Incidence Of BK Virus Nephropathy Research Articles

The Impact of Screening for BK Virus Infection on the Incidence of BK Virus Nephropathy in Kidney Transplant Recipients: A Single-center Experience

Introduction: Kidney allograft survival has increased significantly in the past few decades. However, the more potent immunosuppression has also resulted in a higher incidence of infections including BK virus nephropathy (BKVN). The profile of kidney transplant (KT) recipients including age, basic kidney disease, comorbidities, dialysis vintage, and type of kidney donor in India is different from that of high-income countries. There are very few studies on the incidence and outcomes of BKVN from India. We studied the incidence, clinical features, and the impact of a screening strategy on patients with BKVN at our center. Materials and Methods: This was a single-center retrospective record-based study. We screened the medical records of all KT recipients at our center from March 2012 to December 2020 for patients who were diagnosed with BKVN. We compared the incidence of BKVN before and after the implementation of a proactive screening strategy in 2017. Results: From March 2012 to December 2020, a total of 212 KTs were performed at our center. Twenty-eight patients were diagnosed to have BKVN at this time. The incidence of BKVN in our study was 13.2%. The incidence of BKVN before routine screening was initiated at our center was 11.3% whereas it was 13.6% after routine screening was initiated. Graft loss from BKVN was 7.14%. Conclusion: The incidence of BKVN at our center is higher than previously reported in India; however, the rate of graft loss is low. A proactive screening strategy using nucleic acid test may allow early detection of BKVN and may have a beneficial impact on graft outcomes.

MP37-15 DETECTION OF DECOY CELLS IN SIX MONTHS OR MORE ON URINARY CYTOLOGY EFFICIENTLY AND COST-EFFECTIVELY PREDICTS BK VIRUS NEPHROPATHY IN RENAL TRANSPLANT RECIPIENTS

You have accessJournal of UrologyRenal Transplantation & Vascular Surgery I (MP37)1 Sep 2021MP37-15 DETECTION OF DECOY CELLS IN SIX MONTHS OR MORE ON URINARY CYTOLOGY EFFICIENTLY AND COST-EFFECTIVELY PREDICTS BK VIRUS NEPHROPATHY IN RENAL TRANSPLANT RECIPIENTS Takanori Sekito, Motoo Araki, Kasumi Yoshinaga, Syogo Watari, Yuki Maruyama, Takuya Sadahira, Shingo Nishimura, Koichiro Wada, Tomoko Sako, Kohei Edamura, Yasuyuki Kobayashi, Masami Watanabe, Toyohiko Watanabe, Hiroyuki Yanai, and Yasutomo Nasu Takanori SekitoTakanori Sekito More articles by this author , Motoo ArakiMotoo Araki More articles by this author , Kasumi YoshinagaKasumi Yoshinaga More articles by this author , Syogo WatariSyogo Watari More articles by this author , Yuki MaruyamaYuki Maruyama More articles by this author , Takuya SadahiraTakuya Sadahira More articles by this author , Shingo NishimuraShingo Nishimura More articles by this author , Koichiro WadaKoichiro Wada More articles by this author , Tomoko SakoTomoko Sako More articles by this author , Kohei EdamuraKohei Edamura More articles by this author , Yasuyuki KobayashiYasuyuki Kobayashi More articles by this author , Masami WatanabeMasami Watanabe More articles by this author , Toyohiko WatanabeToyohiko Watanabe More articles by this author , Hiroyuki YanaiHiroyuki Yanai More articles by this author , and Yasutomo NasuYasutomo Nasu More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002046.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: BK virus nephropathy (BKVN) is one of the important causes of graft loss after kidney transplantation (KT). This study analyzed the association between the duration of positive decoy cells in urine cytology and BKVN. METHODS: Totally, 121 kidney transplant recipients were retrospectively evaluated. Urine cytology was routinely monitored every month during first 6 months after KT, every 1 to 2 months during second 6 months, every 1 to 3 months afterward. The best duration of consecutive presence of decoy cells to predict BKVN was analyzed by calculating the area under the curve (AUC) among each duration, and recipients were divided into two groups based on the best predictive performance. The effectiveness of SV40 immunostaining on urinary cytology was also analyzed. RESULTS: In total, 2,534 urine specimens, and 2,241 SV40 immunostaining for urine specimens were analyzed. The six consecutive months of decoy cells had best predictive performance in BKVN (AUC = 0.819). Recipients were divided into two groups based on the six or more consecutive months of decoy cells (decoy ≥ 6M, n=47) or less than six months (decoy < 6M, n=74). The incidence of BKVN in decoy ≥ 6M had significantly higher than those in decoy < 6M (5 vs 0, p = 0.008). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) to predict BKVN by detecting decoy cells was 100%, 64%, 11% and 100% respectively. SV40 immunostaining provided slightly better specificity (68%) and PPV (12%) with equivalent sensitivity (100%) and NPV (100%) (Table 1). The monthly screening by decoy cells can annually save U.S. $256,520 in 121 patients (U.S. $2,120 per patient) compared to the monthly screening by plasma quantitative PCR, and U.S. $55,660 in 121 patients (U.S. $460 per patient) compared to the monthly screening by urinary SV40 immunostaining. CONCLUSIONS: The detection of decoy cells in six months or more on urine cytology can predict BKVN efficiently and cost-effectively in KT recipients. SV40 immunostaining on urine cytology adds minimal effectiveness. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e652-e652 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takanori Sekito More articles by this author Motoo Araki More articles by this author Kasumi Yoshinaga More articles by this author Syogo Watari More articles by this author Yuki Maruyama More articles by this author Takuya Sadahira More articles by this author Shingo Nishimura More articles by this author Koichiro Wada More articles by this author Tomoko Sako More articles by this author Kohei Edamura More articles by this author Yasuyuki Kobayashi More articles by this author Masami Watanabe More articles by this author Toyohiko Watanabe More articles by this author Hiroyuki Yanai More articles by this author Yasutomo Nasu More articles by this author Expand All Advertisement Loading ...

Presence of decoy cells for 6months on urine cytology efficiently predicts BK virus nephropathy in renal transplant recipients.

To investigate the association between duration of consecutive presence of decoy cells on urine cytology and BK virus nephropathy after kidney transplantation. In total, 121 kidney transplant recipients were retrospectively evaluated. The best duration of consecutive presence of decoy cells that could be used to predict BK virus nephropathy was analyzed using the area under the curve for each duration, and recipients were divided into two groups based on the best predictive performance. The effectiveness of SV40 immunostaining on urinary cytology was also analyzed. In total, 2534 urine specimens as well as SV40 immunostaining in 2241 urine specimens were analyzed. Six consecutive months of decoy cell positivity had the best predictive performance for BK virus nephropathy (area under the curve=0.832). The incidence of BK virus nephropathy in recipients with positive decoy cells for 6months or more consecutive months (5/44) was significantly higher than in those who had positive decoy cells for less than 6months (0/77; P=0.005). Decoy cell positivity had a sensitivity, specificity, positive predictive value, and negative predictive value for BK virus nephropathy of 100%, 66%, 11%, and 100% respectively. SV40 immunostaining provided slightly better specificity (68%) and positive predictive value (12%). The detection of decoy cells at 6months or more on urine cytology had high predictive value for BK virus nephropathy in kidney transplant recipients. SV40 immunostaining on urine cytology added minimal diagnostic accuracy.

Infectious Complications of Induction Therapies in Kidney Transplantation.

BackgroundCytomegalovirus (CMV) and BK virus (BKV) are post-transplant opportunistic viral infections that affect patient and graft survival. This study was designed to evaluate the risk of BKV nephropathy and CMV disease in kidney transplant recipients who received induction therapy with ATG or basiliximab.Material/MethodsWe retrospectively analyzed information on 257 adult patients who underwent kidney transplantation between January 2007 and 2017. Patients were categorized into 3 groups according to the induction therapies. The primary endpoint was the onset of CMV disease or biopsy-confirmed BKV nephropathy. The secondary endpoints were biopsy-proven rejection episodes, graft loss, loss to follow-up, and death.ResultsWe followed 257 patients for a median of 55.5 months. The incidence of CMV disease was significantly higher in the only ATG group compared to the group without induction treatment (p<0.001). There was no significant difference in the incidence of BKV nephropathy among groups (p>0.05). The dosage of ATG (OR, 10.685; 95% CI, 1.343 5 to 85.009; P=0.025) was independent risk factor for death.ConclusionsThis study demonstrated that a higher dosage of ATG in high-risk patients is associated with an increased risk of CMV disease and patient death, also, reducing the dosage may be a rational strategy for increasing graft and patient’s survival.

Higher Incidence of BK Virus Nephropathy in Pediatric Kidney Allograft Recipients with Alport Syndrome.

A retrospective review was performed to assess the risk factors and outcomes of BK virus infection and nephropathy (BKVN), an early complication in pediatric kidney allograft recipients. The study investigated the incidence, risk factors, and clinical outcomes of BK viremia and BKVN in a Korean population of pediatric patients who received renal transplantation from 2001–2015 at the Seoul National University Hospital. BKVN was defined as biopsy-proven BKVN or plasma BK viral loads >10,000 copies/mL for >3 weeks. BK viremia was defined as a BK viral load >100 copies/mL in blood. Among 168 patients assessed for BK virus status, 30 patients (17.9%) tested positive for BK viremia at a median of 12.6 months after transplantation. BKVN was diagnosed in six patients (3.6%) at a median of 13.4 months after transplantation. Three of the six BKVN patients had Alport syndrome (p = 0.003), despite this disease comprising only 6% of the study population. Every patient with BK viremia and Alport syndrome developed BKVN, while only 11.1% of patients with BK viremia progressed to BKVN in the absence of Alport syndrome. Multivariate analysis revealed that Alport syndrome was associated with BKVN development (hazard ratio 13.2, p = 0.002). BKVN treatment included the reduction of immunosuppression, leflunomide, and intravenous immunoglobulin. No allografts were lost in the two years following the diagnosis of BKVN. In summary, the incidence of BKVN in pediatric kidney allograft recipients was similar to findings in previous reports, but was higher in patients with underlying Alport syndrome.

Evaluation of Renal Biopsies for BK Virus Nephropathy in Non-Renal Transplant Immunosuppressed Patients

Correspondence Address: Ebru GOk Oguz Diskapi Yildirim Beyazit Egitim ve Arastirma Hastanesi, Nefroloji Bolumu, Ankara, Turkey Phone : + 90 312 341 03 00 E-mail : ebrugokoguz@hotmail.com Received : 01.11.2015 Accepted : 21.11.2015 ABstrACt OBJeCtIVe: Although BK virus nephropathy (BKVN) has mostly been reported to occur in transplanted kidneys, there has been a gradual increase in cases of BKVN in the native kidney. This study was directed towards investigating the incidence of BKVN in patients undergoing renal biopsy due to acute kidney injury (AKI) who were also immunosuppressed due to a condition other than organ transplantation. MAterIAl and MethOds: Out of the 1223 patients undergoing renal biopsy for various conditions between January 2001 and January 2013, 52 patients who underwent a biopsy for AKI and were immunosuppressed at the time of the biopsy were included into the study. After renal biopsies of all patients were reevaluated, all biopsy specimens were exposed to immunohistochemical staining for SV40 antibody. results: Of the 52 patients, 29 had primary glomerulonephritis, 18 had secondary glomerulonephritis and 5 had a malignancy. All patients except one case of acute lymphoblastic leukemia and one case of non-Hodgkin lymphoma were immunosuppressed due to immunosuppressive therapy. None of the patients had any signs of BKVN on immunohistochemical staining of renal biopsy specimens. COnClusIOn: Failure to detect BKVN in this study may be because BKV causes gradual impairment of renal functions and the sample did not include patients frequently observed to have BKVN in the native kidney. keY wOrds: Acute kidney injury, BK virus nephropathy, Immunosuppression, Renal biopsy, Renal transplantation, SV40 antibody

BK virus nephropathy in simultaneous pancreas kidney transplant: a potentially preventable cause of kidney allograft loss

More than half of the simultaneous pancreas kidney transplant (SPK) patients afflicted with BK virus nephropathy (BKVN) lose their kidney allograft. Fear of pancreatic rejection limits the ability to reduce immunosuppression; this may result in inadequate treatment of BKVN. This single-center retrospective review included 138 SPK patients who underwent periodic BKV screening and were managed with IS reduction alone as a treatment of choice for BKVN. All patients underwent rabbit anti-thymocyte globulin (rATG) induction and were maintained on tacrolimus/sirolimus or mycophenolate. The incidence of BKVN was 4.4%. BKVN was diagnosed at a median of 11 months; mean serum creatinine 2.1 mg/dL and the geometric mean BK serum viral load at diagnosis 1,758,000 DNA copies/mL. Median time to BKV clearance was 5.6 months; there was 96% reduction in the mycophenolate dose, 100% reduction in sirolimus, and 40% reduction in the tacrolimus blood level at BKVN clearance. No BKVN-related kidney failure was noted, and patients retained excellent kidney and pancreatic allograft function till last follow-up (43 months). BKVN in SPK is a potentially preventable cause of end-stage kidney disease, and IS reduction alone is an acceptable treatment modality in SPK without a higher risk of kidney/pancreas allograft loss as long as close monitoring can be ensured.

9 Incidence of BK Virus Nephropathy in HIV Positive Renal Transplant Patients

INCIDENCE OF BK VIRUS NEPHROPATHY IN HIV POSITIVE RENAL TRANSPLANT PATIENTS Irfan Ahmed, Dwight Matthew, Satyam Arora, Gary Xiao, Gregory Malat, Alden Doyle, Karthik Ranganna BK virus has been associated with kidney dysfunction by causing tubulointerstitial nephritis and ureteral stenosis in kidney transplant recipients. BK virus nephropathy has been reported to be seen in about 1-10% in non HIV kidney transplant recipients. Incidence of BK virus nephropathy in HIV positive recipients of kidney transplants has not been well characterized. To examine the incidence of BK virus nephropathy in HIV renal transplant recipients. We conducted a retrospective chart review on HIV patients who have received kidney transplant at our institution. A total of 92 HIV patients have received kidney transplants at our institution since 2001. All our HIV positive transplant recipients received induction therapy with basiliximab and were given cyclosporine based immunosuppressive regimen. BK virus urine and plasma BK virus PCRs were checked when there was clinical suspicion of BK nephropathy. SV 40 staining was performed on renal biopsies when there were signs of BK nephropathy. Mean age of recipients was 47 ± 8 yrs, 87% were males, 88% were African-Americans, 91% kidneys were from deceased donors out of which 14% were from extended criteria donors. Delayed graft function was seen in 39% of patients. 72% patients had acute rejection during the follow up, out of these 14% had humoral rejection. 32 patients had SV 40 staining performed on their renal biopsies and none of them had positive results. 9 patients had BK virus plasma PCR checked of which 1 patient had positive PCR (32743 copies/mL), same patient had positive in situ DNA hybridization test positive on renal biopsy confirming BK nephropathy. We found an overall incidence of BK nephropathy of 1.08% which is lower than the reported incidence of BK nephropathy in non HIV kidney transplant recipients. This finding in conjunction with high rate of acute rejection (72%) in these patients reflects that these patients received less aggressive immunosuppressive therapy or may have less risk of BK nephropathy.

Calcineurin-Inhibitor-Free Immunosuppression Based on the JAK Inhibitor CP-690,550: A Pilot Study in De Novo Kidney Allograft Recipients

This randomized, pilot study compared the Janus kinase inhibitor CP-690,550 (15 mg BID [CP15] and 30 mg BID [CP30], n = 20 each) with tacrolimus (n = 21) in de novo kidney allograft recipients. Patients received an IL-2 receptor antagonist, concomitant mycophenolate mofetil (MMF) and corticosteroids. CP-690,550 doses were reduced after 6 months. Due to a high incidence of BK virus nephropathy (BKN) in CP30, MMF was discontinued in this group. The 6-month biopsy-proven acute rejection rates were 1 of 20, 4 of 20 and 1 of 21 for CP15, CP30 and tacrolimus groups, respectively. BKN developed in 4 of 20 patients in CP30 group. The 6-month rates of cytomegalovirus disease were 2 of 20, 4 of 20 and none of 21 for CP15, CP30 and tacrolimus groups, respectively. Estimated glomerular filtration rate was >70 mL/min at 6 and 12 months (all groups). NK cells were reduced by </=77% in CP-690,550-treated patients. In the CP-690,550 arms, there were modest lipid elevations and a trend toward more frequent anemia and neutropenia during the first 6 months. These data suggest that coadministration of CP-690,550 30 mg BID with MMF is associated with overimmunosuppression. At 15 mg BID, the efficacy/safety profile was comparable to the tacrolimus control group, excepting a higher rate of viral infection. Further dose-ranging evaluation of CP-690,550 is warranted.

Obstruction or renal allograft rejection--potential clinical markers of BK virus nephropathy

Sir, BK virus (BKV)-associated nephropathy in renal transplant recipients is an emerging cause of allograft dysfunction and transplant loss.1,,2 BKV is a human polyomavirus which is a member of the Papovaviridae family. These are non-enveloped viruses of small virion size with a closed, circular double DNA-stranded genome.3 Polyomaviruses are ubiquitous in nature and were first isolated from the urine of a renal transplant patient who developed ureteral stenosis post-operatively.3 Up to 80% of adults are seropositive for BKV with the virus subsequently remaining dormant in the uroepithelium. The majority of primary infections are asymptomatic or minimally symptomatic. The incidence of BKV nephropathy among renal transplant recipients is as high as 5%.1 The majority of infections occur within the first 3 months after transplant; however, infections occurring >2 years after transplantation have been reported.4 BKV disease is associated with haemorrhagic and non-haemorrhagic cystitis, ureteric stenosis and tubulointerstitial nephritis.4 Between 30% and 50% of patients with BKV nephropathy develop progressive renal dysfunction leading to eventual allograft loss.5 The risk factors for BKV are not known but it is suggested to be a disease associated with modern day immunosuppression. Apart from the histopathological likeness to acute rejection and hence misdiagnosis, BKV infection can also manifest as ureteric stenosis during the early post-transplant period.1 Reduction in immunosuppression has yielded varying results and evidence with cidofovir and ciprofloxacin are promising.4–8 We report two cases of BKV in renal transplant patients to highlight important teaching points in BKV nephropathy. The first patient was treated for ureteric stenosis and was later diagnosed to have BKV nephropathy resulting in graft loss despite the use of cidofovir and the other developed chronic allograft nephropathy (CAN), which stabilized with immunosuppression reduction. ### Case 1 A 53-year-old female with end stage kidney disease …

Efficacy and safety of universal valganciclovir prophylaxis combined with a tacrolimus/mycophenolate-based regimen in kidney transplantation.

Immunosuppressive and antiviral prophylactic drugs are needed to prevent acute rejection and infection after transplantation. We assessed the efficacy and safety of the introduction of universal valganciclovir prophylaxis in combination with a tacrolimus/mycophenolate-based regimen in kidney transplantation at our centre. We reviewed all consecutive patients who underwent kidney transplantation over a 5.5-year period. Patients transplanted from January 2000 to March 2003 (period 1) were compared to patients from April 2003 to July 2005 (period 2). In period 1 patients were treated with basiliximab, cyclosporine, steroids and mycophenolate (or azathioprine). Prophylaxis with valacyclovir was prescribed in cytomegalovirus (CMV) D+/R- patients, while any R+ patients were managed with a preemptive approach. In period 2, immunosuppression consisted of basiliximab or thymoglobulin induction, tacrolimus, steroids and mycophenolate. Three-month CMV prophylaxis with valganciclovir was used in all at-risk patients. Data analysis included 73 patients (period 1) and 70 (period 2). Acute rejection was more frequent in period 1 than in period 2 (42% vs 7%, p <0.001). Overall, 30% of patients in period 1 were diagnosed with CMV infection/disease requiring antiviral treatment, compared with 11.4% in period 2 (p = 0.003). Late-onset CMV disease remained a problem in D+/R- patients in both periods. There was no difference in incidence of BK virus nephropathy, fungal infections, PTLD, graft loss or mortality. However, 4 cases (5.7%) of delayed transient asymptomatic agranulocytosis were observed in period 2. The present analysis indicates that the combined regimen introduced in period 2 improved clinical results with a significant decrease in acute rejection and in CMV infection/disease incidence. However, a unique syndrome of delayed transient agranulocytosis probably due to drug myelotoxicity was observed in a subset of patients.

Infectious complications in organ transplant recipients with the use of calcineurin-inhibitor agent-based immunosuppressive regimens

The rates and types of infections associated with conventional immunosuppression regimens comprising calcineurin-inhibitor agents, tacrolimus, and cyclosporine could be used to compare similar data with the use of novel immunosuppressive regimens in organ transplant recipients. Tacrolimus appears to be superior to cyclosporine in preventing rejection. The frequency and spectrum of infections in organ transplant recipients does not appear to be notably modified by the choice of calcineurin-inhibitor agents per se. A higher risk of cytomegalovirus and poorer outcomes associated with hepatitis C virus with cyclosporine in some studies may be related to a greater requirement of adjunctive immunosuppression with cyclosporine-based regimens. Potent immunosuppression with tacrolimus, however, particularly when combined with mycophenolate mofetil, is believed to be a significant contributor to a higher incidence of BK virus nephropathy in renal transplant recipients in recent years. Calcineurin-inhibitor agents possess in-vitro activity against a number of fungal pathogens. In the clinical setting, however, the immunosuppressive effect outweighs their antifungal activity. Calcineurin inhibitor-based regimens have been the mainstay of immunosuppression after organ transplantation for almost two decades. However, suboptimal long-term outcomes in transplant recipients have led to a growing interest in the use of calcineurin inhibitor agent-sparing regimens. Whether novel immunosuppressive agents with a more selective mechanism of action would lead to a further reduction in the risk of posttransplant infections remains to be discerned.

Polymerase chain reaction for the diagnosis of human polyomavirus-associated nephropathy in renal transplant recipients

Human polyomavirus type BK may be related to interstitial nephropathy or renal-allograft dysfunction. Patients with nephropathy due to infection with human polyomavirus may be identified early using the polymerase chain reaction(PCR). We attempted to evaluate whether the positive response in the PCR test of BK virus DNA in the plasma of renal transplant recipients affects the function of the renal allograft. Seventy-seven patients were prospectively analyzed according to the operative sex, age, sources of allograft, serum creatinine levels during PCR test for BK virus, postoperative type of immunosuppressant, and presence of graft rejection. Two groups were distinguished according to the PCR result for BK virus: group 1 ( n = 12) positive PCR reaction and group 2 ( n = 65) negative reaction. The mean follow-up was 32.6 weeks. The incidence of positive PCR tests for BK virus replication after renal transplantation was 15.6%. Decoy cells in the urine were detected in 20.7%. The incidence of BK virus nephropathy was 1.3%. The mean serum creatinine levels of group 1 and 2 at the time of the PCR tests were 1.34 and 1.22, respectively. The rejection rates in group 1 and 2 were 8% and 4.5%, respectively ( P > .05). We consider that a PCR assay to detect BK virus in renal recipients blood may be useful to identify patients at risk for nephropathy. It may serve as a noninvasive indicator of BK virus replication, although this study is limited by the short follow-up and small numbers.