The Renal Handling of IgG in the Aging Rat and in Experimental Kidney Disease

Abstract

The urinary excretion of total protein, low-MW proteins, albumin, high-MW proteins, and intact IgG was measured in male Wistar rats between the ages of 5-52 weeks, and in rats with experimentally induced glomerular or tubular proteinuria. About 25% of aging rats spontaneously developed focal glomerulosclerosis and a mild glomerular proteinuria. By age 52 weeks, total protein excretion in rats with glomerulosclerosis exceeded that of unaffected rats by a factor of seven (39.5 vs 5.4 mg/24 hr × 100 g body wt), and albumin excretion was seven times higher than IgG excretion in affected rats (21.2 vs 2.9 mg/24 hr × 100 g body wt). Rats with chromate toxicity exhibited a reversible tubular proteinuria, with low-molecular weight protein excretion reaching 16.8 mg/24 hr × 100 g body wt (75% of total protein excretion) at the time of peak toxicity. IgG excretion remained less than 0.6 mg/24 hr × 100 g body wt. Aminonucleoside induced a massive but reversible glomerular proteinuria (204 mg/24 hr × 100 g body wt), with IgG excretion reaching 11.4 mg/24 hr × 100 g body wt (6% of total protein excretion) at the time of peak toxicity. Biochemical and immunochemical studies showed that, while some intact IgG is present in normal rat urine, most IgG immunoreactivity is derived from low-molecular weight catabolic fragments of IgG which interfere with the immunoassay of intact urinary IgG. One of these fragments, probably Fc fragment, may be involved in the pathogenesis of focal segmental glomerulosclerosis.