Miroslav Sekulic

Key Points: Kidneys from donors with two apolipoprotein L1 (APOL1) risk variants are associated with a higher risk of collapsing glomerulopathy compared with donors with no risk variants. Kidneys with one APOL1 risk variant are associated with intermediate risk of collapsing glomerulopathy. Kidneys from donors with two, but not with one, APOL1 risk variants, have inferior graft survival compared with donors with no risk variants. Introduction: Collapsing glomerulopathy (CG) in the kidney allograft is an infrequent complication, encountered more often in recipients of kidneys from Black donors. Despite its poor prognosis, the genetic susceptibility of this complication remains incompletely understood. Methods: We performed a retrospective study from two major North American transplant centers. We assessed 47 recipients of kidney allografts from Black donors that developed CG and were followed for a median of 2.9 years after transplantation. Donor apolipoprotein L1 (APOL1) genotypes were available in 44 patients with CG and compared with 560 recipients of kidneys from Black donors who did not develop CG. Results: Transplant recipients with CG were 55% of Black race and 40% female, and CG developed at a median of 9.5 months post-transplantation. Donors harboring zero, one, and two APOL1 kidney-risk variants (KRVs) comprised 16%, 41%, and 43% of CG cases and 45%, 43%, and 12% of controls, respectively. Combining cases and controls, receipt of a kidney from donors with two KRVs was associated with a higher risk of CG compared with donors with zero KRVs (adjusted odds ratio=12.51 [95% confidence interval, 4.83 to 32.39], P < 0.001). Receipt of a kidney with one KRV was also associated with a higher risk of CG compared with donors with no KRVs, although with lower effect than those with two KRVs (adjusted odds ratio=3.39 [1.36 to 8.46], P = 0.009). Recipients of kidneys from donors with two KRVs, but not with one KRV, had lower graft survival when compared with donors with zero KRVs (adjusted hazard ratio=1.49 [1.03 to 2.16], P = 0.04). Conclusions: Although the association of CG in the kidney allograft with donor APOL1 KRVs suggests possible dose-dependent effects, lower graft survival was only observed in recipients of kidneys with two KRVs. Identification of additional risk factors for CG may improve utilization of kidneys from Black donors, including these with APOL1 KRVs.

Key Points: C3 glomerulopathy recurs very early and frequently after kidney transplant. Protocol biopsies and the use of electron microscopy alongside immunofluorescence are key to diagnose recurrent C3 glomerulopathy in the allograft. 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. Podcast: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2025_10_09_KTS_October2025.mp3

Despite advances in our understanding of myocardial recovery among left ventricular assist device (LVAD) patients, with 10–30% of patients achieving substantial myocardial improvement, the rates of LVAD support cessation remain extremely low (1–2%). These numbers are in stark contrast to clinical trial data where successful LVAD cessation is reported in up to 47% of patients. The majority of LVAD programs lack structured recovery programs and targeted protocols, likely underscoring the heterogeneity that exists among LVAD patients with myocardial recovery. This perspective summarizes the current medical and surgical challenges with respect to 1) identifying the appropriate candidates for LVAD cessation; 2) methods to wean LVAD support; 3) reviewing surgical techniques for cessation of current generation HeartMate 3 LVAD; and 4) approaching shared decision making for LVAD cessation between patients and providers given the uncertainties that remain in the field.