Male offspring of Han:SPRD-cy heterozygotes received
protein modified diet: ad libidum LP 8%
casein in test or 20%
casein in control group for 8 weeks; 20% heat treated
soy protein or 20%
casein in control group two separate studies for 8 weeks ad libidum and pair feeding in 6 weeks; and 10% flax seed diet or control rat chow for 8 weeks from weaning. Tissue was harvested for histological assessment and metabolic changes in
lipids,
citric acid metabolites and osmolytes. Morphometrically after histochemical and immunohistochemical staining cystic changes, renal tubular proliferation and apoptosis, number of interstitial cells/macrophages infiltration and interstitial
fibrosis were measured. Gas chromatography was used for
lipid analysis in renal and liver tissue. 1-HNMR spectroscopy was used for urine and tissue organic
anion and osmolytes content analysis. RESULTS IN
PROTEIN MODIFIED DIET:
Casein low
protein as well as
soy protein fed animals demonstrated reduced PKD pathology: significant reduction in cystic changes, interstitial
inflammation and
fibrosis and also reduction in tubular cells proliferation and apoptosis. Pair feeding protocol in second soy diet study confirmed that significant effect on renal histology was not because of
protein deprivation and growth retardation. 1-H NMR spectroscopy revealed that progression of
chronic renal failure in Han:SPRD-cy rat PKD is associated with renal depletion of citric acid cycle metabolite and
betaine. Amelioration of PKD by
soy protein diet is associated with renal retention of citric acid cycle
anions, despite increased excretion and preservation of
betaine in renal tissue. Soy feeding increased both hepatic and renal content of
linoleic acid and increased renal
alpha linolenic acid content, while decreased arachidonic hepatic content. RESULTS IN FLAX SEED SUPPLEMENTATION IN DIET: Flax seed fed animals had moderate decrease in cystic size and less interstitial
inflammation and
fibrosis while there were no differences in epithelial cell apoptosis and proliferation.
Lipid analysis revealed significant renal enrichment of 18 and 20
carbon omega 3
polyunsaturated fatty acids. In flax fed animals there was an increased urinary
citrate excretion without significant changes in urinary
ammonia excretion, so increased
citrate excretion was not due to alkaline effect of the diet. Kidney tissue 1H NMR spectroscopy revealed that disease amelioration was associated with tissue retention of
succinate and
betaine.
CONCLUSION: