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); beta2-microglobulin (U-beta2-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-beta2-m (S-beta2-m), CD4 lymphocyte count, or HIV infection stage and therapy. The study involved 76 HIV-infected patients without renal disease, 56 with S-beta2-m < 5 mg/L (Group B1), 20 with S-beta2-m > or = 5 mg/L (Group B2), 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-beta2-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-beta2-m and the prevalence of abnormal U-beta2-m values were higher in the B2 than in the B1 group (P = 0.0001), whereas the average urinary excretion and the prevalence of elevated values of Alb, LMWP (except beta2-m) or NAG were the same in both HIV groups. By stepwise regression analysis, age emerged as a significant determinant of urinary excretion of beta2-m and CC16, whereas male sex was associated with increased U-CC16. S-beta2-m, CD4-lymphocyte count, or HIV infection stage emerged as significant determinants only for U-beta2-m as a consequence of a close correlation between S-beta2-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.
Kabanda
A
A
Nephrology Unit, Catholic University of Louvain, Medical School, Brussels, Belgium.
Vandercam
B
B
Bernard
A
A
Lauwerys
R
R
van Ypersele de Strihou
C
C
D016263:AIDS-Associated Nephropathy / Q000652:urine; D000118:Acetylglucosaminidase / Q000652:urine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000419:Albuminuria; D018791:CD4 Lymphocyte Count; D055316:Cystatin C; D015891:Cystatins / Q000652:urine; D005260:Female; D015658:HIV Infections / Q000652:urine*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D011506:Proteins / Q000032:analysis; D011507:Proteinuria; D012044:Regression Analysis; D012177:Retinol-Binding Proteins / Q000652:urine; D014598:Uteroglobin; D001613:beta 2-Microglobulin / Q000652:urine
C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D011506:Proteins; D012177:Retinol-Binding Proteins; C556389:SCGB1A1 protein, human; D001613:beta 2-Microglobulin; D014598:Uteroglobin; D000118:Acetylglucosaminidase