Induction of glomerulosclerosis by dietary lipids. A functional and morphologic study in the rat.
Clinical and experimental data indicate that glomerular function and morphology may be influenced by plasma lipids. In familial lecithin-cholesterol-acyltransferase (LCAT) deficiency and in Fabry's disease, lipids accumulate in glomeruli and are assumed to induce sclerosis. The present study was undertaken to examine if dietary lipids could exert effects on the glomeruli of normal, unilaterally nephrectomized rats, and of rats with two-kidney, one clip (2-K,1C) hypertension. In rats with two kidneys on a diet rich in fat and cholesterol, cholesterol concentrations in very low density lipoproteins increased. In these rats the number of glomeruli with sclerotic foci was significantly higher than in rats on a low fat, cholesterol free diet. After 6 months on the diet the percentage of glomeruli with sclerosis (SC) was 13.2 +/- 4.1 (N = 9) in rats with a cholesterol diet and 1.8 +/- 0.6 (N = 11) in control rats (p less than 0.05). The fat and cholesterol diet exacerbated glomerular lesions in the remnant kidney model of uninephrectomized rats. The sclerosis in rats with only one kidney was 38.2 +/- 9.5 (N = 6) on a cholesterol diet compared with 8.7 +/- 3.0 (N = 6) in control rats after 6 months (p less than 0.05). After 3 to 4 months on a fat rich diet cholesterylester was increased in isolated glomeruli. The composition of the dietary lipids influenced the development of glomerular lesions. A linseed oil diet that is rich in unsaturated fatty acids, especially linolenic acid, did not cause major plasma lipid abnormalities and was accompanied by a low sclerosis (1.2 +/- 0.3; N = 9) for rats with two kidneys. In rats with chronic 2-K, 1C hypertension the percentage of glomeruli with partially sclerosed tufts in the unclipped kidney was significantly higher on a fat and cholesterol diet (F) than on a control diet (N) (SC: diet F 31.0 +/- 4.0, N = 13; diet N 12.2 +/- 2.6, N = 12; P less than 0.05). In the clipped kidney, protected against the arterial hypertension, only an increased number of glomeruli with mesangial expansion was noted in rats with the cholesterol diet. Glomerular hemodynamic factors seem to play an important pathogenetic role in the induction of glomerular sclerosis by a lipid rich diet. The fact that dietary lipids can aggravate glomerular lesions in states of arterial hypertension and nephron loss may have implications for the progression of renal disease in humans.
Gröne
H J
HJ
Department of Pathology, University Hospital Göttingen, Federal Republic of Germany.
Walli
A
A
Gröne
E
E
Niedmann
P
P
Thiery
J
J
Seidel
D
D
Helmchen
U
U
D000818:Animals; D001794:Blood Pressure; D002791:Cholesterol, Dietary / Q000009:adverse effects; D004041:Dietary Fats / Q000009:adverse effects*; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000209:etiology* / Q000473:pathology; D007678:Kidney Glomerulus / Q000032:analysis / Q000473:pathology*; D008055:Lipids / Q000032:analysis / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000473:pathology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012598:Sclerosis
D002791:Cholesterol, Dietary; D004041:Dietary Fats; D008055:Lipids; D008074:Lipoproteins