Native Kidney BK Nephropathy Post Cardiac Transplantation

Abstract

BK virus reactivation post renal transplantation has become increasingly diagnosed over the last decade, probably as a result of the widespread usage of more potent immunosuppressive agents. Manifestations of viral reactivation post renal transplantation include asymptomatic viruria, hemorrhagic cystitis, ureteric stricture, and interstitial nephritis, the latter often associated with progressive renal impairment and graft loss. For reasons that remain poorly understood, BK virus induced interstitial nephritis (BKIN) and associated renal failure occurs very infrequently in the nonrenal transplant setting even in patients with similar or even greater levels of immune suppression. This is despite the fact that asymptomatic viral reactivation and shedding may be quite common in these patients (1). Only a handful of case reports appear in the literature describing BKIN in native kidneys; in association with HIV infection (2), congenital immunodeficiency (3), post bone marrow transplantation (4), and post pancreatic transplantation (5). We report a unique case of BKIN in native kidneys associated with severe renal failure occurring 2-years post cardiac transplantation. The patient is a 59-year-old female who presented in October 2001 with increasing symptomatic cardiac failure. Past medical history included focal breast carcinoma resected in 1990 and thyroidectomy in 1999. A severe dilated cardiomyopathy was confirmed on echocardiogram and cardiac biopsy revealed giant cell myocarditis. Despite treatment with pulse methylprednisolone and cyclosporine, the patient deteriorated requiring admission to intensive care for inotropic support and insertion of a left ventricular assist device. She remained in intensive care for 3 months until undergoing a heart transplant in January of 2002. This was complicated by three episodes of severe rejection treated with pulse methylprednisolone and antithymocyte globulin as well as by the development of steroid induced diabetes requiring insulin therapy. In view of the recurrent rejection a decision was made for increased maintenance immunosuppression including prednisolone, tacrolimus, mycophenolate mofetil, and sirolimus. Of note, serum creatinine was 0.04 mmol/L on admission and 0.16 mmol/L on discharge. Over the subsequent 12 months, cardiac function remained stable but there was a gradual decline in renal function with serum creatinine climbing to 0.28 mmol/L despite early withdrawal of tacrolimus. In June of 2003 the patient underwent a renal biopsy, which confirmed BKIN (Fig. 1). Urine decoy cells were not detected but urine polyomavirus PCR was found to be strongly positive.FIGURE 1.: Electron microscopy of renal biopsy demonstrates viable and degenerate virions with morphology in keeping with polyoma virus infection.Immunosuppression was considerably reduced to prednisolone 5 mg and sirolimus 4 mg daily with serial cardiac biopsies reintroduced to monitor for cardiac rejection. Although cardiac function remained stable over the subsequent months, serum creatinine continued to rise to 0.40 mmol/L with ongoing strongly positive urine PCR for polyomavirus. The patient was then treated with intermittent low doses of the antiviral agent cidofovir for a period of 3 months. Despite this, there was no improvement in renal function and urine PCR remained strongly positive for polyomavirus. Currently the patient has a serum creatinine of 0.44 mmol/L and preparations are being made for her to commence dialysis. It is unclear why BKIN occurs relatively frequently post renal transplantation and so rarely in any other setting. Some authors have suggested that renal tubular injury specific to the process of renal transplantation or allograft rejection is a necessary co-factor in the pathogenesis of invasive BK virus infection (6). Solomon A. Menahem Katherine M. McDougall Napier M. Thomson Department Renal Medicine Alfred Hospital Melbourne, Australia John P. Dowling Department Anatomical Pathology Alfred Hospital Melbourne, Australia