Experimental IgA nephropathy secondary to hepatocellular injury induced by dietary deficiencies and heavy alcohol intake.
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.


METHODS
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.
Amore
A
A
Institute of Pathology, Case Western Reserve University, Cleveland, Ohio.
Coppo
R
R
Roccatello
D
D
Piccoli
G
G
Mazzucco
G
G
Gomez-Chiarri
M
M
Lamm
M E
ME
Emancipator
S N
SN
D000437:Alcoholism / Q000150:complications* / Q000503:physiopathology; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D003677:Deficiency Diseases / Q000150:complications* / Q000503:physiopathology; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D005922:Glomerulonephritis, IGA / Q000209:etiology* / Q000503:physiopathology; D007070:Immunoglobulin A / Q000032:analysis / Q000378:metabolism / Q000502:physiology; D007408:Intestinal Absorption / Q000502:physiology; D007668:Kidney / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D008854:Microscopy, Electron; D011507:Proteinuria / Q000150:complications; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014994:Xylose / Q000493:pharmacokinetics
D007070:Immunoglobulin A; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D014994:Xylose