Adenovirus in kidney transplantation: an emerging pathogen?

Abstract

Adenovirus commonly causes a mild self-limited infection, but severe disease may occur following immunosuppression. Clusters of such infections, including one from our center, have recently been described. We describe yet another case that manifested in the first month following kidney transplantation. A 35-year-old black female underwent cadaveric kidney transplantation because of end-stage disease secondary to hypertension. Immunosuppression consisted of simulect induction, followed by cyclosporine microemulsion, mycophenolate mofetil, and prednisone. Antimicrobial prophylaxis included valgancyclovir, trimethoprimsulfamethoxazole (TMP-SMZ), and nystatin. An increase in the serum creatinine level from 1.8 to 2.6 mg/dl on day 7 posttransplant prompted a renal allograft biopsy that showed a mixed cellular infiltrate composed of eosinophils and lymphocytes. There were no viral inclusions. Urinalysis showed 95 red blood cells and 6 white blood cells per high-power field, with rare eosinophils. TMP-SMZ was discontinued, and the serum creatinine decreased to 1.6 mg/dl (cyclosporine level: 375 ng/ml) on day 14 posttransplant. The patient was rehospitalized on day 17 posttransplant because of dysuria and gross hematuria. She denied fever, myalgia or arthalgia. The urine specimen was grossly bloody with a few granular casts. Urine culture for bacteria and yeast were negative. Severe hemorrhagic cystitis was noted on cystoscopy, but a biopsy of the urinary bladder mucosa was not performed. There were minor increases in the serum creatinine level during the period of hospitalization that responded to cyclosporine-microemulsion dose reduction (serum creatinine: 1.9 to 2.2 mg/ dl; cyclosporine level: 200 to 273 ng/ml). Hematuria and dysuria resolved over three weeks after decreasing mycophenolate mofetil from 1000 mg to 500 mg twice daily and tapering prednisone from 30 mg to 15 mg daily. Isolation of adenovirus from the urine confirmed a diagnosis of adenovirus associated hemorrhagic cystitis. Shell vial culture with A549 cells and a monoclonal antibody to the adenovirus family was used to isolate the virus, but the specific strain was not determined. Emerging infections, particularly those of viral origin, remain a threat to the success of organ transplantation. The recent clusters of infection due to adenovirus raise important questions in the surveillance of infections among recipients of kidney transplants (1–3). Is adenovirus an emerging pathogen in kidney transplantation or are these recent reports merely isolated events? Adenovirus is a well-recognized cause of significant morbidity and mortality in recipients of bone marrow transplants (4), and appears to be gaining notoriety among recipients of kidney transplants. Over the last 12 months, we have observed three such cases (two confirmed, one highly suspect) at our institution. Recognition of this infection is important because diagnostic delays could result in significant morbidity and possible mortality. The spectrum of illness due to this virus ranges from gross hematuria and strangury, with or without renal allograft dysfunction, to a severe systemic illness. Involvement of the renal allograft without pancreatic involvement has been described in recipients of simultaneous kidney and pancreas transplants. Adenovirus nephropathy is characterized histologically by necrotizing tubulo-interstitial nephritis, with a cellular infiltrate that is predominantly composed of macrophages. The viral inclusion bodies seen in adenovirus nephropathy have some resemblance to those of BK virus nephropathy, but foci of necrosis and interstitial hemorrhage are absent in nephropathy due to BK virus. In the present case, the infection seemed to be limited to the urinary bladder, as evidenced by severe hemorrhagic cystitis and stable renal allograft function. Reduction of maintenance immunosuppression is the mainstay of treatment, but specific therapy is indicated for refractory cases. Intravenous ribavirin has been used either alone or in combination with pooled human intravenous immunoglobulin for treating severe infections. Our recent experience underscores the need to be aware of the risk of new and emerging infections among kidney transplant recipients. Osemwegie E. Emovon Jeffrey Rogers Kenneth Chavin Sally Self