On the relationship between ketonuria and natriuresis during fasting and upon refeeding in obese patients*

Abstract

This study was conducted to assess whether the natriuresis occurring early in a fast, and the renal sodium retention setting in upon carbohydrate or protein refeeding, can be entirely accounted for on the basis of concomitant changes in renal ketone body and ammonia excretion. To this end, the renal excretion of sodium, 3‐hydroxybutyrate (3‐OHB) and ammonium was determined in non‐diabetic obese subjects submitted to total fast according to the following protocols: (1) 6 day fast: considered as control group (n= 11); (2) 8 day fast save for an isolated 100 g oral glucose load on day 4 (n= 12); (3) 8 day fast with, on day 4, the same glucose load followed by a 6 h infusion of glucagon, 1 mg in 500 ml 5% glucose (n= 7); (4) 5 day total fast followed by 3 days of protein refeeding (53 g protein daily; n = 8). All subjects were refed with a mixed 4.2 MJ diet at the end of the studies. During the initial 3 days of fast, natriuresis was proportional to urinary 3‐OHB excretion while urinary ammonium had not yet increased. Glucose administration on day 4 led abruptly to sodium retention, lasting for 2 days, and correlated with the decline in 3‐OHB excretion. The fall in ketonuria resulted from a drop both of plasma 3‐OHB level and of the renal clearance of 3‐OHB. Glucagon prevented this glucose‐induced reduction in urinary Na as well as in 3‐OHB excretion and clearance, through a direct action on the kidney. These results are in keeping with an important role of ketonuria in changes i…