A Proposed Mechanism for Reduced Creatinine Excretion in Severe Chronic Renal Failure

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Abstract
Creatinine appearance, defined as the sum of daily creatinine excretion in urine (averaged 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 l/kg per day). Creatinine appearance/kg body weight in patients with the lowest clearances decreased to values as low as 1/3 of values predicted from age and sex. The absolute value of measured creatinine accumulation was only 11 .+-. 2% of creatinine appearance and could not account for such deficits in appearance and therefore renal excretion. One explanation for these results was that extrarenal clearance, CM, remains constant, i.e., that the quantity of creatinine degraded, M, was 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 are quite constant: 0.042 .+-. 0.004 l/kg per day (SEM [standard error of mean]) in males and 0.041 .+-. 0.004 l/kg per day (SEM) 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 [correlation coefficient] = 0.93). From these calculations, decreased creatinine appearance (and excretion) of uremic patients may be explained by a constant extrarenal clearance, indicating degradation.