Urinary excretion of vasoactive substances in chronic renal failure.

To investigate the patho-physiological role of vasoactive substances in the progression of chronic renal disease, we measured the 24-hour urinary excretion of prostaglandin 6-keto F 1α , 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 1α , TxB 2 and cyclic GMP were evaluated by RIA, and ET-1 was assayed by EIA. NOx were evaluated using a colorimetric assay as nitrate/nitrite. Urinary excretion of prostaglandin 6-keto F 1α averaged 18.1 ± 20.9 ng/g U creat in patients vs. 240.9 ± 257.3 in controls (p < 0.0001), thromboxane B 2 422 ± 374 ng/g U creat in patients vs. 967 ± 589 in controls (p < 2×10 -5 ), NOx 7.07 ± 5.54 mg/g U creat in patients vs. 9.79 ± 3.77 in controls (p<0.01), cGMP 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 × 10 -5 ). While in control subjects significant correlations between urinary excretions of prostaglandin 6-keto F 1 α 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 α and thromboxane B 2 (r = 0.53, p < 0.01) was retained. Our data suggest that in the normal kidney a balance between prostaglandin I 2 and thromboxane A 2 , or nitric oxide and endothelin-1 is present, which contributes to hemodynamic regulation and protects this organ from ischemic damage. This balance is abolished in CRF, where a large increment of vasopressor agent endothelin is present, which, joined to a prevalent decrease of prostaglandin I 2 synthesis, could contribute to the ischemic and fibrogenetic damage of the kidney, leading to progression of renal disease.