Renal concentrating ability in obesity. Effect of modified fasting and the supplementation of T 3, sodium chloride and carbohydrate

Abstract

The renal concentrating ability (RCA) was studied in 30 obese subjects before and after modified fasting (MF) and T 3 supplementation, and during hypocaloric-carbohydrate refeeding. We also studied the effect of sodium supplementation on the RCA during MF. Modified fasting induced a low T 3-high rT 3 state (“sick euthyroid”). During T 3-supplementation plasma T 3 levels increased but were in the normal range for normal weight controls. Plasma sodium, potassium, and calcium remained within the normal range during all study periods. After MF (14 days) the mean maximal urinary osmolality was significantly lower compared to prefast values both after dehydration alone (706 ± 12 mosm/kg H 2O v 975 ± 14, P < 0.001) and after dehydration plus sc vasopressin administration (676 ± 19 v 899 ± 17, P < 0.001). After 14 days MF followed by 14 days MF + T 3-supplementation plasma urea, urinary urea excretion, and the creatinine clearance were significantly greater than after MF alone as was the RCA (764 ± 15 v 652 ± 25, P < 0.002). Sodium chloride supplementation increased RCA ( P < 0.02) but no additive effect of T 3 and sodium chloride supplementation was observed. Severe dietary salt restriction induced a significant decline in RCA ( P < 0.005). Refeeding with carbohydrate increased plasma T 3 from 79.9 ± 7.7 to 97 ± 7.5 ng 100 mL (NS) and decreased plasma rT 3 from 0.33 ± 0.02 to 0.27 ± 0.02 ng/mL, ( P < 0.02); no significant change in RCA was observed. The results show that there are no arguments for ADH deficiency during MF; the fasting-induced decrease in renal concentration ability is due to a partial unresponsiveness to ADH which results from a depletion of the osmolar content of renal medullary tissue which is a consequence of diminished exogenous supply and endogenous generation of osmoles. Correction of the low T 3 state improves the renal concentrating ability only partially, possibly by increasing the interstitial tonicity, although a direct effect on the distal renal tubular cells may also play a role by increasing the sensitivity to ADH.