Low molecular weight proteinuria in human immunodeficiency virus-infected patients

To determine whether human immunodeficiency virus (HIV) infection is associated with incipient tubular or glomerular defects, we determined the urinary excretion of four low molecular weight proteins (LMWP); beta(2)-microglobulin (U-beta(2)-m), cystatin C (U-cyst C), Clara cell protein (U-CC16), and retinol-binding protein (U-RBP), the markers of tubular dysfunction, the excretion of albumin (U-Alb), a marker of glomerular defect, and the excretion of N-acetyl-beta-D-glucosaminidase (U-NAG), a marker of structural damage of the proximal tubular epithelium. Their determinants have been assessed by stepwise regression analysis using as possible predictors age, sex, serum-beta(2)-m (S-beta(2)-m), CD4 lymphocyte count, or HIV infection stage and therapy. The study involved 76 HIV-infected patients without renal disease, 56 with S-beta(2)-m < 5 mg/L (Group B-1), 20 with S-beta(2)-m greater than or equal to 5 mg/L (Group B-2), and 30 HIV-negative controls. Fourteen patients (18.4%) had no abnormal urinary protein loss, and 62 (81.6%) had elevated urinary excretion of at least one protein (Alb, LMWP, or NAG). A single urinary protein was abnormal in 21 patients (U-beta(2)-m, n = 9; U-RBP, n = 2; U-CC16, n = 4; and U-Alb, n = 6). At least two LMWP were abnormal without increased U-Alb in 23 patients (12 with increased and 11 with normal U-NAG). Ten patients had an increased urinary excretion of at least one LMWP together with U-Alb (5 with increased and 5 with normal U-NAG). An increased urinary excretion of all proteins was observed in the last 8 patients. The average urinary excretion of all proteins (except cyst C) was significantly higher in HIV than in the control group. As expected, U-beta(2)-m and the prevalence of abnormal U-beta(2)-m values were higher in the B-2 than in the B-1 group (P = 0.0001), whereas the average urinary excretion and the prevalence of elevated values of Alb, LMWP (except beta(2)-m) or NAG were the same in both HIV groups. By stepwise regression analysis, age emerged as a significant determinant of urinary excretion of beta(2)-m and CC16, whereas male sex was associated with increased U-CC16. S-beta(2)-m, CD4-lymphocyte count, or HIV infection stage emerged as significant determinants only for U-beta(2)-m as a consequence of a close correlation between S-beta(2)-m and either HIV infection stage (r = -0.52, P = 0.0001), or CD4 count (r = -0.45, P = 0.0002). Over 80% of HIV-infected patients without overt renal disease have evidence of glomerular permeability defects or tubular dysfunction, whatever the stage of the disease. U-Alb, RBP, and CC16 appear as the most sensitive and reliable early markers of these abnormalities. Their cause and prognostic value remain to be determined. (C) 1996 by the National Kidney Foundation, Inc.