The Influence of Polyomavirus Infected Glomerular Cells on the Development of Glomerulopathy and the Graft Survival

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IntroductionThe diagnosis of polyomavirus nephropathy (PVN) based on SV-40 positive nuclear staining of tubular cells in allograft biopsies. However, the importance of SV-40 positive parietal cells in glomeruli is unknown. The aim of this study is two-fold; first to evaluate the relationship between the histopathological findings such as the development of glomerulopathy with glomerular SV-40 expression, second to understand the impact of glomerular polyomavirus (GPV) involvement to the graft survival.Materials and MethodsAmong 878 renal transplant patients, 98 recipients (11,2%) had sustained BKV viremia. However, only 71 patients (8%) developed biopsy proved PVN. All indication and follow-up biopsies of 71 patients (M/F: 57/14) with a mean age of 32.6±16.5 years re-evaluated. Follow-up biopsies examined for the development of interstitial fibrosis (IF) and glomerulopathy (GP). Interstitial plasma cells, neutrophil leukocytes and CD3, CD4, CD8 positive lymphocytes and CD68 positive macrophages graded. Patients separated into 2 groups based on glomerular parietal cell SV-40 positivity. Group 1 patients had SV-40+ parietal cells, and Group 2 patients had SV-40- parietal cells.ResultsThe mean interval between the diagnosis of PVN and transplant was 17,2±22,7 months. At the same time with PVN, CMV viremia was found in 27 patients. Tubular SV-40 was positive in 46 cases (64,8%). Glomerular SV40 was positive in 20 cases (28.2%). Biopsies containing both cortex and medulla had a higher rate of SV-40 staining (p<.001).Thrombotic microangiopathy (TMA) found in 16 cases (22.5%). Total 39 cases (54.9%) had proteinuria during follow-up, and only 19 (26.7%) recipients developed GP, while 43 patients (60.6%) developed IF in follow-up biopsies. The mean viral load in urine and plasma at diagnosis was found higher in Group 1 than those Group 2 (p<.001). The mean creatinine at diagnosis and three to six months after PVN noted higher in Group 1 compared to Group 2 (p<.001). Compared to Group 2, the degree of the interstitial neutrophil, plasma, macrophage and lymphocyte infiltration found higher in Group 1 (p<.01). The presence of TMA, Stage C, Pvl 3, CMV viremia at the time of PVN found higher in Group 1 compared to Group 2 (p<.05). The rate of the development of GP and IF noted higher in Group 1 than those Group 2 (p=.001). Mean 35.8±27 months follow-up after PVN, rates of graft loss was higher in Group 1 (95%) than Group 2 (25.5%) (p<.001).ConclusionThe presence of the SV-40 positive parietal cells in glomeruli pointed out the poor prognosis for cases with PVN. Patients with GPV characterized by higher degrees of viral cytopathic nuclear changes (pvl3), higher degrees of interstitial inflammation, higher rates of GP and IF, hence higher incidence of graft loss. Thus it is essential to generate a different therapy schedule for patients with GPV.

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