Studies of abluminuria and proteinuria in normal mice and mice with immune complex glomerulonephritis.
Proteinuria is supposedly a frequent and early manifestation of glomerulonephritis. Since albuminuria rather than proteinuria is the hallmark of glomerular disease, the present studies were designed to study the occurrence of albuminuria in normal mice (SWR/J strain) and in mice with a reproducible and predictable immune complex glomerulonephritis induced by chronic infection with lymphocytic choriomeningitis (LCM) virus. A radial immunodiffusion technique, specific for mouse albumin, was employed to quantify the albuminuria. Column chromatography of concentrated urine obtained from normal and nephritic mice demonstrated that albumin excreted in the urine had the same molecular weight as serum albumin and that identifiable fragments of albumin did not appear in the urine. Some albuminuria did occur in normal mice, 0.12 +/- SD. 0.13 mg. per 18 hours for 80 males and 0.13 +/- 0.09 mg. per 18 hours for 55 females. Increased albuminuria, defined as values greater than a normal mean + 2 S.D. (0.40 mg. per 18 hours) occurred in only 25 per cent of nephritic mice, although in more than 600 animals studied, immunofluorescent microscopy invariably demonstrated abnormal accumulation of immune complexes in the glomeruli of SWR/J mice chronically infected with LCM virus. Values of total proteinuria measured by the sulfosalicylic acid method did not correlate with radial immunodiffusion measured albuminuria. The results indicate that measurement of total proteinuria in mice is not a useful parameter of glomerular disease. Albuminuria, while increased in 25 per cent of nephritic animals, was not abnormal even in the presence of marked histologic alterations in 75 per cent of mice, suggesting that abnormal immunopathology may very commonly not be reflected in increased or pathologic albuminuria. Recent observations also suggest that this is the case in humans.