Bentall, Andrew

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.

Delayed graft function (DGF) is a frequent complication after deceased donor kidney transplantation, yet its long-term impact remains understudied. Heterogeneous populations, short follow-up, and inadequate control of donor-related factors have limited prior studies. Using the Scientific Registry of Transplant Recipients (2005–2024), we evaluated the association between DGF and long-term graft outcomes, including a mate-kidney (same donor, discordant DGF status) analysis to isolate its independent effect. We identified 103,678 dialysis-dependent deceased donor kidney recipients maintained on tacrolimus and mycophenolate. Mixed-effects Cox models, adjusted for donor, recipient, immunologic, and procurement factors. DGF occurred in 30.1% of recipients and was associated with increased death-censored graft failure (HR 1.40; 95% CI 1.33–1.47) and overall graft failure (HR 1.27; 95% CI 1.23–1.31). DGF recipients had higher rejection rates at 6 (6.0% vs. 4.7%) and 12 months (8.9% vs. 7.3%), longer hospital stay, and higher 1-year rehospitalization. In the mate-kidney analysis (6,818 donors), DGF remained strongly associated with death-censored graft failure (HR 1.58; 95% CI 1.39–1.80) and overall graft failure (HR 1.35; 95% CI 1.25–1.46), confirming the independent effect of DGF. DGF is a strong predictor of adverse long-term outcomes irrespective of rejection and warrants targeted prevention strategies and intensified follow-up.

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.

Background. Living kidney donation (KD) evaluation particularly focuses on glomerular filtration rate (GFR). Assessing GFR in living kidney donors can be done by estimation (eGFR) or measurement (mGFR). This study aims to evaluate the impact of eGFR equations, focusing on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation for donor eligibility screening and the reclassification of donors excluded by eGFR criteria to mGFR assessments. Methods. Retrospective, single-center observational study of 2512 kidney donors evaluated between 2011 and 2023, at the Mayo Clinic. We performed analyses and comparisons of 4 eGFR formulae and 2 mGFR methods in terms of performance, eligibility criteria according to Kidney Disease: Improving Global Outcomes guidelines/age-adjusted criteria, eligibility reclassification, and subgroup analyses. Results. The CKD-EPI 2021 resulted in a higher percentage of patients being eligible for KD (81.4%) and achieved the highest P10 (32%–34%) and P30 (87%–88%) across all mGFR methods. When patients were deemed eligible for donation by any eGFR formula, 95% retained this status on reassessment with mGFR. Conversely, when an eGFR formula classified a patient as ineligible, this was revised to be eligible in about 90% of cases on reassessment with mGFR, with a higher reclassification rate observed when the IoCl was used instead of CrCl. Conclusions. The CKD-EPI 2021 performs best for screening potential KD. If a KD is deemed ineligible by CKD-EPI 2021, there is a high likelihood that they will be reclassified as eligible when assessed with mGFR. This study strongly supports using mGFR in donor evaluations, especially when the eGFR does not meet the criteria to ensure equity of access to being a living donor.

ABSTRACT Background Ureteral stents are commonly placed during kidney transplantation (KT) to mitigate urologic complications. The objective of this study was to compare clinical outcomes in KT recipients with either early stent removal when attached to the Foley catheter or late removal via cystoscopy when unattached. Methods We conducted a multi‐center retrospective analysis of consecutive living donor KT patients (8/18/21‐4/21/23) stratified into Foley‐attached and unattached stent groups. Outcomes assessed were ureteral stricture, urine leaks, UTIs at 90 days and allograft failure and BKV DNAemia (BK virus DNAemia) at 1 year. Data are reported as mean and standard deviation. Results Among 247 patients with attached and 260 with unattached stents, baseline demographics (age, sex, diabetes) were similar between groups. There was a difference in race (87.9% vs. 77.8% Caucasian; p = 0.004). Foley catheters remained longer in the attached group (3.7 ± 1.8 vs. 3.0 ± 2.0 days; p < 0.001), but stents were removed earlier (3.7 ± 1.8 vs. 21.9 ± 4.7 days; p < 0.001). Comparing attached versus unattached, there were no differences in ureteral stricture (0.4% vs. 1.5%; p = 0.197), urine leak (0.8% vs. 0.4%; p = 0.533), BKV DNAemia (17.7% vs. 16.9%; p = 0.616), or allograft failure (0% vs. 0.8%; p = 0.167). However, UTI incidence by 90 days was lower in the attached group (5.7% vs. 11.9% p = 0.013). Induction therapy differed significantly between groups, with Alemtuzumab more common in the unattached group (58.1% vs. 19.4%, p < 0.001), Basiliximab more common in the attached group (43.3% vs. 35.0%, p < 0.001), and Thymoglobulin more common in the attached group (36.0% vs. 6.9%, p < 0.001). Baseline steroid use was higher in the unattached group (81.9% vs. 57.9%, p < 0.001). Conclusion Early stent removal via connection to the Foley catheter had similarly low rates of ureteral complications while reducing urinary tract infections and avoiding cystoscopic removal.

The increasing prevalence of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) has led to a growing demand for kidney transplantation (KTx). Identifying risk factors that enable improved allograft survival through novel therapeutic agents, advanced biomarkers, and artificial intelligence (AI)-driven data integration are critical to addressing this challenge. Drugs, such as SGLT2 inhibitors and finerenone, have demonstrated improved outcomes in patients but lack comprehensive long-term evidence in KTx patients. The use of biomarkers, including circulating cytokines and transcriptomics, coupled with AI, could enhance early detection and personalized treatment strategies. Addressing patient self-management and addressing health access disparities may be more achievable using technologies used at home rather than traditional models of healthcare and thus lead to increased transplant success, both in terms of transplantation rates and allograft longevity.

Abstract Background It has been hypothesized that combined heart and kidney transplantation (HKT) may lead to immune modulation and attenuation of cardiac allograft vasculopathy (CAV) progression. Sirolimus (SRL) has been shown to mitigate the progression of CAV and confer renal protection. With the increasing use of SRL as primary immunosuppression in heart transplant (HT) recipients, the effect of HKT on CAV progression compared to HT-only remains undetermined. Purpose We sought to investigate the patterns of conversion from calcineurin inhibitors (CNI) to SRL, and its impact on CAV progression and outcomes in HKT compared to HT-only in a cohort with frequent use of SRL as primary immunosuppression. Methods A cohort of 302 patients who underwent either HT only (n=262) or combined HKT (n=40) was analyzed. CAV progression was assessed by measuring the delta (Δ) annual change in plaque volume (PV) normalized to vessel length (PV/VL in mm3/mm) and plaque index (PI) (%) (calculated as the PV to VV ratio) between baseline and last follow-up coronary intravenous ultrasound (IVUS). Clinical adverse outcomes included all-cause death and CAV-associated events. Secondary outcomes included differences in renal function and incidence of SRL-associated proteinuria (defined as Δ urine protein ≥300 mg/24 h at 1 year after conversion to SRL) between HT-only and HKT recipients. Results Overall, 217 (72%) patients were converted from CNI to SRL as primary immunosuppression. HT recipients were more likely to be converted to SRL than combined HKT recipients (74% vs. 55%, P=0.01). HKT was associated with significantly higher ΔPV/VL (P=0.01) and a trend toward a higher ΔPI (P=0.06) than HT-only, but this association was markedly attenuated after adjustment to SRL conversion. HKT was associated with similar risk of death (adjusted hazard ratio [HR] 0.69, 95%CI: 0.28-1.71, P=0.43) and CAV-related events (adjusted HR 0.83, 95% CI: 0.30-2.31, P=0.72). Conversion to SRL was significantly associated with decreased risk of death and CAV-related events in the overall cohort. This association was not modified by the type of organ transplantation (Pinteraction=NS), and without a significant effect on estimated glomerular filtration rate (eGFR) or proteinuria. Conclusions HKT recipients compared to HT-only were less likely to be converted from CNI to SRL-based immunosuppression and had a greater CAV progression but without significant differences in all-cause mortality or CAV-related events. The clinical benefit and safety of conversion to SRL appeared similar in the HKT and isolated HT cohorts.