Timothy P. Copeland

BACKGROUND Variability exists in acceptance of living kidney donor candidates across the US. This study sought to quantify the extent to which this variation is driven by donor candidate ancestry, transplant centers and providers.METHODS Using a retrospective cohort study of living donor candidates who completed donor evaluation across nine US transplant centers, we examined the Kidney Failure Risk Projection (KFRP) model (estimating donor risk of ESKD at 15 years) as a proxy of the threshold for donor acceptance. Mixed linear models clustered by transplant center and provider were used to relate donor ancestry to center decisions.RESULTS Among 1888 living donor candidates (median age 42 years, 62% women), 39% Black candidates were accepted to donate versus 45% Hispanic and 56% White candidates (p<0.001). KFRP scores were extremely low, with median risk of 0.13% (IQR 0.06-0.27). Accounting for the 15-year KFRP score in adjusted models, the odds of donor acceptance were higher for White candidates (OR 1.46; 95% CI 1.13-1.88) compared with Hispanic (referent) and Black candidates (OR 0.74; 95% CI 0.53-1.04). White donor candidates declined for donation had a higher KFRP score by 0.08% versus Hispanic and Black candidates (p<0.05). In mixed models, residual variability in donor acceptance was observed at the transplant center (SD 0.08% in the KFRP score) and provider levels (SD 0.04%) for those accepted as donors, without variability by donor ancestry.CONCLUSIONS In this cohort, although fewer Black donor candidates were accepted for donation versus White and Hispanic candidates, accepted candidates had extremely low risk of developing ESKD within 15 years, regardless of ancestry. Variability across providers and transplant centers was observed, but absolute differences in their threshold of acceptance (or non-acceptance) were small. Our findings suggest that disparities in living donor access by donor ancestry are not explained by differences in system-level variations in practice.

Background Slower chronic kidney disease (CKD) progression allows more time for transplant preparation. Whether differences in CKD progression by race/ethnicity associate with preemptive or living donor transplantation in youth has not been well studiedMethods We examined the association between time spent with low eGFR (between 10–30 mL/min/1.73 m 2 ) and odds of preemptive or living donor transplantation among youth with CKD. eGFR was estimated using the bedside Schwartz (if < 18 years) and CKD-EPI 2021 equations (if ≥ 18 years) and the CKiD U25 equation in sensitivity analysis. Time spent with low eGFR was compared by race/ethnicityResults Among 333 youth with CKD (median age 11 years [IQR 7,14]), median time spent with low eGFR was 28.8 months. 77% were preemptively waitlisted, and 45% received preemptive transplantation (56% of White and 24% of Black youth). Black (vs. White) youth had shorter time with low eGFR (–6.5 months; 95% CI –11.5, –1.4). Time with low eGFR did not differ across other groups. Findings were similar using the U25 equation. Every additional year spent with low eGFR was associated with higher odds of preemptive (OR 1.45; 95% CI 1.24–1.70) and living donor transplantation (OR 1.42; 95% CI 1.21–1.67), but not preemptive waitlisting (OR 0.96; 95% CI 0.83–1.11) in unadjusted analysesConclusions Longer time spent with low eGFR is associated with greater odds of preemptive and living donor transplantation. Earlier transplant referral for all children, especially Black youth, may help improve access to preemptive and living donor transplantation. Graphical abstract

Objective The aim of this study was to compare and rank the efficacy and safety of four final oocyte maturation trigger strategies—human chorionic gonadotropin (hCG), gonadotropin-releasing hormone agonist (GnRHa), dual, and double trigger—in predicted high responders undergoing in vitro fertilization (IVF) with GnRH antagonist protocols, using a network meta-analysis (NMA) approachMethods A systematic search of MEDLINE, EMBASE, CENTRAL, clinical trial registries, and the Cochrane Database of Systematic Reviews was conducted through December 2024. Eligible studies were randomized controlled trials (RCTs) including high responders, defined by elevated antral follicle count, anti-Müllerian hormone, or estradiol levels. Studies using GnRHa triggers followed by fresh embryo transfer were included only if intensive luteal phase support was provided. Oocyte donation cycles, quasi-randomized designs, and trials lacking outcome data were excluded. Data extraction and risk of bias assessment were independently conducted by two reviewers. Study integrity was evaluated using the TRACT checklist. NMA was performed in STATA (v16), and treatment ranking was based on Surface Under the Cumulative Ranking curve (SUCRA)Results Seven high-quality RCTs comprising 632 women were included. There were no significant differences in the number of oocytes retrieved between GnRHa and hCG triggers (mean difference [MD] 1.08, 95% CI –1.06 to 3.22), dual and hCG (MD 0.61, 95% CI –1.53 to 2.74), or GnRHa and dual (MD 1.08, 95% CI –1.06 to 3.22). Similarly, there were no significant differences in mature oocyte yield, clinical pregnancy rate (CPR), or miscarriage rate across comparisons. However, GnRHa trigger significantly reduced the risk of moderate to severe ovarian hyperstimulation syndrome (OHSS) compared with hCG (RR 0.23, 95% CI 0.07–0.82). There were no significant differences in OHSS risk between dual and hCG (RR 0.28, 95% CI 0.05–1.64) or between GnRHa and dual (RR 0.28, 95% CI 0.05–1.64)Conclusion GnRHa, hCG, and dual triggers demonstrate similar efficacy in terms of oocyte yield, maturity, and clinical pregnancy rates in predicted high responders. The GnRHa trigger, however, offers a superior safety profile by significantly lowering the risk of OHSS. Larger multicenter RCTs are required to evaluate live birth outcomes and the potential role of the double trigger in this population. Systematic review registration https://www.crd.york.ac.uk/prospero/ , identifier CRD42022351423.

Background Severe diabetes insipidus (DI) causes dynamic changes in creatinine before organ donation. It is unknown whether terminal or peak creatinine is the optimal measure of graft quality among donors with severe DIMethods Adult donors after brain death were identified from the United Network for Organ Sharing database, years 2015–2022. Kidney Donor Profile Index (KDPI) was computed using both terminal creatinine (KDPI-Terminal) and peak creatinine (KDPI-Peak). Model fit for the prediction of graft failure and reduced glomerular filtration rate (GFR) was compared. Logistic regression was used to determine the association between KDPI group reclassification and graft functionResults Of 28 718 kidney transplants, 29% of donors met criteria for severe DI. No differences in estimated GFR (eGFR) or all-cause graft failure were observed on the basis of the presence of DI. Among donors with severe DI, KDPI-Peak improved prediction of reduced eGFR at 1 y (eGFR <60 mL/min/1.73 m 2 , eGFR <30 mL/min/1.73 m 2 ). Additionally, patients who received organs from donors with severe DI whose KDPI group would be reclassified on the basis of the use of peak rather than terminal creatinine had 2-fold increased odds of reduced eGFR at 1 y (eGFR <30 mL/min/1.73 m 2 ; odds ratio, 1.92; 95% confidence interval, 1.37-2.69)Conclusions This national analysis confirms that while the presence of severe DI alone is not associated with graft outcomes, the use of peak creatinine significantly improves risk stratification of donor graft quality. Precise risk stratification is critical for efforts to improve appropriate kidney allocation and increase confidence in organ function after transplant.

RATIONALE & OBJECTIVE For transplant recipients with low estimated glomerular filtration rate (eGFR), early preparation is needed to optimize the transition back to dialysis or retransplantation. Our objective was to determine if the amount of time spent with low eGFR was associated with a higher likelihood of relisting or retransplantation within 1 year of graft failure.STUDY DESIGN Retrospective cohort study.SETTING & PARTICIPANTS We included adults who developed graft failure between 2010 and 2021 according to the US Renal Data System.EXPOSURE We modeled the time spent with eGFR between 20 and 5 mL/min/1.73 m2 using available serum creatinine values reported annually (henceforth referred to as time with low eGFR).OUTCOME Relisting or retransplantation within 1 year of graft failure.ANALYTICAL APPROACH We used Fine-Gray models accounting for the competing risk of death to determine the association between time spent with low eGFR (as a categorical variable) and outcomes of interest.RESULTS We included 14,680 patients; median age at graft failure was 53 years (IQR, 42-61). Within 1 year of graft failure, ∼18% (n = 2,690) of patients were relisted and 13% (n = 1,854) were retransplanted. In adjusted models, spending 2-4 years (SHR, 1.43; 95% confidence interval [CI], 1.16-1.75) or >4 years (SHR, 1.28; 95% CI, 1.04-1.57) with low eGFR was associated with a higher likelihood of relisting (vs spending <2 years with low eGFR). Similarly, spending 2-4 years (SHR, 1.37; 95% CI, 1.09-1.72) or >4 years (SHR, 1.73; 95% CI, 1.37-2.19) with low eGFR was also associated with a higher likelihood of retransplantation within 1 year of graft failure.LIMITATIONS Residual confounding; observational nature of study.CONCLUSIONS Timely preparation of patients with low eGFR for retransplantation could increase patients' likelihood of early relisting and retransplantation. For transplant recipients with low kidney function, the vast majority of patients will return to dialysis after graft failure, and many will not receive a second transplant. Our objective in this study was to determine if a longer time spent with low kidney function before the return to dialysis was associated with a higher likelihood of relisting or retransplantation in transplant recipients using national registry data. We found that spending more than 2 years with low eGFR was associated with a much higher likelihood of relisting and retransplantation than spending less than 2 years with low eGFR. Early preparation for retransplantation is needed to improve transplant patients’ likelihood of receiving a second transplant.