Abstract：
OBJECTIVE: We investigated the efficacy of a predetermined protocol that consisted of immunosuppressive drug reduction/withdrawal and intravenous immunoglobulin administration for the treatment of polyoma BK virus nephropathy.
METHODS: Patients with biopsy-proven polyoma BK virus nephropathy received a treatment regimen based on discontinuation of both calcineurin inhibitors and antiproliferative agents and switching to mTOR inhibitors accompanied by intravenous immunoglobulin administration.
RESULTS: Our study included 508 patients, with polyoma BK viremia detected in 80 patients. The mean age was 45.3 ± 9.5 years (range, 18-71 y), 64% were male, and mean follow-up was 37 ± 21 months (6-94 mo). All 16 patients who developed polyoma BK virus nephropathy and 9 patients who had highgrade polyoma BK viremia without nephropathy received intravenous immunoglobulin treatment. Compared with patients with viremia, patients with polyoma BK virus nephropathy had significantly higher rates of graft loss due to rejection (18.8% vs 1.6%; P = .024) and all-cause graft loss (31.2% vs 6.3%; P = .014). Histopathologically, viral inclusion bodies disappeared and SV40 became negative after treatment in all 13 patients who underwent protocol biopsies. Unfortunately, histopathologically complete recovery without chronic tubular and interstitial tissue damage was achieved in only 4 patients after treatment. In addition, 3 patients lost their grafts due to acute antibody-mediated or mixed-type rejection (18.8%).
CONCLUSIONS: In patients with polyoma BK virus nephropathy, clearance of viremia and SV40 should not be the sole outcomes to obtain. Aggressive reductions in maintenance immunosuppression and switching to double-drug therapy combined with high-dose intravenous immunoglobulin leads to high rates of graft loss/rejection and sequalae of chronic histological changes.
METHODS: Patients with biopsy-proven polyoma BK virus nephropathy received a treatment regimen based on discontinuation of both calcineurin inhibitors and antiproliferative agents and switching to mTOR inhibitors accompanied by intravenous immunoglobulin administration.
RESULTS: Our study included 508 patients, with polyoma BK viremia detected in 80 patients. The mean age was 45.3 ± 9.5 years (range, 18-71 y), 64% were male, and mean follow-up was 37 ± 21 months (6-94 mo). All 16 patients who developed polyoma BK virus nephropathy and 9 patients who had highgrade polyoma BK viremia without nephropathy received intravenous immunoglobulin treatment. Compared with patients with viremia, patients with polyoma BK virus nephropathy had significantly higher rates of graft loss due to rejection (18.8% vs 1.6%; P = .024) and all-cause graft loss (31.2% vs 6.3%; P = .014). Histopathologically, viral inclusion bodies disappeared and SV40 became negative after treatment in all 13 patients who underwent protocol biopsies. Unfortunately, histopathologically complete recovery without chronic tubular and interstitial tissue damage was achieved in only 4 patients after treatment. In addition, 3 patients lost their grafts due to acute antibody-mediated or mixed-type rejection (18.8%).
CONCLUSIONS: In patients with polyoma BK virus nephropathy, clearance of viremia and SV40 should not be the sole outcomes to obtain. Aggressive reductions in maintenance immunosuppression and switching to double-drug therapy combined with high-dose intravenous immunoglobulin leads to high rates of graft loss/rejection and sequalae of chronic histological changes.
摘要：
目的：我们研究了预定方案的疗效，该方案包括免疫抑制药物减少/停药和静脉注射免疫球蛋白治疗多瘤性BK病毒肾病。
方法：活检证实为多瘤性BK病毒肾病的患者接受了基于停用钙调磷酸酶抑制剂和抗增殖药并转换为mTOR抑制剂并伴有静脉免疫球蛋白给药的治疗方案。
结果：我们的研究包括508名患者，在80例患者中检测到多瘤性BK病毒血症。平均年龄为45.3±9.5岁(范围，18-71y)，64%是男性，平均随访37±21个月(6～94个月)。所有16例发展为多瘤性BK病毒肾病的患者和9例无肾病的高度多瘤性BK病毒血症的患者均接受了静脉注射免疫球蛋白治疗。与病毒血症患者相比，多瘤性BK病毒肾病患者由于排斥反应(18.8%vs1.6%;P=.024)和全因移植物丢失(31.2%vs6.3%;P=.014),移植物丢失率显著较高.组织病理学,在接受方案活检的所有13例患者中,病毒包涵体消失,SV40在治疗后变为阴性.不幸的是,治疗后仅有4例患者在组织病理学上完全恢复，无慢性肾小管和间质组织损伤。此外,3例患者由于急性抗体介导或混合型排斥反应而失去移植物（18.8％）。
结论：在多瘤性BK病毒肾病患者中，病毒血症和SV40的清除不应该是获得的唯一结果。维持免疫抑制的积极减少和改用双重药物治疗与大剂量静脉注射免疫球蛋白相结合会导致移植物丢失/排斥反应和慢性组织学变化的后遗症率很高。
方法：活检证实为多瘤性BK病毒肾病的患者接受了基于停用钙调磷酸酶抑制剂和抗增殖药并转换为mTOR抑制剂并伴有静脉免疫球蛋白给药的治疗方案。
结果：我们的研究包括508名患者，在80例患者中检测到多瘤性BK病毒血症。平均年龄为45.3±9.5岁(范围，18-71y)，64%是男性，平均随访37±21个月(6～94个月)。所有16例发展为多瘤性BK病毒肾病的患者和9例无肾病的高度多瘤性BK病毒血症的患者均接受了静脉注射免疫球蛋白治疗。与病毒血症患者相比，多瘤性BK病毒肾病患者由于排斥反应(18.8%vs1.6%;P=.024)和全因移植物丢失(31.2%vs6.3%;P=.014),移植物丢失率显著较高.组织病理学,在接受方案活检的所有13例患者中,病毒包涵体消失,SV40在治疗后变为阴性.不幸的是,治疗后仅有4例患者在组织病理学上完全恢复，无慢性肾小管和间质组织损伤。此外,3例患者由于急性抗体介导或混合型排斥反应而失去移植物（18.8％）。
结论：在多瘤性BK病毒肾病患者中，病毒血症和SV40的清除不应该是获得的唯一结果。维持免疫抑制的积极减少和改用双重药物治疗与大剂量静脉注射免疫球蛋白相结合会导致移植物丢失/排斥反应和慢性组织学变化的后遗症率很高。
