , Jhamb is encouraged that the intervention helped PCPs identify and triage patients with kidney disease, improving patient access to specialists and educational materials.

"Despite the null result, we found that the Kidney-CHAMP framework is scalable, provides equitable access and overcomes barriers on the provider, patient and health system levels," said Jhamb, associate chief of the Renal-Electrolyte Division in the University of Pittsburgh School of Medicine and UPMC nephrologist.

"The big positive is that we were able to implement this in more than 100 PCP practices across a large geographic area that included many rural communities in the midst of a global pandemic."

Kidney-CHAMP , which stands for Coordinated HeAlth Management Partnership, uses the electronic health record to flag kidney disease patients for review by a multidisciplinary team of a nephrologist, pharmacist and physician. It then feeds individualized recommendations back to the patient's PCP and their medical chart. During the next appointment, real-time reminders prompt the physician to review recommendations and place or change medication orders. Patients are referred to a telemedicine appointment with a nurse who provides personalized education.

Chronic kidney disease is a leading cause of death in the U.S. and occurs when the kidneys can no longer filter blood as well as they should, allowing excess fluid and waste to build up in the body. If left untreated, the kidneys will shut down and dialysis or a kidney transplant will be needed. But medications and lifestyle changes can delay and even prevent progression.

Starting in May 2019, Jhamb and her colleagues enrolled 101 UPMC-affiliated primary care practices in the Kidney-CHAMP trial, randomizing the practices to either receive the intervention or not. The main goal was to see if Kidney-CHAMP reduced risk of chronic kidney disease progression. Although Kidney-CHAMP neither helped nor hurt patient outcomes compared to those who received regular care, patients in the program were more likely to receive appropriate medications and very few physician practices opted out of the intervention.

Barbara Kevish, M.D., participated in the trial as a physician through Renaissance Family Practice, one of the primary care practices that received Kidney-CHAMP. The intervention continues to be offered to her patients through UPMC Health Plan.

"I say to my patients, 'I have a kidney specialist who looked at your chart and gave me recommendations to help maintain your kidney function.' And the patients love it because they get that specialized care without an extra appointment with a specialist," said Kevish, who is also associate vice president of Medicare Medical Services at UPMC Health Plan. "From a primary care standpoint, it's a no-brainer—this program isn't extra work for me and it's a value-add for my patients."

Jhamb suspects that the COVID-19 pandemic, which shifted physician focus from chronic disease management to acute care nationwide, and too short of a follow-up period may be behind the null results. If they'd had more time, Jhamb suspects the study would start seeing positive outcomes .

In the meantime, Kidney-CHAMP formed a partnership with the UPMC Health Plan, and it has since been rolled out to more than 2,500 patients. Jhamb is especially encouraged because, for the first time in nearly 20 years, new therapies are being introduced to improve and prevent kidney failure.

"As soon as new medications become available, Kidney-CHAMP and its team of nephrologists and pharmacists review patient records to see who is most likely to benefit," Jhamb said. "This provides support to busy PCPs who may not otherwise be aware of a brand-new medication or exactly which of their patients it could help."

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Acute kidney injury (aki), table of contents, about acute kidney injury (aki), signs and symptoms, complications, preparing for your appointment.

Acute kidney injury (AKI) is the sudden loss of kidney function. Learn more about the symptoms to watch for and ways to lower your risk.

Acute kidney injury (AKI) is a term used to describe when your kidneys are suddenly not able to filter waste products from the blood. This can happen within a few hours or a few days. For most people, AKI develops within 48 hours, but sometimes it can take as long as 7 days.

This replaces an older term “acute renal failure” (or ARF) which you may still see or hear occasionally.

The signs and symptoms of AKI can differ depending on many factors like the cause, severity, and your other health conditions. If symptoms do happen, they may include one or more of the following:

• Making less urine (pee) than usual or no urine
• Swelling in legs, ankles, and/or feet
• Fatigue or tiredness
• Shortness of breath (trouble breathing)
• Confusion or mood changes
• High blood pressure
• Decreased appetite (low desire to eat)
• Flank pain (pain on the side of your back - between your ribs and hips)
• Chest pain or pressure
• Seizures or coma (in severe cases)

In some cases, AKI causes no symptoms and is only found through other tests done by your healthcare professional.

AKI can have many different causes. Many people get AKI when a related disease or condition puts extra stress on your kidneys. Another common cause for AKI is when your body is reacting to an urgent or emergent health concern (such as heart surgery or COVID-19 infection). Lastly, AKI can be caused by medications or other substances that you may consume. Examples for each of these scenarios are provided below.

Usually, AKI happens because of a combination of factors. This is especially true for older adults who are at higher risk given their age.

Related disease or condition

• Autoimmune kidney disease, such as glomerulonephritis , lupus , or IgA nephropathy
• Cancer (especially bladder, cervical, ovarian, or prostate cancer)
• Chronic kidney disease
• Diabetes flare-up (also known as diabetes-related ketoacidosis or DKA)
• Heart disease (e.g. heart attack, heart failure, or other condition leading to decreased heart function)
• Kidney infection
• Kidney stones
• Liver disease or cirrhosis
• Multiple myeloma (a specific type of blood cancer)
• Vasculitis (long-term inflammation and scarring in your blood vessels)

Urgent or emergent health concerns

• Acute tubular necrosis (ATN), a situation causing very low blood flow to the kidneys
• Anaphylaxis (severe allergic reaction)
• Blood clot or cholesterol blocking a blood vessel in your kidney(s)
• Hypotension (very low blood pressure) or shock
• Hemorrhage (severe loss of blood)
• Major surgery
• Pregnancy complications
• Severe dehydration (not getting enough water or fluids for your body’s needs)
• Severe diarrhea and/or vomiting
• Severe skin burns

Medications and other substances

Items in this list may not cause AKI by themselves, but when combined with other factors from the other 2 categories above, your risk of AKI goes up significantly.

• Certain antibiotics, especially ones given for severe infections
• Certain blood pressure medicines, like ACE inhibitors/ARBs or diuretics (water pills)
• ibuprofen (Motrin, Advil)
• indomethacin (Indocin)
• naproxen (Aleve, Naprosyn)
• diclofenac tablets or capsules (Cataflam, Zipsor)
• celecoxib (Celebrex)
• meloxicam (Mobic)
• aspirin (only if more than 325 mg per day)
• Iodine-based contrast dye (used for CT scans and other forms of medical imaging)
• Recreational drugs, such as heroin or cocaine
• Some medicines used for cancer or HIV
• Toxic alcohols, such as methanol, ethylene glycol (antifreeze), or isopropyl/isopropanol (rubbing alcohol)

AKI can cause a build-up of waste products in your blood and make it hard to keep the right balance of fluid and minerals in your body. It can also cause permanent damage to your kidneys, leading to chronic kidney disease (CKD) . Without treatment, AKI can also affect other organs such as the brain, heart, and lungs. So, it is important to know what to watch for and how to lower your risk.

If your healthcare professional suspects AKI, they will perform an assessment to identify its potential cause (or causes). This may include performing a physical exam, reviewing your medical conditions and medication use history in the past week (including over-the-counter products and herbal supplements), asking about recent events and experiences (e.g. symptoms, water intake, recreational drug use, relevant travel), and ordering blood and/or urine tests.

Some of the most common tests used to check for AKI, include:

• Serum (blood) creatinine – a blood test used to check how well your kidneys are filtering this waste product from your blood
• Estimated glomerular filtration rate (eGFR) – this is calculated based on your serum (blood) creatinine level, age, and sex to estimate your kidney function
• Blood urea nitrogen (BUN) – similar to creatinine, this test can be used to measure another waste product in your blood to see how well your kidneys are filtering the blood
• Other blood tests , such as sodium, potassium, and bicarbonate (to see if anything is out of balance)
• Urine output – your healthcare professional may track how much urine (pee) you pass each day, especially if you are having AKI in the hospital
• Urine test (urinalysis) – a general urine test may be used to find more clues about the cause of AKI
• Imaging tests , like an ultrasound, may be helpful in some cases
• Kidney biopsy – in some less common situations, your healthcare professional may need to look at a tiny piece of your kidney under a microscope to get a better idea about the cause

Other tests may be ordered based on what your healthcare professional thinks might be causing your AKI.

Treatment for AKI depends on what caused it in the first place. This is why finding the cause is so important. Some most common approaches to treating AKI include:

• Stopping any medicines that may be causing or contributing to your AKI
• Giving you fluids (either by mouth or through your veins)
• Antibiotics (if AKI is caused by a bacterial infection)
• Placing a urine catheter (a thin tube used to drain your bladder, useful if AKI is caused by a blockage)
• In most cases, dialysis treatments are only temporary until the kidneys can recover.

Most people with AKI will need to spend some time in the hospital to be monitored while receiving treatment.

After having AKI, you have a higher risk for other health problems, such as chronic kidney disease (CKD), heart disease, or stroke). You are also at a higher risk of getting AKI again in the future. So, it is important to have regular follow-up visits with your healthcare professional and check your kidney health, starting with two simple tests (ideally within 3 months of finishing treatment for your AKI).

Questions to ask

• What are my biggest risk factors for AKI?
• What can I do to help lower my risk for AKI?
• Are there any medications I should avoid (either now or in the future) due to my kidneys?
• [If having potential symptoms of AKI] Should I go to the emergency room for my symptoms?
• Was the cause of my AKI preventable? If so, what can I do to prevent it from happening again?
• When should I follow up after my AKI treatment is done to check my kidney health?

This content is provided for informational use only and is not intended as medical advice or as a substitute for the medical advice of a healthcare professional.

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Lived Experiences of Patients with Chronic Kidney Disease Receiving Hemodialysis in Felege Hiwot Comprehensive Specialized Hospital, Northwest Ethiopia

Hailemariam tadesse.

1 Felege-Hiwot Comprehensive Specialized Hospital, Bahir Dar, Ethiopia

Hordofa Gutema

2 School of Public Health, College of Medicine and Health Sciences, Bahir Dar University, Bahir Dar, Ethiopia

Yosef Wasihun

Samuel dagne, yonatan menber, pammela petrucka.

3 College of Nursing, University of Saskatchewan, Saskatoon, Canada

Netsanet Fentahun

Associated data.

The datasets supporting the conclusions of this article are included within the article.

Chronic kidney disease is a challenging disease and global public health problem. The burden of chronic kidney disease and hemodialysis is increasing in Ethiopia, but few studies explored the lived experiences of chronic kidney disease patients receiving hemodialysis. This study explored the lived experiences of chronic kidney disease patients receiving hemodialysis, in the Felege Hiwot Comprehensive Specialized Hospital, Bahir Dar City, Northwest Ethiopia, 2019.

A phenomenological study design was conducted with 12 chronic kidney disease patients receiving hemodialysis between September 1 and October 30, 2019. A purposive sampling technique was used to select participants, and a semistructured in-depth interview guide was used to collect the data. The investigators audio-taped the interviews and then transcribed them verbatim. Finally, the transcribed data were imported to Atlas.ti™-7 software for coding, and then, thematic analysis was done. Transferability, dependability, credibility, and conformability were embedded to ensure data quality.

In this study, six major themes were emerged: (1) the seriousness of the disease, (2) challenges to get hemodialysis, (3) financial constraint, (4) restricted life, (5) feeling of dependency, and (6) psychological impacts.

The restrictive nature of the disease affects a participant's financial status which makes it challenging to obtain the service and increases feelings of dependency. These circumstances impact the psychology of the participants. We would recommend that every patient with hemodialysis needs social and psychological support. We would also recommend the need to extend the study to other areas of the country to confirm or disconfirm the findings.

1. Introduction

Chronic kidney disease (CKD) is defined as abnormal kidney composition or function persisting for longer than 3 months [ 1 ]. CKD is a global public health problem due to a rise in common comorbidities such as diabetes, hypertension, and obesity [ 2 ]. By definition, CKD is a progressive, permanent impairment in the renal task, which results in metabolic, fluid, and electrolyte imbalances in the body [ 3 ].

CKD is classified into five stages based on the level of glomerular filtration rate [ 3 ]. Stage 5 is considered as nonreversible kidney failure, so dialysis or a kidney transplant will likely be needed to prolong life [ 4 ]. Any stage of CKD is linked with increased risks of cardiovascular disease, premature mortality, and/or decreased quality of life [ 5 ].

Globally, more than 500 million people are affected by CKD [ 1 , 6 ]. The incidence of CKD has continued to rise at a rate of 8% per year and consumes up to 2% of the overall global health expenditure [ 7 ]. More than one million people in the world with severe CKD are being treated with some form of therapy, with 90% of these patients living in developed countries [ 5 ]. There is a considerable rise in the number of CKD patients who are taking hemodialysis management [ 8 , 9 ]. Hemodialysis is expensive and inaccessible to many in developing countries, and the increased nonadherence rate of supportive treatment is also a common problem in CKD patients due to financial constraints [ 1 , 10 – 12 ].

Annually, in Ethiopia, deaths related to renal disease exceeded 12,000 people (1.47% of total deaths) [ 13 ]. In Ethiopia, hemodialysis is inaccessible and unaffordable for the majority of the target population. Each CKD patient's expenses for each hemodialysis treatment are more than 1000 Ethiopian Birr (30 US$) [ 14 ]. Currently, in Ethiopia, there are few dialysis centers only found in public hospitals [ 15 ].

CKD patients live with significant dietary restrictions, which results in an impairment in health [ 16 , 17 ].

Studying lived experience of CKD patients on hemodialysis will help to improve services by connecting health professionals, researchers, and policy-makers to design solutions for encountered problems. Since limited qualitative researches were done previously, this study will be used to fill the gaps by exploring the real lived experience of patients on hemodialysis.

Therefore, this study explored the lived experiences of CKD patients receiving hemodialysis, in Felege Hiwot Comprehensive Specialized Hospital, Bahir Dar City, Northwest Ethiopia.

2. Materials and Methods

2.1. study setting and design.

The phenomenological study design was conducted between September 1 and October 30, 2019, in Felege Hiwot Comprehensive Specialized Hospital (FHCSH), Bahir Dar City, Amhara Region, Northwest Ethiopia. FHCSH is found 560 km Northwest of Addis Ababa, the Capital City of Ethiopia. It provides health services for more than 5 million people. According to FHCSH 2018/2019 report, the hospital provided a hemodialysis service per year for over 2800 CKD patients. These patients got 2-3 times hemodialysis service in a week. Hemodialysis service is given only in FHCSH in Bahir Dar City.

2.2. Study Participants

The study participants were patients with CKD and use hemodialysis treatment for more than three months in the FHCSH hemodialysis center. Chronic kidney disease with hemodialysis patients aged 18 years and above were included in this study. Twelve CKD patients with hemodialysis were purposively selected for an in-depth interview (IDI) that included both males and females. A purposive sampling technique was used to select the study participants. The criteria for recruiting reflect the potential relevance of the participants in delivering a wealth of information about the lived experience of CKD with hemodialysis. In addition, the maximum variation technique was applied to include participants with variations of characteristics like educational status, residence, age, marital status, distance from the dialysis center, and capability of paying for the service.

The sample size was determined based on theoretical saturation, and 12 participants were involved. Saturation was declared by listing some important findings. Participants were identified from the hemodialysis (HD) center patient registration book and their schedule of HD procedure with the aid of the HD center coordinator.

2.3. Data Collection Methods and Tools

The study adopted a semistructured in-depth interview guide from the evidence/literature [ 18 – 20 ]. It was pretested from three samples in Gondar Comprehensive Specialized Hospital which is found 169 km away from the study area. The guide was developed first in English, translated into Amharic (local language) to collect the data, and then translated back to English to check the consistency.

In-depth interviews were employed to collect the data in the hospital in a separate room. The principal investigator conducted twelve in-depth interviews (IDIs). The principal investigator (PI) conducted face-to-face interviews using the IDI guide. Newly emerging insights and questions were added for clarification and depth in the following IDI. The data were recorded using a tape recorder, and the investigator took notes including memos of the participants' behavior and contextual aspects to augment the data with the record. The IDIs took a minimum of 45 minutes.

During data collection, participants were engaged in a dialogue-like approach, first asking the participant a question, then listening attentively until the individual completes his/her idea, and then probing based on the response of the participant.

2.4. Data Analysis

All IDIs were transcribed verbatim after a minimum of three-repeat listening. The transcribed documents were imported into Atlas.ti™ version 7 for coding and analysis. The investigators then coded the respondent's words, phrases, sentences, and memos relevant to the area of the study. They systematically coded raw data openly and categorized the subthemes under their respective themes. Then, they created nonrepetitive central themes that were constructed based on the formed categories. Finally, investigators also cross-checked the themes that emerged after analysis with the raw data and respective quotes in each category of the themes. Direct quotes of the participants were included in the write-up of the findings.

2.5. Data Quality Assurance

Developed data collection tools were pretested in a similar context to maximize the validity. Probing and multiple data sources were employed to collect the data. At the onset of the study, bracketing the preconceptions of the investigator was employed to minimize the investigator's bias and the risk of reactivity by the participants. Also, the literature review was delayed until the data collection and analysis to minimize bias. The emerging findings were shared with experienced qualitative researchers for peer debriefing before synthesizing the final outputs. Transferability was achieved by describing the study setting, sample, and data collection procedure clearly and in detail. Dependability was obtained to increase the consistency of the study and could be repeated. Confirmability of the study was ensured by the recording of every activity of the participants during the time of the interview.

Twelve participants were involved in this study. Ten of the participants were male, and the mean age of the participants was 37 years with a range of 24 to 50 years. Six of the participants stopped working due to the disease, and five participants were using hemodialysis for more than two years ( Table 1 ).

Sociodemographic characteristics of participants in FHCSH Hemodialysis Center, Bahir Dar City, Northwest Ethiopia, 2020.

3.1. Lived Experiences of CKD Patients with Hemodialysis

The study participants in FHCSH of Bahir Dar City reported their lived experience of CKD with hemodialysis as the seriousness of the disease, challenges to get hemodialysis, financial constraints, restricted life, feeling of dependency, and psychological influence.

Theme 1 . —

The seriousness of the disease.

CKD is recognized as a devastating and life-threatening condition in the theme seriousness of the disease. The conditions that make it too difficult to live with the disease were the poor outcome, lifelong treatment, restriction in full participation in their social life and daily activity, and expenses associated with the treatment.

...it's hard to describe this disease. It's a terrible disease. It hurts my economy, family, neighbors … a generally devastating disease. I don't expect to be cured. If I don't get dialysis, the pain will be worsening. (Participant 12 ).

Lifelong treatment of the disease and limited intake of foods and beverages were described as the most horrible thing by CKD patients when comparing CKD with other diseases they knew.

Living with this disease is more difficult than living with other diseases. Different individuals said that AIDS was hard, but AIDS is easy when compared to chronic kidney disease. They eat what they want, they drink what they need, they live freely, but I can't eat what I get, I can't drink what I get, even water doesn't allow too much. (Participant 2)

Theme 2 . —

Challenges of getting hemodialysis.

Inaccessibility of hemodialysis was the main issue that was mentioned as a deterrent. Most participants travel long distances to access hemodialysis service, two or three times a week. Such situations make it difficult for them to reach a hemodialysis center according to their dialysis schedule. Travel costs and cost of treatment for hemodialysis and other supportive care were described as challenging.

…I separated from my family because of the disease. The hemodialysis center didn't found in the area where I live, but, now I live here with a rent home. Life is always a struggle but living with this disease is challenging. I don't know how I live the remaining life in such a way. Generally, I can't express the effect of this disease on my life, his face changed and his tear was drawn. (Participant 5)

The commonly reported issue was the frequent breakdown of the dialysis machines, fluctuation of electrical power, and absence of filtered water, and some supply which plays a great role in poor adherence to the treatment. It exposes them to wait long queues and then stay for more than a week without getting the service.

I faced a problem light interruption when I was on the bed. My blood in the line of the dialysis machine was discarded due to clotting and I waited for an additional 2-3 hours on a bed. (Participant 11)

Long procedure time is one of the problems mentioned as a challenge by most participants during hemodialysis service. Most of the participants spend their time on HD by sleeping, using Facebook, and watching TV.

It is a long time that seems greater than one full day. It is challenging. If you compare workplace time and hemodialysis procedure time, in the workplace, you entered 8:30 and went out for lunch at 12:30, the time run unconsciously, but here spending time on dialysis bed is boring and looks like a double day. (Participant 3)

Theme 3 . —

Financial constraint.

Financial constraints are challenging issue that prevents participants from accessing hemodialysis service. Almost all participants believed that the service they obtain from the dialysis center was uncertain due to financial constraints. Most participants decreased the frequency of hemodialysis service that they got within a week and also they usually ignore additional ordered supportive medications due to financial constraints.

I did hemodialysis once per week due to the affordability issue of the service. My family was unable to cover 2-3 times hemodialysis payment, and I always think about cost and depressed me. (Participant 7)

Most participants sell their available assets (i.e., goat, ox, house, car, etc.) to afford their treatment; others borrow or beg from families, relatives, and/or others.

I have no remaining asset in my hand. Even I sold my car. All my properties were lost due to the disease. Still, now I survived with my own, but for the future, I fear dependency for others which is the most I hate in my life. (Participant 8)

Participants feel the disease reaches far beyond themselves.

… as I mentioned earlier [angrily], the disease made me paralyze in my economy, then it affects my family, relatives, and neighbors. (Participant 12)

Theme 4 . —

Restricted life.

Almost all of the study participants describe their grief in how CKD has placed limitations on their lives. Even though participants feel as they live a limited life, they strictly adhere to fluid and diet restrictions.

The disease made me a poor man and when the restriction of food and drink is added, it makes the problem double burdened. As you know when I have no resources I can't select food and drinks. Because I had only limited alternatives, I always eat and drink what I had in my hand without selection. This makes the disease worsen, that is why I said earlier double burden. (Participant 8)

The experience of fatigue was described as reducing an individual's potential and energy which results in a decreased capacity to perform daily activities. Such restricted activities affect social life and quality of life. Most participants described their feelings of loss due to fatigue.

... the disease does not make you mobile, work as you want and get income, because the disease is hard. It tends to hurt your bones, hmm..., it's exhausting, your energy is decreased like a baby walk... you look as someone drunk. (Participant 9)

While the participants have different roles in their families and the community, many of them find their role and performance have been disturbed since living with CKD. After the occurrence of the disease, the majority of the participants' plans were distorted.

As a human being, I had the plan to get my Ph.D. In addition to this, I had plans to build a house, writing books, and do other activities, but everything remains a wish. Everything goes to a cliff. Now I have no hope to conduct those plans, everything is dead, just it downgrades your potential and makes your family hopeless. The only thing that I worried about is how to survive. (Participant 4)

The majority of the participants described the consequences of the disease on their marriage in terms of their marital and community relationships.

I expect that she was not happy in her life [sexual life]. When I see this, I say this disease has an impact on marriage. I know she lost the love from me because I am suffering from a disease and I can't give love as she wants at this time (lough), the disease is so challenging. (participant 4)

Some participants described experiencing discrimination concerning participation in community activities. Additionally, the relationships are often impacted due to the potential for kidney donation from their family or relatives affecting their relationships.

Now I stopped all social activities totally what I did before. Stigma and discrimination are high Among CKD patients than HIV/ADIS patients that I observed. Even my family members discriminate against me, so no social life at all, nobody cares about you and helps you… (cried). Rather than giving me solution and strength, most of the people around me make me hurt by different bad speeches. (Participant 4)

Most participants believed that hemodialysis is a blessing from God. They tried to use their faith as a coping mechanism while they live in a stressful situation.

I believe in God. …I believe in God as I receive the grace of God to see what tomorrow brings to me. (Participant 9)

Some participants believed the disease is given by God to punish them as the consequence of sin; hence, participants may be discriminated against in their participation in religious activities. Participants were prevented from fasting, praying together, and baptisms.

In Muslims, I have to bow down three times a day but I can't honor. Because of this, I do not apply all the services of faith. If I don't do that I'll be very bored. Of course, I cannot do everything, I must leave it to the Creator. (participant 7).

Theme 5 . —

Feeling of dependency.

Almost all the participants described as they rely on someone with financial, physical, or social while they live with this disease. Each activity of the participant needs family or social support.

Participant 8 stated the following.

I can't sit in the toilet, without the help of others. Since it was a matter of blood clots, my thighs' were swollen, sore all around, and I had reached the point where I couldn't do all the hygiene myself and use the toilet. So I suffered until I could no longer use the toilet in own and it was very hard. They told me that the dialysis was done with the support of the family.

Most participants believed that they lived dependent on the machine.

Normally it is good, which removed that dangerous pain... and give me hope of living. But when I think my life suspended on the machine is very painful. ( Participant 4)

Sometimes I said thank you, God, because God will never give me a disease, without giving the medicines [saydegs aytalam], when I was in the dialysis center. (Participant 12)

Theme 6 . —

Psychological impacts.

Almost all participants have psychological problems related to body image and mental wellness. Body swelling, abdominal distention, and darkening of the face catalyzed the negative self-perception. Sleep disturbances, anxiety, and depression lead them to suicidal ideations or attempts.

I was deciding to kill myself, to be free from hemodialysis. During that time, I was unable to move. There is no change after this disease happened in my life and I wish I could die. I feel lonely. It is boring to live with such a condition... [She cried]. (Participant 2)

Some of the participants live with anxiety over the poison of the serious disease; others experience worry about the loss of their potential.

Participant 9 described the following.

I couldn't look at the things that you had and my moral is exhausted, I act like a 70 or 80-year old, I passed my time on the bed and I get embarrassed.

4. Discussion

The current study explored the lived experience of CKD patients receiving hemodialysis in the FHCSH of the Amhara Region. According to the current study, the seriousness of the disease was reflected in the “horrible nature” of CKD as needing lifelong treatment, incurring extensive treatment costs and restriction in social life, lacking accessibility to hemodialysis services, and being restricted in intake of diet and fluids. This study finding was in line with the studies conducted in Nigeria [ 18 ] and India [ 21 ], where participants described the loss of their freedom to participate in different activities, restriction in diet, fatigue associated with a lack of strength and energy, and decreased ability to perform their jobs. In the current study, participants clearly described their immense sense of loss on multiple dimensions. This result consistent with studies conducted in Nigeria [ 18 ], Iran [ 22 ], Francisco [ 23 ], Georgia [ 4 ], and the USA [ 19 ], with those living with CKD, described their lives as being filled with pain and suffering, loss of self, and loss of independence.

According to this study, participants frequently experience a shortage of filtered water and repeated breakdowns of the dialysis machines due to frequent electrical power interruptions which are similarly reported in studies from Nigeria [ 18 ] and the USA [ 19 ].

The current study showed that the inaccessibility of the hemodialysis service in health is a barrier to participants making it difficult to reach the dialysis center on time. This finding was consistent with a study conducted in Nigeria [ 18 ] whereas a study conducted in New Zealand [ 24 ] contradicted this result where there is a provision of in-home service and satellite dialysis centers. Also, long procedure times (3-4 hours) were mentioned as a challenge in this study and supported by studies conducted in South Korea [ 25 ], New Zealand [ 24 ], and Australia [ 26 ].

This study showed that participants often opted for a reduction of hemodialysis sessions per week and missed prescribed drugs due to financial constraints related to transportation and lack of ability to work. This finding is similar to the study conducted in Nigeria [ 18 ], where financial constraints were mentioned as a major barrier to service adherence. In addition, participants spoke of the consumption of assets to pay for their treatments, which is also reported in studies conducted in Nigeria [ 18 ] and the USA [ 19 ].

This study revealed that the disease disturbed participants in the performance of their roles in families and community while impacting their ability to plan. Similar results were reported in studies conducted in India [ 21 ] and Iran [ 27 ].

The current study showed that social life complexities like marital relationship disturbance contribute to separation, segregation, and stigma by communities and even families. This finding is supported by a study conducted in Spain [ 28 ]. On the other hand, the current study showed that most participants have a strong religious base which is articulated in the belief that the treatment they obtain in the HD center was blessed by God, resonating with a study from Jordan [ 29 ]. Some participants, however, contradict the above finding stating that the disease was given by God to punish them (a consequence of sin) which limited their participation in religious activity. A study conducted in Nigeria [ 18 ] also reported that CKD patients had a negative sense toward faith and blamed their illness on spiritual factors or on “divine intervention”.

This study revealed participants' experience of multilevel dependencies on financial, physical, social support, and the hemodialysis machine while they live with this disease. This finding is supported by studies conducted in Nigeria [ 18 ], Iran [ 22 ], New York [ 30 ], and India [ 21 ]. The sense of machine dependency is also mentioned by studies conducted in Australia [ 26 ] and India [ 31 ].

Another important finding of the current study is the psychological influence of the disease. Self-image, stigma, and suicidal ideations are all considered within the rubric of mental distress by the participants. This complex and far-reaching result was consistent with the studies conducted in India [ 31 ] Nigeria [ 18 ], Iran [ 22 ], Greece [ 32 ], and the USA [ 19 ], where participants described feelings of isolation in the society, physical limitations, and fears of poor clinical results contributing to feelings of sadness, depression, and despair. Further, the lifelong (chronic) dimension of CKD along with the uncertainties with regard to the ability to continue treatments and afford the medications impacted significantly on psychological wellbeing. This finding is supported by studies conducted in Iran [ 27 ] and Sweden [ 33 ].

5. Conclusions

The lived experiences of CKD patients receiving hemodialysis were found to be broad, significantly negative narratives from the participants in this study. Whether discussing, the seriousness of the disease challenges to get hemodialysis, financial constraints, restricted life, feelings of dependency, or psychological influence was evident where there were many shared experiences. Inaccessibility of hemodialysis service was a major challenge and an extra expense. Restrictions from available foods and drinks were a double burden that limited participants from using an available resource. Financial incapability was another challenge raised due to the loss of income-generating activities. As a result, a feeling of dependency on others was reported as leading to the development of mental distress (psychological influence).

Based on this study, we would recommend the need to extend the study to other areas of the country to confirm or disconfirm the findings. Further, we would recommend that a longitudinal study be considered which would look at the psychosocial domains of CKD to build holistic programs (financial, social, psychological) and other interventions (i.e., universal health coverage; transportation subsidies) which are more responsive to the needs of this challenged population (Tables ​ (Tables2 2 and ​ and3 3 ).

Sociodemographic characteristics of the participants.

Area to be observed.

Acknowledgments

This research was self-funded by author Hailemariam Tadesse.

Abbreviations

Data availability, additional points.

Limitation. The study shows the Inability to generalize this finding to related populations.

Ethical Approval

Ethical clearance was obtained from the Institutional Review Board of the College of Medicine and Health Sciences, Bahir Dar University. An official support letter was obtained from Amhara Public Health Institute. The procedures were compiled with the Helsinki declaration.

Written informed consent was obtained from participants and was taken also from a husband of one participant who cannot read and write after informing them about all the purpose, benefits, and risks of the study.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Authors' Contributions

HT, NF, and HG contributed to the proposal development, data collection, analysis, and result interpretation. HT, YW, SD, and YM contributed to the conceptualization and writing of the paper. PP edited the overall improvement of the manuscript. All authors read and approved the final paper.

Supplementary Materials

Supplement document 1: Filled Consolidated Criteria for Reporting Qualitative Studies (COREQ) checklist Supplement document 2: Information sheet and Consent form Supplement document 3: Interview Guide.

A Narrative Review of Chronic Kidney Disease in Clinical Practice: Current Challenges and Future Perspectives

• Open access
• Published: 05 November 2021
• Volume 39 , pages 33–43, ( 2022 )

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• Marc Evans 1 ,
• Ruth D. Lewis 2 ,
• Angharad R. Morgan 2 ,
• Martin B. Whyte 3 ,
• Wasim Hanif 4 ,
• Stephen C. Bain 5 ,
• Sarah Davies 6 ,
• Umesh Dashora 7 ,
• Zaheer Yousef 8 ,
• Dipesh C. Patel 9 &
• W. David Strain 10  

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Chronic kidney disease (CKD) is a complex disease which affects approximately 13% of the world’s population. Over time, CKD can cause renal dysfunction and progression to end-stage kidney disease and cardiovascular disease. Complications associated with CKD may contribute to the acceleration of disease progression and the risk of cardiovascular-related morbidities. Early CKD is asymptomatic, and symptoms only present at later stages when complications of the disease arise, such as a decline in kidney function and the presence of other comorbidities associated with the disease. In advanced stages of the disease, when kidney function is significantly impaired, patients can only be treated with dialysis or a transplant. With limited treatment options available, an increasing prevalence of both the elderly population and comorbidities associated with the disease, the prevalence of CKD is set to rise. This review discusses the current challenges and the unmet patient need in CKD.

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Introduction

Chronic kidney disease (CKD) is a complex and multifaceted disease, causing renal dysfunction and progression to end-stage kidney disease (ESKD) and cardiovascular disease. Complications associated with the disease contribute to the acceleration of CKD progression and risk of cardiovascular-related morbidities.

Despite its high prevalence and the clinical and economic burden of its associated complications, disease awareness remains profoundly low. Worldwide, only 6% of the general population and 10% of the high‐risk population are aware of their CKD statuses [ 1 ]. In addition, CKD recognition in primary care settings is also suboptimal, ranging from 6% to 50%, dependent upon primary care specialty, severity of disease, and experience. Awareness of CKD remains low in part because CKD is usually silent until its late stages. However, diagnosis of CKD during the later stages results in fewer opportunities to prevent adverse outcomes. Physician awareness of CKD is critical for the early implementation of evidence-based therapies that can slow progression of renal dysfunction, prevent metabolic complications, and reduce cardiovascular-related outcomes.

Currently CKD is not curable, and management of the disease relies on treatments which prevent CKD progression and cardiovascular disease. Despite available treatments, a residual risk of adverse events and CKD progression remains. This article reviews the challenges associated with CKD and the treatments available for patients, highlighting the unmet need for cardio-renal protection in patients with CKD.

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

CKD Prevalence

CKD is a global health problem. A meta-analysis of observational studies estimating CKD prevalence showed that approximately 13.4% of the world’s population has CKD [ 2 ]. The majority, 79%, were at late stages of the disease (stage 3–5); however, the actual proportion of people with early CKD (stage 1 or 2) is likely to be much higher since early kidney disease is clinically silent [ 3 ].

Prevalence of CKD appears to be growing rapidly both in the UK and in the Western world. Based on the 2012 subnational population projections for England [ 4 ], the number of people with CKD stage 3–5 is projected to exceed 4 million by 2036 [ 5 ]. This rise in CKD prevalence is due to an increased aging population and prevalence of type 2 diabetes (T2DM), obesity, hypertension and cardiovascular disease that contribute to CKD [ 6 , 7 , 8 ].

The World Health Organization (WHO) estimated that the annual, global number of deaths caused directly by CKD is 5–10 million [ 9 ]. The presence of CKD advances mortality of comorbidities such as cardiovascular diseases, T2DM, hypertension, and infection with human immunodeficiency virus (HIV), malaria and Covid-19, thereby indirectly adding to CKD mortality [ 9 , 10 ]. A contributing cause of high morbidity and mortality associated with CKD is a lack of awareness of the disease, by both patients and providers [ 11 , 12 ]. Early stages of CKD are clinically silent and patients have no symptoms. Lack of treatment at this stage allows CKD to progress through to advanced stages of the disease, where patients may present complications and/or cardiovascular-related comorbidities, or ESKD. Raising awareness of CKD is therefore paramount to allow for early intervention and reduce the risk of comorbidities and mortality.

Classification of CKD

In order to better manage CKD and provide better care for patients, the classification of CKD was developed by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative [ 13 ] and the international guideline group Kidney Disease Improving Global Outcomes (KDIGO) [ 14 ]. CKD stratification is based upon the estimated glomerular filtration rate (eGFR) and albuminuria.

There are six eGFR categories. An eGFR of less than 60 mL/min per 1.73 m 2 for more than 3 months is indicative of impaired renal function and the severity of kidney damage increases with decreasing eGFR measurements. Patients with early onset of the disease, stage 1–2, have normal to mild decreased levels of eGFR (60 to ≥ 90 mL/min per 1.73 m 2 ). Patients with stage 3a–3b have mild to moderate decreased levels of eGFR (45–59 mL/min per 1.73 m 2 , respectively). Severely decreased levels of eGFR, stage 4–5 (15–29 to < 15 mL/min per 1.73 m 2 , respectively), are indicative of advanced stages of the disease and kidney failure.

Stratification also comprises three categories of albuminuria. Patients with an albumin to creatinine ratio (ACR) of 3 to at most 30 mg/mmol are classified as having microalbuminuria and at moderate risk of adverse outcomes. Those with ACR of greater than 30 mg/mmol are classified as having macroalbuminuria and being severely at risk of developing adverse events [ 15 ]. The eGFR and albuminuria categories independently predict adverse outcomes for patients with CKD, and the combination of both increases this risk further [ 16 ]. The CKD classification system aids clinicians in carrying out accurate assessments of CKD severity and other complications which helps to inform decisions associated with the management and monitoring of patients [ 3 , 17 , 18 ].

Clinical Burden of CKD

CKD is a complex disease, involving both non-modifiable (e.g. older age, family history and ethnicity) and modifiable risk factors (e.g. T2DM, hypertension and dyslipidaemia) which are responsible for the initiation of early CKD, CKD progression (stage 3–5) and ESKD.

In early stages of CKD (stage 1–2), factors such as hypertension, obesity and T2DM can trigger kidney function impairment. This causes glomerular/interstitial damage and results in impaired glomerular filtration, leading to decreased eGFR and increased albuminuria. At this stage, even though clinical symptoms do not present, the presence of additional risk factors, including hypertension, hyperglycaemia, smoking, obesity, dyslipidaemia and cardiovascular disease, may accelerate CKD progression and result in ESKD.

As the disease progresses, the clinical and economic burden of CKD increases (Fig.  1 ) as complications such as CKD mineral bone disorder, anaemia, hypertension and hyperkalaemia may occur and advanced stages of CKD, stage 4–5, ensue. Clinical symptoms, such as fatigue, itching of the skin, bone or joint pain, muscle cramps and swollen ankles, feet or hands, are often present at this stage [ 19 ]. Further deterioration of kidney function causes tubular and glomerular hypertrophy, sclerosis and fibrosis, leading to a significant reduction in eGFR, extreme albuminuria and kidney failure.

A schematic diagram showing the association between CKD progression and clinical and economic burden. Symptoms of CKD typically present during advanced stages of the disease where patients are at increased risk of cardiovascular disease and other comorbidities

Even though CKD progression may lead to kidney failure and renal death, patients with CKD are more likely to die from cardiovascular-related complications before reaching ESKD [ 20 ]. A study using data from a meta-analysis involving 1.4 million individuals found a significant increased risk of cardiovascular-related mortality, even in stage 2 of CKD (eGFR levels < 90 mL/min per 1.73 m 2 ) [ 16 , 21 , 22 ].

As the disease progresses, the risk of cardiovascular disease is markedly increased, such that 50% of patients with late-stage CKD, stage 4–5, have cardiovascular disease. The risk of atrial fibrillation (AF) and acute coronary syndrome (ACS) is doubled in patients with eGFR < 60 mL/min per 1.73 m 2 . AF is associated with a threefold higher risk of progression to ESKD. The incidence of heart failure (HF) is also threefold greater in patients with eGFR < 60 mL/min per 1.73 m 2 compared with > 90 mL/min per 1.73 m 2 and HF is associated with CKD progression, hospitalisation and death [ 23 ].

The increased risk of cardiovascular disease in patients with CKD is due in part to the traditional risk factors associated with cardiovascular disease such as hypertension, T2DM and dyslipidaemia. For instance, a large observational database linked study (Third National Health and Nutrition Examination Survey (NHANES) III) found a strong association between CKD and T2DM combined and an increased risk of mortality [ 24 ]. In this study, the authors observed a 31.1% mortality rate in patients with CKD and diabetes, compared to 11.5% in people with diabetes only. An observational study using both US and UK linked databases showed that the presence of both CKD and T2DM was related to increased risk of major adverse cardiac events (MACE), HF and arrhythmogenic cardiomyopathy (ACM) [ 25 ]. This risk was further elevated in older patients with atherosclerotic cardiovascular disease [ 25 ]. Similarly, the presence of both CKD and T2DM leads to a significant increased risk of all-cause and cardiovascular-related mortality versus T2DM alone [ 24 ].

The direct renal effect on cardiovascular disease is due to generalised inflammatory change, cardiac remodelling, narrowing of the arteries and vascular calcification, both contributing to the acceleration of vascular ageing and atherosclerotic processes, and leading to myocardial infarction, stroke and HF [ 26 ].

Together, these studies highlight the strong relationship which exists between CKD progression, number of comorbidities and heightened risk of cardiovascular disease and cardiovascular-related mortality.

Economic Burden of CKD

In addition to the clinical burden, management of CKD also requires significant healthcare resources and utilisation. In 2009–2010, the estimated cost of CKD to the National Health Service (NHS) in England was £1.45 billion [ 27 ]. Furthermore, in 2016, US Medicare combined expenditure for CKD and ESKD exceeded $114 billion (£86 billion) [ 28 ].

Although estimating the true cost of early CKD is difficult because of the lack of data available for unreported cases, CKD progression is associated with increased healthcare costs [ 29 , 30 ]. A study by Honeycutt et al. combined laboratory data from NHANES with expenditure data from Medicare and found that costs of CKD management increased with disease progression [ 29 ]. Estimated annual medical costs of CKD per person were not significant at stage 1, $1700 at stage 2, $3500 at stage 3 and $12,700 at stage 4.

Healthcare costs associated with early CKD are more likely to be from the sequalae of comorbid disease rather than kidney disease. Hence, patients with CKD stage 1 or 2 are at increased risk of hospitalisation if they also have T2DM (9%), cardiovascular disease (more than twofold), and both cardiovascular disease and T2DM (approximately fourfold) [ 31 ].

ESKD accounts for the largest proportion of CKD management costs. In 2009–2010, 50% of the overall CKD cost to NHS (England) was due to renal replacement therapy (RRT), which accounted for 2% of the CKD population [ 27 ]. The other 50% included renal primary care costs, such as treatment costs for hypertension and tests, consultation costs, non-renal care attributable to CKD and renal secondary care costs. Approximately £174 million was estimated for the annual cost of myocardial infarctions and strokes associated with CKD [ 27 ].

More recently, an economic analysis investigated the burden associated with the management of cardiovascular-related morbidity and mortality in CKD, according to the KDIGO categorisation of both eGFR and albuminuria [ 15 ]. Decreased eGFR levels increased both the risk of adverse clinical outcomes and economic costs, and albuminuria elevated this risk significantly. Furthermore, CKD progression correlated with increased CKD management costs and bed days. Stage 5 CKD (versus stage 1 (or without) CKD) per 1000 patient years was associated with £435,000 in additional costs and 1017 bed days.

The significant economic burden associated with CKD progression and ESKD highlights the importance of optimising CKD management and the unmet need for better treatment options in slowing disease progression in this patient population. Thus, early detection and intervention to slow the progression of the disease has the potential to make substantial savings in healthcare costs.

Current CKD Management Strategies

KDIGO and National Institute for Health and Care Excellence (NICE) have produced detailed guidelines for the evaluation and management of CKD [ 3 , 32 , 33 ]. Both recommend implementing strategies for early diagnosis of the disease in order to reduce the risk of cardiovascular disease, attenuate CKD progression and decrease the incidence of ESKD in this patient population. CKD is a complex disease and thus treatment requires a multifaceted approach utilising both non-pharmacological, e.g. diet and exercise regimes and pharmacological interventions such as antihypertensive and antihyperglycemic drugs [ 34 ]. There has, however, been no significant breakthrough in this area for over 2 decades.

The effect of lifestyle intervention on reducing disease progression is still unclear, although increased physical activity has been shown to slow the rate of eGFR decline [ 35 ] and ESKD progression [ 36 ], improve eGFR levels [ 35 ] and albuminuria [ 37 ], and reduce mortality in patients with CKD [ 35 , 38 , 39 , 40 ]. Similarly, diet regimes such as low-protein diet or Mediterranean diet reduce renal function decline and mortality rate in CKD [ 41 , 42 ]. Hence, dietary advice is recommended in accordance with CKD severity to control for daily calorie, salt, potassium, phosphate and protein intake [ 3 , 33 ]. However, patients with consistently elevated serum phosphate levels or metabolic acidosis [low serum bicarbonate levels (< 22 mmol/l)], associated with increased risk of CKD progression and death, may be treated with phosphate binding agents (e.g. aluminium hydroxide and calcium carbonate) or sodium bicarbonate, respectively [ 3 ].

To reduce the risk of cardiovascular disease, KDIGO and NICE recommend active lipid management and blood pressure control [ 33 , 43 , 44 ]. In early CKD stages 1 and 2, statins are recommended for all patients over 50 years of age, whilst in stage 3 and advanced stages of the disease, stage 4–5 (eGFR < 60 mL/min per 1.73 m 2 ), a combination of statins and ezetimibe is advised [ 43 ].

Management of hypertension includes a target blood pressure of less than 140/90 mmHg for patients with CKD and hypertension and less than 130/80 mmHg for patients with CKD and T2DM, and also in patients with albuminuria [ 3 , 32 ], alongside blood pressure lowering therapies and renin–angiotensin–aldosterone system (RAAS) blocking agents, such as angiotensin receptor blockers (ARB) or angiotensin-converting enzyme inhibitors (ACEi). As such, RAAS inhibitors (RAASi) are currently recommended to treat patients with diabetes, hypertension and albuminuria in CKD [ 45 ]. These RAAS blocking agents confer both renal and cardiovascular protection and are recommended as first-line treatment to treat hypertension in patients with CKD [ 34 , 46 ].

The clinical benefits of RAASi have been demonstrated in patients with CKD with and without diabetes [ 47 , 48 , 49 ]. These clinical benefits are in addition to their effects on reducing blood pressure and albuminuria, including a reduction in eGFR decline and a decreased risk of ESKD cardiac-related morbidity and all-cause mortality [ 47 , 48 , 49 ]. Nevertheless, despite their benefits, RAASi treatment can induce hyperkalaemia, and patients are often advised to reduce RAASi dosage or even discontinue their treatment, which prevents optimum clinical benefits of RAASi therapy being reached. In this instance, combination therapy with potassium binding agents, such as patiromer and sodium zirconium cyclosilicate, may be used alongside RAASi therapy to reduce RAASi-associated hyperkalaemia.

However long-term trials will be required to determine their effect on cardiovascular morbidity and mortality in CKD [ 50 , 51 , 52 ]. Despite these therapies being the mainstay of CKD management, there is still a residual risk of CKD progression and an unmet need for new treatments.

Novel/Emerging Treatments for CKD Management

Over the last 2 years, novel therapeutic approaches for CKD management have emerged, with particular attention on mineralocorticoid receptor antagonists (MRAs) and sodium–glucose co-transporter 2 (SGLT2) inhibitors. The clinical effectiveness of finerenone, a selective oral, non-steroidal MRA, has recently been demonstrated to lower risks of CKD progression and cardiovascular events in diabetic kidney disease (DKD) [ 53 ]. Finerenone is under review for approval by the European Medicines Agency (EMA) and US Food and Drug Administration (FDA).

Of these new and emerging therapies, SGTL2i offers the most clinical benefit with both cardiovascular and renal protective effects, independent of glucose lowering. Clinical trials of SGTL2 in T2DM with and without CKD overall showed a 14–31% reduction in cardiovascular endpoints including hospitalisation for HF and MACE and a 34–37% reduction in hard renal-specific clinical endpoints including a sustained reduction in eGFR, progression of albuminuria and progression to ESKD [ 54 , 55 , 56 , 57 , 58 ]. CREDENCE, was a double-blind, multicentre, randomised trial in diabetic patients with albuminuric CKD (eGFR 30 to < 90 mL/min per 1.73 m 2 and ACR ≥ 30 mg/mmol) [ 57 ]. In this trial, canagliflozin reduced the relative risk of the composite of ESKD, doubling of serum creatinine and renal-related mortality by 34%, relative risk of ESKD by 34% and risk of cardiovascular-related morbidity, including myocardial infarction and stroke, and mortality.

The SGTL2i dapagliflozin has proven its effectiveness in slowing CKD progression in addition to reducing cardiovascular risk in early stages of CKD. The DECLARE-TIMI58 trial involved 17,160 diabetic patients with established atherosclerotic cardiovascular disease and early-stage CKD (mean eGFR was 85.2 mL/min per 1.73 m 2 ) and were randomised to receive either dapagliflozin or placebo. Following a median follow-up of 4.2 years, there was a significant reduction in renal composite endpoints with dapagliflozin versus placebo, with a 46% reduction in sustained decline of at least 40% eGFR to less than 60 mL/min per 1.73 m 2 and a reduction in ESKD (defined as dialysis for at least 90 days, kidney transplantation, or confirmed sustained eGFR < 15 mL/min per 1.73 m 2 ) or renal death.

More recently, these cardiovascular and renal protective effects of SGTLT2i have also been demonstrated in a broad range of patients with more advanced stages of CKD (mean eGFR was 43.1 ± 12.4 mL/min per 1.73 m 2 ) without diabetes [ 58 , 59 ]. In the DAPA-CKD trial, many patients were without diabetes, including IgA nephropathy, ischemic/hypertension nephropathy and other glomerulonephritis [ 59 ]. Patients receiving dapagliflozin had a 39% relative risk reduction in the primary composite outcomes of a sustained decline in eGFR of at least 50%, ESKD and renal- or cardiovascular-related mortality and a 31% relative risk reduction of all-cause mortality compared to placebo [ 58 , 60 ]. Safety outcomes from clinical trials of dapagliflozin have also shown similar incidences of adverse events in both placebo and dapagliflozin arms [ 58 , 61 ].

The clinical benefits and safety outcomes from these trials highlight the potential use of SGTL2i in reducing cardiovascular burden and CKD progression in a broad range of CKD aetiologies at early and late stages where there is an unmet need. Currently, SGTL2i class drugs, including canagliflozin, dapagliflozin and empagliflozin, are approved by the US FDA for the treatment of T2DM and, more recently, dapagliflozin and canagliflozin for CKD and DKD respectively [ 62 , 63 ]. In addition, SGTL2i has been recommended for approval in the European Union (EU) by the Committee for Medicinal Products for Human Use (CHMP) of the EMA, for the treatment of CKD in adults with and without T2D [ 64 ]. Hence, there is now a need to raise awareness of the clinical applicability of these drugs in CKD to ensure full utilisation and maximum benefits are met, for both patients and providers.

This narrative review has summarised some of the key challenges associated with CKD. Early stages of the disease are clinically silent which prevents early intervention to slow the progression of the disease and allows progression of CKD and ESKD. At advanced stages of the disease, when clinical symptoms are present, patients with CKD are already at heightened risk of cardiovascular-related morbidity and mortality. Hence, advanced stages of CKD and ESKD are associated with poor outcomes and a significant clinical and economic burden.

At present, there are no treatments to cure CKD; as such, strategies for CKD management have been developed to target the modifiable risk factors in order to reduce cardiovascular disease morbidity in patients with CKD and slow the progression of CKD to ESKD. However, despite available treatment options, residual risk of adverse events and CKD progression remain; hence, an unmet need exists in CKD treatment. SGTL2i have the potential to fill this gap, with recent evidence from clinical trials showing a reduction in cardiovascular and renal adverse endpoints in a broad range of patients with CKD.

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This manuscript was supported by a grant from AstraZeneca UK Ltd. in respect of medical writing and publication costs (the journal’s Rapid Service and Open Access Fees). AstraZeneca has not influenced the content of the publication, and has reviewed this document for factual accuracy only.

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All authors have been involved in design of this review. Marc Evans, Ruth D. Lewis, and Angharad R. Morgan produced the primary manuscript. All authors have contributed to the drafting and revision of the manuscript and have approved the final version for publication. Marc Evans is responsible for the integrity of the work as a whole.

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Marc Evans reports honoraria from AstraZeneca, Novo Nordisk, Takeda and NAPP, and research support from Novo Nordisk outside the submitted work. Ruth D. Lewis and Angharad R Morgan are employees of Health Economics and Outcomes Research Ltd., Cardiff, UK who received fees from AstraZeneca in relation to this study. Martin B. Whyte reports investigator-led research grants from Sanofi, Eli Lilly and AstraZeneca and personal fees from AstraZeneca, Boehringer Ingelheim and MSD outside the submitted work. Wasim Hanif reports grants and personal fees from AstraZeneca, grants and personal fees from Boerhinger Inglhiem, grants and personal fees from NAPP, from MSD, outside the submitted work. Stephen C. Bain reports personal fees and other from Abbott, personal fees and other from AstraZeneca, personal fees and other from Boehringer Ingelheim, personal fees and other from Eli Lilly, personal fees and other from Merck Sharp & Dohme, personal fees and other from Novo Nordisk, personal fees and other from Sanofi-aventis, other from Cardiff University, other from Doctors.net, other from Elsevier, other from Onmedica, other from Omnia-Med, other from Medscape, other from All-Wales Medicines Strategy Group, other from National Institute for Health and Care Excellence (NICE) UK, and other from Glycosmedia, outside the submitted work. PAK reports personal fees for lecturing from AstraZeneca, Boehringer Inglhiem, NAPP, MundiPharma and Novo Nordisk outside the submitted work. Sarah Davies has received honorarium from AstraZeneca, Boehringer Ingelheim, Lilly, Novo Nordisk, Takeda, MSD, NAPP, Bayer and Roche for attending and participating in educational events and advisory boards, outside the submitted work. Umesh Dashora reports personal fees from AstraZeneca, NAPP, Sanofi, Boehringer Inglhiem, Lilly and Novo Nordisk, outside the submitted work. Zaheer Yousef reports personal fees from AstraZeneca, personal fees from Lilly, personal fees from Boehringer Ingelheim and personal fees from Novartis outside the submitted work. Dipesh C. Patel reports personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Eli Lilly, non-financial support from NAPP, personal fees from Novo Nordisk, personal fees from MSD, personal fees and non-financial support from Sanofi outside the submitted work. In addition, DCP is an executive committee member of the Association of British Clinical Diabetologists and member of the CaReMe UK group. W. David Strain holds research grants from Bayer, Novo Nordisk and Novartis and has received speaker honoraria from AstraZeneca, Bayer, Bristol-Myers Squibb, Merck, NAPP, Novartis, Novo Nordisk and Takeda. WDS is supported by the NIHR Exeter Clinical Research Facility and the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the South West Peninsula.

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Evans, M., Lewis, R.D., Morgan, A.R. et al. A Narrative Review of Chronic Kidney Disease in Clinical Practice: Current Challenges and Future Perspectives. Adv Ther 39 , 33–43 (2022). https://doi.org/10.1007/s12325-021-01927-z

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• Published: 15 April 2024

Outcome data for renal denervation: craving the unattainable?

• Lucas Lauder   ORCID: orcid.org/0000-0003-1434-9556 1 &
• Felix Mahfoud 1 , 2  

Hypertension Research ( 2024 ) Cite this article

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From the outset, registries and studies consistently demonstrated the safety of catheter-based renal denervation (RDN); however, there has been considerable controversy regarding its effectiveness in lowering blood pressure. During the last 5 years, the RADIANCE and SPYRAL trial programs have conclusively proven that ultrasound and radiofrequency RDN using the Paradise (ReCor, Palo Alto, CA, USA) and Symplicity Spyral (Medtronic, Santa Rosa, CA, USA) catheter systems lower office and ambulatory BP compared with sham in a broad range of patients with hypertension, including resistant hypertension [ 1 ]. These trial programs have led to their approval by the US Food and Drug Administration (FDA) for the treatment of uncontrolled hypertension. In recognition of the evidence coming from second-generation sham-controlled trials, both the 2022  European Society of Cardiology (ESC)’s Council on Hypertensio n/ European Association of Percutaneous Cardiovascular Interventions (EAPCI) clinical consensus statement [ 1 ] and the 2023  European Society of Hypertension (ESH)’s hypertension guidelines [ 2 ] consider RDN a treatment option in patients with resistant hypertension and those with uncontrolled hypertension despite the use of antihypertensive drug combination or if drug treatment elicits serious side effects and poor quality of life (class II recommendation in the ESH guidelines [ 2 ]). Additionally, data from three trials conducted in China provide further evidence supporting the BP-lowering efficacy of radiofrequency RDN using the Iberis (CE-marked), Netrod (CE-marked), and SyMap catheter systems. The latter catheter system has a unique approach using electric stimulation to identify hot spots, whose stimulation should increase BP, and which are subsequently ablated, and cold or neutral spots, which should be avoided [ 3 ].

In the first part of their review published in this issue of The Journal , Haider et al. [ 4 ] comprehensively review the statistical methods used by contemporary RDN trials. In the second part, the authors discuss whether cardiovascular (CV) outcome data are needed or if BP reduction is an adequate surrogate outcome. Per definition, surrogates are biomarkers that predict events [ 5 ]. The use of surrogates allows for smaller sample sizes than dichotomous variables, shorter follow-up periods, and thereby lower study costs [ 5 ]. BP is a surrogate outcome accepted by both clinicians and regulators [ 6 , 7 ] since BP lowering with first-class agents has robustly shown to reduce CV morbidity and mortality [ 6 ]. It is worth noting that there are no CV outcome trials conducted for various antihypertensive treatments, such as exercise, metabolic surgery, mineralocorticoid receptor antagonists, clonidine, moxonidine, and doxazosin. Nevertheless, it is yet to be determined whether the BP lowering following device-based therapies, such as RDN, reduces CV disease events. Only observational studies, which naturally have several limitations, suggested associations between RDN and reduced risk for CV disease events [ 8 , 9 ]. However, as Haider et al. acknowledge, reducing BP does not necessarily decrease CV events [ 10 ]. The authors refer to the ALTITUDE trial, which investigated the impact of aliskiren, a renin inhibitor, compared with placebo in addition to a renin-angiotensin system (RAS) inhibitor in type 2 diabetes [ 10 ]. In the trial, BP slightly rose in both treatment groups, but less in the aliskiren than in the placebo group [ 10 ]. The trial was stopped after an interim analysis as the primary composite of cardiorenal events did not differ between treatments, but dual RAS blockade resulted in more adverse events, including hyperkalemia, renal dysfunction, and hypotension [ 10 ]. Hence, the ALTITUDE trial [ 10 ] underscores a general limitation of surrogate markers. In cases where the treatment’s impact on the surrogate marker (e.g., BP-lowering) does not translate into the desired outcome due to known or unknown harmful off-target effects (e.g., hyperkalemia or renal dysfunction) offsetting the overall beneficial impact [ 7 ].

As of now, there is no awareness of any harmful off-target effects associated with RDN. Indeed, by reducing sympathetic nervous system activity, RDN could offer advantages over certain medications. It may not only lower BP but also potentially improve other conditions associated with increased sympathetic nervous system activity, including diabetes, atrial fibrillation, metabolic syndrome, and heart failure [ 11 ]. Moreover, in contrast to antihypertensive medications, RDN lowers BP continuously over 24 h, regardless of patient’s adherence and independent of pharmacodynamics and -kinetics (“always-on effect”) [ 1 ]. Non-adherence is a major contributor to poor BP control rates. Complex medication regimens, including polypharmacy and multiple doses daily, are known to impact adherence [ 12 ]. While the majority of patients undergoing RDN may still require antihypertensive medication, the procedure has the potential to decrease the quantity of pills they need to take. Administering additional drugs may introduce complex drug-drug interactions, while it is likely that there is no interaction between RDN and concomitant medications [ 13 ]. Reducing night-time BP, which is closely linked with the risk of coronary artery disease and heart failure [ 14 ], might be beneficial compared with shorter-acting antihypertensive drugs and is particularly appealing.

Based on recommendations from the GRADE working group [ 15 ] the recent ESH guidelines redefined their criteria for level of evidence grading. To assign a level of evidence “A,” well-conducted randomized controlled trials with CV disease outcomes or meta-analysis thereof are required [ 2 ]. This is because the primary objective of antihypertensive treatments is to mitigate the risk of cardiovascular outcomes, not solely to address blood pressure. Consequently, an outcome trial must be conducted to fulfill these requirements. As discussed in the 2022 ESC/EAPCI consensus document, outcome trials are challenging to conduct as confounding is likely (changes in adherence, lifestyle modification, etc.), they are expensive, and long-term follow-up would be required [ 1 ]. Furthermore, the residual risk observed in recent trials, such as SPRINT and STEP, is very low, necessitating a sample size of up to 20,000 patients [ 1 ]. Haider et al. correctly acknowledge that investigating RDN in high-risk patients with a greater absolute risk would allow for a smaller sample size and could be the next “logical step.” On the other hand, a reduction in hypertension-mediated organ damage (e.g., left ventricular hypertrophy, urinary albumin excretion, etc.) could potentially emerge as a substantial outcome in future trials, thereby addressing the evidence gap on whether the BP decrease associated with RDN translates into organ protection.

Asserting that it is impractical to carry out outcome studies may be shortsighted and should not prompt a lowering of our evidence grading standards. The progress in the development of RDN has provided valuable insights, indicating that sham-controlled trials investigating CV interventions are both feasible and essential. Consequently, we should embrace the challenge and strive to overcome the obstacle of conducting CV outcome trials with contemporary trial designs and methods. The narrative doesn’t conclude at this point.

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LL received speaker honoraria from AstraZenaca, Medtronic, Pfizer, and ReCor. FM is supported by Deutsche Gesellschaft für Kardiologie (DGK), Deutsche Forschungsgemeinschaft (SFB TRR219, Project-ID 322900939), and Deutsche Herzstiftung. His institution (Saarland University) has received scientific support from Ablative Solutions, Medtronic, and ReCor Medical. He has received speaker honoraria/consulting fees from Ablative Solutions, Amgen, Astra-Zeneca, Bayer, Boehringer Ingelheim, Inari, Medtronic, Merck, ReCor Medical, Servier, and Terumo.

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Lauder, L., Mahfoud, F. Outcome data for renal denervation: craving the unattainable?. Hypertens Res (2024). https://doi.org/10.1038/s41440-024-01667-x

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Published : 15 April 2024

DOI : https://doi.org/10.1038/s41440-024-01667-x

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Advances in uremic toxin detection and monitoring in the management of chronic kidney disease progression to end-stage renal disease

Patients with end-stage kidney disease (ESKD) rely on dialysis to remove toxins and stay alive. However, hemodialysis alone is insufficient to completely remove all/major uremic toxins, resulting in the accumulation of specific toxins over time. The complexity of uremic toxins and their varying clearance rates across different dialysis modalities poses significant challenges, and innovative approaches such as microfluidics, biomarker discovery, and point-of-care testing are being investigated. This review explores recent advances in the qualitative and quantitative analysis of uremic toxins and highlights the use of innovative methods, particularly label-mediated and label-free surface-enhanced Raman spectroscopy, primarily for qualitative detection. The ability to analyze uremic toxins can optimize hemodialysis settings for more efficient toxin removal. Integration of multiple omics disciplines will also help identify biomarkers and understand the pathogenesis of ESKD, provide deeper understanding of uremic toxin profiling, and offer insights for improving hemodialysis programs. This review also highlights the importance of early detection and improved understanding of chronic kidney disease to improve patient outcomes.

• This article is part of the themed collections: Analyst Review Articles 2024 and Analyst HOT Articles 2024

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H. Lee, K. Liu, Y. Yang, J. Liao, B. Lin, Z. Wu, A. Chang, C. Tseng, M. Wang and Y. Tsai, Analyst , 2024, Accepted Manuscript , DOI: 10.1039/D4AN00057A

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Chronic Kidney Disease: Help Your Patients Understand Risk Factors and Preventive Measures

Derek Robinson, M.D. ǀ April 16, 2024

Last month, on World Kidney Day, I was interviewed by a local TV station to improve community awareness about chronic kidney disease and CKD prevention. I’m following up here because this information may be helpful when you’re talking with your patients.

Getting the Conversation Started

Many of your patients may know someone with a friend or family member who’s getting dialysis or waiting for a kidney transplant. But unless they’ve experienced CKD themselves, your patients may not know about the condition and why aggressive treatments may be necessary.

I gave a quick overview in the TV segment: CKD is a gradual loss of kidney function. Normal kidneys filter wastes and excess fluids from the blood, which then are removed in the urine. When the kidneys are damaged, they no longer filter blood as they should and CKD sets in, along with a higher risk of heart disease and stroke. Many don’t know that those with CKD may experience anemia, abnormal calcium, potassium and phosphorus levels, loss of appetite, infections, depression, and other conditions. If left unchecked, kidney disease can lead to more serious problems such as end-stage kidney failure, which can be fatal without artificial filtering (dialysis) or a kidney transplant.

Who’s Affected and Who’s at Risk

These facts and figures may help bring the topic of CKD a bit closer to home for some of your patients.

According to the Centers for Disease Control and Prevention and the National Kidney Foundation:

• One in 3 adults in the U.S. (approximately 80 million) is at risk for kidney disease
• About 37 million adults in the U.S. have kidney disease – that’s more than 1 in 7, or 15% of the adult population.
• Nearly 90% of U.S adults with CKD don’t know they have it, including 40% of people with severely reduced kidney function (not on dialysis).
• Every 24 hours, 360 people begin dialysis treatment for kidney failure.
• Diabetes and high blood pressure are the leading causes of kidney failure, accounting for 3 out of 4 new cases.

While anyone can get kidney disease at any age, some primary risk factors include:

• High blood pressure
• Heart disease
• Family history of kidney failure, diabetes, high blood pressure or heart disease

In addition, other important risk factors for kidney disease include:

• Being Black or African American, Hispanic or Latino, Asian American, American Indian, Alaska Native, Native Hawaiian or other Pacific Islander heritage
• Being age 60 or older
• Having had a low birth weight      
• A prolonged use of NSAIDs, such as ibuprofen and naproxen
• Having lupus or other autoimmune disorders
• Having chronic urinary tract infections or kidney stones

Preventive Care and Screening

Your patients need to know they can help protect their kidneys by preventing or managing health conditions that cause kidney damage, such as diabetes and high blood pressure.

Preventive care includes healthy food choices – eating fresh fruits, vegetables, whole grains, low-fat dairy products, and foods low in salt and added sugars. Daily exercise, getting enough sleep, limiting alcohol consumption, stopping smoking, and aiming for a healthy weight also can aid in good kidney health. But it doesn’t stop there.

The best way for patients to know more about their kidney health is to get screened. On TV in February, I encouraged viewers to talk with their doctors about risk factors, a kidney health evaluation, and if they should get tested.

Related Reading

On the topic of screening, I invite you to refer back to this post: Chronic Kidney Disease: Examining Health Disparities in Communities of Color . I hope you find this information useful.

In closing …

On behalf of all of us here at Blue Cross and Blue Shield of Illinois, thank you for working with us to support the health and wellness of our members, their families, and the larger community.

As always, we appreciate your time and value your feedback. If you have any comments you’d like to share, please email our Blue Review editor .

Reference Materials

• National Kidney Foundation, New Report: Advancing Kidney Health: A Call to Action , June 28, 2023.
• National Kidney Foundation website, Kidney Disease: The Basics .
• CDC website. Chronic Kidney Disease Initiative, Chronic Kidney Disease in the United States, 2023 .
• America’s Health Rankings, United Health Foundation website, Chronic Kidney Disease in Illinois .
• Mayo Clinic website, Chronic kidney disease, Symptoms & causes .
• The Journal of Applied Laboratory Medicine, AACC/NKF Guidance Document on Improving Equity in Chronic Kidney Disease Care , June 28, 2023.
• NIH, National Institute of Diabetes and Digestive and Kidney Diseases website, Preventing Chronic Kidney Disease .

The above material is for informational purposes only and is not a substitute for the independent medical judgment of a physician or other health care provider. Physicians and other health care providers are encouraged to use their own medical judgment based upon all available information and the condition of the patient in determining the appropriate course of treatment. References to third party sources or organizations are not a representation, warranty, or endorsement of such organizations. The fact that a service or treatment is described in this material is not a guarantee that the service or treatment is a covered benefit and members should refer to their certificate of coverage for more details, including benefits, limitations, and exclusions. Regardless of benefits, the final decision about any service or treatment is between the member and their health care provider. Further, the information presented is not intended to replace or supersede any requirements set forth in your contract with BCBSIL. Any samples or suggestions in this publication are for illustrative and/or educational purposes only and should not be relied on in determining how a specific provider will be reimbursed.

Mapping the Overlap of Poverty Level and Prevalence of Diagnosed Chronic Kidney Disease Among Medicare Beneficiaries in the United States

GIS SNAPSHOTS — Volume 21 — April 11, 2024

Yun Han, PhD 1 ; Fang Xu, PhD 2 ; Hal Morgenstern, PhD 3 ,4 ; Jennifer Bragg-Gresham, PhD 1 ; Brenda W. Gillespie, PhD 5 ; Diane Steffick, PhD 1 ; William H. Herman, MD, MPH 3 ,6 ; Meda E. Pavkov, MD, PhD 2 ; Tiffany Veinot, PhD 7 ; Rajiv Saran, MD 1 ,3 ( View author affiliations )

Suggested citation for this article: Han Y, Xu F, Morgenstern H, Bragg-Gresham J, Gillespie BW, Steffick D, et al. Mapping the Overlap of Poverty Level and Prevalence of Diagnosed Chronic Kidney Disease Among Medicare Beneficiaries in the United States. Prev Chronic Dis 2024;21:230286. DOI: http://dx.doi.org/10.5888/pcd21.230286 .

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Geographic differences by county in CKD prevalence among US Medicare beneficiaries aged ≥65 years and in poverty levels, with higher rates of CKD in Florida and Appalachia (Panel A) and higher poverty levels in the Southeast (Panel B). Many counties in the South have both high poverty levels and a high prevalence of CKD, while many counties in the Northeast and Midwest have lower poverty levels but a high prevalence of CKD (Panel C). Abbreviation: CKD, chronic kidney disease. Data sources: Centers for Disease Control and Prevention (9); US Census Bureau (11). [A text version of this figure is available.]

Living in high-poverty neighborhoods has been identified as a contributing factor to the development and progression of chronic kidney disease (CKD) (1,2). High-poverty neighborhoods often face inequities related to social determinants of health, such as lower incomes; gaps in educational achievement; inadequate access to healthy food, health care, green space, and high-quality recreational facilities; and greater exposure to air and water pollution (3–8). A limited ability to purchase healthy food and access recreational facilities and preventive health care can delay diagnosis and timely management of CKD. Understanding the distribution of CKD at the county level in relation to poverty level is important: this knowledge can guide population-level interventions for CKD prevention and management. The objectives of this study were to examine the county-level association between poverty level and diagnosed CKD and to illustrate county-level bivariate distribution of poverty and CKD among Medicare fee-for-service beneficiaries aged 65 years or older in the US.

We calculated the county-level prevalence of diagnosed CKD in each US county among Medicare fee-for-service beneficiaries aged 65 years or older based on 5% claims data for 2019. The study population included beneficiaries who had full-year Parts A and B enrollment and at least 1 inpatient or outpatient visit in 2019. The numerator of CKD prevalence included eligible beneficiaries with at least 1 claim in 2019 containing an ICD-10-CM ( International Classification of Diseases, Tenth Revision, Clinical Modification ) diagnosis code for CKD (9,10). We excluded beneficiaries with end-stage kidney disease because they are not at risk for CKD. We also excluded Medicare beneficiaries covered by Part C (managed care/Medicare Advantage plans) because of limited availability of data. The total study population consisted of 1,234,056 beneficiaries in 3,097 counties (98.5% of all 3,143 US counties).

Poverty level was measured as the percentage of the total county population below the poverty threshold extracted from the American Community Survey 5-year data (2015–2019) (11).

We linked measurements of CKD and poverty by using county Federal Information Processing Standards (FIPS) codes. We standardized county-level prevalence of CKD based on strata of demographic characteristics. The 5% sample of the 2019 Medicare population aged 65 years or older (ie, the study population) served as the standard population. We performed 3 analyses: 1) a crude (unstandardized) analysis; 2) standardization on age alone (age categories 65–69, 70–79, 80–89, ≥90 y); and 3) standardization on age, sex (male, female), and race and ethnicity (White, Black, Hispanic, Asian, other [American Indian or Alaska Native, Native Hawaiian or Other Pacific Islander, other], unknown).

We then generated 2 univariate choropleth (color-coded or shaded) maps to separately depict crude county-level distributions of CKD prevalence and poverty levels across the US. In addition, we created a bivariate map (in R version 4.3.1 [R Foundation for Statistical Computing]) that combines the distributions of both variables in each county by using a 2-dimensional (3 × 3) key to show the tertile (high, medium, low) of CKD prevalence and poverty level. Thus, the color of each county represents the association between county poverty level and CKD prevalence, and the bivariate map shows the pattern of those associations across the US, emphasizing the clustering and geographic patterns of counties. Data were suppressed for counties with 10 or fewer beneficiaries (n = 108, 3.4% of all counties) according to the Centers for Medicare & Medicaid Services small-cell suppression rule to protect privacy (12). This suppression had only a minor effect on the map’s appearance, but it may have led to underrepresentation of counties with smaller populations of older adults.

The mean (SD) county-level crude prevalence of CKD in the study population was 22.1% (6.5%). The mean (SD) prevalence of poverty was 15.4% (6.9%). As the poverty level increased, the crude prevalence of CKD also rose, from 20.9% to 23.4% ( Table ). This pattern was nearly the same when standardized measures were used ( Table ), suggesting that age, sex, and race and ethnicity did not confound the association between poverty-level tertile and CKD prevalence.

We observed considerable geographic variations in crude CKD prevalence (Figure A) and poverty level (Figure B). CKD prevalence was higher in Florida and the Appalachian region, which encompasses parts of Ohio, Pennsylvania, West Virginia, Kentucky, Tennessee, and Alabama (Figure A). Poverty levels were clustered, with a high concentration of counties east of the Mississippi River having higher poverty levels (Figure B).

The bivariate map (Figure C) shows the underlying joint distribution of county-level poverty and CKD prevalence. Many counties in the Southeast show high levels of both poverty and CKD, and many counties in New England show low levels of both poverty and CKD. Both patterns indicate a positive association between the 2 measures (high–high or low–low). In contrast, several counties in the mid-Atlantic coast and the upper Midwest show high CKD prevalence and low poverty level, and many counties in the West show high levels of poverty level and low CKD prevalence, indicating an inverse association between the 2 measures (high–low or low–high).

The observed spatial disparities in CKD and poverty suggest that a one-size-fits-all intervention may not be effective in decreasing the prevalence of CKD. Tailored interventions for older adults are necessary. In high-prevalence/high-poverty counties, interventions could focus on local challenges among older adults by improving health care access, addressing socioeconomic barriers to health, and implementing strategies such as subsidized healthy food programs and enhanced health care services. Conversely, in high-prevalence/low-poverty counties, strategies could encompass health education and disease management programs, with a focus on public awareness campaigns about CKD risk factors and promotion of regular health screenings. In these counties, factors other than economic status, including prevalence of comorbidities, health care access, environmental conditions, and lifestyle choices, may influence the prevalence of CKD.

Although our study sheds light on the correlation between county-level poverty and the prevalence of CKD, it has limitations in addressing the multifaceted nature of poverty. First, individual-level poverty, which encompasses personal financial constraints and limited access to health care, also plays a crucial role in CKD risk. Our focus on county-level data may not fully capture individual poverty experiences and their direct effect on CKD. Studies incorporating individual-level socioeconomic data could enhance the understanding of the complex interplay between poverty and CKD prevalence. Second, we identified CKD based on ICD-10-CM diagnosis codes because we lacked laboratory data (eg, estimated glomerular filtration rate). This reliance on diagnosis codes may have resulted in an underestimation of actual CKD prevalence and possible distortions in observed geographic patterns. A third limitation is the choice of geographic unit; using county-level data may mask finer-scale variations and socioeconomic disparities, particularly in urban areas. Fourth, our cross-sectional study examined the relationship between county-level poverty and CKD prevalence at a single time point. As highlighted by Lapedis et al (13), a cross-sectional approach may not fully encapsulate the complex and evolving relationship between neighborhood characteristics and the various stages of CKD, particularly the early stages. The reliance on a single time-point analysis limits our ability to understand these dynamics over the life course. Overall, further research, accounting for confounders and mediators, may be essential to delve into the underlying causes of the observed spatial disparities in CKD and poverty. This research includes identifying factors contributing to high CKD prevalence in low-poverty counties in the Northeast and Midwest. These findings may guide clinical practice and health policy aimed at mitigating CKD disparities across the US.

The publication acknowledges the contribution of resources and facilities provided by the University of Michigan, Ann Arbor, Michigan. This work was supported by the Supporting, Maintaining and Improving the Surveillance System for Kidney Disease in the US (NU58DP006956), funded by the Centers for Disease Control and Prevention. The CKD Surveillance Team at CDC comprises a dedicated group of individuals, including Michael Heung, MD; Zubin Modi, MD; Vahakn Shahinian, MD; Yam Hoon Lim, MEd; Miao Yu, MS; Ana Licon, MS; Jenna Kiryakos, MPH; Austin Stack, MD; and Joe Vassalotti, MD. Rajiv Saran, MD, is principal investigator. The authors have no conflicts of interest to disclose. No copyrighted material, surveys, instruments, or tools were used in this research. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of CDC.

Corresponding Author: Rajiv Saran, MD, Department of Internal Medicine, Division of Nephrology, University of Michigan, 1500 E Medical Center Dr, Ann Arbor, MI 48105 ( [email protected] ).

Author Affiliations: 1 Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor. 2 Division of Diabetes Translation, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia. 3 Department of Epidemiology, University of Michigan, Ann Arbor. 4 Departments of Environmental Health Sciences and Urology, University of Michigan, Ann Arbor. 5 Department of Biostatistics, University of Michigan, Ann Arbor. 6 Department of Internal Medicine, Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, Ann Arbor. 7 School of Information, University of Michigan, Ann Arbor.

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Abbreviation: CKD, chronic kidney disease. a Data source: 2019 Medicare 5% Sample Data and American Community Survey data (2015−2019) (11). All values are mean (SD). b Tertile breaks were used to create the categories for all data from the study population for poverty level (expressed as percentage of the population below the federal poverty threshold): low, < 12%; medium, 12%–17%; high, > 17%). c Standardization was based on strata for age (65−70, 70−80, 80−90, >90 y), sex, and race and ethnicity (White, Black, Hispanic, Asian, other [American Indian/Alaska Native, Native Hawaiian/Other Pacific Islander, other], unknown). The standard population was Medicare fee-for-service beneficiaries aged ≥65 years in 2019.

The opinions expressed by authors contributing to this journal do not necessarily reflect the opinions of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors’ affiliated institutions.

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