Quintiliano, Artur

Abstract Introduction: Surveillance biopsies after kidney transplantation provide an opportunity to assess early renal disease processes, including diabetic nephropathy, before clinical manifestation. This study aimed to identify proteomic alterations in renal allografts at 5 years post-transplant (5yrPT) and their associations with histologic features in diabetic/obese (DM/OB) versus non-diabetic/non-obese (nDM/nOB) recipients. Methods: We studied protocol biopsies from 17 DM/OB and 14 nDM/nOB kidney transplant recipients at Mayo Clinic (2000–2012). Laser capture microdissection followed by mass spectrometry was used for proteomic profiling. Histologic assessment included Banff and Tervaert scoring and morphometric analysis. Statistical comparisons were performed using ANOVA with Tukey post-hoc testing. Results: DM/OB recipients demonstrated greater histologic and metabolic injury at 5yrPT. Proteomic analysis identified 101 glomerular and 86 non-glomerular proteins differentially expressed between groups. Significant alterations were observed in proteins associated with mitochondrial dysfunction, including VDAC1 (fold change [FC] 2.6, p = 0.03), NDUFB9 (FC 0.15, p = 0.009), and NDUFA9 (FC 1.72, p = 0.01). Extracellular matrix remodeling proteins COL6A1, COL6A2, and COL6A3 were upregulated (FC 1.6–1.8, p < 0.05). Immune and inflammatory markers C9 (FC 1.6, p < 0.03) and TGFBI (FC 1.7, p < 0.001), as well as oxidative stress–related CLU, were increased. GGACT showed the greatest decrease (FC 0.30, p < 0.001), implicating altered energy metabolism. Conclusion: Distinct proteomic signatures at 5yrPT in DM/OB recipients highlight early mitochondrial, metabolic, immune, and extracellular matrix pathways involved in diabetic kidney disease. These changes precede clinical disease and identify candidate biomarkers and therapeutic targets to improve graft longevity.

ABSTRACT This study investigated the association between induction type and long‐term outcomes in kidney retransplant recipients who experienced graft loss due to BK virus–associated nephropathy (BKVAN). Using Scientific Registry of Transplant Recipients data (2003–2021), we identified 277 adult kidney‐alone retransplant recipients with BKVAN‐related graft loss and categorized them by induction regimen: depletional ( n = 217) and nondepletional ( n = 60). The groups were similar overall, except the nondepletional cohort had lower panel‐reactive antibodies, a shorter time between transplants, and more live donor kidneys. Kaplan–Meier curves assessed 10‐year recipient and graft survival, and Cox proportional hazards models, adjusted for key donor and recipient factors, evaluated associations between induction type and outcomes. Rates of delayed graft function, one‐year rejection, and estimated glomerular filtration rate were comparable between groups. Ten‐year recipient and death‐censored graft survival did not differ by induction type (recipient survival: HR 1.09; 95% CI 0.43–2.77; p = 0.85; graft survival: HR 0.85; 95% CI 0.24–2.97; p = 0.79). Recurrent BKVAN‐related graft failure occurred only in the depletional group (5 of 217; 2.3%), while rejection‐related graft failure was more common in the nondepletional group (5 of 60; 8.3% vs. 6 of 217; 2.8%). Although these differences did not translate into long‐term graft survival disparities, they highlight the competing risks of viral recurrence and rejection. Thus, clinicians should interpret these results with caution and weigh the risks and benefits of induction choice in retransplant recipients with prior BKVAN, recognizing that this observational study cannot establish causality.