Factors Influencing Graft Outcomes Following Diagnosis of Polyomavirus –Associated Nephropathy after Renal Transplantation

PLOS ONE, Dec 2019

Background Polyomavirus associated nephropathy (PVAN) is a significant cause of early allograft loss and the course is difficult to predict. The aim of this study is to identify factors influencing outcome for PVAN. Methods Between 2006 and 2014, we diagnosed PVAN in 48 (7.8%) of 615 patients monitored for BK virus every 1–4 weeks after modification of maintenance immunosuppression. Logistic or Cox regression analysis were performed to determine which risk factors independently affected clinical outcome and graft loss respectively. Results After 32.1±26.4 months follow-up, the frequencies of any graft functional decline at 1 year post-diagnosis, graft loss and any graft functional decline at the last available follow-up were 27.1% (13/48), 25.0% (12/48), and 33.3% (16/48), respectively. The 1, 3, 5 year graft survival rates were 100%, 80.5% and 69.1%, respectively. The mean level of serum creatinine at 1 year post-diagnosis and long-term graft survival rates were the worst in class C (p<0.05). Thirty-eight of 46 (82.6%) BKV DNAuria patients reduced viral load by 90% with a median time of 2.75 months (range, 0.25–34.0 months) and showed better graft survival rates than the 8 patients (17.4%) without viral load reduction (p<0.001). Multivariate logistic regression analysis showed that extensive interstitial inflammation (OR 20.2, p = 0.042) and delayed fall in urinary viral load (>2.75 months for >90% decrease) in urine (OR 16.7, p = 0.055) correlated with worse creatinine at 1 year post-diagnosis. Multivariate Cox regression analysis showed that extensive interstitial inflammation (HR 46988, p = 0.032) at diagnosis, and high PVAN stage (HR 162.2, p = 0.021) were associated with worse long-term graft survival rates. Conclusions The extent of interstitial inflammation influences short and long-term graft outcomes in patients with PVAN. The degree of PVAN, rate of reduction in viral load, and viral clearance also can be used as prognostic markers in PVAN.

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Factors Influencing Graft Outcomes Following Diagnosis of Polyomavirus –Associated Nephropathy after Renal Transplantation

November Factors Influencing Graft Outcomes Following Diagnosis of Polyomavirus - Associated Nephropathy after Renal Transplantation Gang Huang 0 1 Lin-wei Wu 0 1 Shi-Cong Yang 0 1 Ji-guang Fei 0 1 Su-xiong Deng 0 1 Jun Li 0 1 Guo-dong Chen 0 1 Qian Fu 0 1 Rong-hai Deng 0 1 Jiang Qiu 0 1 Chang-xi Wang 0 1 Li- zhong Chen 0 1 0 Editor: Stanislaw Stepkowski, University of Toledo, UNITED STATES 1 1 Department of Organ Transplantation, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, Guangdong , China , 2 Department of Pathology, The First Affiliated Hospital, Sun Yat-sen University , Guangzhou, Guangdong , China - After 32.1±26.4 months follow-up, the frequencies of any graft functional decline at 1 year post-diagnosis, graft loss and any graft functional decline at the last available follow-up were 27.1% (13/48), 25.0% (12/48), and 33.3% (16/48), respectively. The 1, 3, 5 year graft survival rates were 100%, 80.5% and 69.1%, respectively. The mean level of serum creatinine at 1 year post-diagnosis and long-term graft survival rates were the worst in class C (p<0.05). Thirty-eight of 46 (82.6%) BKV DNAuria patients reduced viral load by 90% with a median time of 2.75 months (range, 0.25–34.0 months) and showed better graft survival rates than the 8 patients (17.4%) without viral load reduction (p<0.001). Multivariate logistic regression analysis showed that extensive interstitial inflammation (OR 20.2, p = 0.042) and delayed fall in urinary viral load (>2.75 months for >90% decrease) in urine (OR 16.7, Polyomavirus associated nephropathy (PVAN) is a significant cause of early allograft loss and the course is difficult to predict. The aim of this study is to identify factors influencing outcome for PVAN. Between 2006 and 2014, we diagnosed PVAN in 48 (7.8%) of 615 patients monitored for BK virus every 1–4 weeks after modification of maintenance immunosuppression. Logistic or Cox regression analysis were performed to determine which risk factors independently affected clinical outcome and graft loss respectively. p = 0.055) correlated with worse creatinine at 1 year post-diagnosis. Multivariate Cox regression analysis showed that extensive interstitial inflammation (HR 46988, p = 0.032) at diagnosis, and high PVAN stage (HR 162.2, p = 0.021) were associated with worse longterm graft survival rates. The extent of interstitial inflammation influences short and long-term graft outcomes in patients with PVAN. The degree of PVAN, rate of reduction in viral load, and viral clearance also can be used as prognostic markers in PVAN. The human BK polyomavirus (BKV) can infect the majority of the population and subsequently remains dormant in the kidney without consequence. However, under conditions of immunosuppression, especially renal transplantation, reactivation, and replication, may occur, causing an interstitial nephritis in the renal allograft. Polyomavirus-associated nephropathy (PVAN) was first diagnosed in Pittsburgh in 1993 by Dr. Randhawa in a renal transplant recipient suspected of having acute rejection [1]. It has emerged as the most common infectious disease in the kidney allograft with an incidence of 2% to 10% [2]. PVAN progressively affects graft function and increases the risk of graft loss from <10% to more than 90% [3–6]. Given the small number of published interventional studies, the clinician is often faced with uncertainty in predicting the clinical outcome of the graft. Clinical factors reported to be associated with worse prognosis include deceased donor, female recipient, high serum creatinine at diagnosis, late diagnosis, and plasma peak viral load [7–9]. Although the biopsy findings at diagnosis are proposed to be a predictive tool for assessing prognosis [10, 11], the rate of BKV viral load reduction and clearance after modification of maintenance immunosuppression have generally not been predictive of outcome. To date, few studies have evaluated both the kinetics of BKV viral load and clinical variables to predict the outcome. In the current investigation, we used quantitative PCR for BKV DNA load in urine and plasma and quantitative urine cytology to evaluate BKV infection in kidney transplant (KTx) recipients who received renal graft biopsies concurrently to identify PVAN. Moreover, we followed up PVAN patients after modification of maintenance immunosuppression to observe the clinical course hoping to identify prognostic variables of PVAN. Materials and Methods Patient selection From March 2006 to August 2014, 615 renal transplant recipients at our institution who underwent an allograft biopsy with an immunohistochemistry assay for polyomavirus were screened for BKV reactivation concomitantly, which consisted of urine cytological evaluation and quantitative PCR of both urine and plasma for BKV DNA. Forty-eight kidney transplant (KTx) recipients diagnosed with definitive PVAN were included in this study. Study approval was obtained from the Ethics Committee o (...truncated)


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Gang Huang, Lin-wei Wu, Shi-Cong Yang, Ji-guang Fei, Su-xiong Deng, Jun Li, Guo-dong Chen, Qian Fu, Rong-hai Deng, Jiang Qiu, Chang-xi Wang, Li-zhong Chen. Factors Influencing Graft Outcomes Following Diagnosis of Polyomavirus –Associated Nephropathy after Renal Transplantation, PLOS ONE, 2015, 11, DOI: 10.1371/journal.pone.0142460