Analytical Reviews in Clinical Biochemistry: The Estimation of Creatinine

PHYSIOLOGY Creatine is synthesised by the body in a two-step process (Fig. 1) involving the initial synthesis of guanidinoacetate, which takes place in the kidneys, small intestinal mucosa, pancreas, and probably the liver. The reaction between glycine and arginine is catalysed by a transamidase, which is subject to feedback inhibition by increased creatine levels. Guanidinoacetate is transported to the liver where it is methylated to creatine, which then enters the blood to be widely distributed, chiefly to muscle cells, in which it is converted to creatine phosphate-a source of high energy phosphate bonds for the immediate reformation of ATP during muscular contraction. Creatinine is formed by a spontaneous and irreversible conversion from creatine and creatine phosphate. Formation of creatinine is reasonably constant, and about 2% of whole body creatine is so transformed every 24 h. Consequently, creatinine formation also has a direct relationship to total muscle mass and roughly to the body weight. Creatinine production rate therefore remains approximately the same from day to day unless the muscle mass changes. It is not altered significantly by illness, sepsis, trauma or fever, nor by the state of hydration; however, increased protein intake can result in increases in creatinine production of the order of 10%.