HIV-1-associated nephropathy and response to highly-active antiretroviral therapy

Abstract

A 37-year-old African-American man with schizophrenia and bipolar disorder was admitted with psychotic symptoms after stopping his medications. Within 2 weeks of admission, his blood urea increased from 8 to 21 mmol/L and creatinine from 203 to 450 mol/L. 3 weeks later his serum sodium was 135 mmol/L, potassium 6·7 mmol/L, chloride 109 mmol/L, bicarbonate 13 mmol/L, urea 32 mmol/L, and creatinine 770 mol/L. Calculated creatinine clearance was 7 mL/min and he required haemodialysis. His blood pressure was 132/70 mm Hg, weight 77 kg, and height 162 cm. He had pharyngeal thrush, penile warts, and prominent jugular veins without peripheral oedema. His medications were olanzapine, haloperidol, sodium valproate, and lorazepam. Additional laboratory tests indicated a normal urinary sediment on microscopy, urinary protein 9·9 g/day with normal urine and serum immunoelectrophoresis. He had a mild normocytic, normochromic anaemia, with haemoglobin of 95 g/L, and a normal platelet count. Serum albumin was 14 g/L and total cholesterol 7·2 mmol/L. Tests for collagen diseases, vasculitic syndromes, or infection with hepatitis or herpes group viruses were negative, and complement levels were normal; these tests were repeated 6 weeks later and remained unchanged. HIV-1 antibodies were present on enzyme-linked immunosorbent assay and western blot. His CD4 lymphocyte count was 0·04 10/L and the CD8 count 0·42 10/L. Serum HIV-1 RNA by branched chain DNA assay was 906 000 copies per mL. An ultrasound examination was remarkable for 13·5 cm kidneys with increased echogenicity. A percutaneous kidney biopsy was done a week before the initiation of dialysis and showed changes typical of HIV-1associated nephropathy. On light microscopy a core of renal cortex had fourteen glomeruli, of which one glomerulus was globally sclerotic. The other glomeruli were normocellular but had significant tuft collapse, with more than 70% having epithelial pseudocrescents. The interstitium showed prominent microcystic tubular dilatation containing proteinaceous casts (figure, A). The vessels were unremarkable, and glomerular immunofluorescence staining was negative. Electron microscopy confirmed collapsing glomerulopathy without endocapillary hypercellularity, plus marked hypertrophy and hyperplasia of the podocytes leading to epithelial pseudocrescents. Endothelial cells contained tubuloreticular cytoplasmic inclusions. Triple antiretroviral therapy with stavudine 20 mg/day, lamivudine 50 mg/day, and nelfinavir 1250 mg twice daily was started 1 week before haemodialysis. After13 weeks of treatment and 12 weeks of haemodialysis three times per week, a 24-hour urine collection (3·5 L) contained 0·7 g protein and 10·6 mmol creatinine. 2 weeks later repeat 24hour urine tests were similar and dialysis was discontinued. A repeat percutaneous renal biopsy at that time showed 18