Saudi Journal of Kidney Diseases and Transplantation

: 2018  |  Volume : 29  |  Issue : 6  |  Page : 1366--1370

BK Virus nephropathy in living donor renal allograft recipients: An observational study from a large transplant center in India

Pallav Gupta1, Ashwani Gupta2, A. K. Bhalla1, Manish Malik1, Anurag Gupta1, Vinant Bhargava1, D. S. Rana1,  
1 Department of Histopathology, Sir Ganga Ram Hospital, New Delhi, India
2 Department of Nephrology, Sir Ganga Ram Hospital, New Delhi, India

Correspondence Address:
Dr. Pallav Gupta
Department of Histopathology, Sir Ganga Ram Hospital, New Delhi - 110 060


BK virus is a polyoma virus which remains in latent phase in the urinary tract, particularly in the renal tubular epithelial cells. In immunosuppressed patients, it is activated and manifests as tubule-interstitial nephritis causing renal allograft dysfunction. A total of 402 patients who underwent renal allograft biopsy from 2013 to 2016 were included in this study; six patients were diagnosed to have BK virus nephropathy. Histopathology showed ground glass intra-nuclear inclusions accompanied by acute tubular injury, interstitial inflammation, and varying degree of interstitial fibrosis and tubular atrophy. Patients were managed with reduction in the overall immunosuppression. Only one patient progressed to graft failure on follow-up. The overall prevalence of polyoma virus at our center is 1.49%.

How to cite this article:
Gupta P, Gupta A, Bhalla AK, Malik M, Gupta A, Bhargava V, Rana DS. BK Virus nephropathy in living donor renal allograft recipients: An observational study from a large transplant center in India.Saudi J Kidney Dis Transpl 2018;29:1366-1370

How to cite this URL:
Gupta P, Gupta A, Bhalla AK, Malik M, Gupta A, Bhargava V, Rana DS. BK Virus nephropathy in living donor renal allograft recipients: An observational study from a large transplant center in India. Saudi J Kidney Dis Transpl [serial online] 2018 [cited 2021 Sep 20 ];29:1366-1370
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The seroprevalence of BK virus nephropathy in the general adult population is up to 90%.[1] BK viral infection usually occurs in childhood and becomes latent in the renal tubular epithelial cells. It is reactivated in immuno-suppressed individuals.[2] In renal transplant recipients receiving immunosuppressive medication, BK virus nephropathy can be seen in the form of tubulointerstitial nephritis.[3] BK virus can be demonstrated in urine samples of up to 50% of renal transplant recipients three months after transplantation.[4],[5] Limited literature is available from the Asian subcontinent regarding the prevalence and histopathological features of BK virus nephropathy.

 Materials and Methods

Renal allograft biopsies were performed on 402 kidney transplant recipients from January 2013 to December 2016. The paraffin sections (2–3 μ) were stained with hematoxylin and eosin (HE), periodic acid–Schiff and periodic acid silver methanamine and assessed by light microscopy. The histological findings of renal allograft biopsies were evaluated using Banff 2013 diagnostic criteria.[6] Immunohistochemistry (IHC) for BK virus was performed using mouse monoclonal anti-SV40 large T-cell antigen-antibody (Clone MRQ-4, Cell Marque); IHC for cytomegalovirus and C4d was also performed in all the cases. The clinical, bio-chemical findings and polymerase chain reaction results were collected.


Out of a total of 402 renal allograft biopsies performed between January 2013 and December 2016, six cases were diagnosed as BK virus nephropathy on histopathology. The mean age of the patients was 50.6 ± 14.2 years. There were 289 males (71.8%). Basic renal disease before transplantation was, biopsy-proven chronic glomerulonephritis in 13 patients (3%), chronic interstitial nephritis in 17 patients (4%), focal and segmental glomerulo-sclerosis in two patients (0.04%) and two patients (0.04%) had autosomal dominant polycystic kidney disease. The remaining patients had an unknown cause for chronic kidney disease. All the six patients with BK virus nephropathy had received induction therapy with 3 mg/kg anti-thymocyte globulin and triple-drug immunosuppression with tacrolimus, mycophenolate and steroids. There was no evidence of prior acute rejection episode in any of the six patients. Mean serum creatinine at the time of biopsy was 2.13 ± 0.45 mg/dL. Average time from transplantation to detection of BK virus nephropathy on renal biopsy was 19.6 ± 10.4 months [Table 1]. Urinary polymerase chain reaction (PCR) was performed in five cases and was positive in all of them; the blood PCR for BK virus was performed in four cases, and all the four had tested positive. The renal biopsy showed acute tubular injury and interstitial lympho-plasmacytic infiltrate along with the presence of ground glass intranuclear inclusion (type I) within the tubular epithelial cells in all the patients [Figure 1]. Type III inclusion was seen in two cases whereas type IV inclusion was seen in only one case. In all but one case, interstitial fibrosis and tubular atrophy were seen (<50% of the cortex) suggestive of stage 2 disease. In patient number 5, no interstitial fibrosis or tubular atrophy was seen (stage 1 disease). However, there was accompanying mild tubulitis in five cases. Parietal epithelial cell proliferation along with intra-nuclear inclusions in these cells was seen in patients number 2 and 4. Detailed histopathological features are illustrated in [Table 2]. No glome-rulitis, peritubular capillaritis or intimal arte-ritis was seen in any of the cases. IHC for BK virus was performed in all the cases and all six patients showed nuclear positivity in the renal tubular epithelial cells [Figure 2]. Inpatient number 2 and 4, nuclear positivity for SV40 was also seen in the parietal epithelial cells lining of Bowman’s capsule. Immunohisto-chemistry for cytomegalovirus was negative in all the cases; C4d staining was also negative in all the cases. All the patients were managed by lowering the overall target serum concentration of tacrolimus (2–4 ng/mL) and with-drawing mycophenolate mofetil.{Table 1}{Figure 1}{Table 2}{Figure 2}

Postbiopsy follow-up of these six patients ranged from 4–33 months (mean 12.6 ± 11.7). Only one patient progressed to end-stage renal disease (patient number 2). His serum crea-tinine increased to 6.8 mg/dL at 33 months posttransplantation. The other patients had stable renal function after reduction of immu-nosuppression medication at up to 36 months posttransplantation.


BK virus is a DNA virus and a member of the polyomavirus family.[2] The common clinical manifestations of BK virus infection include transient renal dysfunction, BK virus-associated nephropathy, ureteric stenosis, and hemorrhagic cystitis.[1] BK virus-associated nephropathy may be accompanied by increased graft loss among renal transplant recipients.[3] Donor-related factors, such as deceased donor, female gender, high BK virus-specific anti-body titers, HLA mismatch and ischemia-reperfusion injury, are important risk factors associated with increased risk of development of BK virus nephropathy. One of the important risk factors in the posttransplant period is the high degree of immunosuppression. Others include ureteral stenosis, ureteral stent, diabetes mellitus, delayed graft dysfunction and cytomegalovirus infection.[7] In our study, there were four male and two female patients, all patients received live donor kidney transplantation and none of the patients had concurrent cytomegalovirus infection or delayed graft function. All the patients were on triple-drug immunosuppression with tacrolimus, predni-solone and mycophenolate mofetil with strict monitoring of serum tacrolimus levels (mean 7.9 + 1.8 ng/mL). BK virus nephropathy can occur in 1%–10% of renal allograft recipients and can result in graft loss in up to 50% of the affected patients.[8] In our study, the prevalence of BK virus nephropathy was just 1.49% which is much lower than previously published studies from India.[9],[10]

The reason for a lower incidence for BK virus nephropathy appears to be the protocol based immune monitoring through regular drug levels and lower level of immunosup-pression. Lower levels of immunosuppression were not associated with a high risk of rejection since all the donors were live related, and hence, had presumably better immune compatibility with their respective recipients. Detection of BK virus in the blood and urine correlated with the presence of BK virus nephropathy in the presence of graft dysfunction. Graft dysfunction and viremia seen in patients with BK virus nephropathy are secondary to necrosis of the tubular epithelial cells.[11],[12] Based on the extent of tubular injury, denudation of tubular basement membrane, interstitial inflammation and extent of interstitial fibrosis and tubular atrophy, polyoma-virus nephropathy can be divided into three Stages A, B, and C.[13],[14] The treatment of BK virus nephropathy includes reduction or modification in the immunosuppression received by the patient. Reduction in the target concentration of calcineurin inhibitors, conversion of tacrolimus to cyclosporine, replacement of cyclosporine with sirolimus or reduction in the dose of mycophenolate are found to be useful in treatment of these patients.[3],[7] Some studies have described the use of fluoroquinolones, anti-viral agents such as cidofovir, lefluno-mide, and intravenous immunoglobulin as an adjuvant therapy in the treatment of BK virus nephropathy.[15],[16] However, these results have not been validated by other researchers and reduction in the dose of immunosuppression forms the mainstay of treatment.


The prevalence of BK virus-associated nephro-pathy at our center is 1.49%. BK virus is reactivated in the renal tubular epithelial cells in immunosuppressed individuals and leads to allograft dysfunction. Clinically, it mimics acute rejection and therefore histopathology along with immunohistochemistry is essential in making a correct diagnosis and planning appropriate patient management.

Conflict of interest: None declared.


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