Preemptive kidney transplantation: Has it come of age?

The benefits of preemptive kidney transplantation are manifold. By avoiding complications associated with dialysis, preemptive kidney transplantation offers significant benefits in terms of patient welfare and societal cost-saving. Patients transplanted preemptively also tend to enjoy better patient and graft survival, especially when done with a living-donor organ. While dialysis exposure limited to 6 to 12 months may not significantly impact post-transplant outcomes, longer period of dialysis has been shown to increase the risk of mortality, delayed graft function, acute rejection, and death-censored graft loss. The benefits of preemptive transplantation also extend to different age groups and end-stage kidney disease (ESKD) diagnoses. However, multiple barriers have prevented wider adoption of preemptive transplantation as the primary treatment of ESKD around the world. Timely preparation for ESKD and identification of living donors should be encouraged in all patients with advanced chronic kidney disease to increase the chance of preemptive transplantation.     

Exercise and cognitive function in patients with end‐stage kidney disease

In this review we summarize the research pertaining to the role of exercise in preventing cognitive decline in patients with end‐stage kidney disease (ESKD). Impairment in cognitive function, especially in executive function, is common in patients with ESKD, and may worsen with maintenance dialysis as a result of retention of uremic toxins, recurrent cerebral ischemia, and high burden of inactivity. Cognitive impairment may lead to long‐term adverse consequences, including dementia and death. Home‐based and intradialytic exercise training (ET) are among the nonpharmacologic interventions identified to preserve cognitive function in ESKD. Additionally, cognitive training (CT) is an effective approach recently identified in this population. While short‐term benefits of ET and CT on cognitive function were consistently observed in patients undergoing dialysis, more studies are needed to replicate these findings in diverse populations including kidney transplant recipients with long‐term follow‐up to better understand the health and quality of life consequences of these promising interventions. ET as well as CT are feasible interventions that may preserve or even improve cognitive function for patients with ESKD. Whether these interventions translate to improvements in quality of life and long‐term health outcomes, including dementia prevention and better survival, are yet to be determined.     

Public policy and programs – Missing links in growing home dialysis in the United States

Patients with end-stage kidney disease (ESKD) require dialysis or a kidney transplant for survival and over 760 000 patients now benefit from these therapies in the United States. Dialysis in the United States in the late 1960s and early 1970s was often done in the home. After the advent of Medicare coverage for ESKD in 1972 and the subsequent easier access to center based hemodialysis, the use of home modalities dramatically declined. This stands in contrast to home dialysis uptake in other industrialized healthcare systems where both peritoneal dialysis and home hemodialysis are more frequently used. Characteristics unique to the US healthcare system as well as the cultures of providers (physicians and dialysis providers) and recipients of ESKD care are hypothesized as the main reasons for observed differences in home dialysis use. To address these issues, the Centers for Medicare and Medicaid Services have recently proposed new payment programs under an Executive Order from the President of the United States, with the explicit goal of increasing the number of patients using home dialysis. This perspective outlines policy opportunities and programs with a proven track record of home dialysis growth in other countries or hypothesized promise based on identified barriers and needs.     

Obesity as a barrier to kidney transplantation: Time to eliminate the body weight bias?

There is clear evidence that survival rates following transplantation far exceed those for remaining on dialysis, regardless of body size measured by body mass index (BMI). Studies over the past 15 years also suggest little to no difference in long‐term outcomes, including graft survival and mortality, irrespective of BMI, in contrast to earlier evidence. However, weight bias still exists, as access to kidney transplantation remains inequitable in centers using arbitrary BMI limits. Clinicians faced with the decision regarding listing based on body size are not helped by conflicting recommendations in national and international guidelines. Therefore, in clinical practice, obesity, and recommendations for weight loss, remain a controversial issue when assessing suitability for kidney transplantation. Obesity management interventions in end‐stage kidney disease (ESKD), whether for weight loss for transplantation listing or for slowing kidney disease progression, are under‐explored in trial settings. Bariatric surgery is the most successful treatment for obesity, but carries increased risk in the ESKD population, and the desired outcome of kidney transplant listing is not guaranteed. Centers that limit transplants to those meeting arbitrary levels of body mass, rather than adopting an individualized assessment approach, may be unfairly depriving many ESKD patients of the survival and quality of life benefits derived from kidney transplantation. However, robotic kidney transplantation surgery holds promise for reducing perioperative risks related to obesity, and may therefore represent an opportunity to remove listing criteria based on size.     

When ESKD complicates cancer screening and cancer treatment

End-stage kidney disease (ESKD) affects the recommended screening, incidence, treatment, and mortality of cancer. Cancer occurring in a patient with ESKD can influence candidacy for kidney transplantation as well as dialysis decision-making and cancer treatment. Certain cancers are more common among ESKD patients, notably, viral-mediated cancers that are associated with human papilloma or hepatitis viruses, and urothelial cancers associated with analgesic and Balkan nephropathies. Solid tumors are not believed to occur more frequently in ESKD patients. The presence of ESKD may confer a higher risk of post-surgical complications as well as mortality. The cost-effectiveness of cancer screening depends upon individual cancer risk and estimated overall survival. The high mortality associated with ESKD argues against routine cancer screening in dialysis patients. Cancer treatment in ESKD may be complicated by the need to avoid, adjust doses of and/or coordinate the timing of administration of imaging contrast, chemotherapy, and immunotherapy with dialysis treatments. There is a general dearth of information on the treatment of cancer in ESKD patients. These issues will be discussed, and some general guidelines presented based upon the current literature.     

Current state of kidney transplantation in patients with HIV,hepatitis C,and hepatitis B infection

Human immunodeficiency virus (HIV), hepatitis C (HCV), and hepatitis B (HBV) are common chronic viral infections in the end-stage kidney disease (ESKD) patient population that were once considered relative contraindications to kidney transplantation. In this review, we will summarize the current state of kidney transplantation in patients with HIV, HCV, and HBV, which is rapidly evolving. HIV+ patients enjoy excellent outcomes in the modern transplant era and may have new transplant opportunities with the use of HIV+ donors. Direct-acting antivirals for HCV have substantially changed the landscape of care for patients with HCV infection. HBV+ patients now have excellent patient and allograft survival with HBV therapy. Currently, kidney transplantation is a safe and appropriate treatment for the majority of ESKD patients with HIV, HCV, and HBV.     

Chronic kidney disease in the general population

End-stage kidney disease (ESKD), defined as the need for dialysis, receipt of a transplant, or death from chronic kidney failure, generally affects fewer than 1% of the population. However ESKD is the end result of chronic kidney disease (CKD), a widely prevalent but often silent condition with elevated risks of cardiovascular morbidity and mortality and a range of metabolic complications. A recently devised classification of CKD has facilitated prevalence estimates that reveal an "iceberg" of CKD in the community, of which dialysis and transplant patients are the tip. Hypertension, smoking, hypercholesterolemia, and obesity, currently among the World Health Organization's (WHO's) top 10 global health risks, are strongly associated with CKD. The factors, together with increasing diabetes prevalence and an aging population, will result in significant global increases in CKD and ESKD patients. Treatments now available effectively reduce the rate of progression of CKD and the extent of comorbid conditions and complications. The challenges are (1) to intervene effectively to reduce the excess burden of cardiovascular morbidity and mortality associated with CKD, (2) to identify those at greatest risk for ESKD and intervene effectively to prevent progression of early CKD, and (3) to ultimately introduce cost-effective primary prevention to reduce the overall burden of CKD. The vast majority of the global CKD burden will be in developing countries, and policy responses must be both practical and sustainable in these settings.     

Immigration status and end-stage kidney disease: Role of policy and access to care

Immigration status is an important mitigating factor in determining the provision of dialysis and kidney-related care. Immigrants make up the largest uninsured group in the country. For immigrants with end-stage kidney disease (ESKD), dialysis access varies by insurance type and by state, leading to great variability in the availability of kidney care. In some states, undocumented immigrants may only qualify for hemodialysis when critically ill (emergency hemodialysis), which is associated with higher mortality, hospital length of stay, and cost, in addition to an emotional burden on patients, their caregivers, and healthcare professionals. Barriers to effective care for immigrants with ESKD include immigration status, insurance access, and availability of pre-end stage kidney disease care, vascular access, and transplant. Effective strategies for improving dialysis care for immigrants include advocacy at the state and federal level, broadening definitions under Emergency Medicaid, and improving benefits for home therapies and transplantation options.     

Epidemiology of end-stage kidney disease

End-stage kidney disease (ESKD) is a common and morbid disease that affects patients’ quality and length of life, representing a large portion of health care expenditure in the United States. These patients commonly have associated diabetes and cardiovascular disease, with high rates of cardiovascular-related death. Management of ESKD requires renal replacement therapy via dialysis or transplantation. While transplantation provides the greatest improvement in survival and quality of life, the vast majority of patients are treated initially with hemodialysis. However, outcomes differ significantly among patient populations. Barriers in access to care have particularly affected at-risk populations, such as Black and Hispanic patients. These patients receive less pre-ESKD nephrology care, are less likely to initiate dialysis with a fistula, and wait longer for transplants—even in pediatric populations. Priorities for ESKD care moving into the future include increasing access to nephrology care in underprivileged populations, providing patient-centered care based on each patient’s “life plan,” and focusing on team-based approaches to ESKD care. This review explores ESKD from the perspective of epidemiology, costs, vascular access, patient-reported outcomes, racial disparities, and the impact of the COVID-19 crisis.     

Policies to promote timely referral for kidney transplantation

There are numerous patient, provider, and health system barriers to accessing kidney transplantation. Patient barriers such as sociocultural and clinical characteristics and provider factors such as provider knowledge and awareness of transplantation play important roles in facilitating transplant. Health system factors like misaligned incentives and quality metrics for dialysis facilities and transplant centers also influence transplant access. While numerous studies have documented the impact of these barriers on wait-listing and transplant, few studies have examined referral from a dialysis facility to a transplant center and start of the transplant evaluation process. While the Centers for Medicare and Medicaid Services (CMS) require that dialysis facilities educate patients about transplant, there are no guidelines for the content and objectives for this education. In addition, policies to require timely referral for transplantation have been considered by CMS but are difficult to implement without national data on referral. Federal policies should be amended to mandate transplant center submission of referral data—while decreasing the unfunded mandate to collect other unusable data currently collected as part of regulatory monitoring of transplant centers—to promote timely access to transplant, increased transplant rates, and to better understand the multilevel barriers and facilitators to transplant referral.     

Breaking the adherence barriers: Strategies to improve treatment adherence in dialysis patients

Nonadherence to therapy (dietary/fluid restrictions, medications, and dialysis treatment), is common in patients with end-stage kidney disease (ESKD) undergoing dialysis. It is associated with a higher risk of mortality and adverse outcomes. Clinical trials evaluating adherence improvement interventions have largely addressed patient-related factors by employing educational/cognitive, counselling/behavioral, psychological strategies, or combinations thereof. A major barrier to progress in addressing ESKD-related adherence is the difficulty in comparing these trials due to the highly diverse nature of interventions and adherence outcomes. Surrogate outcomes like changes in inter-dialysis weight gain or phosphate levels are frequently used without adjusting for confounders, with the potential for biased efficacy estimates. A majority of trials reported improvement in some adherence measures, but some of the same studies showed no improvement in other adherence markers, questioning the validity of outcome measurement. Among the interventions, cognitive/behavioral strategies, combination strategies, and individually delivered interventions may have some advantages. Relapse of nonadherence, which is common on follow-up, should be managed to sustain long-term adherence. Technology-based interventions hold great future potential for addressing ESKD nonadherence. Streamlining intervention strategies and standardizing outcome measures in future clinical trials will provide reliable guidance to manage nonadherence effectively, which may improve clinical outcomes in dialysis patients.     

Racial disparities in paediatric kidney transplantation

Background

Transplantation is the preferred treatment for children with end-stage kidney disease (ESKD). Pre-emptive transplants, those from live donors and with few human leukocyte antigen (HLA) mismatches provide the best outcomes. Studies into disparities in paediatric transplantation to date have not adequately disentangled different transplant types.

Methods

We studied a retrospective cohort of 823 patients aged <18 years who started renal replacement therapy (RRT) in Australia 1990–2011, using the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA). The primary outcomes were time to first kidney transplant and kidney donor type (deceased or living), analysed using competing risk regression.

Results

Caucasian patients were most likely to receive any transplant, due largely to disparities in live donor transplantation. No Indigenous patients received a pre-emptive transplant. Indigenous patients were least likely to receive a transplant from a live donor (sub-hazard ratio 0.41, 95 % confidence interval 0.20–0.82, compared to Caucasians). Caucasian recipients had fewer HLA mismatches, were less sensitised and were more likely to have kidney diseases that could be diagnosed early or progress slowly.

Conclusions

Caucasian paediatric patients are more likely to receive optimum treatment—a transplant from a living donor and fewer HLA mismatches. Further work is required to identify and address barriers to live donor transplantation among minority racial groups.     

Simultaneous liver and kidney transplants: optimizing use of this double resource

Simultaneous liver and kidney transplantation is a life saving procedure for patients with combined liver and kidney failure; however, it remains controversial because of the need to balance individual patient need versus resource allocation. As waiting lists for transplantation become longer and patients become increasingly ill, there will be greater numbers of patients referred for liver and kidney transplantation. Acute kidney injury even requiring dialysis may potentially be reversible making combined transplant decisions difficult. Similarly, selected compensated cirrhotic patients with renal failure may be managed with renal transplant alone. Shared multicenter experience or clinical trials or both will be required to refine our ability to optimally manage these patients with combined liver and kidney dysfunction.     

We Wait Too Long to Refer Patients for Transplantation

Late referral of patients with chronic kidney disease (CKD) and end‐stage renal disease (ESRD) for evaluation of kidney transplantation is common. Even though renal transplantation offers a clear survival benefit to patients with advanced CKD and ESRD and should be considered the renal replacement therapy of choice, numerous barriers to early renal transplant referral have been observed. Some of these barriers can be overcome by improving the communication between the referring providers and the transplant centers. Furthermore, providing more intensive education to both patients and referring providers with regard to the eligibility of CKD and ESRD patients for a transplant will likely result in higher referral rates. This in turn will lead to improved survival outcomes in this group of patients with otherwise significantly increased morbidity and mortality.     

Achieving equity in dialysis care and outcomes: The role of policies

Socially disadvantaged persons, including racial and ethnic minorities, individuals with low incomes, homeless persons, and non-US citizens bear a disproportionate burden of end-stage kidney disease (ESKD). Inequities in nephrology referral, vascular access, use of home dialysis modalities, kidney transplantation, and mortality are prominent. Public policies, including the Patient Protection and Affordable Care Act, end-stage renal disease Quality Incentive Program, and the Prospective Payment System, were enacted to improve healthcare access and dialysis care. Here, we highlight inequities in dialysis care and outcomes, how current ESKD and other public policies may influence or exacerbate these inequities, and gaps in the literature needed to inform future policies toward achieving equity in ESKD. We give special attention to the 2019 Advancing American Kidney Health Executive Order, which has high potential to radically transform dialysis care.     

New Solutions to Reduce Discard of Kidneys Donated for Transplantation

Kidney transplantation is a cost-saving treatment that extends the lives of patients with ESRD. Unfortunately, the kidney transplant waiting list has ballooned to over 100,000 Americans. Across large areas of the United States, many kidney transplant candidates spend over 5 years waiting and often die before undergoing transplantation. However, more than 2500 kidneys (>17% of the total recovered from deceased donors) were discarded in 2013, despite evidence that many of these kidneys would provide a survival benefit to wait-listed patients. Transplant leaders have focused attention on transplant center report cards as a likely cause for this discard problem, although that focus is too narrow. In this review, we examine the risks associated with accepting various categories of donated kidneys, including discarded kidneys, compared with the risk of remaining on dialysis. With the goal of improving access to kidney transplant, we describe feasible proposals to increase acceptance of currently discarded organs.     

Improvement in the Care of Patients With Kidney Transplant Failure: Recommendations of the Spanish Society of Nephrology

Although long-term outcomes have improved, graft loss caused by chronic allograft nephropathy remains an important obstacle. This situation, together with the progressive increase in the number of renal transplant patients, means that the population of transplant patients readmitted to a dialysis program will be progressively greater. The variable mortality rates among patients starting dialysis after graft loss are consistently higher than those observed among patients with functioning grafts or on dialysis treatment. However, the manner in which the management of chronic kidney disease patients in the transplant setting differs from that of patients with native kidney disease who display a similar degree of renal dysfunction is not known. Many patients in stages 4T–5T have chronic kidney disease-related complications that fall below the targets established for nontransplant chronic kidney disease subjects. A limited number of studies have evaluated patients returning to dialysis after graft failure. The distinct guidelines in the setting of transplantation have not analyzed this important aspect. From this premise, a working group of the Spanish Society of Nephrology specialying in the field of kidney transplantation and dialysis reviewed each clinical aspect of care of kidney transplant patients with renal failure returning to dialysis, yielding this consensus document to optimize management.     

Sequential liver-kidney transplantation

The indications for sequential liver and kidney transplantation have not been well defined. Two categories of patients may benefit from this procedure: patients with primary renal disease associated with hepatic disorders (glomerulonephritis, tubulointerstitial nephritis, metabolic diseases, and structural diseases) and patients who develop renal failure after liver transplantation. Chronic renal failure is a frequent long-term complication after liver transplantation. End-stage renal disease develops in 2% to 10% of cases by 10 years after transplantation. Kidney transplantation appears to be a better option than dialysis for the treatment of end-stage renal disease after liver transplantation. In contrast, survival rates, after kidney transplantation are significantly lower among liver transplant patients than primary-only kidney transplant recipients. Considering the donor shortage, kidney transplantation should be cautiously considered in liver transplantation patients. New immunosuppressive drugs and protocols are needed to reduce chronic renal failure after liver transplantation.     

When ESKD complicates the management of pain

Pain is one of the most common symptoms reported by patients with end-stage kidney disease (ESKD) and negatively impacts their health-related quality of life (HRQOL), dialysis adherence, healthcare utilization, and mortality. There are a number of patient-related and health system-related barriers that make it very challenging to treat pain in these patients. Moreover, the limited availability of efficacious and safe nonopiate analgesic options has led to over-use of opioids in this population. We propose a framework for pain assessment and tailored treatment using nonpharmacological and pharmacological approaches to optimize pain management and opioid use. Additionally, we recommend system-level changes to improve care coordination and pain management in ESKD patients.