Urinary excretion of vasoactive substances in chronic renal failure

To investigate the pathophysiological role of vasoactive substances in the progression of chronic renal disease, we measured the 24-hour urinary excre tion of prostaglandin 6-keto F(1)alpha, thromboxane B-2, NOx, cGMP and ET-1 in 26 patients with chronic renal failure under conservative treatment and in 40 control subjects. Urinary 6-keto PgF(1 alpha), TxB(2) and cyclic GMP were evaluated by RIA, and ET-1 was assayed by EIA. NOx were evaluated usi ng a colorimetric assay as nitrate/nitrite. Urinary excretion of prostaglan din 6-keto F(1)alpha averaged 18.1 +/- 20.9 ng/g U-creat in patients vs. 24 0.9 +/- 257.3 in controls (p < 0.0001), thromboxane B-2 422 +/- 374 ng/g U- creat in patients vs. 967 +/- 589 in controls (p < 2 x 10(-5)), NOx 7.07 +/ - 5.54 mg/g U-creat in patients vs. 9.79 +/- 3.77 in controls (p < 0.01), c GMP 310 +/- 200 pg/g U-creat in patients vs. 488 +/- 241 in controls (p < 0 .001). In contrast, ET-1 urinary excretion was almost doubled in patients ( 13.45 +/- 5.84 ng/g of U-creat) in comparison with controls (6.84 +/- 2.81 p < 1 x 10(-5)). While in control subjects significant correlations between urinary excretions of prostaglandin 6-keto F(1)alpha and thromboxane B-2 ( r = 0.69, p < 0.001) or NOx and ET-1 (r = 0.54, p < 0.001) were present, in patients only the relationship between urinary excretions of prostaglandin 6-keto F(1)alpha and thromboxane B-2 (r = 0.53, p < 0.01) was retained. Ou r data suggest that in the normal kidney a balance between prostaglandin 1, and thromboxane A(2), or nitric oxide an endothelin-1 is present, which co ntributes to hemodynamic regulation and protects this organ from ischemic d amage. This balance is abolished in CRF, where a large increment of vasopre ssor agent endothelin is present, which, joined to a prevalent decrease of prostaglandin I-2 synthesis, could contribute to the ischemic and fibrogene tic damage of the kidney, leading to progression of renal disease.