"Long-term effects of center volume on transplant outcomes in adult kidney transplant recipients".

BACKGROUND: The influence of center volume on kidney transplant outcomes is a topic of ongoing debate. In this study, we employed competing risk analyses to accurately estimate the marginal probability of graft failure in the presence of competing events, such as mortality from other causes with long-term outcomes. The incorporation of immunosuppression protocols and extended follow-up offers additional insights. Our emphasis on long-term follow-up aligns with biological considerations where competing risks play a significant role. METHODS: We examined data from 219,878 adult kidney-only transplantations across 256 U.S. transplant centers (January 2001-December 2015) sourced from the Organ Procurement and Transplantation Network registry. Centers were classified into quartiles by annual volume: low (Q1 = 28), medium (Q2 = 75), medium-high (Q3 = 121), and high (Q4 = 195). Our study investigated the relationship between center volume and 5-year outcomes, focusing on graft failure and mortality. Sub-population analyses included deceased donors, living donors, diabetic recipients, those with kidney donor profile index >85%, and re-transplants from deceased donors. RESULTS: Adjusted cause-specific hazard ratios (aCHR) for Five-Year Graft Failure and Patient Death were examined by center volume, with low-volume centers as the reference standard (aCHR: 1.0). In deceased donors, medium-high and high-volume centers showed significantly lower cause-specific hazard ratios for graft failure (medium-high aCHR = 0.892, p<0.001; high aCHR = 0.953, p = 0.149) and patient death (medium-high aCHR = 0.828, p<0.001; high aCHR = 0.898, p = 0.003). Among living donors, no significant differences were found for graft failure, while a trend towards lower cause-specific hazard ratios for patient death was observed in medium-high (aCHR = 0.895, p = 0.107) and high-volume centers (aCHR = 0.88, p = 0.061). CONCLUSION: Higher center volume is associated with significantly lower cause-specific hazard ratios for graft failure and patient death in deceased donors, while a trend towards reduced cause-specific hazard ratios for patient death is observed in living donors.

Comparison of Short-Term Outcomes in Kidney Transplant Recipients from SARS-CoV-2-Infected versus Noninfected Deceased Donors.

BACKGROUND: Acceptable post-transplant outcomes were reported in kidney transplant recipients from donors with coronavirus disease 2019 (COVID-19); however, there are no comparative studies with well-matched controls. METHODS: This multicenter, prospective observational study, which included three transplant centers in the United States, enrolled 61 kidney recipients from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected deceased donors. Using optimal matching methods, we matched every recipient to three comparators receiving kidneys from SARS-CoV-2-negative deceased donors with otherwise highly similar characteristics in the same transplant centers to compare 6-month eGFR. RESULTS: Among recipients of SARS-CoV-2-infected donor kidneys, one recipient died with a functional graft within 6 months. Mean 6-month eGFR was not significantly different between SARS-CoV-2-infected and noninfected donor groups (55±21 and 57±25 ml/min per 1.73 m 2 , respectively; P = 0.61). Six-month eGFR in recipients from SARS-CoV-2-infected donors who died of reasons other than COVID-19 was not significantly different from those from SARS-CoV-2-negative donors (58±22 and 56±25 ml/min per 1.73 m 2 , respectively; P = 0.51). However, recipients from donors who died of COVID-19 had significantly lower 6-month eGFR than those from SARS-CoV-2-negative donors (46±17 and 58±27 ml/min per 1.73 m 2 , respectively; P = 0.03). No donor-to-recipient SARS-CoV-2 transmission was observed. CONCLUSIONS: Six-month eGFR was not significantly different between recipients of kidneys from SARS-CoV-2-infected and noninfected donors. However, those receiving kidneys from donors who died of COVID-19 had significantly lower 6-month eGFR. Donor-to-recipient SARS-CoV-2 transmission was not observed.

CMV specific T cell immune response in hepatitis C negative kidney transplant recipients receiving transplant from hepatitis C viremic donors and hepatitis C aviremic donors.

Kidney transplants (KT) from hepatitis C (HCV) viremic donors to HCV negative recipients has shown promising renal outcomes, however, high incidence of cytomegalovirus (CMV) viremia were reported. We performed a prospective cohort study of 52 HCV negative KT recipients from Methodist University Hospital including 41 receiving transplants from HCV aviremic donors and 11 from HCV viremic donors. CMV specific CD4+ and CD8 + T cell immunity was measured by intracellular flow cytometry assay. Primary outcome was the development of positive CMV specific CD4+ and CD8 + T cell immune response in the entire cohort and each subgroup. The association between donor HCV status and CMV specific CD4+ and CD8 + T cell immune response was analyzed by Cox proportional hazard models. Mean recipient age was 48 ± 13 years, with 73% male and 82% African American. Positive CMV specific CD4+ and CD8 + T cell immune response was found in 53% and 47% of the cohort at 1 month, 65% and 70% at 2 months, 80% and 75% at 4 months, 89% and 87% at 6 months, and 94% and 94% at 9 months post-transplant, respectively. There was no significant difference in the incidence of positive CMV specific T cell immune response between recipients of transplants from HCV aviremic donors compared to HCV viremic donors in unadjusted (for CD8+: HR = 1.169, 95%CI: 0.521-2.623; for CD4+: HR = 1.208, 95%CI: 0.543-2.689) and adjusted (for CD8+: HR = 1.072, 95%CI: 0.458-2.507; for CD4+: HR = 1.210, 95%CI: 0.526-2.784) Cox regression analyses. HCV viremia in donors was not associated with impaired development of CMV specific T cell immunity in this cohort.

Association of donor hepatitis C virus infection status and risk of BK polyomavirus viremia after kidney transplantation.

Kidney transplantation (KT) from deceased donors with hepatitis C virus (HCV) into HCV-negative recipients has become more common. However, the risk of complications such as BK polyomavirus (BKPyV) remains unknown. We assembled a retrospective cohort at four centers. We matched recipients of HCV-viremic kidneys to highly similar recipients of HCV-aviremic kidneys on established risk factors for BKPyV. To limit bias, matches were within the same center. The primary outcome was BKPyV viremia ≥1000 copies/ml or biopsy-proven BKPyV nephropathy; a secondary outcome was BKPyV viremia ≥10 000 copies/ml or nephropathy. Outcomes were analyzed using weighted and stratified Cox regression. The median days to peak BKPyV viremia level was 119 (IQR 87-182). HCV-viremic KT was not associated with increased risk of the primary BKPyV outcome (HR 1.26, p = .22), but was significantly associated with the secondary outcome of BKPyV ≥10 000 copies/ml (HR 1.69, p = .03). One-year eGFR was similar between the matched groups. Only one HCV-viremic kidney recipient had primary graft loss. In summary, HCV-viremic KT was not significantly associated with the primary outcome of BKPyV viremia, but the data suggested that donor HCV might elevate the risk of more severe BKPyV viremia ≥10 000 copies/ml. Nonetheless, one-year graft function for HCV-viremic recipients was reassuring.

Association between ezetimibe usage and hepatitis C RNA levels in uninfected kidney transplant recipients who received hepatitis C infected kidneys.

Kidney transplantation (KT) from hepatitis C virus infected (HCV+) donors to HCV negative recipients achieve excellent graft function but have relatively higher rates of post-KT co-infections presumably due to prolonged HCV viremia in transmission-and-treat approach. Ezetimibe acts as an antagonist of Niemann-Pick C1-Like 1 receptor required for HCV entry and theoretically can reduce HCV viremia. However, no data is available to examine the role of ezetimibe as a bridge therapy between KT surgery and direct acting antiviral (DAA) initiation. A retrospective cohort study including 70 HCV+ to HCV negative KT recipients from Methodist University Hospital and Vanderbilt University Medical Center was performed to determine the association between ezetimibe usage and HCV viremia. Twenty patients received ezetimibe daily while 50 patients did not. Primary outcome of study was mean HCV RNA level at 1-2 weeks post-KT and before initiation of DAA. Median (IQR) viral load (VL) in log copies/ml was one log lower in ezetimibe group versus non-ezetimibe group (4.1 [3.7-5.3] vs. 5.1 [4.4-5.5], P = .01), and highest VL was also lower in ezetimibe group (4.2 [3.7-5.4] vs. 5.4 [4.7-5.9], P = .006). We concluded that ezetimibe bridge therapy might be associated with reduction in HCV VL while waiting for DAA initiation in HCV+ to HCV negative KT recipients.

Obesity, Chronic Kidney Disease, and Kidney Transplantation: An Evolving Relationship.

Obesity has a fundamental role in driving the global kidney disease burden. The perplexing relationship of obesity with chronic kidney disease remains debated. However, a thorough understanding of the interplay of obesity in conjunction with chronic kidney disease and appropriate management options is lacking, leading to further increases in morbidity and mortality. Moreover, underutilization of bariatric procedures and unrealistic expectations of weight reduction based on body mass index, leading to poor access to kidney transplantation, are fueling the fire. In this review, we summarize the available data related to the obesity and chronic kidney disease association and its novel management options.

Transplantation of Kidneys From Hepatitis C Virus-Infected Donors to Hepatitis C Virus-Negative Recipients: One-Year Kidney Allograft Outcomes.

RATIONALE & OBJECTIVE: Transplant centers in the United States are increasingly willing to transplant kidneys from hepatitis C virus (HCV)-infected (HCV+) donors into HCV- recipients. We studied the association between donor HCV infection status and kidney allograft function and posttransplantation allograft biopsy findings. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: We examined 65 HCV- recipients who received a kidney from a HCV+ donor and 59 HCV- recipients who received a kidney from a HCV- donor during 2018 at a single transplant center. EXPOSURE: Predictor(s) of donor infection with HCV. OUTCOMES: Kidney allograft function and allograft biopsy findings during the first year following transplantation. ANALYTICAL APPROACH: We compared estimated glomerular filtration rate (eGFR), findings on for-cause and surveillance protocol biopsies, development of de novo donor-specific antibodies (DSAs), and patient and allograft outcomes during the first year following transplantation between recipients of HCV+ and HCV- kidneys. We used linear regression to estimate the independent association between allograft function and HCV viremic status of the kidney donor. RESULTS: The mean age of recipients was 52 ± 11 (SD) years, 43% were female, 19% and 80% of recipients were White and Black, respectively. Baseline characteristics were similar between the HCV+ and HCV- groups. There were no statistically significant differences between the HCV+ and HCV- groups in delayed graft function rates (12% vs 8%, respectively); eGFRs at 3, 6, 9, and 12 months post-transplantation; proportions of patients with cellular rejection (6% vs 7%, respectively); and proportions with antibody-mediated rejection (7% vs 10%, respectively) or de novo DSAs (31% vs 20%, respectively). HCV viremic status was not associated with eGFR at 3, 6, 9, or 12 months. LIMITATIONS: Generalizability from a single-center study and small sample size was limited. CONCLUSIONS: Recipients of kidneys from donors infected with HCV had similar kidney allograft function and probability of rejection in the first year after transplantation compared to those who received kidneys from donors without HCV infection.

The incidence of cytomegalovirus infection after deceased-donor kidney transplantation from hepatitis-C antibody positive donors to hepatitis-C antibody negative recipients.

BACKGROUND: Deceased-donor kidney transplantation (KT) from hepatitis C (HCV)-infected donors into HCV-uninfected recipients (HCV D+/R-) could become standard care in the near future. However, HCV viral replication by viral transmission might lead to a higher incidence of cytomegalovirus (CMV) infection in these recipients. METHODS: A national-registry-based retrospective cohort study was conducted using the Scientific Registry of Transplant Recipients (SRTR) data set. We assessed the incidence of CMV infection in HCV antibody (Ab) negative recipients receiving kidneys from HCV Ab positive (HCVAb D+/R-) and negative (HCVAb D-/R-) donors. The risk of CMV infection was analyzed by Cox regression analysis in a propensity score (PS) matched-cohort of HCVAb D+/R- (n = 950) versus HCVAb D-/R- (n = 950). Sensitivity analysis was also conducted in the entire cohort (n = 181 082). RESULTS: The mean age at baseline was 54 years, 75% were male, and 55% of the patients were African American in PS-matched cohort. Compared to the HCVAb D-/R - patients, recipients with HCVAb D+/R - showed identical probability for the incidence of CMV infection (Hazard Ratio (HR) = 1.00, 95% Confidence Interval (CI): 0.82-1.22). In the sensitivity analysis, compared to the HCVAb D-/R - patients, the HCVAb D+/R - group had a significantly lower risk of CMV infection in the unadjusted analysis (HR = 0.75, 95%CI: 0.65-0.85), while this risk difference disappeared after the adjusted analysis (HR = 0.99, 95%CI: 0.87-1.14). CONCLUSION: The incidence of CMV infection was similar in recipients who received HCVAb D + and HCVAb D - KT. Further studies are needed to assess this association in KT from HCV nucleic acid positive donors.

Donor hepatitis C antibody positivity misclassifies kidney donor profile index in non-hepatitis C-infected donors: time to revise the kidney donor profile index - a retrospective cohort study.

The kidney donor profile index (KDPI) defines an hepatitis C (HCV) positive donor based on HCV antibody (Ab) and/or nucleic acid amplification test (NAT) positivity, with donors who are not actively infected (Ab+/NAT-) also classified as HCV positive. From Scientific Registry of Transplant Recipients dataset, we identified HCV-negative recipients, who received a kidney transplant from HCV Ab+/NAT- (n = 116) and HCV Ab-/NAT- (n = 25 574) donor kidneys. We then compared recipients' estimated glomerular filtration rate (eGFR) at 6 months in matched cohorts, using combined exact matching (based on KDPI) and propensity score matching. We created two separate matched cohorts: for the first cohort, we used the allocation KDPI, while for the second cohort we used an optimal KDPI, where the HCV component of KDPI was considered negative in Ab+/NAT- patients. The mean ± SD age of the allocation KDPI-matched cohort at baseline was 59 ± 10 years, 69% were male, 61% were white. Recipients' eGFR at 6 months after transplantation was significantly higher in the HCV Ab+/NAT- group compared to the HCV Ab-/NAT- group (61.1 ± 17.9 vs. 55.6 ± 18.8 ml/min/1.73 m2 , P = 0.011) in the allocation KDPI-matched cohort, while it was similar (61.8 ± 19.5 vs. 62.1 ± 20.1 ml/min/1.73 m2 , P = 0.9) in the optimal KDPI-matched cohort. Recipients who received HCV Ab positive, but NAT-negative donor kidneys did not experience worse 6-month eGFR than correctly matched HCV Ab-/NAT- recipients.

Outcomes of critically ill solid organ transplant patients with COVID-19 in the United States.

National data on patient characteristics, treatment, and outcomes of critically ill coronavirus disease 2019 (COVID-19) solid organ transplant (SOT) patients are limited. We analyzed data from a multicenter cohort study of adults with laboratory-confirmed COVID-19 admitted to intensive care units (ICUs) at 68 hospitals across the United States from March 4 to May 8, 2020. From 4153 patients, we created a propensity score matched cohort of 386 patients, including 98 SOT patients and 288 non-SOT patients. We used a binomial generalized linear model (log-binomial model) to examine the association of SOT status with death and other clinical outcomes. Among the 386 patients, the median age was 60 years, 72% were male, and 41% were black. Death within 28 days of ICU admission was similar in SOT and non-SOT patients (40% and 43%, respectively; relative risk [RR] 0.92; 95% confidence interval [CI]: 0.70-1.22). Other outcomes and requirement for organ support including receipt of mechanical ventilation, development of acute respiratory distress syndrome, and receipt of vasopressors were also similar between groups. There was a trend toward higher risk of acute kidney injury requiring renal replacement therapy in SOT vs. non-SOT patients (37% vs. 27%; RR [95% CI]: 1.34 [0.97-1.85]). Death and organ support requirement were similar between SOT and non-SOT critically ill patients with COVID-19.