Effect of atorvastatin on IgA nephropathy in the rat.
BACKGROUND
IgA nephropathy (IgAN) is the most common chronic glomerulonephritis in humans and is a major cause of end-stage kidney disease worldwide. There is no agreement on the exact underlying mechanism or therapeutic intervention for this disorder. Mesangial proliferation typifies the renal histopathology in IgAN. Statin drugs, as prenylationinhibitors, have been shown to have an antiproliferative effect on renal mesangial cells and to reduce IgAN-associated glomerulusclerosis and proteinuria. The aim of this study is to examine the effect of atorvastatin on kidney function, proteinuria and kidney histology changes in IgANinduced rats.


METHODS
IgAN was induced in Wistar-Kyoto rats by bovine γ-globulin (BGG). Four groups of rats were treated in metabolic cages: 1) control; 2) atorvastatin (2 mg/kg body weight/day through nasogastric tube) - treated rats; 3) IgAN-rats; 4) IgAN-rats treated with atorvastatin. Urine volume, urine protein excretion, blood urea and creatinine concentrations in addition to creatinine clearance were examined every 14 days, throughout the duration of the study (56 days). All kidneys from sacrificed rats were examined for histology including glomerular cell nuclei count and immunofluorescence.


RESULTS
There were no differences in blood creatinine concentrations between the groups. Creatinine clearance was lower on the 42nd day and proteinuria was higher on Days 14, 42 and 56, in rats in Group 3 compared to all others; additionally, histology examination revealed a higher glomerular cell nuclei count in this group. Immunofluorescence was equally positive for IgA in mesangial cells in the kidneys from rats of Groups 2, 3 and 4.


CONCLUSIONS
Atorvastatin attenuates kidney-function impairment, proteinuria and mesangial cell proliferation in BGG model of IgANinduced rats.
Institute of Nephorolgy, E. Wolfson Medical Center, Holon, Israel. Katzir@wolfson.health.gov.il
Ze'ev
Z
Katzir
Elena
E
Leibovitch
Hanan
H
Vaknin
Letizia
L
Schreiber
Esther
E
Berger
Zipora
Z
Matas
Asora
A
Fux
Mona
M
Boaz
Alexander
A
Briliant
Alexander
A
Biro
D000818:Animals; D000069059:Atorvastatin; D003404:Creatinine / Q000097:blood; D005455:Fluorescent Antibody Technique; D005922:Glomerulonephritis, IGA / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D006538:Heptanoic Acids / Q000627:therapeutic use*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D008297:Male; D011758:Pyrroles / Q000627:therapeutic use*; D051381:Rats; D011921:Rats, Inbred WKY
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D003404:Creatinine