Geetha Duvuru, Parkhie Shyam, Nadkarni Girish N, He Chun, Shafi Tariq
From Department of Medicine (DG, SP, TS), Johns Hopkins University School of Medicine, Baltimore, Maryland; Department of Medicine (GNN), St.Luke's-Roosevelt Hospital Center, New York, New York; Department of Pathology (CH), Medical College of Wisconsin, Milwaukee, Wisconsin; and Welch Center for Prevention, Epidemiology and Clinical Research (TS), Johns Hopkins Medical Institutions, Baltimore, Maryland.
Medicine (Baltimore). 2011 Sep;90(5):296-302. doi: 10.1097/MD.0b013e31822f238e.
Polyomavirus-associated nephropathy (PVAN) is an increasing cause of renal allograft dysfunction, but the optimal management of immunosuppression for these patients is unclear. We examined the clinical course of 58 patients with biopsy-proven PVAN diagnosed from 1997 to 2008 at Johns Hopkins Medical Institutions. Immunosuppression management was analyzed as 2 different immunosuppression reduction strategies, the first centered on eliminating a single immunosuppressive drug and reducing the doses of all other immunosuppressive drugs (Strategy A, n = 40), compared with the second, centered on reducing the doses of all immunosuppressive drugs and eliminating none (Strategy B, n = 18). Primary outcome was graft failure, defined as a 50% reduction in estimated glomerular filtration rate, or the need for dialysis within 2 years of PVAN diagnosis. Graft failure developed in 17 (29%) patients during follow-up. In unadjusted and adjusted Cox models, both strategies of immunosuppression reduction had similar efficacy in preventing graft failure (hazard ratio [HR], 0.61; 95% confidence interval, 0.18-2.06; p = 0.43). Rejection after PVAN occurred in 24 of 58 patients and was associated with a 3-fold higher risk of graft failure (HR, 2.99; p = 0.005). Ancillary therapies (cidofovir or leflunomide) were associated with a trend toward faster clearance of viremia (p = 0.65) but were not predictive of outcome.In conclusion, the 2 strategies of immunosuppression reduction had similar efficacy in preventing graft failure. Post-PVAN rejection leads to graft failure. Early repeat allograft biopsy should be considered in the management of PVAN with persistent graft dysfunction.
多瘤病毒相关性肾病（PVAN）是导致肾移植功能障碍的一个日益常见的原因，但这些患者免疫抑制的最佳管理尚不明确。我们研究了1997年至2008年在约翰霍普金斯医疗机构经活检证实为PVAN的58例患者的临床病程。免疫抑制管理被分析为两种不同的免疫抑制减量策略，第一种以停用单一免疫抑制药物并减少所有其他免疫抑制药物的剂量为中心（策略A，n = 40），与之相比，第二种以减少所有免疫抑制药物的剂量且不停用任何药物为中心（策略B，n = 18）。主要结局为移植失败，定义为估计肾小球滤过率降低50%，或在PVAN诊断后2年内需要透析。随访期间17例（29%）患者发生了移植失败。在未校正和校正的Cox模型中，两种免疫抑制减量策略在预防移植失败方面具有相似的疗效（风险比[HR]，0.61；95%置信区间，0.18 - 2.06；p = 0.43）。58例患者中有24例在PVAN发生后出现排斥反应，且与移植失败风险高3倍相关（HR，2.99；p = 0.005）。辅助治疗（西多福韦或来氟米特）与病毒血症清除更快的趋势相关（p = 0.65），但不能预测结局。总之，两种免疫抑制减量策略在预防移植失败方面具有相似的疗效。PVAN后排斥反应导致移植失败。对于持续存在移植功能障碍的PVAN患者，应考虑早期重复进行移植肾活检。
