Urinary excretion of endothelin was measured by radioimmunoassay in ch
ildren with diabetes mellitus during severe ketoacidosis and 12 days l
ater when blood pH and blood glucose concentrations were normal. Metab
olically stable diabetic children served as controls. Results from app
arently healthy children without diabetes mellitus were used as normal
values. Renal tubular injury was evaluated by the urinary excretion o
f the proximal tubular marker alpha(1)-microglobulin and the distal tu
bular marker Tamm-Horsfall protein (THP). During ketoacidosis we detec
ted a decreased glomerular filtration rate associated with highly sign
ificant changes in the excretion of eel-microglobulin, indicating prox
imal tubular damage, and THP, suggesting disturbance of cells of the a
scending loop of Henle. The daily excretion of endothelin was unaltere
d but the ratio of endothelin/creatinine or endothelin excretion/creat
inine clearance were significantly enhanced. In conclusion, we could d
emonstrate that, despite a proximal and distal tubular cell dysfunctio
n, endothelin excretion is not elevated during ketoacidosis. The incre
ased endothelin excretion when related to creatinine clearance may be
a consequence of disturbed proximal tubular function or dysfunction of
the renal medulla.