BACKGROUND: In humans, alcoholic liver disease is frequently associated with IgA mesangial deposits, microscopic hematuria and a small amount of proteinuria, identifying a secondary form of IgA nephropathy. Alcoholic liver disease is almost always associated with nutritional deficiencies. EXPERIMENTAL DESIGN: In order to examine the relationship between alcohol intake and/or inadequate diet and IgA nephropathy, groups of 4 week-old-male Lewis rats were maintained on a lipotrope-deficient (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. RESULTS: All rats given the LD diet had marked steatosis and elevated "liver" enzymes. Changes were more severe, and with early bridging fibrosis and nodule formation in those also given whiskey, associated with increased hepatic content of mRNA encoding transforming growth factor-beta. A moderate steatosis without alteration in serum enzymes or transforming growth factor-beta expression was found in rats given whiskey (all p < 0.0001) compared with controls. IgA accumulated in hepatic sinusoids instead of in canaliculi and bile ducts, suggesting impaired transport of IgA and IgA immune complexes from blood to bile, in rats given an LD diet and/or whiskey infusion. A moderate increase in mesangial matrix was observed only in rats given both whiskey and an LD diet. Bright granular IgA and mild granular C3 mesangial deposits and electron-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. Moderate IgG codeposits were present in 34 to 55% of rats given the LD diet and/or whiskey (all p < 0.02), versus trace deposits in 10% of controls. Significant hematuria and proteinuria were observed in rats given the LD diet and/or whiskey (p < 0.0001) versus controls. Intestinal permeability measured by xylose absorption was significantly increased 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 mimics the human alcoholic condition, promotes hepatic and renal changes, leading to hepatocellular injury and a secondary form of IgA nephropathy.
BACKGROUND: In humans, alcoholic liver disease is frequently associated with IgA mesangial deposits, microscopic hematuria and a small amount of proteinuria, identifying a secondary form of IgA nephropathy. Alcoholic liver disease is almost always associated with nutritional deficiencies. EXPERIMENTAL DESIGN: In order to examine the relationship between alcohol intake and/or inadequate diet and IgA nephropathy, groups of 4 week-old-male Lewis rats were maintained on a lipotrope-deficient (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. RESULTS: All rats given the LD diet had marked steatosis and elevated "liver" enzymes. Changes were more severe, and with early bridging fibrosis and nodule formation in those also given whiskey, associated with increased hepatic content of mRNA encoding transforming growth factor-beta. A moderate steatosis without alteration in serum enzymes or transforming growth factor-beta expression was found in rats given whiskey (all p < 0.0001) compared with controls. IgA accumulated in hepatic sinusoids instead of in canaliculi and bile ducts, suggesting impaired transport of IgA and IgA immune complexes from blood to bile, in rats given an LD diet and/or whiskey infusion. A moderate increase in mesangial matrix was observed only in rats given both whiskey and an LD diet. Bright granular IgA and mild granular C3 mesangial deposits and electron-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. Moderate IgG codeposits were present in 34 to 55% of rats given the LD diet and/or whiskey (all p < 0.02), versus trace deposits in 10% of controls. Significant hematuria and proteinuria were observed in rats given the LD diet and/or whiskey (p < 0.0001) versus controls. Intestinal permeability measured by xylose absorption was significantly increased 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 mimics the human alcoholic condition, promotes hepatic and renal changes, leading to hepatocellular injury and a secondary form of IgA nephropathy.
Authors: John C LaMattina; Joshua D Mezrich; Luis A Fernandez; Anthony M D'Alessandro; Arjang Djamali; Alexandru I Musat; John D Pirsch; David P Foley Journal: Clin Transplant Date: 2013-01-07 Impact factor: 2.863
Authors: John C Lamattina; David P Foley; Joshua D Mezrich; Luis A Fernandez; Vijay Vidyasagar; Anthony M D'Alessandro; Alexandru I Musat; Milagros D Samaniego-Picota; Julio Pascual; Munoz D R Alejandro; Glen E Leverson; John D Pirsch; Arjang Djamali Journal: Clin J Am Soc Nephrol Date: 2011-07-22 Impact factor: 8.237
Authors: Jang Soo Han; So Dug Lim; Won Hyeok Choi; Sung Chul Hong; Jung Hee Park; Eugene Park; Mi Jin Hong; Cho I Lee; Jung Hwan Park; Jong Ho Lee; Jong Oh Song; Young Il Jo Journal: Kidney Res Clin Pract Date: 2013-01-02