DIABETIC RENAL-FAILURE AND SERUM ACCUMULATION OF THE CREATININE OXIDATIVE METABOLITES CREATOL AND METHYLGUANIDINE

Diabetic patients (n = 23) with chronic renal failure (CRF) accumulate the creatinine (Cr) oxidative metabolites creatol (CTL) and methylgua nidine (MG; a uremic toxin) in their sera. Analysis of serum CTL, a ke y intermediate in mammalian Cr catabolism into MG, is shown to offer s ome useful diagnostic information on CRF, especially in the determinat ion of an initial stage of pathological renal failure. The sera of all diabetic (n = 23) and nondiabetic (n = 20) patients with CRF (s-Cr > 1.25 mg/dl) contained s-CTL (>2 mu g/dl), whereas those from normal su bjects (n = 18) and diabetic patients (n = 18) without CRF contained n o detectable s-CTL. A similar accumulation of s-MG was observed, but o nly when s-Cr was higher than 2.0 mg/dl. Although each s-CTL (Y: mu g/ dl, Y': mol/l) and s-MG level (Z: mu g/dl, Z': mol/l) is highly correl ated with s-Cr (X: mg/dl, X': mol/l) in a normal equation, Y or Z = AX + B, an alternative correlation in a second-order equation, Y or Z = alpha X(2) + beta X, could also fit well. Since the quadratic equation can be convertible to Y/X or Z/X = alpha X + beta [Y'/X' or Z'/X' = a lpha'X + beta'] and active oxygen species, especially hydroxyl radical s, convert Cr into CTL, Y/X, Y'/X', Z/X and Z'/X' values which might b e a kind of indices for oxygen stress (oxidative stress) increased in proportion to the increased severity of CRF in such patients. Although its meaning and interpretation are still debatable, diabetic CRF pati ents had a significantly higher alpha' value (2.2) than that (0.89) of nondiabetic CRF patients. All serum values for Cr, CTL and MG were me asured with HPLC.