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
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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)