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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.