A proposed mechanism for reduced creatinine excretion in severe chronic renal failure

Creatinine appearance, defined as the sum of daily creatinine excretion in urine (average over 5 days) plus accumulation in body water, measured over the same interval, was calculated in 27 patients with severe chronic renal failure (creatinine clearance less than 0.15 liter/kg/day). Creatinine appearance per kg body weight in patients with the lowest clearances decreased to values as low as one third of values predicted from age and sex. The absolute value of measured cratinine accumulation was only 11 +/- 2% of creatinine appearance and thus could not account for such deficits in appearance and therefore renal excretion. One explanation for these results is that extrarenal clearance, CM, remains constant, that is, that the quantity of creatinine degraded, M, is proportional to serum creatinine, S: CM = M/S. When the values for extrarenal clearance necessary to account for the measured deficit in creatinine appearance were calculated, they were found to be quite constant: 0.042 +/- 0.004 liter/kg/day (SEM, n=13) in males and 0.041 +/- 0.004 liter/kg/day (SEM, n=14) in females. Renal creatinine clearance in these patients, predicted from age, sex, serum creatinine, and the assumed constant value for extrarenal clearance, corresponded closely to observed clearance (r = 0.93). From these calculations, decreased creatinine appearance (and excretion) of uremic patients may be explained by a constant extrarenal clearance, indicating degradation.