Renal concentrating ability in obesity. Effect of modified fasting and the supplementation of T3, sodium chloride and carbohydrate

The renal concentrating ability (RCA) was studied in 30 obese subjects before and after modified fasting (MF) and T3 supplementation, and during hypocaloric-carbohydrate refeeding. We also studied the effect of sodium supplementation on the RCA during MF. Modified fasting induced a low T3-high rT3 state (“sick euthyroid”). During T3-supplementation plasma T3 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 H2O 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 + T3-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 T3 and sodium chloride supplementation was observed. Severe dietary salt restriction induced a significant decline in RCA (P < 0.005). Refeeding with carbohydrate increased plasma T3 from 79.9 ± 7.7 to 97 ± 7.5 ng100 mL (NS) and decreased plasma rT3 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 T3 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.