Albert M. Mattocks

Influence of range of renal function and liver disease on predictability of creatinine clearance

Several formulas for predicting creatinine clearance (Ccr) are used for adjusting drug dosages but limited data are available on their accuracy in patients with significant renal impairment or concurrent disease. We measured 144 Ccr in 103 patients and compared results using four separate predictive methods. Of nine common diseases in these patients, liver disease was associated with a large (p < 0.02) prediction error (overprediction). After data from eight patients with liver disease were removed, there was good overall correlation between predicted and measured Ccr (r2 = 0.91 for each method) but only two of the methods (I and IV) were consistently accurate in all ranges of renal function. Methods for predicting Ccr should not be used in patients with liver disease.

Creatinine kinetics in the rabbit

To evaluate the kinetics of creatinine in the rabbit, two radiotagged creatinine forms were used, with14C in the amidino group or with it in the carboxyl group. Five animals were injected intravenously with tracer amounts, and plasma samples were taken for 250–300 min; urine and feces samples were taken over longer periods. A chromatographic method was used to separate unchanged creatinine from other components of the samples prior to measurement for chemical and radioactivity content. Equations for the proposed flow model were derived and fitted to specific activity data, and values for transfer constants, production rates, and pool sizes were calculated. Evidence supported the concept that a two-compartment model is required and that production occurs in the peripheral compartment. Evidence also indicated that muscle represents a major part of the peripheral compartment. Small amounts of metabolites, chiefly guanido compounds, were detected when amidino-labeled creatinine was used. Also, small amounts of unchanged creatinine and metabolites were found in the feces.