Renal adaptation to altered dietary sulfate in rats

Proximal tubular reabsorption is of primary importance in the regulation of the homeostasis of inorganic sulfate, an electrolyte that is necessary for biosynthetic and detoxification reactions. The objective of the present investigation was to determine the effect of dietary sulfate deprivation, produced by a diet low in methionine, on the renal transport of sulfate. Female Lewis rats were fed a diet containing negligible amounts of sulfate and cystine and low in methionine (0.37%) or a control diet (methionine 1.12%, cystine 0.07%) for 8 days to examine the urinary excretion rate and renal clearance of sulfate. The sulfate excretion rate was decreased by day 4 of the low methionine diet and remained low. Both the urinary excretion rates and renal clearance values were significantly decreased on day 8 (144 ± 71 vs. 517 ± 264 μmol/12 hr in controls, mean ± S.D., n = 7, P < .005 and 0.38 ± 0.19 vs. 1.07 ± 0.61 ml min^-1 kg^-1 in controls, n = 5-6, P < .05, respectively), although the serum sulfate concentrations were unchanged. In vitro transport studies were performed in kidney cortex brush border membrane (BBM) and basolateral membrane vesicles isolated from rats fed either the low methionine or control diet for 7 to 9 days. The V(max) for BBM sodium/sulfate cotransport was increased in kidneys from animals that received the low methionine diet (1.1 ± 0.10 vs. 0.75 ± 0.08 nmol mg of protein^-1 10 sec^-1 in controls, n = 5, P < .001); there were no significant differences in the K(m). Bicarbonate-driven anion exchange of sulfate in basolateral membrane vesicles was not different between treatment groups. Administration of a low methionine diet did not alter the membrane motional order (fluidity), as assessed by the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene, which indicates that changes in membrane fluidity do not represent the mechanism of the altered sodium/sulfate cotransport. Therefore, sulfate deprivation, produced by the administration of a diet low in methionine, elicits an adaptive increase in renal BBM sodium-dependent cotransport of sulfate, as demonstrated by the increased V(max) for the process.