Home About us Current issue Back issues Submission Instructions Advertise Contact Login   

Search Article 
  
Advanced search 
 
Saudi Journal of Kidney Diseases and Transplantation
Users online: 3119 Home Bookmark this page Print this page Email this page Small font sizeDefault font size Increase font size 
 

CASE REPORT Table of Contents   
Year : 2006  |  Volume : 17  |  Issue : 2  |  Page : 203-207
Polyoma Virus Nephropathy, First Reported Case in Saudi Arabia


1 Department of Medicine, King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia
2 Department of Pathology, King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia

Click here for correspondence address and email
 

   Abstract 

Polyoma virus nephropathy (BK virus) is being recognized as an important cause of graft failure. It is usually confused with acute rejection. No cases have been reported from the kingdom of Saudi Arabia. We report a case of a Saudi gentleman, who was transplanted outside the country, with persistently elevated creatinine and urethral stenosis. He was treated for acute rejection on more than one occasion with no significant improvement in his renal function. Polyoma virus nephropathy was diagnosed by detecting the virus DNA by the Poly chain reaction technique (PCR). The patient's renal function stabilized after the calcineurin inhibitors were discontinued.

Keywords: Polyoma Virus, Acute rejection, Graft dysfunction, Urethral stenosis.

How to cite this article:
Siddiqi N A, Hamid M H, El-Tayeb A, Bokhari E. Polyoma Virus Nephropathy, First Reported Case in Saudi Arabia. Saudi J Kidney Dis Transpl 2006;17:203-7

How to cite this URL:
Siddiqi N A, Hamid M H, El-Tayeb A, Bokhari E. Polyoma Virus Nephropathy, First Reported Case in Saudi Arabia. Saudi J Kidney Dis Transpl [serial online] 2006 [cited 2020 May 30];17:203-7. Available from: http://www.sjkdt.org/text.asp?2006/17/2/203/35791

   Case Report Top


A 38-year-old Saudi gentleman with history of hepatitis C viral infection and chronic hemodialysis for three years underwent living unrelated transplantation in Egypt in September 2002. He presented to our hospital one month after transplantation with a serum creatinine of 100 µmol/L . He was continued on his immunosuppressive regimen that included cyclosporine, mycophenolate mofetil, and prednisone. His creatinine increased to 174 µmol/L in the second month post transplant. Partial obstruction was diagnosed with renal ultrasound (US), and nuclear scan demonstrated delayed excretion at the uretero-pelvic junction. The cystogram revealed a huge bladder divert­iculum, which was confirmed by cystoscopy; there was no evidence of reflux. The patient was also found to have urethral stricture. Urethral dilatation was performed and an indwelling Foley's catheter was placed. The renal function improved over ten days from a high of 211 µmol/L to 118 µmol/L. The Foley's catheter was removed but subsequently his creatinine increased again to 176 µmol/L, which necessi­tated a second urethral dilatation, but there was no further improvement of the creatinine.

In the third month post transplantation the patient was admitted with fever and elevated creatinine to 259 µmol/L. He underwent a third urethral dilatation with no significant improvement. The repeated renal US showed no progression of the hydronephrosis, and the nuclear scan showed no change. The patient underwent a graft biopsy, which revealed acute rejection (BANF1B) with evidence of cytomegalovirus (CMV). The patient was treated with IV gancyclovir for two weeks; the MMF was withheld during this period. The patient's creatinine stabilized between 233-260 µmol/L. A repeat biopsy was performed one month after completion of gancyclovir because of the persistently elevated creatinine. This also revealed acute rejection (BANF1B), but without evidence of CMV infection. The patient was pulsed with methyl predni­sone 250 mg IV for three doses, after which his creatinine declined to 243 Emol/L but subsequently started to rise gradually again to a high of 424 Jmol/L five months post transplantation.

At that time, the patient was admitted with a presumed urinary tract infection. He was empirically treated with IV ciprofloxacillin for 5 days, but the cultures were negative. A micturating cystourethrogram revealed vesi­couretric reflux and moderate graft hydro­nephrosis. A Foley's catheter was placed, with which his creatinine improved to 286 µmol/L.

Two months later the patient underwent a repeat cystoscopy and dilatation of urethral stricture and bladder neck incision. A repeat graft biopsy at this time also revealed acute rejection (BANF1A). He was treated with an IV pulse of steroids and discharged with Foley's catheter. His creatinine remained elevated after completion of the course of steroid, and we repeated the graft biopsy to assess the steroid resistant rejection. The biopsy revealed that the interstitium was infiltrated by chronic inflammatory cells - mainly lympho­cytes, plasma cells, and few eosinophils. Focal neutrophilic infiltration was also present. The infiltrates were present in >25% of the inter­stitium. Tubulitis was moderate (>4 mono­nuclear cells / cross-section). The glomeruli showed focal peritubular fibrosis, but were otherwise unremarkable. Focal tubular atrophy and fibrosis were noted. The blood vessels were unremarkable. Some large dense nuclei were seen [Figure - 1],[Figure - 2].

The patient received six daily doses of anti­thymocyte globulin without any significant change in his renal function. In the meanwhile, the patient's serum was sent outside the kingdom for polyoma DNA detection by PCR, which was reported positive for BK virus RFLP subtype.

According to the BK positive result, the cyclosporine was discontinued, and the patient was maintained on MMF and prednisone for the past nine months. The serum creatinine stabilized around 220 Emol/L.


   Discussion Top


Polyoma virus is a DNA virus associated with allograft nephropathy. [1] There are three serotypes known to infect humans: BK virus (BK), JC virus (JC) and Simian virus 40 (SV40). [2] The BK virus was named after the patient from whom it was first isolated. [3] These viruses tend to affect different organs. [4] The BK virus is urotropic with nearly 60-80% of the adult general population is seropositive; however, it does not cause significant disease in immunocompetent hosts. [4],[5] In renal transplant patients, the virus has been associated with hemorrhagic cystitis and urethral stenosis along with nephropathy that causes deterioration of the graft function. [3],[7],[8],[9] The incidence of the BK virus nephropathy has been reported to be between 2-7% in the western litera­ture. [10],[11] Recently, a retrospective analysis from India reported a much higher incidence of 9.8%. [12] The hallmark of the BK virus replication is the presence of decoy cells in the urine, which are viral inclusion bearing cells; it does not indicate renal involvement. In 1995, Randjawa et al reported the first case of allograft dys-function associated histologically with the BK virus. [13] The JC virus has also been implicated in some cases of nephropathy. [14]

Since BK virus nephropathy was virtually unknown before 1995, some new risk factors for this infection have been implicated. It has been suggested that tacrolimus and MMF may increase the risk of polyoma virus nephropathy.[1] The recognition of polyoma virus nephropathy followed the introduction of these two potent immunosuppressive drugs. There is no prospective comparison of tacro­limus or cyclosporine with regard to the BK virus viremia. [15] Interestingly, in the study reported from India with high incidence of polyoma virus nephropathy, all the patients were receiving cyclosporine. [12] Recently, a case of BK nephropathy with sirolimus has been reported.[16]

Hirsch et al also reported an association of the BK nephropathy with higher number of HLA mismatches.[17] Furthermore, treatment of acute rejection episodes with anti-lymphocyte preparations may lead to poorer outcomes. [18]

The light microscopy usually shows nuclear inclusions in tubular cells, which may be eosinophillic with prominent cytopathic changes, including enlarged nuclei and chromatin smudging. [19],[20] Infiltrates of neutrophils, mono­cytes, and lymphocytes along with fibrosis have been described - hence the term inter­stitial nephritis. Sachdeva also reported a high number of plasma cells in the infiltrates.[12] Among the lymphocytes predominance of CD 20 B cells has been observed. [21] This may help in differentiating the BK nephropathy from acute rejection.

Immunohistochemistry, using antibody to SV 40 that cross-reacts with BK virus, has helped in diagnosing the BK virus nephropathy. However, this technique cannot differentiate between the different subtypes (i.e. the BK and the JC viruses). [21] Analysis of the serum for the DNA of the BK virus by PCR is considered to be 100% sensitive and currently is the most widely used test for the diagnosis of BKV nephropathy. [22] Quantitative PCR is being used by some centers to monitor the response to treatment. [23]

Currently, there is no specific antiviral therapy available for treatment. Reduction of the immunosuppression has been shown to decrease the viral load. [23] More than the type of immunosuppressive medication used, it is probably the overall immunosuppression that contributes to the development of the infection. Thus, a judicious reduction in the immuno­suppression to allow the immune system to overcome the infection is the current standard therapy. [18]

Cidofovir, an antiviral, has been tried with some initial success. [23] Recently, it has been used in 15 patients at 20-30% of its regular dose and was found to be effective. [24] There have been few case reports of successful retransplantation after removal of the first BK virus infected graft.[25]

Our patient had multiple episodes of urethral stenosis, which were not present prior to trans­plantation; secondly, he had repeated episodes of rejection unresponsive to treatment. Currently, he is stable with improvement in his renal function after the calcineurin inhibitors were discontinued. Polyoma virus infection is common and requires a high index of suspicion, especially in patients with recurrent acute rejection and/or urethral stenosis. Currently, there are no facilities to diagnose this infection in the kingdom. The actual rate of polyoma virus nephropathy is unknown in the kingdom. We suspect that the rate may be higher than what is reported in the western literature because of the high number of living unrelated transplants performed abroad.

 
   References Top

1.Binet I, Nickeleit V, Hirsch HH, et al. Polyomavirus disease under new immuno­suppressive drugs: a cause of renal graft dysfunction and graft loss. Transplantation 1999;67(6):918-22.  Back to cited text no. 1    
2.Kwak EJ, Vilchez RA, Randhawa P, Shapiro R, Butel JS, Kusne S. Pathogenesis and management of Polyomavirus infection in transplant recipients. Clin Infect Dis 2002;35:1081-7.  Back to cited text no. 2  [PUBMED]  [FULLTEXT]
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  [PUBMED]  
4.Khalili K, Stoner GL. Human Polyoma­viruses: molecular and clinical perspectives. New York: Wiley-Liss, 2001.  Back to cited text no. 4    
5.Gardner SD. Prevalence in England of antibody to human polyoma virus (BK). British Med J 1973;1:77.  Back to cited text no. 5    
6.Baksh FK, Finkelstein SD, Swalsky PA, Stoner GL, Ryschkewitsch CF. Randhawa PS. Molecular genotyping of BK and JC viruses in human polyomavirus-associated interstitial nephritis after renal transplant­ation. Am J Kidney Dis 2001;38(2):354-65.  Back to cited text no. 6    
7.Hogan TF, Borden EC, McBain JA, Padgett BL, Walker DL. Human Polyomavirus infections with JC virus and BK virus in renal Transplant patients. Ann Intern Med 1980;92:373-8.  Back to cited text no. 7  [PUBMED]  
8.Arthur RR, Shah KV, Baust SJ, Santos GW, Saral R. Association of BK viruria with hemorrhagic cystitis in recipients of bone marrow transplants. N Engl J Med 1986; 315:230-4.  Back to cited text no. 8  [PUBMED]  
9.Hirsch HH, Knowles w, Dickenmann M, et al. Prospective study of Polyomavirus type BK replication and nephropathy in renal transplant recipients. N Engl J Med 2002; 347:488-96.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Gardner SD, Mackenzie EF, Smith C, Porter AA. Prospective study of the human Polyomaviruses BK and JC and cyto­megalovirus in renal transplant recipients. J Clin Pathol 1984;37:578-86.  Back to cited text no. 10  [PUBMED]  [FULLTEXT]
11.Li RM, Mannon RB, Kleiner D, et al. BK virus and SV40 co-infection in polyoma­virus nephropathy. Transplantation 2002; 74:1497-504.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]
12.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. 12  [PUBMED]  [FULLTEXT]
13.Randhawa PS, Demetris AJ. Nephropathy due to polyomavirus type BK. N Engl J Med 2000;342:1361-3.  Back to cited text no. 13  [PUBMED]  [FULLTEXT]
14.Kazory A, Ducloux D, Chalopin JM, et al. The first case of JC virus allograft nephro­pathy. Transplantation 2003;76:1653-5.  Back to cited text no. 14  [PUBMED]  [FULLTEXT]
15.Barri YM, Ahmad I, Ketal BL, et al. Polyoma viral infection in renal transplantation: the role of immunosuppressive therapy. Clin Transplant 2001;15:240-6.  Back to cited text no. 15    
16.Hirsch HH, Mohaupt M, Klimkait T. prospective monitoring of BK virus load after discontinuing sirolimus treatment in a renal transplant patient with BK virus nephropathy. J Infect Dis 2001;184:1494-5.  Back to cited text no. 16  [PUBMED]  [FULLTEXT]
17.Hirsch HH, Knowles W, Dickenmann M, et al. Prospective study of polyomavirus type BK replication and nephropathy in renal transplant recipients. N Engl J Med 2002; 347:488-96.  Back to cited text no. 17  [PUBMED]  [FULLTEXT]
18.Hussian S, Bresnahan BA, Cohen EP, Hariharan S. Rapid kidney allograft failure in patients with Polyoma virus nephritis with prior treatment with antilymphocyte agents. Clin Transplant 2002;16:43-7.  Back to cited text no. 18    
19.Drachenberg CB, Beskow CO, Cangro CB, et al. Human Polyoma virus in renal allograft biopsies morphological findings and correlation with urine cytology. Human Pathol 1999;30:970-7.  Back to cited text no. 19    
20.Randhawa PS, Finkelstein S, Scantlebury V, et al. Human Polyoma virus associated interstitial nephritis in the allograft kidney. Transplantation 1999;67:103-9.  Back to cited text no. 20  [PUBMED]  [FULLTEXT]
21.Ahuja M, Cohen EP, Dayer AM, et al Polyoma virus infection after renal trans­plantation. Use of immunostaining as a guide to diagnosis. Transplantation 2001; 71:896-9.  Back to cited text no. 21    
22.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. 22  [PUBMED]  [FULLTEXT]
23.Vats A, Shapiro R, Randhawa PS, et al Qualitative viral load monitoring and cido­fovir therapy for the management of BK virus associated nephropathy in children and adults. Transplantation 2003;75:105-12.  Back to cited text no. 23    
24.Bjorang O, Tveitan H, Midtvedt K, Broch LU, Scott H, Andresen PA. Treatment of polyomavirus infection with cidofovir in a renal-transplant recipient. Nephrol Dial Transplant 2002;17:2023-5.  Back to cited text no. 24  [PUBMED]  [FULLTEXT]
25.Poduval RD, Meehan SM, Woodle ES, et al. Successful retransplantation after allograft loss to Polyoma virus interstitial nephritis. Transplantation 2002;73:1166-9.  Back to cited text no. 25  [PUBMED]  [FULLTEXT]

Top
Correspondence Address:
N A Siddiqi
Consultant Nephrologist, King Fahd Armed Forces Hospital, P.O. Box 9862, Jeddah 21159
Saudi Arabia
Login to access the Email id


PMID: 16903628

Rights and Permissions


    Figures

  [Figure - 1], [Figure - 2]



 

Top
 
 
    Similar in PUBMED
    Search Pubmed for
    Search in Google Scholar for
  Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  
 


 
    Abstract
    Case Report
    Discussion
    References
    Article Figures
 

 Article Access Statistics
    Viewed2339    
    Printed66    
    Emailed0    
    PDF Downloaded361    
    Comments [Add]    

Recommend this journal