ELEVATED URINARY-EXCRETION OF ENDOTHELIN-LIKE IMMUNOREACTIVITY IN CHILDREN WITH RENAL-DISEASE IS RELATED TO URINE FLOW-RATE

Endothelin 1-21 belongs to a family of locally produced regulatory pep tides with potent vasoconstrictor activity and profound renal effects. To study the biological significance of endothelin in children with r enal diseases, we measured urinary endothelin-like immunoreactivity (E Tir) excretion in children and adolescents (60 normal controls and 57 patients with renal disease). ETir excretion was constant during child hood and adolescence (4-18 years). Compared to these normal controls e levated urinary excretions of ETir were found in children with chronic renal failure, following renal transplantation and with idiopathic hy percalciuria (all groups p < 0.001). However, ETir excretion was uncha nged in children with idiopathic steroid sensitive nephrotic syndrome, with stable chronic glomerulonephritis and in 4 patients with hemolyt ic uremic syndrome. Urinary ETir concentrations were similar in contro ls and in various patient groups. ETir excretion correlated positively with urine flow rate in normal controls (r = 0.71) and in all patient s studied (r = 0.91); Fractional excretion of ETir correlated negative ly with glomerular filtration rate. Eight healthy volunteers (23-27 ye ars old, 4 female, 4 male) were studied before and after oral water lo ad (20 ml/kg) to investigate the effect of ETir excretion on urine flo w rate. Urine flow rose tenfold in response to water load and urine co ncentration of ETir fell only by factor 3 and urinary ETir excretion r ose fivefold. These results indicate that urinary ETir excretion is re lated to and depends at least in part on urine flow rate. ETir excreti on may so reflect a role of ETir in renal disease, especially in the d iuretic state.