Dietary betaine modifies hepatic metabolism but not renal injury in rat polycystic kidney disease

We undertook a morphometric and proton nuclear magnetic resonance (H-1-NMR) study to test the hypothesis that 1% dietary betaine supplementation would ameliorate renal disease in the heterozygous Han:SPRD-cy rat, a model of p olycystic kidney disease (PKD) and progressive chronic renal failure. After 8 wk of pair feeding, betaine had no effect on renal cystic change, renal interstitial fibrosis, serum creatinine, serum cholesterol, or serum trigly cerides. H-1-NMR spectroscopy of renal tissue revealed no change in renal o smolytes, including betaine, or renal content of other organic anions in re sponse to diet. H-1-NMR spectroscopy of hepatic tissue performed to explore the metabolic fate of ingested betaine revealed that heterozygous animals fed the control diet had elevated hepatic levels of gluconeogenic amino aci ds, increased beta -hydroxybutyrate, and increased levels of some citric ac id cycle metabolites compared with animals without renal disease. Betaine s upplementation eliminated these changes. Chronic renal failure in the Han:S PRD-cy rat is associated with disturbances of hepatic metabolism that can b e corrected with betaine therapy, suggesting the presence of a reversible m ethylation defect in this form of chronic renal failure.