移植技术与研究

Clinical and Pathological Study of Polyomavirus-Associated Nephropathy after Renal Transplantation

Abstract

JI Shu-ming, Xie Ke-nan, Chen Jin-song, Wen Ji-qiu, Cheng Dong-rui, LI xu, NI Xue-feng and Liu Zhi-hong

Polyomavirus infection has emerged as an important cause of polyomavirus-associated nephropathy (PVAN) leading to allograft dysfunction and loss. The aim of this study is to investigate pathological features and clinical characteristics of PVAN. We prospectively investigated 351 renal allografts performed in Jinling Hospital. PVAN was diagnosed by light microscopic examination and a positive immunohistochemistry staining of anti-SV40 large T antibody in a biopsy specimen. 31 patients were diagnosed with PVAN (8.8%). The patients with PVAN typically presented as allograft dysfunction with an asymptomatic rise in serum creatinine about 3 to 39 months posttransplant. Urinary decoy cells were positive in 4 patients (12.9%). The histologic changes of PVAN are not pathognomonic and can be mistaken for allograft rejection, i.e. tubulointerstitial nephritis with varying degrees of inflammatory infiltrates, tubulitis, tubular atrophy and fibrosis. Typical findings on histology are focal interstitial mononuclear inflammatory cell infiltrates, presence of plasma cells, necrotic tubular epithelium, and presence of homogenous intranuclear inclusion bodies. Immunohistochemistry with SV40 staining is positive in allograft. CD3, CD4, CD8, CD68 positive cells are increased in PVAN group than the non-PVAN group, but none of HLA-DR and IL-2R expression is positive in PVAN patients. MPA AUC 0-12 and TAC trough levels are increased in PVAN group than non-PVAN group at biopsy. We have treated 31 patients with biopsy-proven PVAN with leflunomide. Increased intensity of immunosuppression appears to increase the likelihood of PVAN. The definitive diagnosis of PVAN requires renal biopsy. Immunohistochemistry with SV40 staining has been used as an indirect method to document the presence of PVAN.