To explain the occurrence of tubular and glomerular proteinuria in patients with primarily tubular or glomerular dysfunction, it is usually assumed that the mechanisms responsible for the renal tubular transport of small and large proteins are different. The present in vivo study does not support this hypothesis since it clearly shows that small and large proteins (e.g., β₂-microglobulin and albumin) can compete for renal uptake. Our results lead us to postulate the existence of common tubular reabsorption sites for which proteins exhibit different affinities depending on their charge, size and conformation.

beta 2-microglobulin (beta 2-m) was measured in the urine of rats by a specific immunoassay based on latex particles agglutination. The excretion of this protein was compared to the excretion of the enzyme beta-N-acetyl-D-glucosaminidase (NAG), albumin and amino acids in rats treated with either a single dose of sodium chromate (5 and 10 mg kg-1), repeated doses of gentamicin (5 and 20 mg kg-1), or cadmium (1 mg kg-1), and in aging rats (from 2 to 20 months). All treatments resulted in an early increased excretion of beta 2-m indicative of functional alterations of the proximal tubular cells. An increased NAG excretion was observed only at the highest dose of chromate and in the cadmium model but the relative increases of beta 2-m were much larger (up to 200 times the control values against four times the control values for NAG). From 2 to 20 months of age, urinary beta 2-m increases by a factor of four. Aminoacids excretion showed little sensitivity in the various models. Albumin showed little variations in purely tubular or in the tubular phase of renal injury but the chronic progressive nephrosis of aging rats caused a 40-fold increase in its excretion between 2 and 20 months of age. Therefore urinary beta 2-m, albumin and albumin/beta 2-m ratio provide useful tools in the assessment of nephrotoxicity and of its mechanisms in various experimental models.

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The urinary excretion of beta 2-microglobulin, retinol-binding protein and albumin was measured in 65 workers exposed to styrene at levels averaging 50 percent of the current threshold limit value (215 mg/m2) for 1-13 years (mean: 6 years). By comparison with a control group matched for age and socioeconomic status, no significant difference was observed in the urinary excretion of proteins. In rats, styrene was weakly nephrotoxic. No functional or morphological renal change could be disclosed in rats exposed to 565 mg of styrene/m3, 5 days/week for 13 weeks. The repeated i.p. injection of 1 g styrene/kg (1/5 of oral LD50) for 10 days induced only a slight tubular dysfunction as evidenced by a 5-fold increase in beta 2-microglobulinuria. Altogether, these epidemiological and experimental data suggest that the current threshold limit value for styrene (215 mg/m3) proposed by the American Conference of Governmental and Industrial Hygienists does not entail any risk of renal toxicity.

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