URINARY ENDOTHELIN IN GLOMERULONEPHRITIS PATIENTS WITH NORMAL RENAL-FUNCTION

The vasoconstrictor peptide endothelin-1 (ET(1)) has only recently bee n characterized and its effects are at present largely speculative. It has been hypothesized that ET(1) acts on mesangial cells to cause vas oactive changes which might ultimately contribute to the development o f glomerulosclerosis. Opposite to ET(1), nitric oxide (NO) inhibits me sangial cell contraction and proliferation. NO activates soluble guany lic acid cyclase and the final product, cyclic GMP (cGMP), has been re cently used as a marker of NO action. Urinary levels of ET(1) and cGMP were detected in 58 patients with biopsy-proven glomerulonephrits (GN ), including 36 IgA nephropathy (IgAGN), 30 with normal and 6 with imp aired renal function, 10 patients with non-IgA mesangial GN and 12 pts with membranous GN (MGN) with normal renal function. Compared to norm al controls (0.019 +/- 0.006 ng/min), urine ET(1) levels were signific antly higher in patients with normal renal function having IgAGN (0.03 5 +/- 0.017, p < 0.01), MGN (0.028 +/- 0.013, p < 0.05), non-IgA mesan gial GN (0.027 +/- 0.012, p < 0.05) and those with IgAGN and renal fai lure (0.032 +/- 0.011, p < 0.01). However no difference was found betw een MGN patients and normals by deleting MGN cases with mild to modera te mesangial proliferation. The mean value of urinary cGMP in IgAGN pa tients with renal failure (0.186 +/- 0.117 nmol/min) was lower (p < 0. 05) than that of each group with normal renal function (IgAGN: 0.378 /- 0.010 nM/min; MGN: 0.338 +/- 0.064 nmol/min, non-IgAGN: 0.436 +/- 0 .168 nmol/min). The same significant differences were obtained by corr ecting cGMP values for creatinine urinary excretion. Urinary ET/cGMP r atio (assumed as an index of the relative balance between vasoconstric tor and vasorelaxing factors) was found to be higher than normal(0.570 +/- 0.010 ng/nmol) both in IgAGN patients with normal renal function (0.103 +/- 0.064 ng/mol, p < 0.05), and in those with renal failure (0 .203 +/- 0.108 ng/nmol, p < 0.02). Urinary cGMP values were not relate d to plasma levels of atrial natriuretic peptide (ANP). These data sho w that hyperexcretion of ET(1) occurs in a number of patients with mes angial proliferative GN. In some of them, mainly those with establishe d glomerular damage, the local production of ET(1) is not counterbalan ced by adequate cGMP biosynthesis.