research topics in renal transplantation

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Recent Advances and Clinical Outcomes of Kidney Transplantation

Charat thongprayoon.

1 Division of Nephrology, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA; [email protected]

Panupong Hansrivijit

2 Department of Internal Medicine, University of Pittsburgh Medical Center Pinnacle, Harrisburg, PA 17105, USA; ude.cmpu@ptijivirsnah

Napat Leeaphorn

3 Department of Nephrology, Department of Medicine, Saint Luke’s Health System, Kansas City, MO 64111, USA; [email protected]

Prakrati Acharya

4 Division of Nephrology, Department of Medicine, Texas Tech University Health Sciences Center, El Paso, TX 79905, USA; [email protected]

Aldo Torres-Ortiz

5 Department of Medicine, Ochsner Medical Center, New Orleans, LA 70121, USA; moc.liamtoh@68t_odlA

Wisit Kaewput

6 Department of Military and Community Medicine, Phramongkutklao College of Medicine, Bangkok 10400, Thailand; moc.liamg@orhpentisiw

Karthik Kovvuru

7 Division of Nephrology, Department of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA; ude.cmu@uruvvokk (K.K.); ude.cmu@irudnaks (S.R.K.)

Swetha R. Kanduri

Tarun bathini.

8 Department of Internal Medicine, University of Arizona, Tucson, AZ 85724, USA; moc.liamg@bbocajnurat

Wisit Cheungpasitporn

Recent advances in surgical, immunosuppressive and monitoring protocols have led to the significant improvement of overall one-year kidney allograft outcomes. Nonetheless, there has not been a significant change in long-term kidney allograft outcomes. In fact, chronic and acute antibody-mediated rejection (ABMR) and non-immunological complications following kidney transplantation, including multiple incidences of primary kidney disease, as well as complications such as cardiovascular diseases, infections, and malignancy are the major factors that have contributed to the failure of kidney allografts. The use of molecular techniques to enhance histological diagnostics and noninvasive surveillance are what the latest studies in the field of clinical kidney transplant seem to mainly focus upon. Increasingly innovative approaches are being used to discover immunosuppressive methods to overcome critical sensitization, prevent the development of anti-human leukocyte antigen (HLA) antibodies, treat chronic active ABMR, and reduce non-immunological complications following kidney transplantation, such as the recurrence of primary kidney disease and other complications, such as cardiovascular diseases, infections, and malignancy. In the present era of utilizing electronic health records (EHRs), it is strongly believed that big data and artificial intelligence will reshape the research done on kidney transplantation in the near future. In addition, the utilization of telemedicine is increasing, providing benefits such as reaching out to kidney transplant patients in remote areas and helping to make scarce healthcare resources more accessible for kidney transplantation. In this article, we discuss the recent research developments in kidney transplants that may affect long-term allografts, as well as the survival of the patient. The latest developments in living kidney donation are also explored.

1. Introduction

Kidney transplantation is the optimal treatment for improving survival and quality of life for patients with end-stage kidney disease (ESKD) [ 1 ]. Advances in surgical, immunosuppressive and monitoring protocols have led to a significant improvement in overall one-year kidney allograft survival of >95% [ 2 ]. Nonetheless, there has not been a significant change in long-term kidney allograft outcomes. In fact, chronic and acute antibody-mediated rejection (ABMR) has continued to cause kidney allograft failures [ 3 ]. In addition, non-immunological complications following kidney transplantation, such as the recurrence of primary kidney disease and other complications, such as cardiovascular diseases, infections, and malignancy also play important roles in poor long-term allografts and patient survival [ 4 , 5 , 6 ].

In their research into immunologic monitoring and diagnostics in kidney transplants [ 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ], a number of groups have made attempts in the recent past towards determining the peripheral molecular fingerprints of ongoing rejection [ 7 , 8 ] and predicting acute rejection [ 7 ]. Contemporary researchers have measured the levels of donor-derived cell-free DNA (dd-cfDNA) and showed higher predictive abilities for acute rejection [ 9 , 10 , 11 , 12 ], especially antibody-mediated rejection (ABMR) diagnostics in cases with a combination of donor specific antibodies (DSA) and dd-cfDNA [ 13 , 14 ]. In addition, a molecular microscope diagnostic system for the evaluation of allograft biopsies has been recently introduced within transplant practice, particularly in complex cases. This has mainly been introduced for the purpose of enhancing histological diagnostics [ 15 ].

Recent studies have been conducted aimed at preventing or treating ABMR [ 16 , 17 ]. In 2017, imlifidase (IdeS), an endopeptidase derived from Streptococcus pyogenes, was utilized in a desensitization regimen in an open-label phase 1–2 trial [ 16 ]. An instant impact was observed by a significant decline in plasma IgG levels. Another single-center phase 2 study that focused mainly on the pharmacokinetics, effectiveness and safety of IdeS treatment was conducted and proved a reduction in anti-human leukocyte antigen (HLA) antibodies using a complement-dependent cytotoxicity test [ 17 ].

In recent years, there has been significant progress in research into kidney transplantation and kidney donation [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 ], including articles [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ] published in our current Special Issue "Recent Advances and Clinical Outcomes of Kidney Transplantation" ( https://www.mdpi.com/journal/jcm/special_issues/outcomes_kidney_transplantation ).

In this article, we discuss the recent research developments in kidney transplantation that may impact long-term allografts and patient survival, as well as the latest developments in living kidney donation.

2. Non-HLA Antibodies in Transplantation

When it comes to solid organ transplantation, one major immunological obstacle is the detection the non-self structures that exist in the donor cells. Human leukocyte antigens (HLA) are considered the most important non-self allo-antigens in organ transplantation. In addition, patients can form antibodies against targets other than HLA [ 85 ]. Multiple targets for these non-HLA antibodies have been studied in kidney transplantation over the last decade ( Figure 1 ). Recent studies have provided findings that suggest the an importance of non-HLA mismatches between donors and recipients in the development of acute rejection and long-term kidney allograft outcomes [ 68 , 78 , 86 , 87 , 88 , 89 , 90 , 91 , 92 ].

Post-transplant antibodies against human leukocyte antigen (HLA) and non-HLA antigens [ 68 , 78 , 86 , 87 , 88 , 89 , 90 , 91 , 92 ]. Abbreviations: human leukocyte antigen (HLA), major histocompatibility complex class I related chain A antigen (MICA); angiotensin type 1 receptor (AT1R); endothelin-1 type A receptor (Anti-ETAR); FMS-like tyrosine kinase 3 (FLT3); Epidermal growth factor-like repeats and discoidin I-like domain 3 (EDIL3); Intercellular adhesion molecule 4 (ICAM4).

3. Active AMR

Chronic active ABMR is one of the major causes of long-term allograft loss [ 93 , 94 , 95 ]. Tocilizumab, a humanized monoclonal antibody targeting the interleukin (IL)-6 receptor, has been assessed in patients with acute and chronic active ABMR [ 96 , 97 , 98 ], given that IL-6 mediates various inflammatory and immunomodulatory pathways, including the expansion and activation of T cells and B cells [ 98 ]. Furthermore, there is a genetically engineered humanized Immunoglobulin (Ig)G1 monoclonal antibody that binds to IL-6, inhibiting its interaction with IL-6R. Direct inactivation of IL-6 may limit a rebound induced by the accumulation of IL-6 [ 99 , 100 ]. Preliminary investigations from phase 1–2 trials demonstrated the efficacy of the C1q inhibitor for the prevention of a delayed graft function (DGF) and to lessen the occurrence of chronic active ABMR [ 101 , 102 ]. Although the inhibition of the first step in both the classical and lectin pathways of complement activation may serve as another tool to overcome critical sensitization, such data need to be validated in larger cohorts. Several trials are currently being conducted, and new developments will conceivably provide us with practical ways to counteract the deleterious consequences of ABMR [ 103 ].

4. Cardiovascular Diseases in Kidney Transplant Recipients

The burden of cardiovascular diseases on ESKD is improved after kidney transplantation [ 104 ]. However, it remains the leading cause of reduced early renal graft loss and mortality, as it is associated with significant morbidity and healthcare costs [ 104 ]. Major phenotypes of cardiovascular diseases among kidney transplant recipients include ischemic heart disease, congestive heart failure, valvular heart disease, arrhythmias and pulmonary hypertension ( Figure 2 ).

Incidence (%) of cardiovascular disease in kidney transplant recipients.

Reported risk factors for cardiovascular disease in kidney transplant recipients include inflammatory and immunosuppressive agents, episodes of allograft rejection, as well as traditional cardiovascular risk factors, such as hypertension, hyperlipidemia, smoking, obesity, chronic kidney disease, proteinuria, and diabetes mellitus, all of which add to a transplant recipient’s cardiovascular risk profile [ 104 ]. Hypertension is common among kidney transplant recipients and uncontrolled hypertension in kidney transplant recipients is associated with increased cardiovascular mortality and morbidity, and reduced allograft survival [ 105 ]. Furthermore, weight gain is also a significant problem in post-kidney transplant patients. Weight gain after transplantation can unfavorably affect patient outcomes [ 106 ]. Identifying these risk factors and adopting strategies to abolish these risk factors may potentially prevent, and help manage, post-transplant obesity. The underlying mechanisms for the increased occurrence of dyslipidemia post-transplant are due to immunosuppressive medications, proteinuria, and post-transplant diabetes [ 107 , 108 ].

The medical management of risk factors includes strategies employed in the chronic kidney disease (CKD) population, with credence given to approaches specific for kidney transplant recipients, such as the choice of maintenance immunosuppression, steroid tapering or withdrawal, and particular anti-hypertensive regimens ( Table 1 ). Overall, cardiovascular morbidity and mortality in kidney transplant recipients has decreased over the last few decades, likely due to improved detection and the timely management of risk factors. Recognition of these complications is important in assessing cardiovascular disease risk in kidney transplant recipients, and optimizing screening and therapeutic approaches. These include lifestyle and immunosuppressive regimen modification, as well as the best feasible regimen for glycemic and lipid controls according to an individual’s metabolic profile and medical history.

Cardiovascular risk factors among kidney transplant recipients and suggested management.

American College of Cardiology (ACC); angiotensin-converting enzyme inhibitor (ACEI); American Heart Association (AHA); angiotensin-II receptor blocker (ARB); aspirin (ASA); body mass index (BMI); blood pressure (BP); complete blood count (CBC); calcium-channel blockers (CCB); chronic kidney disease (CKD); cardiovascular disease (CVD); diabetes mellitus (DM); electrocardiography (ECG); estimated glomerular filtration rate (eGFR); Kidney Diseases Improving Global Outcomes (KDIGO); kidney transplant (KTx).

5. Preexisting Diabetes and Post-Transplantation Diabetes

Preexisting diabetes and post-transplantation diabetes confer reduced patient and graft survival in kidney transplant recipients [ 71 , 73 , 125 ]. Hyperglycemia is present in nearly 90% of kidney transplant recipients in the immediate postoperative period, but it is not sustained in the majority [ 126 ]. In addition to the general risk factors for diabetes, there are also certain transplantation-related factors (e.g., specific immunosuppressive agents, surgical stress and inflammation, nutritional interventions) placing kidney transplant recipients at elevated risk of hyperglycemia [ 126 ]. Some transplant immunosuppressive medications, including corticosteroids, calcineurin Inhibitors (CNIs), and mammalian target of rapamycin (mTOR) inhibitors, are associated with a higher incidence of metabolic complications such as post-transplantation diabetes. CNIs impair insulin secretion and sensitivity and directly damage pancreatic islet cells [ 127 ].

A robust evidence base guiding precise glycemic goals is currently lacking in kidney transplant recipients. Management is largely guided by evidence from the general diabetes population [ 71 , 73 , 125 ]. Hospital management of hyperglycemia is primarily achieved through an insulin regimen that takes into account rapid changes in glucocorticoid doses, nutritional modalities and renal function during the immediate post-transplantation period. There is an opportunity to use oral or non-insulin injectable agents in a considerable number of patients by the time they are discharged from the hospital, or in the long run. The use of specific oral or non-insulin injectable agents is guided by patient specifics and the pharmacologic properties of medications. Although several studies have suggested the safe use of sodium glucose transport 2 (SGLT2) inhibitors in kidney transplant recipients [ 128 ], future studies assessing their efficacy and safety are needed, since SGLT2 inhibitor treatment also carries an increased risk of genital tract infections and, possibly, of urinary tract infections [ 129 ]; kidney transplant recipients are particularly susceptible to infections due to immunosuppressive regimens.

6. Posttransplant Malignancy

Cancer is one of the three major causes of death after kidney transplantation [ 130 , 131 ]. Posttransplant malignancy occurrence is widely recognized ( Table 2 ). The effect of viral infections, induction and immunosuppressive maintenance regimens have been proposed as important risk factors for posttransplant malignancy. The increased risk of cancer may be due to viral reactivation induced by immunosuppressive agents or impaired immune surveillance leading to faster tumor growth [ 132 ]. A higher degree of immunosuppression is associated with an increased risk of malignancy, and calcineurin inhibitors can promote carcinogenesis [ 132 ].

Standardized incidence ratio of cancers in kidney transplant recipients [ 133 ].

Confidence Interval (CI).

7. Infection

Solid organ transplant recipients are at greater risk of infection than the non-immunosuppressed population ( Table 3 ) [ 134 ]. Infections are the most common non-cardiovascular causes of mortality following kidney transplantation, accounting for 15%–20% of mortality [ 131 , 135 ]. The first six months post-transplant is the time of greatest infection risk. There are also times when patients encounter adverse reactions to immunosuppressive agents [ 136 , 137 ]. Among all infectious complications, viruses are considered to be the most common agents [ 138 ]. Herpes simplex virus, varicella zoster virus, BK polyomavirus, cytomegalovirus, Epstein–Barr virus, hepatitis B virus, and adenovirus are well-known etiologic agents of viral infections in kidney transplant patients worldwide [ 138 ]. In order to prevent opportunistic infections in kidney transplant recipients, antimicrobial prophylaxis is recommended after kidney transplantation. The recommended prophylactic method after transplant differs based on the organism, as well as individual patient characteristics.

Infection post kidney transplantation.

* Center-dependent multidrug resistant bacteria like Methicillin-resistant Staphylococcus aureus (MRSA), Vancomycin-resistant Enterococcus (VRE), extended-spectrum beta-lactamases (ESBLs); ** With prophylaxis – with Bactrim and Gancyclovir/Valganciclovir; Abbreviations: cytomegalovirus (CMV), lymphocytic choriomeningitis virus (LCM), Epstein-Barr Virus (EBV), hepatitis B virus (HBV), hepatitis C virus (HCV), Trypanosoma cruzi (T. cruzi), Varicella Zoster virus (VZV), human herpes virus 8 (HHV-8).

8. Latest Developments in Living Kidney Donation

Living donor kidney transplants are the best option for many patients with ESKD for several reasons, including (1) better long-term graft survival, (2) no need to wait on the transplant waiting list for a kidney from a deceased donor, (3) transplant surgery can be planned and (4) lower risks of rejection and DGF [ 139 ]. Living donor kidney transplantation is the optimal treatment for patients with ESKD [ 139 ]. The expansion of living donor programs was made possible by new modes of living donation and by the extension of the living donor pool [ 139 ].

To expand the donor pool, a well-developed paired kidney donation program and the adequate reimbursement of costs associated with donation are fundamental elements [ 140 ]. Paired kidney donation provides living kidney donation for noncompatible donor/recipient pairs that otherwise would not be feasible or need desensitization [ 141 ]. Other possible approaches for increasing the donor pool include ABO-incompatible transplantation [ 142 ], the utilization of higher risk donors, advanced donation with a voucher system, and providing donors with financial incentives [ 141 , 143 , 144 ].

Over the past decade, the long-term risks of kidney donation have been described. Living donors seem to have a higher risk of ESKD, particularly in obese donors and also for African American donors with an apolipoprotein L1 (APOL1) high-risk genotype. In African American living kidney donors, those with the APOL1 high-risk genotype (prevalent in about 13% of African Americans in the United States) had an almost three times more accelerated decline in estimated glomerular filtration rate (eGFR) after adjusting for pre-donation eGFR than those with a low-risk genotype [ 145 ].

9. Post-Transplant Hyperparathyroidism and Bone Disease

Successful renal transplantation results in a reduction in parathyroid hormone (PTH), especially during the first 3 months after transplantation [ 146 ]. However, elevated PTH levels can still be found in 30% to 60% of patients 1 year after transplantation. Persistent hyperparathyroidism following kidney transplantation can result in notable complications, such as fracture/bone diseases, cardiovascular disease, vascular calcification, and allograft dysfunction ( Figure 3 ). Associated factors for persistent hyperparathyroidism are long dialysis duration, high PTH levels prior to transplantation, lower eGFR post-transplant, post-transplant hypercalcemia, and post-transplant high alkaline phosphatase.

Effects and risk factors of post-transplant hyperparathyroidism.

10. Potential Directions and Future Scope

Researchers need to instantly shift their focus on the unaddressed concerns with respect to kidney transplants. Because of the limited supply of organs, numerous potential recipients still have to spend more time in dialysis, waiting for a transplant. Sensitization to HLA antigens inhibits the recipients’ access to transplants, compromising the survival of the graft due to chronic and acute AMR. The publication of complete data from a multi-center second-phase test that explores how IdeS is useful in desensitization is underway ( {"type":"clinical-trial","attrs":{"text":"NCT02790437","term_id":"NCT02790437"}} NCT02790437 ). The phase 3 trial, uncovering the impact of clazakizumab following transplantation, was launched recently, with the outcomes of the phase 2 trial to be released soon.

Moreover, the lack of experienced and skilled professionals could hinder the diagnostic correctness of complications following transplantation. Furthermore, medication non-adherence among patients could increase the alloimune reaction. Notably, medical research on the costimulation blockade during kidney transplantation is underway. A randomized sixty-month multi-center study (CIRRUS, {"type":"clinical-trial","attrs":{"text":"NCT03663335","term_id":"NCT03663335"}} NCT03663335 ) in kidney transplant is also underway, with the aim of defining the range of dosage and assessing the tolerability, safety, and effectiveness of some newly developed anti-CD40 monoclonal antibodies in two distinct cohorts in comparison to a tacrolimus-based regimen. Recently, a phase 2a clinical trial, with the purpose of assessing how effective the dual costimulation blockade with anti-CD40 (VIB4920) is when combined with belatacept in kidney transplantation patients ( {"type":"clinical-trial","attrs":{"text":"NCT04046549","term_id":"NCT04046549"}} NCT04046549 ), was registered.

Big data is increasingly being utilized, with the establishment of a large collection of cohorts and the usage of electronic health records (EHRs) in kidney transplantation and artificial intelligence, which might be useful in solving problems related to the survival analysis of patients who have gone through kidney transplantation [ 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 ]. In the present era, it is strongly believed that big data and artificial intelligence will greatly reshape the research done on kidney disease and, consequently, improve the general clinical practice of nephrology [ 156 ].

The benefits of telemedicine include reaching out to patients in remote areas and helping to make scarce healthcare resources more accessible. As telemedicine applications continue to proliferate, studies have demonstrated that telehealth for transplant care may be associated with a reduction in cost and time, and may also improve access to transplantation for ESKD patients [ 157 , 158 ].

11. Conclusions

The most recent endeavors in kidney transplantation tend to mainly focus on noninvasive monitoring, as well as the improvement of histological diagnostics with the aid of molecular techniques. Such studies offer creative means that can be used to find immunosuppressive agents, which can effectively overcome critical sensitization, prevent the creation of anti-HLA antibodies, treat chronic active ABMR, and reduce non-immunological complications following kidney transplantation, such as the recurrence of primary kidney disease and other complications, such as cardiovascular diseases, infections, and malignancy. In the present era of utilizing EHRs, it is strongly believed that big data and artificial intelligence will reshape the research done on kidney transplantation in the near future. In addition, the utilization of telemedicine is increasing, providing benefits such as reaching out to kidney transplant patients in remote areas and helping to make scarce healthcare resources more accessible for kidney transplantation.

This research received no external funding.

Conflicts of Interest

We do not have any potential financial or non-financial conflicts of interest.

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Collection  01 April 2017

Kidney Transplantation

Kidney transplantation is the preferred therapeutic approach for patients with end-stage renal disease. Many challenges remain, however, including a shortage of donor organs, immunological barriers, and the need for long-term immunosuppression, which is associated with an increased risk of infections and malignancies. This collection of articles from Nature Reviews Nephrology discusses a wide range of important topics in kidney transplantation, including long-term risks to living kidney donors, desensitization strategies to enable ABO-incompatible transplantation, antibody-mediated rejection, mechanisms of allograft inflammation, long-term outcomes in paediatric recipients, and the impact of hepatitis C virus infection in transplantation.

• Collection content
• Opinion and comment
• Research Highlights

Renal and cardiac assessment of living kidney donor candidates

To ensure suitability for living kidney donation, donor candidates must be thoroughly evaluated. This Review describes current approaches to the assessment of renal function, haematuria, and cardiac risk in living kidney donor candidates as well as strategies to improve efficiency in the evaluation process, focusing on additional investigations that are commonly ordered by transplant centres rather than the minimum initial screening requirements.

• Ngan N. Lam
• Krista L. Lentine
• Amit X. Garg

Roles of mTOR complexes in the kidney: implications for renal disease and transplantation

The mTOR pathway has a role in the development of renal disease, kidney transplant rejection and malignancies. Here, the authors discuss the mechanisms by which mTOR complexes drive the pathogenesis of these diseases as well as the therapeutic potential of mTOR inhibitors.

• Daniel Fantus
• Natasha M. Rogers
• Angus W. Thomson

The importance of non-HLA antibodies in transplantation

Antibodies directed against non-HLA antigens such as angiotensin type 1 receptor, perlecan and collagen have been implicated in antibody-mediated rejection. Here, Elaine Reed and Qiuheng Zhang discuss the clinical relevance and pathogenesis of these non-HLA antibodies in renal, heart and lung transplantation.

• Qiuheng Zhang
• Elaine F. Reed

Molecular assessment of disease states in kidney transplant biopsy samples

Molecular phenotyping of renal biopsy samples from transplant recipients has the potential to improve diagnostic precision and understanding of disease processes. In this Review, Philip Halloran et al . describe their strategy to develop a system that enables the molecular assessment of transplant biopsy samples. They discuss the molecular phenotypes of rejection and injury, and how these studies have improved understanding of the processes that occur in renal transplants over time.

• Philip F. Halloran
• Konrad S. Famulski

Complement in disease: a defence system turning offensive

The functions of the complement system are diverse and extend beyond its role in host defence; complement activation is now known to contribute to numerous immunological, inflammatory and age-related conditions, including kidney disorders. Here, John Lambris and colleagues discuss the key activating, regulatory, and effector mechanisms of the complement system. They highlight important crosstalk connections with other regulatory systems, and, with a focus on kidney disease and transplantation, describe the involvement of complement in clinical conditions as well as promising therapeutic approaches.

• Daniel Ricklin
• Edimara S. Reis
• John D. Lambris

Role of TLRs and DAMPs in allograft inflammation and transplant outcomes

Graft necrosis resulting from ischaemia–reperfusion injury leads to the release of endogenous molecules — damage-associated molecular patterns (DAMPs) — which trigger a sterile inflammatory reaction. The resulting immune response can impair transplant tolerance or result in acute or chronic graft rejection. In this Review, Braza et al . discuss the nature of DAMPs and their downstream signalling pathways, with a focus on Toll-like receptors. They outline various strategies to inhibit DAMP-induced inflammation with the aim of improving the outcomes of solid organ transplantation, and discuss the challenge of inhibiting the innate immune response within the graft without compromising the patient's response to pathogens.

• Faouzi Braza
• Sophie Brouard
• Daniel R. Goldstein

Memory T cells in organ transplantation: progress and challenges

Memory T cells and their ability to generate an anamnestic response are vital for protective immunity, but have a potentially detrimental impact on allograft survival. Here, Allan Kirk and colleagues discuss the generation of memory T cells, their role in allograft rejection and therapeutic strategies that target allospecific memory T-cell responses and might improve outcomes in organ transplantation.

• Jaclyn R. Espinosa
• Kannan P. Samy
• Allan D. Kirk

Mesenchymal stromal cells in renal transplantation: opportunities and challenges

The unique immunomodulatory properties of multipotent mesenchymal stromal cells (MSCs) make them a promising candidate for cell therapy in organ transplantation. Here, the authors review preclinical data that support the potential tolerance-inducing effects of MSCs in transplant models and the results of initial clinical studies in kidney transplantation.

• Federica Casiraghi
• Norberto Perico
• Giuseppe Remuzzi

Long-term effects of paediatric kidney transplantation

Renal transplantation can be successfully performed in patients of all ages, and the short-term and medium-term outcomes have improved over the past decades. In this Review, Christer Holmberg and Hannu Jalanko discuss the long-term effects of kidney transplantation on paediatric recipients. They outline the adverse effects that can occur with regard to growth, bone health, metabolic and cardiovascular complications, and malignancies, and highlight the challenges that remain in managing the care of paediatric renal transplant recipients.

• Christer Holmberg
• Hannu Jalanko

Phosphate and FGF-23 homeostasis after kidney transplantation

Dysregulated phosphate metabolism is a common consequence of kidney disease and renal transplantation. In this Review, Martin H. de Borst and colleagues outline the pathophysiology of dysregulated phosphate metabolism in renal transplant recipients and discuss the effect of this dysregulation on the cardiovascular system, bone, and the kidney graft. They also propose possible strategies to correct phosphate abnormalities in these patients.

• Leandro C. Baia
• Ita Pfeferman Heilberg
• for the NIGRAM investigators

Strategies to overcome the ABO barrier in kidney transplantation

The development of effective desensitization strategies has enabled ABO incompatible (ABOi) kidney transplantation to become an established treatment option for patients with end-stage renal disease. Here, the authors review the mechanisms that underlie acceptance and rejection of ABOi grafts, recipient desensitization strategies, patient outcomes and novel treatment strategies that might promote graft acceptance and enable minimization of immunosuppression.

• Georg A. Böhmig
• Andreas M. Farkas
• Thomas Wekerle

Microbiota—implications for immunity and transplantation

Resident microorganisms in the human body vastly outnumber host cells and have an important role in human physiology. In this Review, Bromberg and colleagues discuss the basic principles that guide analyses of the microbiota, including the challenges of measuring and quantifying microbiota. They also discuss the influence of the microbiota on the immune system and the implications of these effects on organ failure and transplantation.

• Jonathan S. Bromberg
• W. Florian Fricke
• Emmanuel F. Mongodin

Long-term medical risks to the living kidney donor

Transplantation of kidneys from living donors benefits patients with end-stage renal disease, but living donation is associated with short-term and long-term risks. In this Review, the authors summarize studies that have examined the long-term medical outcomes for living kidney donors, focusing on the first 10 years after donation. They also consider the need to further assess risk in specific populations of donors.

Primary disease recurrence—effects on paediatric renal transplantation outcomes

Renal transplantation is the optimal form of renal replacement therapy for children with end-stage renal disease; however, disease recurrence can lead to graft loss, morbidity and death. In this Review, Justine Bacchetta and Pierre Cochat provide an update on the epidemiology, pathophysiology, effects and management of disease recurrence after paediatric renal transplantation. They also describe pretransplantation and post-transplantation risk-reduction strategies that aim to minimize the possibility of disease recurrence, and thus improve both graft and patient outcomes.

• Justine Bacchetta
• Pierre Cochat

Emerging treatments for post-transplantation diabetes mellitus

Post-transplantation diabetes mellitus (PTDM) is a frequent complication among renal transplant recipients, and is associated with cardiovascular disease and reduced lifespan. In this Review, Jenssen and Hartmann discuss the diagnostic criteria for PTDM and evaluate available and emerging treatment options, highlighting the considerations that should be made when selecting an appropriate therapeutic regimen.

• Trond Jenssen
• Anders Hartmann

Hepatitis C and its impact on renal transplantation

Hepatitis C virus (HCV) infection imposes a substantial economic, clinical, and societal burden worldwide. In this Review, Morales and Fabrizi compare the treatment options that are available to patients with HCV infection, before and after renal transplantation. The development of novel therapeutic strategies and the clinical complications associated with HCV infection are discussed. The authors conclude with an assessment of the safe use of organs donated from individuals with active HCV infection.

• Jose M. Morales
• Fabrizio Fabrizi

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A systematic review of kidney transplantation outcomes in patients with end-stage renal disease due to childhood lower urinary tract malformations

• Urology – Review
• Published: 21 May 2024

Cite this article

• Hakan Bahadir Haberal 1   na1 ,
• Muhammet Irfan Donmez 2   na1 ,
• Alberto Piana 3 ,
• Alessio Pecoraro 4 ,
• Thomas Prudhomme 5 ,
• Beatriz Bañuelos Marco 6 ,
• Alicia López-Abad 7 ,
• Riccardo Campi 4 , 8 ,
• Romain Boissier 9 ,
• Alberto Breda 10 ,
• Angelo Territo 10 on behalf of

EAU Young Academic Urologists (YAU) Kidney Transplantation Working Group

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Patients with lower urinary tract malformations (LUTM) were suspended from kidney transplantation (KT) programs in the past due to various concerns. Consequently, only a limited number of studies have explored this topic at hand. In this study, our objective was to perform a systematic review (SR) to evaluate the current evidence regarding KT outcomes as well as patient survival (PS), postoperative complications and urinary tract infections (UTI) in individuals with childhood LUTM.

The search encompassed databases of Web of Science, Medline (via PubMed), and Embase (via Scopus) to identify all studies reporting outcomes on KT for patients with LUTM. The research included articles published in English from January 1995 till September 2023.

Of the 2634 yielded articles, 15 met the inclusion criteria, enrolling a total of 284,866 KT patients. There was significantly better 5-year graft survival (GS) in recipients with LUTM compared to the control group (RR, 1.04; 95% CI 1.02–1.06); while GS at 1-year and 10-year, and PS at 1-year, 5-year and 10-year were similar between groups. On the other hand, the postoperative UTI rate was significantly higher in the LUTM group (RR: 4.46; 95% CI 1.89–10.51). However, data on serum creatinine and estimated glomerular filtration rate on follow-up were insufficient.

GS and PS rates appear to be similar in patients with childhood LUTM and those with normal lower urinary tract functions. Despite a higher postoperative UTI rate within this patient group, it appears that this has no effect on GS rates.

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Long-term outcome of kidney transplantation in patients with congenital anomalies of the kidney and urinary tract

Endourological Management of Urological Complications Following Renal Transplantation

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Hakan Bahadir Haberal and Muhammet Irfan Donmez have contributed equally to this article.

Authors and Affiliations

Department of Urology, Ankara Ataturk Sanatorium Training and Research Hospital, Ministry of Health, University of Health Sciences, 06290, Ankara, Turkey

Hakan Bahadir Haberal

Department of Urology, Division of Pediatric Urology, Istanbul University Istanbul Faculty of Medicine, Istanbul, Turkey

Muhammet Irfan Donmez

Department of Urology, San Luigi Gonzaga Hospital, University of Turin, Orbassano, Turin, Italy

Alberto Piana

Unit of Urological Robotic Surgery and Renal Transplantation, Careggi Hospital, University of Florence, Florence, Italy

Alessio Pecoraro & Riccardo Campi

Department of Urology and Kidney Transplantation, Rangueil University Hospital, Toulouse, France

Thomas Prudhomme

Department of Urology, Renal Transplant Division, University Hospital Clínico San Carlos, Madrid, Spain

Beatriz Bañuelos Marco

Department of Urology, Virgen de La Arrixaca University Hospital, Murcia, Spain

Alicia López-Abad

Department of Experimental and Clinical Medicine, University of Florence, Florence, Italy

Riccardo Campi

Department of Urology and Renal Transplantation, La Conception University Hospital, Marseille, France

Romain Boissier

Uro-Oncology and Kidney Transplant Unit, Department of Urology at “Fundació Puigvert” Hospital, Autonoma University of Barcelona, Barcelona, Spain

Alberto Breda & Angelo Territo

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Study concept and design: H.B.H., M.I.D., A.P., A.P., T.P., B.B.M., A.B., and A.T.; analysis and interpretation of data: H.B.H., M.I.D., and A.T.; drafting of the manuscript: H.B.H., M.I.D., A.P., A.P., T.P., B.B.M., A.L., R.C., R.B., A.B., and A.T.; statistical analysis: H.B.H. and M.I.D.; supervision: R.C., R.B., and A.B. All authors reviewed the manuscript.

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Haberal, H.B., Donmez, M.I., Piana, A. et al. A systematic review of kidney transplantation outcomes in patients with end-stage renal disease due to childhood lower urinary tract malformations. Int Urol Nephrol (2024). https://doi.org/10.1007/s11255-024-04079-5

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Transplant Research Center

Kidney and pancreas transplant research program.

The Kidney and Pancreas Transplant Research Program within the Mayo Clinic Transplant Research Center focuses its research efforts on overcoming the challenges that limit the success of kidney and pancreas transplantation.

Research focus areas

Research focus areas in the Kidney and Pancreas Transplant Research Program include:

Overcoming antibody barriers

Reducing disease recurrence, improving long-term success, expanding living-donor transplants, pre-emptive transplantation, immunosuppression characteristics and new treatments, managing cardiovascular complications.

Here's a closer look at the focus areas.

Researchers in the Kidney and Pancreas Transplant Research Program have led the way in developing treatment strategies that reduce antibody levels, which allowed for successful living-donor kidney transplants even with incompatible blood types.

Antibodies are proteins produced by the body to protect it against substances, cells or organs that are foreign. These antibodies are essential for health. However, at times these antibodies can prevent a patient from receiving a transplant, because they can quickly destroy the transplanted kidney or pancreas. Antibodies can be directed against blood groups or against donor cells (called a positive crossmatch).

Researchers have developed several strategies to allow transplantation even in the presence of antibodies.

• At Mayo Clinic, investigators apply sophisticated techniques to differentiate which antibodies pose a problem for transplantation and which don't.
• Researchers also apply techniques to remove these antibodies from blood before transplant and to control negative effects of these antibodies on the kidney with medications.
• Patients with kidney failure and high levels of antibodies can receive kidneys from a larger pool of living donors and may be able to participate in Mayo Clinic's paired donation program . As a result, qualified patients with kidney failure are able to avoid lengthy or indefinite waiting periods for deceased-donor transplants.

Ongoing research in the area of antibody resistance includes:

• The effect of antibody development on the transplanted kidney and pancreas
• Laboratory investigations of the cells responsible for producing damaging antibodies
• Clinical testing of new treatments for reducing or preventing the production of donor-specific antibodies

Researchers in the Kidney and Pancreas Transplant Research Program are studying ways to identify treatments that reduce the risk of recurrent disease after a kidney transplant.

Several of the diseases that can cause kidney failure can come back and attack a newly transplanted kidney. In fact, approximately 20% to 25% of kidney transplants are lost because of disease recurrence.

To address this problem, Mayo Clinic researchers have taken several steps.

• First, researchers identified diseases that are most likely to recur in the transplanted kidney.
• Second, with the use of protocol biopsies, researchers identified the earliest signs of disease recurrence in the transplanted kidney, with the intent of improving outcomes by treating patients when disease recurrence is detected.
• Third, researchers developed new treatments that can be given to the patient to prevent disease recurrence or to treat it when it occurs.

Researchers have made significant advances in the prevention and treatment of some of the most dangerous diseases for the transplanted kidney, including focal segmental glomerulosclerosis , membranous nephropathy and membranoproliferative glomerulonephritis.

Research in this area continues to further refine disease classification and identify optimal treatment options to prevent disease recurrence because each of these diseases seems to require specific management strategies.

The premature loss of transplanted organs traditionally has been attributed to poorly characterized diseases that are frequently lumped together under the term "chronic rejection."

Researchers in the Kidney and Pancreas Transplant Research Program have taken a different approach to this problem by first questioning what precisely causes the loss of kidney and pancreas transplants.

Using kidney biopsies and careful examination of laboratory and clinical parameters, the Mayo Clinic researchers determined that kidney transplants can be lost for multiple reasons. In most cases, the cause of the kidney loss was because of known diseases that could potentially be prevented and treated.

These investigations also make it abundantly clear that a comprehensive approach addressing all the threats that can harm the transplanted organ is needed for transplant success.

Researchers developed a series of tools that allow them to monitor outcomes-particular management strategies.

These tools include:

• A continually updated database to gather information about a multitude of clinical, laboratory and biopsy parameters in thousands of patients over time
• Protocol biopsies for pathology review of kidney transplants at specific time points during the first 10 years after transplant
• Microarray studies examining the expression of thousands of genes within kidney transplant tissues, helping researchers understand how the kidney reacts in response to injury
• Screening tests for potentially damaging viral infections and immune responses in kidney transplant recipients
• Monitoring of the production of antibodies against the transplanted kidney or pancreas, thus allowing researchers to determine whether immunosuppressive medications that the patient receives after the transplant are effective

Mayo Clinic has performed living-donor kidney transplants since 1963 and has the largest single-living-donor program in the United States.

In order for the practice of living-donor transplant to remain successful and safe for both donor and recipient, researchers in the Kidney and Pancreas Transplant Research Program have placed a high priority on research into the short- and long-term outcomes for kidney donation.

Ongoing clinical investigations include:

• Effect of kidney donation on blood pressure
• Impact of obesity on kidney donation
• Long-term outcomes of kidney donation
• Impact of donor age on transplant success

Researchers in the Kidney and Pancreas Transplant Research Program also have a strong commitment to expand pre-emptive transplantation — transplantation of a kidney in patients who have never received dialysis.

Investigators have shown in the past that dialysis prior to transplantation limits the life span of the recipient. Avoiding dialysis, particularly for more than one year, has beneficial consequences for the patient and perhaps the transplanted organ. In addition, pre-emptive transplantation reduces medical costs.

At times, patients are told that a period of dialysis is required before receiving a transplant. Researchers at Mayo Clinic believe that patients should be encouraged to consider transplantation as their kidneys start to fail.

The success of this program is closely tied to the success of living-donor kidney transplantation in the Kidney and Pancreas Transplant Research Program. However, it's possible to achieve pre-emptive transplantation with deceased-donor kidneys if patients are placed on the waiting list soon enough.

Ongoing investigations include:

• Evaluation of medical, psychological, quality of life and financial implications of pre-emptive transplantation
• Evaluation on how collaborative efforts with referring physicians and even insurance companies can facilitate pre-emptive transplantation

The Kidney and Pancreas Transplant Research Program has conducted and participated in many clinical studies designed to examine the benefits associated with new immunosuppressive medications and combinations of medications compared with established regimens.

Because most organ transplants require the use of two or more medications combined over time, the design of optimal immunosuppression regimens for individual organs and patient groups has grown more complex.

Mayo Clinic researchers have examined changes in the structure of transplanted kidneys using protocol biopsies and determined that prolongation of kidney survival likely will require re-examination of the approach to immunosuppression after the first year post-transplant.

By understanding what is happening inside the transplanted organ, researchers can design new strategies to achieve long-term success. Protocol biopsies are essential tools to achieve this goal.

Mayo Clinic researchers and physicians are conducting research to identify the causes of cardiovascular disease in kidney transplant recipients and the benefits of different treatment and prevention strategies.

Certain kidney transplant recipients are at higher risk of developing cardiovascular complications, such as heart attack, stroke and loss of blood supply to the limbs, typically from underlying medical diseases and medication-related toxicities.

Research studies using database information and measuring heart biomarkers in thousands of kidney transplant recipients at Mayo Clinic have improved the ability to identify patients who are at risk of heart problems after transplant

Investigators have found that the biomarker troponin levels can provide a more accurate measure of cardiac risk than can traditional cardiac measurements, such as a cardiac stress test, and can indicate whether surgical intervention is needed prior to kidney transplant.

The goals of this research are to achieve lower risk for patients and to conduct cardiac studies for patients who can benefit the most.

Ongoing studies include:

• Determining whether troponin can also be used to assess heart status after kidney or pancreas transplant
• Assessing how modifications in the treatment of patients before the transplant can reduce levels of troponin and perhaps reduce risk

Program faculty

Here's a list of faculty in the Kidney and Pancreas Transplant Research Program by campus location.

• Chakkera, Harini, M.D.
• Heilman, Raymond L., M.D.
• Huskey, Janna L. M.D.
• Kaplan, Bruce, M.D.
• Khamash, Hasan A, M.D.
• Mathur, Amit K., M.D.
• Morales, Alejandro, M.D.
• Moss, Adyr A., M.D.
• Petrides, Savas, M.D.
• Reddy, Kunam S., M.B.B.S.
• Singer, Andrew L., M.D., Ph.D.
• Sukumaran, Sumi Nair, M.B.B.S.
• Croome, Kristopher (Kris) P., M.D.
• Gonwa, Thomas A., M.D.
• Lee, David D., M.D.
• Mai, Martin L., M.D.
• Oshel, Katherine, M.D.
• Perry, Dana K., M.D.
• Prendergast, Mary B., M.D.
• Taner, Burcin C., M.D.
• Wadei, Hani M., M.D.
• Amer, Hatem, M.D.
• Cosio, Fernando G., M.D.
• Cramer, Carl H. II., M.D.
• Dean, Patrick G., M.D.
• Heimbach, Julie K., M.D.
• Hickson, LaTonya J., M.D.
• Issa, Naim S., M.D.
• Kudva, Yogish C., M.B.B.S.
• Kukla, Aleksandra M.D.
• Larsen, Brandon T., M.D., Ph.D.
• Lorenz, Elizabeth C., M.D.
• Norby, Suzanne M., M.D.
• Nyberg, Scott M.D., Ph.D.
• Prieto, Mikel, M.D.
• Schinstock, Carrie A., M.D.
• Stegall, Mark D., M.D.
• Taler, Sandra J., M.D.

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Kidney Transplantation

There is a national transplant waiting list for people who are waiting for all types of transplants.  Every 10 minutes, a new person is added to the list. Most of the people on the list are waiting for a kidney transplant. How long one has to wait is different for each person.  The average time to wait for a kidney is 3-5 years.  For some it might be shorter and for others it might be longer. You should ask your kidney care team to tell you about kidney transplantation as a treatment option for your kidney disease.

Most people on Hemodialysis or Peritoneal Dialysis can consider getting a kidney transplant.  Some in CKD Stage 4 or 5 may be able to get a transplant and not have to go on any type of dialysis – this is called a pre-emptive transplant.  

What are the Types of Kidney Transplants?

Living Donation is when a person donates a kidney to a friend or someone related to them.  Living donated kidneys take away the long wait for a transplant.  These kidneys usually function longer than a kidney from someone who has died. 

A donor will be told about any risks related to donating a kidney.  Living donors can live a healthy life with one kidney.  They can apply for money to help cover travel and lodging.  There are living donor assistance program such as, www.livingdonorassistance.org and www.transplantfoundation.org   where the donor may find help.  Help for a donor might include:

• Travel expenses
• Food and lodging
• Medications
• Hospital and physician charges

Paired/Exchange Donation may be an option for those who know someone who wants to donate a kidney. Sometimes the donor is cleared to donate but is not a good match for the patient.  If this happens, the patient and donor may be able to enter into a paired kidney donation program. These programs pair the kidney and the patient with the best kidney match.  This can start a “chain” of kidney donations.  Ask the transplant team if they have a program like this.  If they don't, they can tell you about transplant centers who do.      

Deceased Donation is the most common form of kidney donation.  These kidneys come from people who have died and donated their organs for transplant.  These kidneys need to be transplanted soon after the donor has died. It is important for their family to know that they want to be a donor.  If not, the family may decide not to donate their organs.  Anyone can sign up to be an organ donor.  Go to the link DonateLife America www.donatelife.net to find out more.

Altruistic Donation is when someone donates a kidney to any patient on the wait list.  These kidneys might be given to a patient on the waitlist at a transplant center.  They might used for a paired kidney transplant chain. These donors usually do not know the person they are giving a kidney to.  

Pre-emptive Transplant is when a patient gets a transplant before they have to go on dialysis.  Studies show this can result in better kidney and health outcomes.  This type of transplant is more likely if a person has a living donor.  The sooner you learn about your treatment choices, the better.  This will give you time to decide if a transplant is best for you.    

Find a Transplant Center

To find a transplant center in your area visit the  Organ Procurement and Transplantation Network (OPTN) website . Then follow these steps:

• Select "Transplant Centers by Organ" under Member Type
• Select "Kidney" for Organ Type
• Select your state or region

donor-seeker program*

The Donor Seeker® is the only 15-minute video course that will help you "talk up" your search for a living kidney donor. This fast-tracked program includes confidence-building conversation examples, and key talking points on how to share your story and ask others to help you spread the word. You’ll also find a robust resource section full of informative links, downloadable forms, and a course completion certificate. Whether listening in English or Spanish—the universal language is sure to increase your odds for attracting interested individuals who can advance your path to transplant. *If you prefer to use your mobile device, you can now access the "Donor Seeker" app from the  Apple App Store  or  Google Play Store .

Learn how to apply these powerful communication tips—and start attracting interested donors today! Click here to start.

*AAKP is a Simon Says Seminars, inc. | TransplantStrong Community Partner.

AAKP's Top Resources on Kidney Transplantation education

For more information on this topic, check out the following resources!

• Understanding Kidney Transplantation brochure
• Kidney Transplant Today e-newsletter*
• AAKP HealthLine webinars  
• aakpRENALIFE magazine*
• AAKP Delicious! kidney-friendly recipes
• VIDEO, Northwestern Medicine -Inside the OR: Kidney Transplant Surgery
• CDC Fact Sheet on Kidney Disease (2023)  

*Benefit of membership, join today! 

iChoose Kidney Risk Calculator*

The iChoose Kidney risk calculator is a tool that educates patients about the risk of available treatment options for kidney disease. This tool shows estimated risks of patient survival  (probability of staying alive)  and mortality  (probability of dying)  with different treatment options  (dialysis or transplant) given the patient's demographic and clinical history at dialysis start. 

My Dialysis Choice* If you kidneys fail, dialysis can save your life. But, dialysis is not just a medical treatment. It can also affect every aspect of your lifestyle. This online tool will help you choose the right treatment for you, so you feel your best and live the way you want to.

*iChoose Kidney Risk Calculator is an online application tool created by a team of researchers at Emory University, funded by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Number ULl TR000454 and KL2TR000455, and further supported through a grant from the Carlos and Marguerite Mason Trust Foundation (Emory University).

*My Dialysis Choice is an online application tool created by the non-profit Medical Education Institute.

Visit our Post-Kidney Transplant Care and Your Health web page!

Proper care of your kidney transplant is a lifelong process. You will need to take care of yourself and actively monitor your health. You will also need to be aware of signs and symptoms that should be reported to your transplant team immediately. The more you know, the more power you have to keep you and your donor kidney healthy. Visit our post-kidney transplant care and your health web page for more information on post-transplant care.

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Power lifechanging research, education and advocacy to ensure that every person facing kidney disease gets the chance to thrive—not simply survive. Give today and help us provide FREE resources, support, and hope for patients, loved ones and healthcare heroes.

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Masks Strongly Recommended but Not Required in Maryland, Starting Immediately

Due to the downward trend in respiratory viruses in Maryland, masking is no longer required but remains strongly recommended in Johns Hopkins Medicine clinical locations in Maryland. Read more .

• Vaccines  
• Masking Guidelines
• Visitor Guidelines  

New Research Supports Expansion of Kidney Donation to Include Organs from Deceased Patients Who Once Had Dialysis

New @hopkinsneph study investigates potential remedy for kidney donor shortage. @KidneydrChirag ›

Researchers from Johns Hopkins Medicine propose a novel approach to addressing the pressing issue of a kidney donor shortage through findings that suggest a promising method to expand the pool of available kidney donors by utilizing deceased donors on dialysis for kidney transplants.  

The findings, published in the May 23rd issue of  JAMA , identifies that while those who received such kidneys experienced a “significant delay” in the function of the transplanted organ compared to those whose donors did not have dialysis, there was no significant difference in rates of transplant failure or death.

According to the  United Network for Organ Sharing , (UNOS) approximately 100,000 patients are on the waiting list for kidney transplants in the United States. Some 25,000 successful kidney transplants were performed in 2022, the latest year for which complete data are available, and it is estimated that fewer than 20,000 of those on the list will receive transplants from deceased donors.  

Historically, according to UNOS, more than 20% of deceased donor kidneys are not used each year, largely several of them are not utilized due to concerns that acute kidney injury (AKI) in the kidneys and dialysis used to treat the donors renders the kidneys too damaged for transplantation.  

However, recent studies suggest there might not be much long-term difference between how the organ recipient’s body responds to a deceased donor kidney exposed to dialysis prior to transplant surgery and a diseased donor kidney not exposed to dialysis before transplant surgery.      

These deceased donors are receiving dialysis treatment because they have severe AKI around the time of their death. It is known that kidneys with AKI are at a higher risk of delayed graft function (DGF) in recipients—a term for when the transplanted kidney does not work right away. What has been unclear, is whether DGF predicts shortened life expectancy and organ function over the long term.

Suppose studies prove that the risks associated with the transplantation of kidneys from deceased donors on dialysis are minimal in regard to long term life expectancy of the graft and quality of life of the recipient. In that case, this will go a long way toward increasing the number of available kidney donors.

“With patients waiting many years to receive a kidney, and a significant portion of them deteriorate or succumb to their condition while on the waiting list, we need to rapidly increase the pool of available kidneys,” says  Chirag Parikh, M.D., Ph.D. , professor of medicine and the director of the division of Nephrology at Johns Hopkins Medicine and key investigator for the study.

For the study, researchers analyzed medical records for 1,944 kidney transplant patients gathered from 58 U.S. organ transplant organizations from the years 2010 and 2018 with 954 receiving kidneys from deceased donors who underwent dialysis and matched them to 990 receiving kidneys from deceased donors who had not undergone dialysis.

Results showed there was higher incidence of DGF in patients who received kidneys from donors who were deceased and who underwent dialysis than there was for patients with kidneys from donors who were deceased and who did not receive dialysis. However, the kidney recipients with higher DGF did not show any significant differences in long-term graft failure (permanent loss of function of the transplanted organ).

“There is significant variability in the utilization of kidneys from high risk deceased donors across the country,” Parikh says. “The findings from this study should encourage organ procurement organizations and transplant professionals to cautiously bring kidneys with severe AKI, from deceased donors who received dialysis, into the allocation pool.”  

Along with Dr. Parikh, members of the study team from Johns Hopkins Medicine are Yumeng Wen, MD, PhD; Nitya Srialluri, MD, MS, MHS, and Heather Thiessen Philbrook, M, Math.

Funding for the study was provided by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) grant T32DK007732-27, grant U01DK-116097, grant U01DK-116066, grant R01DK-126739, and grant U01DK130058, the National Institute on Minority Health and Health Disparities grant R01MD-014161, the National Institute of Biomedical Imaging and Bioengineering grant R01EB-032910; grants R01DK-123041, U01DK-126654, and U01DK-110961, the National Institute of Allergy and Infectious Diseases grant K24AI-146137; the NIDDK and grant P30DK079310 from the George M. O’Brien Kidney Center at Yale University grants R01DK-93770, K24DK090203 and grant P30DK079310.

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Research indicates kidneys from deceased donors who were on dialysis are suboptimal

by Elana Gotkine

Receipt of a kidney from a deceased donor who underwent dialysis is associated with an increased incidence of delayed graft function, according to a study published online May 23 in JAMA .

Yumeng Wen, M.D., Ph.D., from Johns Hopkins University in Baltimore, and colleagues compared outcomes of transplant recipients who received kidneys from deceased donors who underwent dialysis prior to kidney donation versus recipients of kidneys from deceased donors who did not undergo dialysis in a retrospective cohort study using data from 58 U.S. organ procurement organizations.

Among the donors with kidneys transplanted, 514 underwent dialysis prior to transplantation and were matched to 514 who did not undergo dialysis. The researchers found that compared with kidney transplants from donors who did not receive dialysis, kidney transplants from donors who received dialysis prior to donation had an increased risk for delayed graft function (59.2 versus 24.6%; adjusted odds ratio, 4.17).

At a median follow-up of 34.1 months, the incidence rates did not differ significantly for all-cause graft failure, death-censured graft failure, or death for transplants from donors who received dialysis prior to donation versus donors who did not receive dialysis.

"Future research should investigate whether the higher procurement and acceptance rates of kidneys from deceased donors who received dialysis are associated with shorter waiting times and better outcomes for patients," the authors write.

Xingxing S. Cheng et al, Expanding the Overton Window in Deceased Kidney Donor Eligibility—Enough to Make a Difference?, JAMA (2024). DOI: 10.1001/jama.2024.8734

Copyright © 2024 HealthDay . All rights reserved.

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Ozempic Cuts Risk of Chronic Kidney Disease Complications, Study Finds

A major clinical trial showed such promising results that the drug’s maker halted it early.

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By Dani Blum

Dani Blum has reported on Ozempic and similar drugs since 2022.

Semaglutide, the compound in the blockbuster drugs Ozempic and Wegovy , dramatically reduced the risk of kidney complications, heart issues and death in people with Type 2 diabetes and chronic kidney disease in a major clinical trial, the results of which were published on Friday. The findings could transform how doctors treat some of the sickest patients with chronic kidney disease, which affects more than one in seven adults in the United States but has no cure.

“Those of us who really care about kidney patients spent our whole careers wanting something better,” said Dr. Katherine Tuttle, a professor of medicine at the University of Washington School of Medicine and an author of the study. “And this is as good as it gets.” The research was presented at a European Renal Association meeting in Stockholm on Friday and simultaneously published in The New England Journal of Medicine .

The trial, funded by Ozempic maker Novo Nordisk, was so successful that the company stopped it early . Dr. Martin Holst Lange, Novo Nordisk’s executive vice president of development, said that the company would ask the Food and Drug Administration to update Ozempic’s label to say it can also be used to reduce the progression of chronic kidney disease or complications in people with Type 2 diabetes.

Diabetes is a leading cause of chronic kidney disease, which occurs when the kidneys don’t function as well as they should. In advanced stages, the kidneys are so damaged that they cannot properly filter blood. This can cause fluid and waste to build up in the blood, which can exacerbate high blood pressure and raise the risk of heart disease and stroke, said Dr. Subramaniam Pennathur, the chief of the nephrology division at Michigan Medicine.

The study included 3,533 people with kidney disease and Type 2 diabetes, about half of whom took a weekly injection of semaglutide, and half of whom took a weekly placebo shot.

Researchers followed up with participants after a median period of around three and a half years and found that those who took semaglutide had a 24 percent lower likelihood of having a major kidney disease event, like losing at least half of their kidney function, or needing dialysis or a kidney transplant. There were 331 such events among the semaglutide group, compared with 410 in the placebo group.

People who received semaglutide were much less likely to die from cardiovascular issues, or from any cause at all, and had slower rates of kidney decline.

Kidney damage often occurs gradually, and people typically do not show symptoms until the disease is in advanced stages. Doctors try to slow the decline of kidney function with existing medications and lifestyle modifications, said Dr. Melanie Hoenig, a nephrologist at Beth Israel Deaconess Medical Center who was not involved with the study. But even with treatment, the disease can progress to the point that patients need dialysis, a treatment that removes waste and excess fluids from the blood, or kidney transplants.

The participants in the study were extremely sick — the severe complications seen in some study participants are more likely to occur in people the later stages of chronic kidney disease, said Dr. George Bakris, a professor of medicine at the University of Chicago Medicine and an author of the study. Most participants in the trial were already taking medication for chronic kidney disease.

For people with advanced kidney disease, in particular, the findings are promising. “We can help people live longer,” said Dr. Vlado Perkovic, a nephrologist and renal researcher at the University of New South Wales, Sydney, and another author of the study.

While the data shows clear benefits, even the researchers studying drugs like Ozempic aren’t sure how, exactly, they help the kidneys. One leading theory is that semaglutide may reduce inflammation, which exacerbates kidney disease.

And the results come with several caveats: Roughly two-thirds of the participants were men and around two-thirds were white — a limitation of the study, the authors noted, because chronic kidney disease disproportionately affects Black and Indigenous patients. The trial participants taking semaglutide were more likely to stop the drug because of gastrointestinal issues, which are common side effects of Ozempic.

Doctors said they wanted to know whether the drug might benefit patients who have kidney disease but not diabetes, and some also had questions about the potential long-term risks of taking semaglutide.

Still, the results are the latest data to show that semaglutide can do more than treat diabetes or drive weight loss. In March, the F.D.A. authorized Wegovy for reducing the risk of cardiovascular issues in some patients. And scientists are examining semaglutide and tirzepatide, the compound in the rival drugs Mounjaro and Zepbound, for a range of other conditions , including sleep apnea and liver disease.

If the F.D.A. approves the new use, it could drive even more demand for Ozempic, which has faced recurrent shortages .

“I think it’s a game changer,” Dr. Hoenig said, “if I can get it for my patients.”

Dani Blum is a health reporter for The Times. More about Dani Blum

A Close Look at Weight-Loss Drugs

Reduced Disease Complications: Semaglutide, the compound in Ozempic and Wegovy, dramatically reduced the risk of kidney complications , heart issues and death in people with Type 2 diabetes and chronic kidney disease in a major clinical trial.

Supplement Stores: GNC and the Vitamin Shoppe are redesigning displays and taking other steps  to appeal to people who are taking or are interested in drugs like Ozempic and Wegovy.

Senate Investigation: A Senate committee is investigating the prices that Novo Nordisk charges  for Ozempic and Wegovy, which are highly effective at treating diabetes and obesity but carry steep price tags.

A Company Remakes Itself: Novo Nordisk’s factories work nonstop turning out Ozempic and Wegovy , but the Danish company has far bigger ambitions.

Transforming a Small Danish Town: In Kalundborg, population under 17,000, Novo Nordisk is making huge investments to increase production  of Ozempic and Wegovy.