Introduction to Kidney Transplantation: Long-Term Management Challenges

Kidney transplantation is the optimal treatment for kidney failure, associated with a lower risk of mortality compared with dialysis (1) and improved quality of life (2). The number of kidney transplants in the United States continues to increase on an annual basis; 23,401 kidney transplants were performed in 2019, an 11% increase over the year prior (3). Advances in immunosuppression management have led to a marked decrease in early acute rejection episodes (4) as well as excellent 1-year allograft survival (>95%) (5); however, this success has been slow to translate into improved long-term graft longevity. Although there has been an incremental decline in late graft-loss rates over time, the median kidney transplant survival in the United States is only 11.2 years, compared with >14 years in the United Kingdom, Australia, and New Zealand (6).

Several factors contribute to the observed outcomes. Recipients of kidney transplants have aged over time and have more comorbidities; the number of recipients over age 65 has doubled since 2001, and the percentage of recipients with a body mass index >30 kg/m² or long dialysis vintage has also risen (7). Increased medical complexity has translated into diminished long-term patient and graft survival. Despite rigorous pretransplant screening, cardiovascular disease is the primary cause of mortality among recipients of kidney transplants; infection and malignancy represent the other main contributors. Simultaneously, due to a mismatch in organ supply and growing transplant demand, there has been greater use of more “marginal” kidneys for transplantation; although these organs are associated with reduced patient mortality compared with dialysis (8,9), they contribute negatively to national allograft survival rates. Late graft loss is frequently multifactorial (10), due to both immunologic and nonimmune-mediated mechanisms. It presents as slowly progressive kidney dysfunction, with generic histopathologic findings, historically called “chronic allograft nephropathy” (11), and now, more commonly, “interstitial fibrosis and tubular atrophy,” for lack of a better term. This and other progressive conditions, such as recurrent glomerular disease, eventually lead to graft failure. Recipients of transplants transitioning back to dialysis or being evaluated for retransplantation merit additional consideration in how their immunosuppression withdrawal is handled to maximize their KRT options. Unique populations, such as pediatric recipients of transplants, require special attention from clinicians, especially when they transition to care by adult nephrologists. Likewise, for female recipients of childbearing potential, transplantation offers an opportunity to become pregnant; their care also requires dedicated expertise and immunosuppression modifications to optimize outcomes for both mother and child.

Historically, due to the regulations of Centers for Medicare and Medicaid Services (12), 1- and 3-year patient and allograft survival had been the predominant focus, often to the detriment of longer-term outcomes, but this approach is changing (13). Given the large and growing number of recipients of transplants with a functioning allograft, long-term management of recipients of kidney transplants often falls to general nephrologists—frequently, but not always, in consultation with the transplant center. Thus, we believe this series of reviews will serve as an important resource for the larger nephrology community when caring for transplant patients in their practice and highlight the clinical issues that general nephrologists are most likely to encounter. With that in mind, we have created a series of 13 reviews authored by basic scientists and clinical experts in the field that will focus on two main areas of practice: (1) contemporary immunosuppression regimens and innovative immune-monitoring strategies, and (2) post-transplant complications (Table 1). Reviews will cover state-of-the-art immunosuppression regimens and novel immune-monitoring strategies that provide additional insights beyond the kidney biopsy; sequelae of immune dysfunction, such as chronic allograft rejection and injury, will be reviewed. The long-term management concerns discussed will include common complications seen beyond the first post-transplant year, such as cardiovascular disease, infections, post-transplant malignancy, recurrent and de novo glomerular disease, and bone and mineral disease. The care of special populations, including recipients with a failing allograft, pediatric recipients transitioning to adult care, and pregnant recipients of kidney transplants, will also be reviewed in this series.

Table 1.

Topic areas included in “Kidney Transplantation: Long-Term Management Challenges”

Topic Areas
Immunosuppression and monitoring
Contemporary immunosuppression management strategies
Immune monitoring and biomarkers
Chronic allograft injury
Transplant complications
Nephroprotective medication strategies
Recurrent and de novo glomerular disease
Cardiovascular disease
Malignancy
Infections
Bone and mineral disease
Care of the failing allograft
Special populations
Pediatric recipients
Pregnancy and contraception

Successful kidney transplantation requires a team-based approach. In the early post-transplant period, this is centered around transplant nephrologists and surgeons, but partnership between general and transplant nephrologists is crucial in the long-term care of their mutual patients. We hope this series will foster a deeper understanding of the major clinical issues faced by recipients of transplants and prompt consideration of how we can optimize our joint care of this patient population.

Disclosures

All authors have nothing to disclose.

Funding

None.