Barriers to kidney transplantation in ESKD

Kidney transplantation is the ideal treatment option for patients with end-stage kidney disease (ESKD). Since there is clear mortality benefit to receiving a transplant regardless of comorbidities and age, the gold standard of care should focus on attaining kidney transplantation and minimizing, or better yet eliminating, time on dialysis. Unfortunately, only a small percentage of patients with ESKD receive a kidney transplant. Several barriers to kidney transplantation have been identified. Barriers can largely be grouped into three categories: patient-related, physician/provider-related, and system-related. Several barriers fall into multiple categories and play a role at various levels within the healthcare system. Acknowledging and understanding these barriers will allow transplant centers and dialysis facilities to make the necessary interventions to mitigate these disparities, optimize the transplant evaluation process, and improve patient outcomes. This review will discuss these barriers and potential interventions to increase access to kidney transplantation.     

Variation in Access to Kidney Transplantation Across Renal Programs in Ontario,Canada

In the United States, kidney transplant rates vary significantly across end‐stage renal disease (ESRD) networks. We conducted a population‐based cohort study to determine whether there was variability in kidney transplant rates across renal programs in a health care system distinct from the United States. We included incident chronic dialysis patients in Ontario, Canada, from 2003 to 2013 and determined the 1‐, 5‐, and 10‐year cumulative incidence of kidney transplantation in 27 regional renal programs (similar to U.S. ESRD networks). We also assessed the cumulative incidence of kidney transplant for “healthy” dialysis patients (aged 18–50 years without diabetes, coronary disease, or malignancy). We calculated standardized transplant ratios (STRs) using a Cox proportional hazards model, adjusting for patient characteristics (maximum possible follow‐up of 11 years). Among 23 022 chronic dialysis patients, the 10‐year cumulative incidence of kidney transplantation ranged from 7.4% (95% confidence interval [CI] 4.8–10.7%) to 31.4% (95% CI 16.5–47.5%) across renal programs. Similar variability was observed in our healthy cohort. STRs ranged from 0.3 (95% CI 0.2–0.5) to 1.5 (95% CI 1.4–1.7) across renal programs. There was significant variation in kidney transplant rates across Ontario renal programs despite patients having access to the same publicly funded health care system.     

Obesity and bariatric surgery in kidney transplantation: A clinical review

Obesity is increasing worldwide, and this has major implications in the setting of kidney transplantation. Patients with obesity may have limited access to transplantation and increased posttransplant morbidity and mortality. Most transplant centers incorporate interventions aiming to target obesity in kidney transplant candidates, including dietary education and lifestyle modifications. For those failing nutritional restriction and medical therapy, the use of bariatric surgery may increase the transplant candidacy of patients with obesity and end-stage renal disease (ESRD) and may potentially improve the immediate and late outcomes. Bariatric surgery in ESRD patients is associated with weight loss ranging from 29.8% to 72.8% excess weight loss, with reported mortality and morbidity rates of 2% and 7%, respectively. The most commonly performed bariatric surgical procedures in patients with ESRD and in transplant patients are laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass. However, the correct timing of bariatric surgery and the ideal type of surgery have yet to be determined, although pretransplant LSG seems to be associated with an acceptable risk-benefit profile. We review the impact of obesity on kidney transplant candidates and recipients and in potential living kidney donors, exploring the potential impact of bariatric surgery in addressing obesity in these populations, thereby potentially improving posttransplant outcomes.     

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.     

Simultaneous Liver–Kidney Transplantation: Evaluation to Decision Making

Questions about appropriate allocation of simultaneous liver and kidney transplants (SLK) are being asked because kidney dysfunction in the context of liver failure enhances access to deceased donor organs. There is specific concern that some patients who undergo combined liver and kidney transplantation may have reversible renal failure. There is also concern that liver transplants are placed prematurely in those with end-stage renal disease. Thus to assure allocation of transplants only to those truly in need, the transplant community met in March 2006 to review post-MELD (model for end-stage liver disease) data on the impact of renal function on liver waitlist and transplant outcomes and the results of SLK.     

Geographic disparities in access to organ transplantation in the United Kingdom

In the United Kingdom, geographic variations in access to transplantation seem to exist-median waiting time to transplantation ranges between 305 and 1,236 days for kidney recipients, 36 and 73 days for liver recipients, and 66 and 667 days for heart recipients (although this latter example must be interpreted with caution). These variations may result from a number of factors. Different patterns of end-stage organ disease are particularly relevant for patients with kidney failure. Protocols for transplant assessment are now available and may reduce inequality. Regional variations in donation rates also exist but are poorly understood.     

Kidney Transplantation Halts Cardiovascular Disease Progression in Patients with End-Stage Renal Disease

Morbidity and mortality from cardiovascular disease have a devastating impact on patients with chronic kidney disease (CKD) and end-stage renal disease. Renal function decline in itself is thought to be a strong risk factor for cardiovascular disease (CVD). In this study, we investigated the hypothesis that the elevated CV mortality in kidney transplant patients is due to the preexisting CVD burden and that restoring renal function by a kidney transplant might over time lower the risk for CVD. We analyzed 60,141 first-kidney-transplant patients registered in the USRDS from 1995 to 2000 for the primary endpoint of cardiac death by transplant vintage and compared these rates to all 66813 adult kidney wait listed patients by wait listing vintage, covering the same time period. The CVD rates peaked during the first 3 months following transplantation and decreased subsequently by transplant vintage when censoring for transplant loss. This trend could be shown in living and deceased donor transplants and even in patients with end-stage renal disease secondary to diabetes. In contrast, the CVD rates on the transplant waiting list increased sharply and progressively by wait listing vintage. Despite the many mechanisms that may be in play, the enduring theme underlying rapid progression of atherosclerosis and cardiovascular disease in renal failure is the loss of renal function. The data presented in this paper thus suggest that the development or progression of these lesions could be ameliorated by restoring renal function with a transplant.     

Inequalities in access to pediatric ESRD care: a global health challenge

The increasing attention paid to chronic kidney disease (CKD) as a major cause of mortality and disability, as well as the advances in management of CKD in children, have created a growing demand for pediatric renal replacement therapy (RRT) worldwide. A study by Koch Nogueira and colleagues of children on the transplant waiting list showed large disparities in access to pediatric kidney transplantation between regions in Brazil. This finding raises a wider question about inequalities in access to CKD care in children. Here we review the available data on the global burden of end-stage renal disease in children, the need for pediatric RRT, and its actual provision worldwide. We focus on inequalities in access to renal care for children that currently exist between and within countries. Reduction in worldwide inequalities in access to RRT in children remains a challenge, which requires greater awareness and effective interventions and policies.     

Kidney transplantation: recent developments and recommendations for anesthetic management

Kidney transplantation is the treatment of choice for patients with end-stage renal disease. After receiving a transplant, survival rates are higher and comorbidities may resolve. As a consequence, more patients with significant comorbidities such as advanced cardiovascular disease will present for transplantation. This review highlights commonly encountered issues in patients undergoing kidney transplantation and recommendations are made for their anesthetic management.     

Impact of obesity on dialysis and transplant and its management

Obesity is increasing to unprecedented levels, including in the end-stage kidney disease population, where upwards of 60% of kidney transplant patients are overweight or obese. Obesity poses additional challenges to the care of the dialysis patient, including difficulties in creating vascular access and inserting Tenckhoff catheters, higher rates of catheter malfunction and peritonitis, the need for longer and/or more frequent dialysis (or peritoneal dialysis [PD] exchanges) to achieve adequate clearance, increased metabolic complications particularly with PD, and obesity is a barrier to kidney transplantation. In this article, we review special considerations in performing PD, hemodialysis and transplant in the obese patient, as well as the evidence behind medical and surgical management of obesity in dialysis patients.     

Non-medical factors influencing access to renal transplantation

Considering the scarcity of available donor kidneys and the increasing number of patients with end-stage renal disease (ESRD) who would potentially benefit from renal transplantation, objective and equitable patient selection and equitable access to renal transplantation bear substantial importance. Inequalities in access to renal transplantation have been extensively documented over the last 2 decades with regard to age, gender, ethnicity, socioeconomic and psycho-social factors. In this paper we review a wide spectrum of social, patient and system-related factors along the transplantation process that may be associated with disparities, and we aim to describe the complex interrelationship between these factors that might influence treatment decisions by patients and health-care professionals. Understanding potentially modifiable barriers to kidney transplantation may allow designing targeted interventions in order to guarantee fair recipient selection and equal access to renal transplantation.     

Controversies in combined liver-kidney transplantation: indications and outcomes

Controversy surrounds simultaneous transplantation of a kidney and a liver because the practice is increasing, and organs for transplant are limited. Not only do recipients of both organs use 2 rather than 1 organ, but the kidney in dual transplantation jumps to the front of a very long kidney wait-list. Furthermore, there is suspicion that some patients who undergo combined liver and kidney transplantation may have reversible renal failure. Likewise, inappropriate liver transplantation in those with end-stage renal disease is possible given the heavy weighting of kidney dysfunction in the calculation of the model for end-stage liver disease score. Thus, a better way to determine the recoverability of renal dysfunction in liver transplant candidates and the degree of liver disease in end-stage renal disease is needed. Standardized strategies for candidate evaluation, selection, and process review are also necessary to improve organ allocation in those with both liver and kidney disease. However, basic and clinical investigation will be needed before an optimal algorithm is possible.     

Ethical implications of ethnic disparities in chronic kidney disease and kidney transplantation

Chronic kidney disease (CKD) is a major epidemic in underserved and minority populations largely due to excess rates of hypertensive and diabetic kidney disease. Multiple complex socioeconomic barriers to early diagnosis and optimal therapies as well as delayed referral for kidney transplantation have created disparities in CKD care provided to ethnic minorities. Disparities exist in wait list time and kidney transplant rates for Native Americans and blacks, independent of insurance status. Moreover, independent of genetic matching, long-term transplant outcomes in blacks remain significantly lower than all other ethnic groups, suggesting that poorly understood social factors contribute to these survival differences. The existence of these disparities raises ethical concerns of equity and social justice in terms of the allocation of scarce resources. Although current changes in allocation policies will improve some disparities, more efforts are ultimately needed to improve access to care and the overall health and survival for all individuals at risk for CKD, independent of their race, ethnicity, or socioeconomic status.     

Pancreas transplantation

Pancreas transplantation is now the standard of care for selected patients with diabetes and end-stage renal failure or life-threatening diabetic complications. The morbidity and mortality of pancreas transplantation is higher than other transplant types, and for this reason selection criteria for both donors and recipients are more stringent. Meticulous organ retrieval technique and back-table preparation, and a standard implantation technique using enteric drainage are central to good outcomes. Modern immunosuppression has reduced acute rejection rates and lowered the need for long-term corticosteroids. Results have improved over time and recipients of a simultaneous kidney–pancreas transplant can now expect 5-year transplant survival of around 75%. The addition of a pancreas to a kidney transplant for suitable recipients has clear benefits in both length and quality of life, and there is increasing evidence that pancreatic transplantation can reduce or halt the progression of diabetic nephropathy, neuropathy, retinopathy and cardiovascular disease. In patients with normal renal function, pancreatic islet transplantation offers an alternative with reduced peri-procedural morbidity and mortality, at the expense of lower rates of long-term insulin independence.     

Pancreas transplantation

Pancreas transplantation is now standard of care for selected patients with diabetes and end-stage renal failure or life-threatening diabetic complications. The morbidity and mortality of pancreas transplantation is higher than other transplant types, and for this reason selection criteria for both donors and recipients are more stringent. Meticulous organ retrieval technique and back-table preparation, and a standard implantation technique using enteric drainage are central to good outcomes. Modern immunosuppression has reduced acute rejection rates and lowered the need for long-term corticosteroids. Results have improved over time and recipients of a simultaneous kidney–pancreas transplant can now expect 5-year transplant survival of around 75%. The addition of a pancreas to a kidney transplant for suitable recipients has clear benefits in both length and quality of life, and there is increasing evidence that pancreatic transplantation can reduce or halt the progression of diabetic nephropathy, neuropathy, retinopathy and cardiovascular disease. In patients with normal renal function, pancreatic islet transplantation offers an alternative with reduced peri-procedural morbidity and mortality, at the expense of lower rates of long-term insulin independence.     

Transplantation osteoporosis

Transplantation is an established therapy for end-stage diseases of the kidney, endocrine pancreas, heart, liver, and lung, and for many hematologic disorders. Improved survival rates have been accompanied by increased recognition of previously neglected long-term complications of transplantation such as fractures and osteoporosis. Pretransplantation bone disease and immunosuppressive therapy result in rapid bone loss and increased fracture rates early after transplantation. Patients should be assessed and pretransplantation bone disease should be treated. Preventive therapy initiated in the immediate posttransplantation period is indicated in patients with osteopenia or osteoporosis, as further bone loss will occur in the first several months after transplantation. Long-term organ transplant recipients should also have bone mass measurement and treatment of osteoporosis. Bisphosphonates are the most promising approach for the management of transplantation osteoporosis. Active vitamin D metabolites may have additional benefits in reducing hyperparathyroidism, particularly after kidney transplantation. Large, multicenter treatment trials with oral or parenteral bisphosphonates and calcitriol are recommended.     

Can the renal transplant patient be really considered as a patient with chronic renal insufficiency?

To assess if the renal transplant patient can really be considered as a patient with chronic renal insufficiency, disease progression and outcomes were compared in both groups. At the same stage of chronic kidney disease (CKD), the deterioration of renal function was slower and graft survival was longer in renal transplant patients. Despite slower rates of kidney function decline, overall patient survival was similar between the two groups. Interestingly, stage 3 adjusted mortality rates were greater in kidney transplant recipients, most likely because of the disease burden (history of end-stage renal disease in renal transplant recipients) and immunosuppression. The three major causes of mortality in transplant patients (cardiovascular, infectious and malignant) may present with specific characteristics in transplant patients. Renal transplantation is thus a specific form of CKD, controlled by 3 factors, a single kidney, immunosuppression and the burden of the disease. The general application of the KDOQI and KDIGO guidelines to kidney transplant recipients requires therefore further evaluation.     

Acute Humoral Rejection in an ABO Compatible Combined Liver–Kidney Transplant—The Kidney Is Not Always Protected

Combined liver–kidney transplantation has become a common practice for the treatment of patients with concurrent end-stage renal disease and end-stage liver disease. Liver transplantation in the setting of multiorgan transplantation is thought to have a protective effect against humoral rejection even when a positive crossmatch is obtained prior to surgery. In most centers, a pre liver–kidney transplant crossmatch is rarely performed because of the known immunoprotective effect of the liver allograft. In this report, a case of acute humoral rejection in the kidney allograft after a combined liver–kidney transplant is described. Although humoral rejection was treated using plasmapheresis, intravenous immunoglobulin and rituximab, the kidney required 3 months to recover function and finally progressed to chronic allograft nephropathy. A heightened index of suspicion for acute humoral rejection of the renal allograft is necessary when performing combined liver–kidney transplants to highly sensitized patients due to previous organ transplants.     

Racial Disparities in Pediatric Access to Kidney Transplantation: Does Socioeconomic Status Play a Role?

Racial disparities persist in access to renal transplantation in the United States, but the degree to which patient and neighborhood socioeconomic status (SES) impacts racial disparities in deceased donor renal transplantation access has not been examined in the pediatric and adolescent end-stage renal disease (ESRD) population. We examined the interplay of race and SES in a population-based cohort of all incident pediatric ESRD patients <21 years from the United States Renal Data System from 2000 to 2008, followed through September 2009. Of 8452 patients included, 30.8% were black, 27.6% white-Hispanic, 44.3% female and 28.0% lived in poor neighborhoods. A total of 63.4% of the study population was placed on the waiting list and 32.5% received a deceased donor transplant. Racial disparities persisted in transplant even after adjustment for SES, where minorities were less likely to receive a transplant compared to whites, and this disparity was more pronounced among patients 18-20 years. Disparities in access to the waiting list were mitigated in Hispanic patients with private health insurance. Our study suggests that racial disparities in transplant access worsen as pediatric patients transition into young adulthood, and that SES does not explain all of the racial differences in access to kidney transplantation.