KIDNEY BIOPSY TEACHING CASE Acute Renal Failure in a Renal Allograft: An Unusual Infectious Cause of Thrombotic Microangiopathy Sanjeev Sethi, MD, PhD INDEX WORDS: Renal allograft; histoplasmosis; thrombotic microangiopathy. W E PRESENT the case of a 50-year-old woman with acute renal failure 2 months after receiving a living-related renal transplant. A differential diagnosis of acute rejection versus calcineurin-inhibitor toxicity was the prelimi- nary clinical diagnosis. A renal biopsy was per- formed to determine the cause of renal failure. Renal biopsy showed a relatively common cause of renal dysfunction from an uncommon etiol- ogy, which, on recognition, is easily treatable. CASE REPORT A 50-year-old white woman with a renal transplant was admitted to our hospital with mild fever and an elevated serum creatinine level. She appeared to be in no distress. Two months previously, she had received a living-related renal transplant from her brother. Her primary disease was end-stage renal disease secondary to polycystic kid- ney disease. At admission, there was no history of hema- turia, frequency of urination, or difficulty passing urine. There was no history of recent diarrhea or vomiting and there was no pain over the renal transplant. She had been compliant with her medications and denied use of any new medications. On physical examination, blood pressure was 146/82 mm Hg, pulse was regular at 98 beats/min, respirations were 20 breaths/min, oxygen saturation was 97%, and there was no peripheral edema. Cardiovascular system examination showed normal heart sounds, and there was no tenderness over the allograft site. The patient’s medications at admis- sion included prednisone, tacrolimus, mycophenolate mofetil, acyclovir, trimethoprim-sulfamethoxazole, nystatin, vitamin E, and hydromorphone. Initial laboratory findings were as follows: white blood cells, 5.5  10 3 /L (6  10 9 /L); hemoglobin, 10.4 g/dL (104 g/L); hematocrit, 31%; platelets, 178  10 3 /L (178  10 9 /L); serum creatinine, 3.1 mg/dL (274 mol/L); blood urea nitrogen, 56 mg/dL (20 mmol/L); creatinine clearance, 16 mL/min (0.27 mL/s); sodium, 130 mEq/L (mmol/L); potassium, 4.0 mEq/L (mmol/L); chloride, 99 mEq/L (mmol/L); and carbon dioxide, 16 mEq/L (mmol/ L). The patient’s baseline serum creatinine level was in the 2.5-mg/dL (221-mol/L) range after transplantation. During the next few days, her serum creatinine level continued to increase and reached 6.9 mg/dL (610 mol/L) within a week. Blood tacrolimus levels at admission were elevated at 28.7 ng/mL. The renal ultrasound was unremarkable, and an initial diagnosis of renal allograft dysfunction, probably secondary to rejection, was made. She was administered 1 dose of methylprednisolone sodium succinate, and a renal biopsy was performed to determine the cause of the increasing serum creatinine level. Renal Biopsy Findings The specimen received for light microscopic examina- tion consisted of 3 cores of tissue and contained both cortex and medulla. Seventeen glomeruli were present. None of the glomeruli were globally sclerotic. The pre- served glomeruli showed normal cellularity. In 2 glo- meruli, there were segmental lesions that showed fibrin within the capillary loops. Scattered within the fibrin were small collections of 2- to 5-m thin-walled uninucleate yeast forms that were compatible with Histoplasma cap- sulatum (Fig 1). The Histoplasma stained positively with silver and periodic acid–Schiff stains. In another glomeru- lus, a few capillary loops showed fibrin, but there were no yeast forms within the fibrin strands. The remaining glomeruli were unremarkable, and there was no evidence of glomerulitis or capillary loop thrombosis. Tubules showed focal acute tubular necrosis with necrotic debris in the lumen, mild vacuolization of epithelial cells, and rare mitotic figures. Signs of tacrolimus toxicity, such as isometric vacuolization of tubular epithelium and hyalino- sis of arteriolar walls, were not present. The interstitium showed mild edema and minimal focal interstitial inflam- mation. There was no evidence of tubulitis. The intersti- tium showed mild, approximately 15%, interstitial fibro- sis. Arteries and arterioles were unremarkable. There was no evidence of arteritis. Kidney Biopsy Diagnosis The diagnosis was disseminated histoplasmosis with thrombotic microangiopathy and acute tubular necrosis. From the Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, IA. Received September 17, 2004; accepted in revised form November 2, 2004. Originally published online as doi:10.1053/j.ajkd.2004.11.026 on May 31, 2005. Address reprint requests to Sanjeev Sethi, MD, PhD, Department of Laboratory Medicine and Pathology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905. E-mail: sethi.sanjeev@mayo.edu © 2005 by the National Kidney Foundation, Inc. 0272-6386/05/4601-0020$30.00/0 doi:10.1053/j.ajkd.2004.11.026 American Journal of Kidney Diseases, Vol 46, No 1 (July), 2005: pp 159-162 159