Nephrotoxicity of antiretroviral therapy in an HIV-infected patient

A 31-year-old human immunodeficiency virus (HIV)-positive Hispanic male presented with gross hematuria and renal insufficiency. The patient had an episode of gross hematuria 3 months before that lasted 1 week and subsided spontaneously. Urologic workup including abdominal and pelvic computed tomography (CT) scan, cystoscopy, and renal ultrasound was negative. Gross hematuria recurred a few weeks later. During this 3-month time period, the patient's serum creatinine increased from 1.6mg/dl (141 mu mol/l) to 2.7mg/dl (239 mu mol/l). Past medical history was significant for HIV infection for 7 years, acquired via homosexual contact, and bipolar disorder. At the time of presentation, the patient was on multiple antiretroviral medications including indinavir (800mg twice a day), ritonavir (100mg twice a day), and lamivudine (150mg a day), all of which had been initiated 26 months before. The patient was also being treated for bipolar disorder with olanzapine (10mg a day) and lamotrigine (100mg a day). Other medications included AndroGel (R) (testosterone replacement gel) (once a day) and dronabinol (2.5mg a day). On physical examination, the patient had a blood pressure of 120/80mm Hg, a heart rate of 62/min, and a weight of 155 pounds. He was afebrile. Cardiovascular, pulmonary, and abdominal examinations were unremarkable. He had a rash on his hands and lower abdomen. The rash was pruritic with excoriations, presumably allergic, and subsequently resolved. There was no evidence of edema. Laboratory examination showed a total leukocyte count of 8000/mm(3) (normal range 3800-10 800/mm(3)) with an absolute lymphocyte count of 2688/mm(3) (normal range 850-3900/mm(3)), eosinophil count 128/mm(3) (normal range 15-550/mm(3)), hematocrit 39% (normal range 38.5-50.0%), platelet count 634 x 10(9)/l (normal range 140-400 x 10(9)/l), 24 h urine protein 1.3 g, serum albumin 4.5 g/dl (45g/l) (normal range 3.7-5.1 g/dl (37-51 g/l)), and creatinine clearance 27cm(3)/min. The following serologies were negative: antinuclear antibody, anti-double-stranded DNA antibody, anti- neutrophil cytoplasmic antibody, anti-GBM antibody, hepatitis B surface antigen, and hepatitis C antibody. His viral load was < 50 HIV-1 RNA copies/ml (reference range < 50 copies/ ml). The CD4 count was 515/mm(3) (reference range 490-1740/mm(3)). Urinalysis showed trace protein, moderate blood, pH 6.0, negative nitrite, and positive leukocytes. Microscopic evaluation of the urine sediment (performed once) revealed 10 red blood cells/high power field, no casts, and no crystals. The clinical differential diagnosis included HIV-associated nephropathy (HIVAN), immune complex glomerulonephritis, and highly active antiretroviral therapy (HAART)-associated nephrotoxicity. A renal biopsy was performed.