Stabilization of renal function after the first year of follow-up in kidney transplant recipients treated for significant BK polyomavirus infection or BK polyomavirus-associated nephropathy.

BACKGROUND: BK polyomavirus virus (BKPyV) screening and immunosuppression reduction effectively prevent graft loss due to BKPyV-associated nephropathy (BKPVAN) during the first year after transplantation. The aim of our study was to evaluate the impact of this infection during longer follow-up periods. METHODS: We reviewed the outcome of our screening and immunosuppression reduction protocol in 305 patients who received a kidney transplant between March 2008 and January 2013. Quantitative BKPyV DNA surveillance in plasma was performed at 1, 2, 3, 6, 9, and 12 months after transplantation. Patients with significant viremia and/or biopsy-proven BKPVAN were treated with immunosuppression reduction and leflunomide. RESULTS: During the first post-transplant year, 24 patients (7.9%) developed significant viremia at a median time of 95 days, and 18 patients had BKPVAN; 23 of the 24 (7.5%) were treated according to our protocol (group BKV+); 225 patients (73.8%) did not develop any BK viremia (group BKV-). Allograft function was similar in both groups at 1 month post transplantation (P=.87), but significantly worse at 1 year in the BKV+ group (P=.002). Thereafter, kidney function stabilized in the BKV+ group and no differences in patient and graft survival were seen between the groups after a median follow-up of 4 years. CONCLUSIONS: We confirm the early occurrence of BKPyV replication after transplantation and the short-term decline in renal function. However, early detection of BKPyV replication, prompt diagnosis, and reduction in immunosuppression may offer long-term benefits for graft function.

Increased risk of thrombotic microangiopathy in patients receiving a cyclosporin-sirolimus combination.

A single-center cohort study of kidney and kidney-pancreas recipients was conducted to evaluate the association between new immunosuppressive regimens and risk of thrombotic microangiopathy (TMA). From January 1st,1996 to December 31, 2002, 368 patients received a kidney or kidney-pancreas transplant at our center. Four immunosuppressive regimens were evaluated as potential risk factors of TMA: cyclosporin + mycophenolate mofetil (CsA + MMF), cyclosporin + sirolimus (CsA + SRL), tacrolimus + myophenolate mofetil (FK + MMF), and tacrolimus + sirolimus (FK + SRL). Thirteen patients developed biopsy-proven TMA in the absence of vascular rejection. The incidence of TMA was significantly different in the four immunosuppressive regimens studied (p < 0.001). The incidence of TMA was highest in the CsA + SRL group (20.7%). The relative risk of TMA was 16.1 [95% confidence interval (CI): 4.3-60.8] for patients in the CsA + SRL group as compared with those in the FK + MMF group. We also investigated in vitro the pathophysiological basis of this association. The CsA-SRL combination was found to be the only regimen that concomitantly displayed pro-necrotic and anti-angiogenic activities on arterial endothelial cells. We propose that this combination concurs to development of TMA through dual activities on endothelial cell death and repair.