Severe BK polyomavirus‐induced hemorrhagic cystitis in a kidney transplant recipient with the absence of renal allograft involvement

BK polyomavirus mostly manifests as polyomavirus‐associated nephropathy (PyVAN) in kidney transplant patients and polyoma virus‐associated hemorrhagic cystitis (PyVHC) in bone marrow transplant patients. PyVHC in kidney transplant patients is only reported in four cases in the literature. Our patient had severe hemorrhagic cystitis without renal involvement. We postulate that our patient's exposure to ifosfamide and radiation 8 years prior transplantation might predispose him to this disease.     

BK virus nephropathy in a heart transplant recipient: case report and review of the literature

The human polyomavirus BK virus (BKV) remains latent in the urinary tract and may be reactivated in immunocompromised states. BKV is noted to be the etiologic agent of polyomavirus-associated nephropathy (PVAN), which is a significant cause of allograft failure in renal transplant patients. Renal dysfunction following non-renal solid organ transplantation is common and is typically attributed to drug toxicity or patient comorbidities. In this article we describe a case of PVAN in the native kidneys of a heart transplant recipient and review the literature. Although this is only the fourth case reported, BKV nephropathy should be considered in the differential diagnosis of new renal failure following non-kidney solid organ transplantation, as early diagnosis of PVAN is necessary to prevent irreversible renal damage.     

JC virus‐associated nephropathy in a renal transplant recipient and comparative analysis of previous cases

G. Kantarci, Z. Eren, A. Demira?, I. Dogan, F. Çakalagaoglu, G. Yilmaz.
JC virus‐associated nephropathy in a renal transplant recipient and comparative analysis of previous cases.
Transpl Infect Dis 2011: 13: 89–92. All rights reserved Abstract: We report JC virus (JCV)‐associated nephropathy in a renal allograft recipient and summarize the clinical and laboratory data of the 8 previous cases. A 28‐year‐old male renal allograft recipient received a preemptive transplant from his father. Six months later, a kidney biopsy was performed because of deterioration of allograft function. Biopsy revealed tubulointerstitial mononuclear infiltrates with normal glomeruli; on hematoxylin and eosin staining, basophilic nuclear inclusions were seen in the nucleus of tubular cells. Urinary cytology failed to demonstrate decoy cells, but polymerase chain reaction of a urinary sample was positive for JCV 3.15 × 10¹⁰ copies/mL. Additionally, polyomavirus (SV40) immunohistochemical staining was performed and was positive in the enlarged nuclei of tubular epithelial cells in the kidney biopsy sample. After the diagnosis of polyomavirus‐associated nephropathy (PVAN) was confirmed by kidney biopsy, immunosuppressive agents were reduced. Intravenous immunoglobulin was administered 5 times at a dose of 500 mg/kg every other 3 weeks. Two months after diagnosis, the serum creatinine became stable and urinary viral load of JCV was decreased. Because viruria was still present, tacrolimus was converted to sirolimus. Four months after immunosuppressive agent conversion from tacrolimus to sirolimus, the viruria had disappeared. Review of the literature and our case demonstrates that male gender, previous acute rejection episode, low incidence of JCV viremia, PVAN pattern B histology, and reducing immunosuppression are the diagnostic touchstones for PVAN due to JCV.     

JC polyomavirus nephropathy,a rare cause of transplant dysfunction: Case report and review of literature

JC polyomavirus‐associated nephropathy (JC‐PVAN) is a rare but challenging cause of renal dysfunction. We report JC‐PVAN in a renal allograft recipient and highlight the obstacles in definitive diagnosis of this disease entity. A deceased‐donor renal transplant recipient was diagnosed with JC polyomavirus nephritis 4 years after transplantation. Immunosuppressive agents were subsequently reduced, resulting in an initial stabilization of renal function. We present this interesting case and discuss the challenges with diagnosing and treating this rare entity.     

A prospective cross-sectional study of BK virus infection in non-renal solid organ transplant recipients with chronic renal dysfunction

BACKGROUND: Polyomavirus (primarily BK virus [BKV]) infection is an important cause of chronic renal dysfunction in renal transplant recipients, but its possible contribution to chronic renal dysfunction in non-renal solid organ transplant (NRSOT) recipients has not been fully explored. METHODS: We performed a prospective, cross-sectional study of consecutive NRSOT recipients with unexplained chronic renal dysfunction of at least a 3 months duration. Medical records were reviewed, and polymerase chain reaction was used to amplify BKV-specific sequences from serum and urine samples. The potential associations between various demographic and transplant variables and BKV infection were assessed. RESULTS: Thirty-four consecutive NRSOT recipients (23 lung, 8 liver, 2 heart, 1 heart-lung) with chronic renal dysfunction were enrolled at a median of 3.5 years (range 0.3-12.5 years) post transplantation. Five of the 34 (15%) patients had BKV viruria (range 1040-1.8 x 10(6) copies/mL), but none had BKV viremia. BK viruria was associated with mycophenolate mofetil use (5 of 19 [26%] vs. 0 of 15, P = 0.03) and a history of cytomegalovirus disease (3 of 4 [75%] vs. 2 of 30 [7%], P < 0.01). However, the mean estimated creatinine clearance was similar in patients with or without BKV viruria (49 vs. 47 mL/min). CONCLUSIONS: BKV viruria was present in a proportion of NRSOT patients with otherwise unexplained chronic renal dysfunction. The possibility that BKV infection might contribute to chronic renal dysfunction in this setting warrants further investigation.     

Factors and outcome in BK virus nephropathy in a Hispanic kidney transplant population

D. Pérez‐Torres, J. Bertrán‐Pasarell, E. Santiago‐Delpín, M. González‐Ramos, S. Medina‐Mangual, L. Morales‐Otero, Z. González‐Caraballo. Factors and outcome in BK virus nephropathy in a Hispanic kidney transplant population.
Transpl Infect Dis 2010: 12: 16–22. All rights reserved BK virus nephropathy (BKVN) is an increasingly recognized cause of kidney allograft loss and is thought to be related to the newer, more potent immunosuppressive agents. Conflicting information has been reported on risk factors for BK infection. Purpose. To determine incidence, associated factors, and outcome of BKVN in our kidney transplant population in order to improve identification and management. Methods. Kidney transplants from January 2000 to December 2005 were retrospectively reviewed. Data were collected for patients with biopsy‐proven BKVN including age, sex, body mass index (BMI), etiology of renal failure, other medical diseases, donor type, surgical complications, rejection and infection, time to diagnosis, induction, immunosuppressive and antiviral therapy, and clinical outcome. A control group of patients matched for sex, age, type of graft, etiology of kidney disease, and BMI, was established for comparison. Results. Study group: During this period, 20 (4%) of 497 transplanted patients were diagnosed with BKVN. Thirteen (65%) were males, 8 (40%) were young adults (ages 21–40), and 18 (90%) received grafts from cadaveric donors (P=0.05). Twelve (60%) had hypertensive renal disease, 2 (10%) also had diabetes, and 16 (80%) had a BMI >25 (P=0.01). Lymphoceles occurred in 5 patients (25%). Mean creatinine level at diagnosis was 2.7 mg/dL and mean time to diagnosis was 23 months. Ten patients (50%) had leukopenia at or within a year before biopsy (P=0.001). Viruses other than BK occurred in 9 patients: varicella zoster virus in 3, cytomegalovirus in 2, herpes simplex virus in 1, molluscum contagiosum in 1, Epstein–Barr virus in 1, and human papillomavirus in 1. Eighteen patients (90%) had related rejection (P= 0.001) and 4 (20%) suffered allograft loss (P= 0.001). Basiliximab (living donors) and anti‐thymocyte globulin (cadaver donors) were given for induction. All patients were on triple therapy; 15 on prednisone and sirolimus, with either tacrolimus in 8, cyclosporine in 4, mycophenolate in 1, or mycophenolate and tacrolimus in 2. The other 5 received prednisone with tacrolimus and mycophenolate. Graft loss occurred in 2 patients on tacrolimus and mycophenolate, 1 patient on tacrolimus and sirolimus, and 1 patient on cyclosporine and sirolimus. Immunosuppression was decreased in all patients. Two were given cidofovir for 6 months and had stable creatinine levels at the end of the study. Records were reviewed until April 2007. There were no deaths in this cohort. Control group: The number of rejections experienced by patients with BKV was much higher (P<0.0001), but the rate of graft loss was similar between the 2 groups (P=0.19). Viral co‐infection was more frequent in patients with BKV (P=0.04). No episodes of leukopenia were reported for any of the patients in the control group (P=0.001). Immunosuppression with tacrolimus and sirolimus was more frequent in the BKV group, but this was not statistically significant (P=0.18, 0.28, respectively). The number of lymphoceles was larger in patients with BKV, but the difference was not statistically significant (P=0.35). Conclusion. BKVN is present in our transplant population and results in a high rate of allograft rejection with varying rates of graft loss. Associated factors were deceased donor and immunosuppression with potent agents, particularly tacrolimus and sirolimus. We also found a higher frequency of obesity, viral co‐infection, and leukopenia. Routine screening and timely biopsy could prove cost‐effective and significantly reduce morbidity.     

Polyomavirus-associated nephropathy: update of clinical management in kidney transplant patients

Over the last decade, polyomavirus-associated nephropathy (PVAN) has occurred with increasing frequency after renal transplantation, leading to significant renal dysfunction and graft loss. More than 95% of all cases are caused by the human polyomavirus type 1 called the BK virus. The primary treatment for PVAN is immunosuppression reduction, which must be carefully balanced against increased risks of rejection. Although no validated protocols exist, a first step commonly involves reduction of calcineurin inhibitors with antiproliferative agents by more than one-third, e.g., reaching trough levels of tacrolimus <6 ng/mL, of cyclosporine <150 ng/mL, dosing of mycophenolate mofetil to <1 g/day, and azathioprine <75 mg/day. When rejection is diagnosed together with PVAN, a transient pulse treatment is recommended before subsequent reduction in immunosuppression. No antiviral treatments for PVAN have been approved by the United States Food and Drug Administration. The antiviral drug cidofovir has shown in vitro activity against murine polyomaviruses, and has been used in some patients in lower doses in an effort to minimize the nephrotoxic effects of cidofovir while treating PVAN. Small series of PVAN patients treated with leflunomide, intravenous immune globulin therapy, and fluoroquinolones have also been reported recently.     

JC virus‐associated nephropathy in a post‐heart and ‐kidney transplantation patient

JC virus‐associated nephropathy is rare in kidney transplant recipients, and even rarer in recipients of other solid organ transplants. We present a case of JC virus‐associated nephropathy in a heart‐kidney transplant recipient, which to our knowledge is the first case reported in the literature. We discuss the findings on renal biopsy for JC virus nephropathy and our management approach to this rare complication.     

Renal transplantation and polyomavirus infection: recent clinical facts and controversies

Abstract: Although many articles have been published on polyomavirus‐induced pathologies in transplant recipients, our knowledge regarding their clinical aspects remains relatively limited. In fact, the number of questions and controversies on the subject seems even to be increasing as new publications continue to appear. This article presents some of these controversies through a brief review of recent clinical facts about the three polyomaviruses that infect humans – JC virus, simian virus 40, and BK virus – as they relate to renal transplantation.     

A very early and acute renal impairment due to polyomavirus allograft nephropathy

G. Comai, G. La Manna, G. Liviano D'Arcangelo, F. Centofanti, C. Valentini, B. Fabbrizio, R. Tardanico, G. Camaggi, S. Venturoli, M.P. Scolari, S. Stefoni. A very early and acute renal impairment due to polyomavirus allograft nephropathy.
Transpl Infect Dis 2010: 12: 521–525. All rights reserved Abstract: Polyomavirus‐associated nephropathy (PVAN) has become an important cause of graft loss in the last few years. The typical course of PVAN is characterized by an asymptomatic period of viruria followed, within weeks, by the development of viremia in the context of stable renal function. The persistence of viral replication characterized by high viremia, leads to parenchymal injuries and causes the development, within months, of PVAN that could lead to deterioration in graft function and graft loss. We reported, in a patient who received a renal transplant, an unusual presentation of PVAN characterized by the development of acute renal failurte earlier than would be expected after transplantation, where the histological presentation alone could be confused with an acute rejection. We underline the importance of the association of histological findings with the viral load in urine and blood and with ancillary techniques such as immunohistochemistry and polymerase chain reaction (PCR) in situ for virus detection. We also want to emphasize that decoy cells and PCR for BK virus DNA research could be considered among the diagnostic tools for possible acute renal failure in kidney transplant.