A 47-year-old woman with type one diabetes and end stage renal disease received a simultaneous kidney and pancreas transplant with thymoglobulin induction and enteric drainage. Five months after transplant, she came to the emergency room for two weeks of hematuria. On physical exam vital signs were within normal limits and she had no abdominal pain, pain over the allograft site, or lower extremity edema. She was complaint with her immunosuppression of prednisone, tacrolimus, and mycofenolate mofetil.
Labs showed a creatinine of 2.5 mg/dL (baseline 1 mg/dL) and urinalysis with numerous red blood cells. Tacrolimus level was within range. Blood glucose and pancreatic function were normal. A renal and pancreatic ultrasound showed patent vessels. On hospital day two she began having fevers and leukopenia. Blood cultures, urine cultures, chest x-ray, donor specific antibodies, Epstein-Barr virus, cytomegalovirus, and BK virus serum polymerase chain reactions were all negative. Her immunosuppression regimen was decreased due to concern of infection. A urine adenovirus polymerase chain reaction was positive.
Her leukopenia continued to progress and a bone marrow biopsy was positive for adenovirus by polymerase chain reaction. Renal biopsy showed no evidence of acute rejection, but was also positive for adenovirus by polymerase chain reaction. Electron microscopy showed crystalline arrays of viral particles consistent with adenovirus in the cytoplasm of the tubular epithelium and cells in the interstitum. Her creatinine continued to increase to 3.7 mg/dL. She was diagnosed with disseminated adenovirus nephritis and started on cidofovir with the understanding the medication may be nephrotoxic.
Her creatinine continued to increase and she was given intravenous immunoglobulin and cidofovir was stopped. Her creatinine peaked at 7.6 mg/dL and her urine output decreased. She was started on hemodialysis and was discharged with brincidofovir on hemodialysis days. On brincidofovir, her urine adenovirus polymerase chain reaction was negative for two consecutive weeks but then returned positive on the third week. Her renal function did not improve and she continues to be on hemodialysis. Repeat kidney biopsy two months later showed acute tubular necrosis and viral tubulointerstitial nephritis. Adenovirus polymerase chain reaction of the kidney biopsy remained positive.
Discussion:
Adenovirus infection of kidney allografts is rare and most commonly presents with hemorrhagic cystitis. Treatment options are limited to case reports and expert opinion. Treatment involves decreasing immunosuppression, cidofovir, brincidofovir, and possibly intravenous immunoglobulin. In patients with simultaneous kidney and pancreas transplants, there appears to be a predilection for adenovirus to kidney tissue with pancreas sparing. This case demonstrates the importance to maintain a high degree of suspicion for adenovirus as a possible cause for acute renal failure and hematuria in a transplant patient.
Conclusions:
Disseminated adenovirus should be considered in the differential diagnosis in kidney transplant patients with hematuria, fevers, and acute kidney injury. While typically self-limiting adenovirus infection can be a cause for morbidity, mortality, and transplant rejection in recipients.Rapid detection and initiating aggressive early treatment may improve prognosis of this disease.