Pretransplant screening for coronary artery disease: data are required before practice change.

Declining rates of peritransplant cardiovascular death, an increasing burden of pretransplant tests, and concerns about the effectiveness of screening candidates for coronary artery disease have led many transplant programs to de-escalate screening protocols. Recent Kidney Disease: Improving Global Outcomes and American Heart Association scientific statements and guidelines neatly summarize current evidence, but also identify areas of need. Here, we argue that key questions should be addressed by adequately powered clinical trials before our long-held screening paradigms are completely rewritten.

Medical Suitability and Willingness for Living Kidney Donation Among Older Adults.

RATIONALE & OBJECTIVE: The benefits of kidney transplantation compared to treatment with dialysis, including in older adult, are primarily limited by the number of donated kidneys. We studied the potential to expand the use of older living kidney donors. STUDY DESIGN: Secondary analysis of the Berlin Initiative Study, a population-based cohort. SETTING: & Participants: 2069 adults aged ≥70 years in Germany. EXPOSURES: Age and sex. OUTCOMES: Suitability for living donation assessed by the absence of kidney-related exclusions for donation including albuminuria and low estimated glomerular filtration rate (eGFR) as well as absence of other medical exclusions. Willingness for living and deceased kidney donation assessed by participant survey. ANALYTICAL APPROACH: Descriptive analysis. RESULTS: Among the 2069 participants (median age 80 years, 53% women, median eGFR 63 ml/min/1.73m2), 93% had ≥1 medical contraindication for living donation at study entry unrelated to eGFR or albuminuria. Using two published eGFR and albuminuria thresholds for donor acceptance, 38% to 54% of participants had kidney-related exclusions for donation. Among the 5% to 6% of participants with neither medical nor kidney-related exclusions for living donation at baseline, 11% to 12% remained suitable for donation during 8 years of follow-up. Willingness for living or deceased donation was high (73% and 60%, respectively). LIMITATIONS: GFR was not measured and medical exclusions unrelated to eGFR and albuminuria were assessed using a cohort database complemented by claims data. CONCLUSIONS: One in twenty older adults were potentially suitable for living kidney donation and willingness for living donation was high. Further studies are warranted to define the feasibility of expanding living kidney donation among older adults.

Enhancing Kidney Transplantation and the Role of Xenografts: Report of a Scientific Workshop Sponsored by the National Kidney Foundation.

Chronic kidney disease affects an estimated 37 million people in the United States; of these,>800,000 have end-stage renal disease requiring chronic dialysis or a kidney transplant to survive. Despite efforts to increase the donor kidney supply, approximately 100,000 people are registered on the kidney transplant wait-list with no measurable decrease over the past 2 decades. The outcomes of kidney transplantation are significantly better than for chronic dialysis: kidney transplant recipients have lower rates of mortality and cardiovascular events and better quality of life, but wait-list time matters. Time on dialysis waiting for a deceased-donor kidney is a strong independent risk factor for outcomes after a kidney transplant. Deceased-donor recipients with wait-list times on dialysis of<6 months have graft survival rates equivalent to living-donor recipients with waitlist times on dialysis of>2 years. In 2021,>12,000 people had been on the kidney transplant waitlist for ≥5 years. As the gap between the demand for and availability of donor kidneys for allotransplantation continues to widen, alternative strategies are needed to provide a stable, sufficient, and timely supply. A strategy that is gaining momentum toward clinical application is pig-to-human kidney xenotransplantation. This report summarizes the proceedings of a meeting convened on April 11-12, 2022, by the National Kidney Foundation to review and assess the state of pig-to-human kidney xenotransplantation as a potential cure for end-stage renal disease.

Hypertension and Kidney Function After Living Kidney Donation.

Importance: Recent guidelines call for better evidence on health outcomes after living kidney donation. Objective: To determine the risk of hypertension in normotensive adults who donated a kidney compared with nondonors of similar baseline health. Their rates of estimated glomerular filtration rate (eGFR) decline and risk of albuminuria were also compared. Design, Setting, and Participants: Prospective cohort study of 924 standard-criteria living kidney donors enrolled before surgery and a concurrent sample of 396 nondonors. Recruitment occurred from 2004 to 2014 from 17 transplant centers (12 in Canada and 5 in Australia); follow-up occurred until November 2021. Donors and nondonors had the same annual schedule of follow-up assessments. Inverse probability of treatment weighting on a propensity score was used to balance donors and nondonors on baseline characteristics. Exposure: Living kidney donation. Main Outcomes and Measures: Hypertension (systolic blood pressure [SBP] ≥140 mm Hg, diastolic blood pressure [DBP] ≥90 mm Hg, or antihypertensive medication), annualized change in eGFR (starting 12 months after donation/simulated donation date in nondonors), and albuminuria (albumin to creatinine ratio ≥3 mg/mmol [≥30 mg/g]). Results: Among the 924 donors, 66% were female; they had a mean age of 47 years and a mean eGFR of 100 mL/min/1.73 m2. Donors were more likely than nondonors to have a family history of kidney failure (464/922 [50%] vs 89/394 [23%], respectively). After statistical weighting, the sample of nondonors increased to 928 and baseline characteristics were similar between the 2 groups. During a median follow-up of 7.3 years (IQR, 6.0-9.0), in weighted analysis, hypertension occurred in 161 of 924 donors (17%) and 158 of 928 nondonors (17%) (weighted hazard ratio, 1.11 [95% CI, 0.75-1.66]). The longitudinal change in mean blood pressure was similar in donors and nondonors. After the initial drop in donors' eGFR after nephrectomy (mean, 32 mL/min/1.73 m2), donors had a 1.4-mL/min/1.73 m2 (95% CI, 1.2-1.5) per year lesser decline in eGFR than nondonors. However, more donors than nondonors had an eGFR between 30 and 60 mL/min/1.73 m2 at least once in follow-up (438/924 [47%] vs 49/928 [5%]). Albuminuria occurred in 132 of 905 donors (15%) and 95 of 904 nondonors (11%) (weighted hazard ratio, 1.46 [95% CI, 0.97-2.21]); the weighted between-group difference in the albumin to creatinine ratio was 1.02 (95% CI, 0.88-1.19). Conclusions and Relevance: In this cohort study of living kidney donors and nondonors with the same follow-up schedule, the risks of hypertension and albuminuria were not significantly different. After the initial drop in eGFR from nephrectomy, donors had a slower mean rate of eGFR decline than nondonors but were more likely to have an eGFR between 30 and 60 mL/min/1.73 m2 at least once in follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT00936078.

The living kidney donor profile index fails to discriminate allograft survival: implications for its use in kidney paired donation programs.

The inclusion of blood group- and human leukocyte antigen-compatible donor and recipient pairs (CPs) in kidney paired donation (KPD) programs is a novel strategy to increase living donor (LD) transplantation. Transplantation from a donor with a better Living Donor Kidney Profile Index (LKDPI) may encourage CP participation in KPD programs. We undertook parallel analyses using data from the Scientific Registry of Transplant Recipients and the Australia and New Zealand Dialysis and Transplant Registry to determine whether the LKDPI discriminates death-censored graft survival (DCGS) between LDs. Discrimination was assessed by the following: (1) the change in the Harrell C statistic with the sequential addition of variables in the LKDPI equation to reference models that included only recipient factors and (2) whether the LKDPI discriminated DCGS among pairs of prognosis-matched LD recipients. The addition of the LKDPI to reference models based on recipient variables increased the C statistic by only 0.02. Among prognosis-matched pairs, the C statistic in Cox models to determine the association of the LKDPI with DCGS was no better than chance alone (0.51 in the Scientific Registry of Transplant Recipient and 0.54 in the Australia and New Zealand Dialysis and Transplant Registry cohorts). We conclude that the LKDPI does not discriminate DCGS and should not be used to promote CP participation in KPD programs.

Addressing sex-based disparities in solid organ transplantation in the United States - a conference report.

Solid organ transplantation provides the best treatment for end-stage organ failure, but significant sex-based disparities in transplant access exist. On June 25, 2021, a virtual multidisciplinary conference was convened to address sex-based disparities in transplantation. Common themes contributing to sex-based disparities were noted across kidney, liver, heart, and lung transplantation, specifically the existence of barriers to referral and wait listing for women, the pitfalls of using serum creatinine, the issue of donor/recipient size mismatch, approaches to frailty and a higher prevalence of allosensitization among women. In addition, actionable solutions to improve access to transplantation were identified, including alterations to the current allocation system, surgical interventions on donor organs, and the incorporation of objective frailty metrics into the evaluation process. Key knowledge gaps and high-priority areas for future investigation were also discussed.

Immunosuppressant Medication Use in Patients with Kidney Allograft Failure: A Prospective Multicenter Canadian Cohort Study.

BACKGROUND: Patients with kidney transplant failure have a high risk of hospitalization and death due to infection. The optimal use of immunosuppressants after transplant failure remains uncertain and clinical practice varies widely. METHODS: This prospective cohort study enrolled patients within 21 days of starting dialysis after transplant failure in 16 Canadian centers. Immunosuppressant medication use, death, hospitalized infection, rejection of the failed allograft, and anti-HLA panel reactive antibodies were determined at 1, 3, 6, and 12 months and and then twice yearly until death, repeat transplantation, or loss to follow-up. RESULTS: The 269 study patients were followed for a median of 558 days. There were 33 deaths, 143 patients hospitalized for infection, and 21 rejections. Most patients (65%) continued immunosuppressants, 20% continued prednisone only, and 15% discontinued all immunosuppressants. In multivariable models, patients who continued immunosuppressants had a lower risk of death (hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.17 to 0.93) and were not at increased risk of hospitalized infection (HR, 1.81; 95% CI, 0.82 to 4.0) compared with patients who discontinued all immunosuppressants or continued prednisone only. The mean class I and class II panel reactive antibodies increased from 11% to 27% and from 25% to 47%, respectively, but did not differ by immunosuppressant use. Continuation of immunosuppressants was not protective of rejection of the failed allograft (HR, 0.81; 95% CI, 0.22 to 2.94). CONCLUSIONS: Prolonged use of immunosuppressants >1 year after transplant failure was not associated with a higher risk of death or hospitalized infection but was insufficient to prevent higher anti-HLA antibodies or rejection of the failed allograft.

Transplantation of Patients With Long Dialysis Vintage in the Current Deceased Donor Kidney Allocation System (KAS).

RATIONALE & OBJECTIVE: In 2014 the wait-time calculation for deceased donor kidney transplantation in the United States was changed from the date of first waitlisting to the date of first maintenance dialysis treatment with the aim of minimizing disparities in access to transplantation. This study examined the impact of this policy on access to transplantation, patient survival, and transplant outcomes among patients treated with maintenance dialysis for a prolonged duration before waitlisting. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Patients identified in the US Renal Data System between 2008 and 2018 aged 18-70 years and in the 95th percentile of dialysis treatment duration (≥6.5 years) before waitlisting. EXPOSURE: Waitlisting for transplantation before versus after implementation of the policy. OUTCOME: Time from date of waitlisting to deceased donor transplantation and death, and from date of transplantation to all cause graft loss. ANALYTICAL APPROACH: Univariate and multivariable time to event analyses. RESULTS: Patients waitlisted after the policy change had a higher likelihood of deceased donor transplantation (HR, 3.12 [95% CI, 2.90-3.37]) and lower risk of death (HR, 0.74 [95% CI, 0.63-0.87]). The risk of graft loss was lower in the post-kidney allocation system (KAS) cohort (HR, 0.66 [95% CI, 0.55-0.80]). The proportion of adult patients treated with dialysis ≥6.5 years who were never waitlisted for transplantation remained high (73%) and did not decrease after the policy implementation. LIMITATIONS: Cannot determine causality in this observational study. CONCLUSIONS: The policy change was associated with an increase in deceased donor transplantation and marked improvement in patient survival for patients waitlisted after long periods of dialysis treatment without decreasing the utility of available deceased donor kidney supply. The policy was not associated with increased waitlisting of this disadvantaged population.

Bold policy changes are needed to meet the need for organ transplantation in India.

Twenty-five years after India passed legislation to legalize brain death, deceased donor transplantation remains underdeveloped while the country has established formidable capacity for living donor transplantation. Because of a large number of potential deceased donors, there is hope that deceased donation could help meet India's enormous need for organ transplantation. However, significant policy and practical barriers limit progress. The vast majority of potential deceased donors are poor motor vehicle accident victims who present for care in hospitals without the necessary infrastructure or expertise to support deceased donation. In contrast, transplant infrastructure and expertise are concentrated in private hospitals and are only accessible to those with the ability to pay. Given these realities, the potential of deceased donor transplantation can only be recognized if Indians who are likely to donate organs are also provided access to transplantation. In this viewpoint, we review the current status of organ transplantation in India and propose new policies to establish a national organization to oversee deceased donor services in all states, to fund resources needed to support deceased donation, to leverage the existing living donor infrastructure to advance deceased donor transplantation, and call for establishment of government policy on funding for posttransplant care and immunosuppression.

Economic Evaluation of Extending Medicare Immunosuppressive Drug Coverage for Kidney Transplant Recipients in the Current Era.

BACKGROUND: Kidney transplant recipients must take immunosuppressant drugs to prevent rejection and maintain transplant function. Medicare coverage of immunosuppressant drugs for kidney transplant recipients ceases 36 months after transplantation, potentially increasing the risk of transplant failure. A contemporary economic analysis of extending Medicare coverage for the duration of transplant survival using current costs of immunosuppressant medications in the era of generic equivalents may inform immunosuppressant drug policy. METHODS: A Markov model was used to determine the incremental cost and effectiveness of extending Medicare coverage for immunosuppressive drugs over the duration of transplant survival, compared with the current policy of 36-month coverage, from the perspective of the Medicare payer. The expected improvement in transplant survival by extending immunosuppressive drug coverage was estimated from a cohort of privately insured transplant recipients who receive lifelong immunosuppressant drug coverage compared with a cohort of Medicare-insured transplant recipients, using multivariable survival analysis. RESULTS: Extension of immunosuppression Medicare coverage for kidney transplant recipients led to lower costs of -$3077 and 0.37 additional quality-adjusted life years (QALYs) per patient. When the improvement in transplant survival associated with extending immunosuppressant coverage was reduced to 50% of that observed in privately insured patients, the strategy of extending drug coverage had an incremental cost-utility ratio of $51,694 per QALY gained. In a threshold analysis, the extension of immunosuppression coverage was cost-effective at a willingness-to-pay threshold of $100,000, $50,000, and $0 per QALY if it results in a decrease in risk of transplant failure of 5.5%, 7.8%, and 13.3%, respectively. CONCLUSIONS: Extending immunosuppressive drug coverage under Medicare from the current 36 months to the duration of transplant survival will result in better patient outcomes and cost-savings, and remains cost-effective if only a fraction of anticipated benefit is realized.