Effect of products of proteic catabolism on EDRF/NO production in rabbit aorta rings

Abstract

Levels of 15 guanidino compounds and urea were determined in serum and urine of nondialyzed patients with chronic renal insufficiency subdivided according to etiology and creatinine clearances. No significantly different guanidino compound levels in serum and urine were found for the interstitial nephritis, glomerulonephritis, nephrangiosclerosis, and diabetic nephropathy subgroups. Subdividing the patients according to creatinine clearance yields the following results: (1) Serum guanidinosuccinic acid (GSA) and methylguanidine levels of patients with end-stage renal failure (creatinine clearance < 10 mL/min) are up to 100 and 35 times higher than control levels, while guanidine, creatinine, and symmetrical dimethylarginine (SDMA) are increased about 10 times. Serum levels of asymmetrical dimethylarginine (ADMA) are only doubled in end-stage renal failure. Serum levels of guanidinoacetic acid (GAA) and homoarginine are significantly decreased. (2) Urinary excretion levels of most guanidino compounds decrease with decreasing creatinine clearance except for GSA and methylguanidine. (3) Greater than 90% of patients with creatinine clearance ranging from subnormal to 40 mL/min have serum SDMA levels higher than the upper-normal limit; up to 80% have increased GSA levels. (4) The clearance rates of some of the guanidino compounds could be calculated: with the exception of arginine, they decrease with decreasing creatinine clearance. This study shows specific abnormal guanidino compound levels in serum and urine of nondialyzed patients with chronic renal insufficiency that can be used as complementary diagnostic parameters. The best correlation between serum guanidino compound levels and the degree of renal insufficiency is found for GSA, SDMA, methylguanidine, and guanidine. Urinary excretion levels of ADMA correlate best with decreasing creatinine clearance. Serum levels of GSA and especially SDMA are candidate indicators for the onset of renal failure.