The impact of diabetes on young transplant recipients: An American perspective.

Despite advancements in diabetic care, diabetic kidney transplant recipients have significantly worse outcomes than non-diabetics. AIM: Our study aims to demonstrate the impact of diabetes, types I and II, on American young adults (18-40 years old) requiring kidney transplantation. METHODS: Using the United Network for Organ Sharing database, we conducted a population cohort study that included all first-time, kidney-only transplant recipients during 2002-2019, ages 18-40 years old. Patients were grouped according to indication for transplant. Primary outcomes were cumulative all-cause mortality and death-censored graft failure. Death-censored graft failure and patient survival at 1, 5, and 10 years were calculated via the Kaplan-Meier method. Multivariate Cox regression was used to assess for potential confounders. RESULTS: Of 42 466 transplant recipients, 3418 (8.1%) had end-stage kidney disease associated with diabetes. At each time-point, cumulative mortality was higher in diabetics compared to patients with non-diabetic causes of renal failure. Conversely, cumulative graft failure was similar between the groups. Adjusted hazard ratios for all-cause mortality and graft failure in diabetics were 2.99 (95% CI 2.67-3.35; p < .01) and 0.98 (95% CI 0.92-1.05, p < .01), respectively. CONCLUSION: Diabetes mellitus in young adult kidney transplant recipients is associated with a nearly three-fold increase in mortality, reflecting a relatively vulnerable patient population. Identifying the underlying causes of poor outcomes in this population should be a priority for future study.

The impact of COVID-19 on kidney transplantation and the kidney transplant recipient - One year into the pandemic.

The COVID-19 pandemic has significantly changed the landscape of kidney transplantation in the United States and worldwide. In addition to adversely impacting allograft and patient survival in postkidney transplant recipients, the current pandemic has affected all aspects of transplant care, including transplant referrals and listing, organ donation rates, organ procurement and shipping, and waitlist mortality. Critical decisions were made during this period by transplant centers and individual transplant physicians taking into consideration patient safety and resource utilization. As countries have begun administering the COVID vaccines, new and important considerations pertinent to our transplant population have arisen. This comprehensive review focuses on the impact of COVID-19 on kidney transplantation rates, mortality, policy decisions, and the clinical management of transplanted patients infected with COVID-19.

Donor and transplant candidate selection for solid organ transplantation during the COVID-19 pandemic.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel coronavirus responsible for a worldwide pandemic has forced drastic changes in medical practice in an alarmingly short period of time. Caregivers must modify their strategies as well as optimize the utilization of resources to ensure public and patient safety. For organ transplantation, in particular, the loss of lifesaving organs for transplantation could lead to increased waitlist mortality. The priority is to select uninfected donors to transplant uninfected recipients while maintaining safety for health care systems in the backdrop of a virulent pandemic. We do not yet have a standard approach to evaluating donors and recipients with possible SARS-CoV-2 infection. Our current communication shares a protocol for donor and transplant recipient selection during the coronavirus disease 2019 (COVID-19) pandemic to continue lifesaving solid organ transplantation for heart, lung, liver, and kidney recipients. The initial results using this protocol are presented here and meant to encourage dialogue between providers, offering ideas to improve safety in solid organ transplantation with limited health care resources. This protocol was created utilizing the guidelines of various organizations and from the clinical experience of the authors and will continue to evolve as more is understood about SARS-CoV-2 and how it affects organ donors and transplant recipients.

Outcomes after anti-thymocyte globulin vs Basiliximab induction before deceased donor kidney transplants.

BACKGROUND: Deceased donor kidney transplants represent an important source of renal replacement for the 100 000 patients initiating hemodialysis annually. We compared the association of induction therapy, anti-thymocyte globulin [rabbit] (rATG) or basiliximab, with posttransplant rejection, graft and patient survival. METHODS: Using the United Network for Organ Sharing (UNOS) database, we identified patients that received deceased donor kidney transplants. The outcomes analyzed were 6- month rejection, 1-year rejection, patient survival and graft survival. Multivariate logistic regression models were constructed to understand the association of induction therapy and rejection. Cox-proportional hazards models were constructed to ascertain the association of choice of induction therapy with both patient and graft survival. RESULTS: Of 45 339 patients, 33 906 patients received rATG induction therapy and 11 433 patients received basiliximab induction therapy. The rATG group were younger (53.44 years vs 55.28 years, P < 0.001), more frequently female (58.74% male vs 66.08%, P < 0.001) and more frequently Black (34.78% vs 25.66%, p < 0.001) compared with patients in the basiliximab group. Rejection was more likely with basiliximab compared with rATG at 6 months(OR = 1.64, P < 0.001; 7.81% Basiliximab vs 5.23% rATG)and at 12 months (OR = 1.56, P < 0.001; 8.81% Basiliximab vs 6.31% rATG). Basiliximab induction therapy was associated with worse patient survival, (HR = 1.05, P = 0.017). Basiliximab induction therapy was associated with worse graft survival, (HR = 1.03, P = 0.037). CONCLUSION: The analysis of the national experience demonstrated favorable rejection, patient survival, and graft survival with rATG usage. Further prospective data are necessary to provide treatment recommendations.

Cigarette use and cardiovascular risk in chronic kidney disease: an unappreciated modifiable lifestyle risk factor.

Tobacco use is a major modifiable cardiovascular risk factor in the general population and contributes to excess cardiovascular risk. Emerging evidence from large-scale observational studies suggests that continued tobacco use is also an independent cardiovascular risk factor among patients with chronic kidney disease (CKD). The benefits of smoking cessation programs on improving the heath status of patients and reducing mortality are unequivocal in the general population. Despite this, there has been little effort in pursuing tobacco cessation programs in dialysis cohorts or those with lesser degrees of kidney impairment. Most of our attention to date has focused on the development of "kidney-specific" interventions that reduce rates of renal disease progression and improve dialysis outcomes. The purpose of this current review is to describe the epidemiology of tobacco use among patients with CKD, draw attention to its negative impact on cardiovascular morbidity and mortality, and finally highlight potential strategies for successful intervention. We hope that this study heightens the importance of tobacco use in CKD, stimulates renewed interest in the barriers and challenges that exist in achieving smoking cessation, and endorses the efficacy of intervention strategies and the immeasurable benefits of quitting on cardiovascular and noncardiovascular outcomes.

Is Organ Retransplantation Among Undocumented Immigrants in the United States Just?

Numerous undocumented children in the United States with end-stage renal disease undergo kidney transplantation funded by charitable donation or state-sponsored Medicaid. However, when these funding sources expire by adulthood, most are unable to pay for follow-up appointments and immunosuppressive medications necessary for maintenance of their organ. The organs fail and patients are then left with the options of retransplantation or a lifetime of dialysis. The dilemma of retransplantation introduces many questions regarding justice and fairness. This commentary addresses several ethical concerns about the special case of organ retransplantation for undocumented patients. Clinical guidelines and a clear public policy for best practices are needed to adequately address the challenge of retransplantation and maintenance immunosuppression in this population.

Profiling risk for acute rejection in kidney transplantation: recipient age is a robust risk factor.

Careful management of immunosuppression is paramount to prevent acute rejection in kidney transplantation. We studied a cohort of 139,875 kidney transplant recipients from the Organ Procurement and Transplantation Network (OPTN) database between 2002 and 2013. We confirmed the analysis with a cohort of 35,277 who received thymoglobulin induction with tacrolimus maintenance, and a third cohort of 12,161 recipients who received basiliximab induction with tacrolimus maintenance. We performed multivariate logistic regression analyses on data from all three cohorts and identified independent risk factors for treated acute rejection at 1 year. Recipient age was a robust risk factor for rejection in all three cohorts in a dose response pattern. Young age (18-25 years) was among the strongest risk factors for rejection in all three cohorts; thymoglobulin cohort: OR 1.87 (1.59-2.19); basiliximab cohort: OR 2.41 (1.89-3.05); and inclusive cohort: OR 1.97 (1.83-2.12). The opposite was true for old age (65-69 years); thymoglobulin cohort: OR 0.69 (0.59-0.81); basiliximab cohort: OR 0.77 (0.62-0.96); and inclusive cohort: OR 0.75 (0.70-0.80). This study is unique because it is the largest and most comprehensive multivariate analysis that demonstrates recipient age is a robust risk factor for acute rejection in an inverse dose response pattern.

Association of physical activity with mortality in the US dialysis population.

BACKGROUND: It is unclear whether the protective benefits of regular physical activity on mortality extend to patients with end-stage renal disease (ESRD). We tested this hypothesis in a national cohort of new patients with ESRD in the United States. METHODS: Data for a subset of patients (n = 2,507; 62%) from the Dialysis Morbidity and Mortality Wave 2 study were used to explore the associations of exercise and limitations in physical activity with mortality. RESULTS: Overall, 56% of patients exercised less than once a week, whereas the remainder reported more frequent physical activity; 2 to 3 times/wk in 18%, 4 to 5 times/wk in 6%, and daily exercise in 20%. Severe limitations in vigorous and moderate physical activities were reported by 75% and 42%, respectively. Mortality risks were greatest for those with severe limitations in either moderate (relative risk [RR], 1.72; 95% confidence interval [CI], 1.44 to 2.05) or vigorous physical activities (RR, 1.51; 95% CI, 1.20 to 1.90) compared with those reporting minimal or no limitations. Conversely, mortality risks were lower for patients who exercised 2 to 3 (RR, 0.74; 95% CI, 0.58 to 0.95) or 4 to 5 times/wk (RR, 0.70; 95% CI, 0.47 to 1.07), whereas no advantage was associated with daily exercise (RR, 1.06; 95% CI, 0.86 to 1.30). CONCLUSION: Although limitations in physical activity are common among new patients with ESRD in the United States and correlate highly with increased mortality risk, this study shows an association of frequent exercise of up to 4 to 5 times/wk with improved survival. The surprising lack of association of daily exercise with increased survival deserves additional study.

Exercise and limitations in physical activity levels among new dialysis patients in the United States: an epidemiologic study.

PURPOSE: Epidemiologic studies of physical activity among patients with end-stage renal disease (ESRD) are lacking. The aim of this study was to describe the patterns of physical activity among new dialysis patients in the United States. METHODS: Multivariate logistic regression analyses examined associations of self-reported limitations in physical activity and exercise frequency with sociodemographic and clinical variables in 2,264 patients from Wave 2 of the Dialysis Morbidity and Mortality Study. RESULTS: Overall, 56% of patients exercised less than once a week, 75% reported severe limitations in vigorous activities, whereas 42% had severe limitations in moderate physical activities. Fewer limitations in moderate or vigorous activities correlated positively with male gender (odds-ratio [OR] = 1.61), black race OR =1.49), Hispanic ethnicity (OR = 2.39), serum albumin (OR = 1.69 per 1 g/L higher), positive affect (OR = 2.33), peritoneal dialysis (OR = 1.90), and negatively with age (OR = 0.67), heart failure (OR = 0.75), peripheral vascular disease (OR = 0.69), malnutrition (OR = 0.67), and depression (OR = 0.39). Patients reporting fewer limitations in moderate or vigorous activities (OR = 1.35 and 1.28, respectively), or frequent visits with a dietitian (2 to 3 times per week vs. less) (OR = 1.21) in the pre-ESRD period exercised more frequently. CONCLUSIONS: Limitations in physical activity are common among new ESRD patients and these, in part, are related to pre-existing cardiovascular disease, malnutrition, and mental health.

Accumulation of metals and minerals from phosphate binders.

Metals and minerals that depend on renal clearance may accumulate to toxic levels in patients with marginal kidney function. Toxicities of aluminum-based phosphate binders became apparent approximately 25 years ago. Nephrologists now recognize cardiovascular calcification may follow use of calcium-based phosphate binders. Five lessons can be learned: (1)safety must not be assumed in absence of data; (2) all evidence for causal linkage of toxicities from therapeutics must be considered, including animal data; (3) clinical trials are unlikely to reveal the spectrum of problems from long-term drug exposure; (4) complications can remain unrecognized until late in post-introduction surveillance; (5) minerals important for normal function can be toxic with excess accumulation. Introduction of new agents necessitates caution - it is difficult to change practice once a therapeutic is commonplace. Lessons learned about hazards of past phosphate binders must be applied judiciously when evaluating long-term risks/safety of novel metal-based binders such as lanthanum carbonate.

Survival advantage of Hispanic patients initiating dialysis in the United States is modified by race.

Differences in survival have been reported among ethnic groups in the general population. Whether these extend to patients with ESRD is unclear. Using national data, mortality risks of ethnic groups who began dialysis treatment in the United States between May 1, 1995, and July 31, 1997, were compared over 2 yr. Patients were classified as Hispanic or non-Hispanic and then subclassified by race forming six race-specific subgroups: Hispanic white, black, and other and non-Hispanic white, black, and other. Mortality rates for Hispanics compared with non-Hispanics were 19.2 versus 26 per 100 patient-years at risk for those with diabetes and were 14.7 versus 22.7 per 100 patient-years at risk for those without diabetes. For those with diabetes, adjusted mortality risks for Hispanics versus non-Hispanics were 30% lower (95% confidence interval [CI], 26 to 34%). In subgroup analysis, mortality risks for Hispanic whites and Hispanic blacks were 35% (95% CI, 31 to 39%) and 33% (95% CI, 12 to 48%) lower than non-Hispanic whites and were similar in magnitude to those of non-Hispanic blacks (32% lower; 95% CI, 29 to 35%) and non-Hispanic other (33% lower; 95% CI, 28 to 39%). Interestingly, mortality risks for Hispanic others were not significantly different from non-Hispanic whites. For those without diabetes, adjusted mortality risks for Hispanics versus non-Hispanics were 17% lower (95% CI, 9 to 23%), and subgroup analysis yielded similar patterns to those of individuals with diabetes. The survival advantage of Hispanic over non-Hispanic patients who receive chronic dialysis treatment in the United States is not consistent across subgroups and is modified by race. Cultural and genetic differences as well as variation in the access and delivery of care before and while on dialysis may account for these differences.

Survival differences between peritoneal dialysis and hemodialysis among "large" ESRD patients in the United States.

BACKGROUND: It has been hypothesized that peritoneal dialysis compared to hemodialysis may be less effective in large patients with end-stage renal disease (ESRD). METHODS: We tested this hypothesis in a cohort of 134,728 new ESRD patients who were initiated on dialysis from May 1, 1995 to July 31, 1997 using data from United States Renal Data System (USRDS). Cox regression models evaluated the association of body mass index (BMI) in quintiles (8.8-20.9, 20.9-23.5, 23.5-26.1, 26.1-30.0, 30.0-75.2 kg/m(2)) with mortality over 2 years in peritoneal dialysis and hemodialysis patients separately, while time-dependent models evaluated the relative risk (RR) of death by modality for each BMI quintile. RESULTS: For hemodialysis, the adjusted RR of death was greatest for patients with BMI 30.0 (RR = 0.97, 95% CI 0.96-0.99 for diabetic and RR = 0.97, 95% CI 0.95-0.98 for nondiabetic patients) compared with the referent (23.5-26.1; RR = 1.00). For peritoneal dialysis, the RR of death was also higher for patients with a BMI <20.9 (RR = 1.20, 95% CI 1.00-1.43 for diabetic and RR = 1.39, 95% CI 1.19-1.64 for nondiabetic patients) but no survival advantage was associated with higher BMI values. The RR of death (peritoneal dialysis/hemodialysis) for each BMI quintile was 0.99, 1.12, 1.26 (P < 0.01), 1.15 (P < 0.01), and 1.44 (P < 0.0001) for diabetic and were 1.07, 1.01, 0.96, 1.04, and 1.22 (P < 0.01) for nondiabetic patients, respectively. CONCLUSION: We conclude that body size modifies the impact of dialysis modality on mortality risk among new ESRD patients in the United States. The selection of hemodialysis over peritoneal dialysis was associated with a survival advantage in patients with large body habitus.

Impact of dialysis modality on survival of new ESRD patients with congestive heart failure in the United States.

BACKGROUND: It is hypothesized, but not proven, that peritoneal dialysis might be the optimal treatment for end-stage renal disease (ESRD) patients with established congestive heart failure (CHF) through better volume regulation compared with hemodialysis. METHODS: National incidence data on 107,922 new ESRD patients from the Center for Medicare and Medicaid Services (CMS) Medical Evidence Form were used to test the hypothesis that peritoneal dialysis was superior to hemodialysis in prolonging survival of patients with CHF. Nonproportional Cox regression models evaluated the relative hazard of death for patients with and without CHF by dialysis modality using primarily the intent-to-treat but also the as-treated approach. Diabetics and nondiabetics were analyzed separately. RESULTS: The overall prevalence of CHF was 33% at ESRD initiation. There were 27,149 deaths (25.2%), 5423 transplants (5%), and 3753 (3.5%) patients lost to follow-up over 2 years. Adjusted mortality risks were significantly higher for patients with CHF treated with peritoneal dialysis than hemodialysis [diabetics, relative risk (RR) = 1.30, 95% confidence interval (CI) 1.20 to 1.41; nondiabetics, RR = 1.24, 95% CI 1.14 to 1.35]. Among patients without CHF, adjusted mortality risk were higher only for diabetic patients treated with peritoneal dialysis compared with hemodialysis (RR = 1.11, 95% CI 1.02 to 1.21) while nondiabetics had similar survival on peritoneal dialysis or hemodialysis (RR = 0.97, 95% CI 0.91 to 1.04). CONCLUSION: New ESRD patients with a clinical history of CHF experienced poorer survival when treated with peritoneal dialysis compared with hemodialysis. These data suggest that peritoneal dialysis may not be the optimal choice for new ESRD patients with CHF perhaps through impaired volume regulation and worsening cardiomyopathy.