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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2014  |  Volume : 25  |  Issue : 1  |  Page : 101-104
Recurrent renal allograft dysfunction due to ureteric stenosis in a patient with the BK virus infection

1 Madras Medical Mission Hospital, Pondicherry Institute of Medical Sciences, Puducherry, Chennai, India; University Hospitals Case Medical Center, Cleveland, Ohio, USA
2 Johann Wolfgang Goethe University, Frankfurt, Germany
3 Madras Medical Mission Hospital, Pondicherry Institute of Medical Sciences, Puducherry, Chennai, India

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Date of Web Publication7-Jan-2014


Diseases of the genitourinary tract in association with the BK virus (BKV) infec­tion are increasing among renal allograft recipients. We herewith report a young, female renal transplant recipient who presented with allograft dysfunction secondary to proximal ureteric stenosis. The allograft function improved dramatically after correction and stenting of the ste­nosis. Our case suggests that screening for BKV infection should be an integral part of evaluation of allograft dysfunction.

How to cite this article:
Reddy YN, Trabert J, Wunderer F, Abraham G, Reddy YN. Recurrent renal allograft dysfunction due to ureteric stenosis in a patient with the BK virus infection. Saudi J Kidney Dis Transpl 2014;25:101-4

How to cite this URL:
Reddy YN, Trabert J, Wunderer F, Abraham G, Reddy YN. Recurrent renal allograft dysfunction due to ureteric stenosis in a patient with the BK virus infection. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2021 Jun 18];25:101-4. Available from: https://www.sjkdt.org/text.asp?2014/25/1/101/124508

   Introduction Top

The pathologies of the genitourinary tract associated with the BK virus (BKV) in renal transplant recipients are increasing, especially in India, where the incidence is reported to be up to 9.3% among patients with renal allograft dysfunction. [1]

The BKV has a sero-prevalence of about 75% in the general population, [2] but active organ manifestation only occurs in patients with immunodeficiency as seen in acquired immu­nodeficiency syndrome or those on immunosuppressive therapy. BKV-associated nephropathy, hemorrhagic cystitis and stenosis of the ureter and urethra are the most common urological manifestations. [2]

We present an unusual case of proximal ureteric stenosis at the uretero-pelvic junction in a renal transplant recipient who was detected to have BKV disease two years after transplan­tation.

   Case Report Top

A 34-year-old lady from Seychelles who had chronic kidney disease due to hypertension and was on maintenance hemodialysis for one year was referred in July 2007 for spousal transplantation. Serological work-up for human immunodeficiency virus, hepatitis B, hepatitis C, venereal disease research laboratory and Cytomegalovirus (CMV) IgM was negative; CMV IgG was positive. The patient had one child and history of one abortion. At transplantation, renal artery anastomosis was per­formed end-to-side to the common iliac artery. Her immunosuppressive medication after sur­gery was prednisolone 25 mg PO, mycophenolate mofetil (MMF) 1 g PO BD and tacrolimus (TAC) 2 mg PO BD.

On the third post-operative day (POD), she developed gram-negative sepsis and Staphylococcus pneumonia necessitating antibiotic treat­ment and reduction in immunosuppression.

On the seventh POD, she developed graft dysfunction, and allograft biopsy showed acute humoral rejection for which she was treated with single-dose rituximab 500 mg, three do­ses of methylprednisolone (1 × 250 mg, 2 × 500 mg), four doses of intravenous immunoglobulin 1.5 g and three cycles of plasmapheresis. Immunosuppression was changed to prednisolone 20 mg OD, sirolimus (SIR) 2 mg OD and TAC 2 mg BD. At discharge six weeks after surgery, the TAC trough level was 12.1 ng/mL. She was subsequently followed-up in Seychelles. She returned in January 2009 with painless hematuria of one week duration. Tests for BKV in serum and urine by quali­tative polymerase chain reaction (PCR) were negative. There was mild graft dysfunction. Renal allograft biopsy was negative for C4d staining but showed mild tubulitis, interstitial inflammation and inclusion bodies. These re­sults, together with negative blood and urine cultures, prompted us to pre-emptively start parenteral gancyclovir [Figure 1], which was discontinued a few days later as quantitative PCR for CMV was negative.
Figure 1. Nephrostogram showing dilation of the pelvi–calyceal system and obstruction at the uretero–pelvic junction(*).

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The TAC trough level at this juncture was 20.1 ng/mL, which was much higher than the desired level for maintenance immunosuppression; hence, the drug dose was reduced to main­tain a satisfactory trough level of 4 ng/mL.

Two weeks later, the patient had recurrence of fever with hematuria and the urine culture grew gram-negative bacilli that necessitated appropriate antibiotic treatment. As part of the fever work-up, a bone marrow biopsy and aspiration, multiple urine samples for Mycobacterium tuberculosis (MTB) and cystoscopic biopsy were performed, which did not show any evidence of tuberculosis. Because she continued to have hematuria with low-grade fever, after an infectious disease consult, she was initiated on a four-drug regimen of anti-tuberculous therapy for one year. The level of immunosuppressive medication was adjusted. She recovered from both hematuria and fever.

She was seen again in May 2009 when a follow-up ultrasound of the allograft showed dilation of the pelvi-calyceal system (PCS) in the transplant kidney with allograft dysfunc­tion. However, as the dilatation was minimal, we did not intervene.

In October 2009, the patient presented with oligoanuria. An ultrasound of the abdomen showed dilatation of the PCS and narrowing at the uretero-pelvic junction, which was con­firmed by a computerized tomography scan of the kidney-ureter-bladder. At this time, allo-graft biopsy showed tubulitis with C4d positivity and features of chronic allograft nephropathy. A repeat test for BKV detected the virus in the serum (but not in the urine) by quali­tative PCR and immunosuppressive drugs were reduced while monitoring blood trough levels and renal function.

Two weeks later, her urine output dropped suddenly with a rise in creatinine. Hence, cystoscopy with ureteric stenting (4, 7 French JD) was performed that promptly produced diu­resis and improvement in graft function. Urine cytology was negative for malignant cells.

The ureteric stent was removed in February 2010. However, the patient developed oligoanuria again with hydronephrosis and impaired graft function, which required percutaneous nephrostomy followed by ureteric stenting (Resonance Ureteric Metallic Stent) [Figure 1]. The allograft function promptly improved after this procedure. Qualitative PCR for BKV in the urine and serum was repeated, and was found to be negative. At discharge, her immunosuppressive medication dosage was TAC 3 mg and SIR 3 mg.

   Discussion Top

BKV-associated allograft ureteric stenosis is well known and has been reported since the first isolation of the virus in 1971. [3] However, the location of the stenosis in our patient is atypical as BKV-associated stenosis is usually described in the distal part of the ureter, especially around the site of anastomosis at the uretero-vesical junction. [1]

Although we could not perform a biopsy at the site of obstruction, we saw a strong link between BKV infection and the development of ureteric stenosis in our patient. Other causes including malignancy and extrinsic compres­sion were ruled out. Stenosis due to a technical procedure would be located at the site of anas­tomosis and would occur earlier. A cicatrized stricture due to a lengthy allograft ureter was also excluded. Investigations for MTB, inclu­ding nuclear amplification technique, urine culture and bladder biopsy, were non-contri­butory. Additionally, the stricture was not typical of Mycobacterial infection.

However, MTB infection is a likely possibi­lity as a causative factor for the initial episode of hematuria. However, the urine specimen that was sent did not grow MTB. Multiple urine specimens may be required, sometimes up to a dozen, for isolation of MTB as yield is very low in the urine. A bladder biopsy at the time of cyctoscopy did not show caseating granulomas suggestive of MTB. This may be due to a sampling error as there was definite inflammation on the biopsy and the culture for other microorganisms was negative. The tem­poral response to the anti-tuberculous treat­ment for over one year is also suggestive of MTB infection.

The episodes of acute rejection that the pa­tient had with recurrent steroid pulse therapy could have contributed to the re-activation of BKV. TAC blood trough levels above 8 ng/mL and prior acute rejection within the first month after transplantation are reported to be signi­ficantly associated with BKV-associated neph­ritis (BKVAN). [2]

It is also notable that BKV-associated ureteric stenosis has not been reported in non-renal transplants, suggesting local ischemia and in­jury as another possible contributing factor.

The allograft dysfunction with increase of serum creatinine might also be due to BKV disease. [2] The tubulitis and inclusion bodies found on allograft biopsy may be a manifes­tation of viral infection. However, one should keep in mind that the initial blood sample sent for BKV was on only one single occasion and, hence, negativity does not rule out the exis­tence of a low-grade BKV co-infection. In renal allograft recipients, both BKVAN and acute cellular rejection (ACR) can histologically present as interstitial inflammation with mononuclear infiltrate and focal invasion of the tubules. [4] Hence, BKVAN should always be considered as a cause of dysfunction in renal allograft recipients, especially considering the fact that the prevalence of BKVAN has increased from 1% in 1995 to 8% in 2007, [5] with loss of the transplanted organ in 30-80% of the cases.

The presence of viral inclusion bodies in tubular epithelial cells may help to distinguish this entity from ACR. "Decoy Cells" in urine cytology smears can be easily detected by light microscopy, and represent a simple marker of viral replication. However, it requires special staining techniques and expertise, and while the negative predictive value is high, the posi­tive predictive value is supposed to be below 30%. [6]

The definitive diagnosis of BKVAN requires tissue immunehistopathology, electron mic­roscopy or BKV-PCR of a biopsy sample. As non-invasive markers for BKV infection, both urine BKV-PCR and plasma BKV-DNA-PCR have shown a sensitivity of 100% and speci­ficity of 95% (urine) and 88% (plasma). [6]

It has been shown that early diagnosis and treatment of BKVAN yields a better response to intervention. Thus, we strongly believe that screening and monitoring for BKV in renal transplant recipients should be an essential part of post-renal transplant follow-up, especially when one encounters graft dysfunction. [7]

In conclusion, we present a young lady with chronic allograft injury and BKV-associated renal allograft dysfunction due to proximal uretric stenosis that responded to permanent stent placement and tailoring of immunosuppressive regimen.

   References Top

1.Sachdeva MS, Nada R, Jha V, Sakhuja V, Joshi K. The high incidence of BK Polyoma virus infection among renal transplant recipients in India. Transplantation 2004;77:429-31.  Back to cited text no. 1
2.Hirsch HH, Steiger J. Polyomavirus BK. Lancet Infect Dis 2003;3:611-23.  Back to cited text no. 2
3.Gardner SD, Field AM, Coleman DV, Hulme B. New human papovavirus (BK) isolated from urine after transplantation. Lancet 1971; 1:1253-7.  Back to cited text no. 3
4.Mylonakis E, Goes N, Rubin RH, Cosmi AB, Colvin RB, Fishman JA. BK Virus in solid organ transplant recipients: An emerging syndrome. Transplantation 2001;72:1587-92.  Back to cited text no. 4
5.Basse G, Mengelle C, Kamar N, et al. Prospective evaluation of BK virus DNAemia in renal transplant patients and their transplant outcome. Transplant Proc 2007;39:84-7.  Back to cited text no. 5
6.Nickeleit V, Klimkait T, Binet IF, et al. Testing for Polyomavirus type BK-DNA in plasma to identify renal-allograft recipients with viral nephropathy. N Engl J Med 2000; 342:1309-15.  Back to cited text no. 6
7.Hirsch HH. Polyoma BK nephropathy: A (re-) emerging complication in renal transplant. Am J Transplant 2002;2:25-30.  Back to cited text no. 7

Correspondence Address:
Yogesh N.V. Reddy
Department of Internal Medicine, University Hospitals Case Medical Center, Cleveland, Ohio, USA

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DOI: 10.4103/1319-2442.124508

PMID: 24434390

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