The serum creatinine concentration is widely interpreted as a measure of the glomerular filtration rate (GFR) and is used as an index of renal function in clinical practice. Glomerular filtration of creatinine, however, is only one of the variables that determines its concentration in serum. Alterations in renal handling and metabolism of creatinine and methodological interferences in its measurement may have a profound impact on the serum concentration of creatinine. We review the fundamental principles of physiology, metabolism, and analytical chemistry that are necessary to correctly interpret the serum creatinine concentration. These principles are then applied to important clinical circumstances, including aging, pregnancy, diabetes mellitus, drug administration, and acute and chronic renal failure. Despite numerous limitations, serum creatinine remains a useful clinical tool, but more accurate measures of renal function are frequently necessary.

Serum creatinine as an index of renal function: new insights into old concepts.

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%.

https://journals.sagepub.com/doi/pdf/10.1177/000456328602300101

Analytical Reviews in Clinical Biochemistry: The Estimation of Creatinine:

Serum creatinine concentrations are widely used clinically as an index of renal function. In stable normal or reduced renal function they are determined by the rate of creatinine production and the endogenous creatinine clearance, and, during changing renal function, also by the apparent volume of distribution of creatinine. These determinants of serum creatinine concentrations, however, are affected by age, sex and body weight. The rate of creatinine production is proportional to body weight, and it decreases with age and is slower in females than in males. The endogenous creatinine clearance decreases with age and is lower in females than in males. The apparent volume of distribution of creatinine is equal to the total body water, which is proportional to body weight, and it decreases with age and is lower in females than in males. The individual relationships between the determinants of serum creatinine concentrations and age, sex, and body weight on the relationship between normal and reduced renal function and serum creatinine concentrations are illustrated by simulations. Equations are derived to predict endogenous creatinine clearance from serum creatinine concentrations, and a nomogram is presented for determining relative renal function from serum creatinine concentrations, which take into account the age, sex and body weight of the individual patient. It is recommended for rapid clinical evaluation of stable normal or reduced renal function. When rapid changes are expected clinically, however, it is recommended to use a mid urine collection period serum creatinine sample for creatinine clearance determination.

Use of serum creatinine concentrations to determine renal function.

Diagnostic value of serum cystatin C for evaluation of hepatorenal syndrome

We describe a "high-performance" liquid-chromatographic procedure for determination of creatinine in serum. Creatinine is separated from other species by cation-exchange chromatography. Absorbance of the creatinine in the eluate is monitored at 234 nm. Results from this procedure on sera correspond closely to those of a manual Jaffe-reaction procedure involving use of a protein-free filtrate with additional cleanup of the sample with Lloyd's reagent. None of the 21 endogenous and exogenous substances that we screened interfered. The overall CV at 138 mumol of creatinine per liter is 1.35% and at 539 mumol/L is 0.72%.

Creatinine determined by "high-performance" liquid chromatography.

Specific method for serum creatinine determination based on ion exchange chromatography and an automated alkaline picrate reaction — A proposed reference method

R.B.B. Trotman

Papers

Specific method for serum creatinine determination based on ion exchange chromatography and an automated alkaline picrate reaction — A proposed reference method