As part of the Spare-the-Nephron trial, we evaluated the combination mycophenolate mofetil (MMF) and sirolimus (SRL) as a calcineurin inhibitor (CNI)-free regimen for the preservation of renal function in renal allograft recipients. This 2-year, open-label, multicenter trial randomized 299 patients of which 151 were maintained on MMF and a CNI, 148 on MMF plus SRL (n=120, tacrolimus; n=31, cyclosporine). Baseline characteristics including measured (iothalamate) glomerular filtration rate (GFR) were similar between groups. After 1 year, the mean percentage change from baseline in the primary end point of measured GFR was significantly higher in the MMF/SRL group compared with the MMF/CNI group. After 2 years, the change was indistinguishable. Calculated creatinine clearance and GFR were significantly greater with MMF/SRL at 2 years within which biopsy-proven acute rejection (BPAR) occurred in 14 MMF/SRL-treated patients (3 graft losses) and in 17 receiving the MMF/CNI (6 graft losses). Significantly, no patients receiving MMF/SRL but five treated with MMF/CNI died. Thus, compared with MMF/CNI treatment, a 2-year regimen of MMF/SRL resulted in similar measures of renal function but with fewer deaths and a trend to less BPAR and graft loss.

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Polyomavirus nephropathy (PVN) remained inadequately classified until 2018 when the Banff Working Group published a new 3‐tier morphologic classification scheme derived from in‐depth statistical analysis of a large multinational patient cohort. Here we report a multicenter “modern‐era” validation study that included 99 patients with definitive PVN transplanted post January 1, 2009 and followed the original 2018 study design. Results validate the PVN classification, that is, the 3 PVN disease classes predicted clinical presentation, allograft function, and outcome independent of therapeutic intervention. PVN class 1 compared to classes 2 and 3 was diagnosed earlier (16.9 weeks posttransplant [median], P = .004), and showed significantly better function at 24 months postindex biopsy (serum creatinine 1.75 mg/dl, geometric mean, vs class 2: P = .037, vs class 3: P = .013). Class 1 presented during long‐term follow‐up with a low graft failure rate: 5% class 1, vs 30% class 2, vs 50% class 3 (P = .009). Persistent PVN was associated with an increased risk for graft failure (and functional decline in class 2 at 24 months postdiagnosis; serum creatinine with persistence: 2.48 mg/dL vs 1.65 with clearance, geometric means, P = .018). In conclusion, we validate the 2018 Banff Working Group PVN classification that provides significant clinical information and enhances comparative data analysis.