Faculty Bibliography

BACKGROUND:C3 glomerulopathy (C3G), which encompasses C3GN and dense deposit disease (DDD), results from dysregulation of the alternative complement pathway. Data on disease recurrence after kidney transplantation are limited, and details on histologic features of recurrent C3G are scarce. We aimed to evaluate C3G recurrence in the allograft, with a focus on histologic presentation and progression. METHODS:We retrospectively analyzed 18 patients with native kidney failure attributed to C3G (12 C3GN and six DDD), who received a kidney transplant from January 2016 to January 2023. Demographic, genetic, clinical, and histologic data were studied. The NanoString 770 genes PanCancer Immune Profiling Panel was used for transcriptomic analysis. Disease recurrence was the primary outcome. RESULTS:During a median (interquartile range) follow-up period of 37 (18–56) months, C3G recurrence occurred in 16 (89%) patients (11 with C3GN and five with DDD) at a median (interquartile range) of 33 (13–141) days after transplantation. Over a third (38%) of recurrent cases were detected in protocol biopsies, and only 31% of patients presented with >300 mg/g of proteinuria. Recurrence in index biopsies was mainly established through a combination of immunofluorescence and electron microscopy findings, while it showed only subtle histologic alterations and no characteristic transcriptomic signals. Over time, histologic chronicity indices increased, but all the allografts were functioning at the end of follow-up. Patients with recurrence of C3GN and DDD showed overlapping immunofluorescence and electron microscopy findings and had similar recurrence rate and time to recurrence. CONCLUSIONS:Most of the patients with native kidney failure attributed to C3G developed disease recurrence very early after kidney transplantation, usually with minimal proteinuria, mild histologic alterations, and favorable short-term allograft survival. Immunofluorescence and electron microscopy played a crucial role in detecting early, subclinical recurrence of C3GN and DDD, which showed significant overlapping features.

Transmitted donor-derived glomerular diseases in the allograft kidney are rare, especially when encountered in an allograft from a living donor. To date, only individual reports of donor-derived membranous nephropathy (MN) have been described. In this report, we present a case of MN discovered in a postreperfusion biopsy of a living-donor allograft. A follow-up biopsy 3 weeks later demonstrated persistent deposits. Thirteen months posttransplant, the recipient showed mildly worsening proteinuria but stable kidney function. To further our understanding of this exceedingly rare complication, we share our experience with 7 additional in-house cases together with 6 cases described in the literature to date. A minority of the donors were living. Most donors did not exhibit significant proteinuria illustrating how predonation screening could potentially miss donor-derived MN. Reactivity for phospholipase A2 receptor and thrombospondin type 1 domain containing 7A were negative in all stained cases. On follow-up, recipients variably exhibited slow resolution of the immune deposits, variable degrees of proteinuria (mainly subnephrotic), and no significant impairment of kidney function. Donor-derived MN is rare, phospholipase A2 receptor-negative, and can still be encountered in living donors despite rigorous screening. This report provides a brief examination of the pathology, clinical, and laboratory features of such patients involved.

Although a few registry-based studies have shown associations between receiving kidney allografts from Black donors and shorter allograft survival, detailed, large, single-center studies accounting for common confounding factors are lacking. Furthermore, pathologic alterations underlying this potential disparity have not been systematically studied. We performed a retrospective clinical-pathological study of kidney transplant recipients who received kidney allografts from either Black (n = 407) or White (n = 1,494) donors at Columbia University Irving Medical Center from 2005 to 2018, with median follow-up of 4.5 years post-transplantation. Black donor race was independently associated with allograft failure (adjusted HR = 1.34, p = 0.02) and recipients of kidney allografts from Black donors had a higher incidence of collapsing glomerulopathy [7.4% vs. 1.9%, OR = 4.17, p < 0.001]. When causes of allograft failure were examined, only allograft failure following development of collapsing glomerulopathy was more frequent in recipients of allografts from Black donors [15% vs. 5%, OR = 3.16, p = 0.004]. Notably, when patients who developed collapsing glomerulopathy were excluded from analysis, receiving kidney allografts from Black donors was not independently associated with allograft failure (adjusted HR = 1.24, p = 0.10). These findings revealed that, compared with recipients of kidney allografts from White donors, recipients of kidneys from Black donors have modestly shorter allograft survival and a higher probability of developing collapsing glomerulopathy, which negatively impacts allograft outcome. Identification of collapsing glomerulopathy risk factors may help decrease this complication and improve allograft survival, which optimally may reduce racial disparities post-transplantation.

Though belatacept is administered with a weight-based dosing schema, there has been higher clearance reported in obese patients. Therefore, we evaluated the association between body mass index (BMI) and transplant outcomes in kidney transplant recipients who were randomized to cyclosporine- or belatacept-based immunosuppression in the BENEFIT and BENEFIT-EXT randomized clinical trials. A total of 666 and 543 patients underwent randomization and transplantation in BENEFIT and BENEFIT-EXT, respectively, of which 1056 had complete data and were included in this analysis. Patients were grouped categorically according to BMI: <25, 25 to <30, and ≥30 kg/m². BMI did influence both the incidence and severity of acute rejection. Obese patients with BMI >30 kg/m² in the low intensity belatacept group experienced significantly more rejection at 12 months than did patients with BMI <25 kg/m² or BMI 25 to <30 kg/m². In both the moderate intensity belatacept and low intensity belatacept groups, obese patients with BMI >30 kg/m² experienced significantly more severe acute rejection than did patients with BMI < 25 kg/m² or BMI 25 to <30 kg/m². These results suggest that obese kidney transplant recipients are at an increased risk for acute rejection when under belatacept-based immunosuppression when compared to nonobese patients.

INTRODUCTION/BACKGROUND:Anemia occurs before and after kidney transplantation. Determining the impact of perioperative transfusion on post-transplant outcomes can help determine best management of anemia. PROJECT AIM/UNASSIGNED:The current study aims to describe clinical outcomes associated with packed red blood cell transfusions in the peri-operative management of anemia after transplantation. DESIGN/METHODS:This was a single-center, retrospective study of adult kidney recipients with anemia at the time of transplantation. 1271 patients were stratified by donor-type due to the potential variability in underlying recipient and transplant characteristics; living donor (n = 698, 62%) or deceased donor (n = 573, 38%). RESULTS:Living donor recipients that received blood during the index hospitalization were more likely to experience rejection within 30 days (18% vs. 10%, p = 0.008) and 1 year of transplant (32% vs. 16%, p = 0.038). In multivariate analysis, receiving both blood and darbepoetin (HR: 1.89 [1.20,3.00], p = 0.006), age at transplant (HR: 0.98 [0.97, 0.99], p = 0.02), number of HLA mismatches (HR: 1.17 [1.05,1.30], p = 0.003), and whether the case was a repeat transplant (HR: 2.77 [1.93,3.97], p < 0.01) were significantly associated with hazard of rejection. For deceased donor recipients, there were no differences in acute rejection, graft failure or mortality at 30 days or 1 year. When analyzing hazard of rejection in a multivariate model, treatment received was not found to be significantly associated with rejection. CONCLUSION/CONCLUSIONS:Our findings suggest there may be a role for more aggressive pre-transplant treatment of anemia for those patients undergoing living donor transplants.

BACKGROUND:We aimed to understand the association between cold ischemia time (CIT) and delayed graft function (DGF) after kidney transplantation and the impact of organ pumping on that association. METHODS:Retrospective cohort study using US registry data. We identified kidney pairs from the same donor where both kidneys were transplanted but had a CIT difference >0 and ≤20 h. We determined the frequency of concordant (both kidneys with/without DGF) or discordant (only 1 kidney DGF) DGF outcomes. Among discordant pairs, we computed unadjusted and adjusted relative risk of DGF associated with longer-CIT status, when then repeated this analysis restricted to pairs where only the longer-CIT kidney was pumped. RESULTS:Among 25 831 kidney pairs included, 71% had concordant DGF outcomes, 16% had only the longer-CIT kidney with DGF, and 13% had only the shorter-CIT kidney with DGF. Among discordant pairs, longer-CIT status was associated with a higher risk of DGF in unadjusted and adjusted models. Among pairs where only the longer-CIT kidney was pumped, longer-CIT kidneys that were pumped had a lower risk of DGF than their contralateral shorter-CIT kidneys that were not pumped regardless of the size of the CIT difference. CONCLUSIONS:Most kidney pairs have concordant DGF outcomes regardless of CIT difference, but even small increases in CIT raise the risk of DGF. Organ pumping may mitigate and even overcome the adverse consequences of prolonged CIT on the risk of DGF, but prospective studies are needed to better understand this relationship.

RATIONALE & OBJECTIVE:Some living donor kidneys are found to have biopsy evidence of chronic scarring and/or glomerular disease at implantation, but it is unclear if these biopsy findings help predict donor kidney recovery or allograft outcomes. Our objective was to identify the prevalence of chronic histological changes and glomerular disease in donor kidneys, and their association with donor and recipient outcomes. STUDY DESIGN:Retrospective cohort study. SETTING & PARTICIPANTS:Single center, living donor kidney transplants from January 2010 to July 2022. EXPOSURE:Chronic histological changes, glomerular disease in donor kidney implantation biopsies. OUTCOME:at 6 months after donation; for recipients, death-censored allograft survival. ANALYTICAL APPROACH:Biopsies were classified as having possible glomerular disease by pathologist diagnosis or chronic changes based on the percentage of glomerulosclerosis, interstitial fibrosis/tubular atrophy, and vascular disease. We used logistic regression to identify factors associated with the presence of chronic changes, linear regression to identify the association between chronic changes and single-kidney estimated glomerular filtration rate (eGFR) recovery, and time-to-event analyses to identify the relationship between abnormal biopsy findings and allograft outcomes. RESULTS:. There were no differences in time-to-death-censored allograft failure in unadjusted or adjusted Cox proportional hazards models when comparing kidneys with chronic changes to kidneys without histological abnormalities. LIMITATIONS:Retrospective, absence of measured GFR. CONCLUSIONS:Approximately 1 in 7 living donor kidneys had chronic changes on implantation biopsy, primarily in the form of moderate vascular disease, and 1% had possible donor glomerular disease. Abnormal implantation biopsy findings were not significantly associated with 6-month donor eGFR outcomes or allograft survival. PLAIN-LANGUAGE SUMMARY:Kidney biopsies are the gold standard test to identify the presence or absence of kidney disease. However, kidneys donated by healthy living donors-who are extensively screened for any evidence of kidney disease before donation-occasionally show findings that might be considered "abnormal," including the presence of scarring in the kidney or findings suggestive of a primary kidney disease. We studied the frequency of abnormal kidney biopsy findings among living donors at our center. We found that about 14% of kidneys had chronic abnormalities and 1% had findings suggesting possible glomerular kidney disease, but the presence of abnormal biopsy findings was not associated with worse outcomes for the donors or their recipients.