EXPERIMENTAL IGA NEPHROPATHY SECONDARY TO HEPATOCELLULAR INJURY-INDUCED BY DIETARY DEFICIENCIES AND HEAVY ALCOHOL INTAKE

BACKGROUND: In humans, alcoholic liver disease is frequently associate d with IgA mesangial deposits, microscopic hematuria and a small amoun t of proteinuria, identifying a secondary form of IgA nephropathy. Alc oholic liver disease is almost always associated with nutritional defi ciencies. EXPERIMENTAL DESIGN: In order to examine the relationship be tween alcohol intake and/or inadequate diet and IgA nephropathy, group s of 4 week-old-male Lewis rats were maintained on a lipotrope-deficie nt (LD) diet (N = 20), intragastric infusions of a commercial whiskey (1.5 ml/ 100 gm body weight) three times a week, and regular chow (N = 23) or both intragastric whiskey infusion and an LD diet (N = 17). A fourth control group (N = 19) was given no whiskey and normal chow. RE SULTS: All rats given the LD diet had marked steatosis and elevated '' liver'' enzymes. Changes were more severe, and with early bridging fib rosis and nodule formation in those also given whiskey, associated wit h increased hepatic content of mRNA encoding transformimg growth facto r-beta. A moderate steatosis without alteration in serum enzymes or tr ansforming growth factor-beta expression was found in rats given whisk ey (all p < 0.0001) compared with controls. IgA accumulated in hepatic sinusoids instead of in canaliculi and bile ducts, suggesting impaire d transport of IgA and IgA immune complexes from blood to bile, in rat s given an LD diet and/or whiskey infusion. A moderate increase in mes angial matrix was observed only in rats given both whiskey and an LD d iet. Bright granular IgA and mild granular C3 mesangial deposits and e lectron-dense deposits were evident in 63 to 70% of experimental rats (all p < 0.001) versus only trace deposits in 5 to 11% of controls. Mo derate IgG codeposits were present in 34 to 55% of rats given the LD d iet and/or whiskey (all p < 0.02), versus trace deposits in 10% of con trols. Significant hematuria and proteinuria were observed in rats giv en the LD diet and/or whiskey (p < 0.0001) versus controls. Intestinal permeability measured by xylose absorption was significantly increase d relative to controls only in rats given both whiskey and the LD diet (p < 0.001). Serum IgA specific for selected alimentary antigens was increased relative to controls in 75 to 100% of the experimental rats. CONCLUSIONS: The combination of LD diet and alcohol intake, which mim ics the human alcoholic condition, promotes hepatic and renal changes, leading to hepatocellular injury and a secondary form of IgA nephropa thy.