Creatinine, production

In the muscle, phosphocreatine and creatine undergo cyclisation to form creatinine (Figure 8.20(b)). Since creatinine cannot be metabohsed, it is released from muscle and is then excreted in the urine. This biochemical process is useful in clinical practice, since creatinine production is spontaneous and is remarkably constant 1.7% of the phosphocreatine and creatine in muscle cyclises each day, so that its concentration in blood provides an indication of the glomerular filtration rate, and hence provides an indication of the function (i.e. the health) of the kidney. 

Drugs cleared by the renal route often require adjustment of clearance in proportion to renal function. This can be conveniently estimated from the creatinine clearance, calculated from a single serum creatinine measurement and the predicted creatinine production rate. 

The predicted creatinine production rate in women is 85% of the calculated value, because they have a smaller muscle mass per kilogram and it is muscle mass that determines creatinine production. Muscle mass as a fraction of body weight decreases with age, which is why age appears in the Cockcroft-Gault equation. ... 

The decrease of renal function with age is independent of the decrease in creatinine production. Because of the difficulty of obtaining complete urine collections, creatinine clearance calculated in this way is at least as reliable as estimates based on urine collections. Fat-free mass (equation [14]) should be used for obese patients, and correction should be made for muscle wasting in severely ill patients. 

Reference values for amino acids in the urine show a rather sharp decrease from the neonatal period to adulthood (Table 2.1.6). This is mainly due to the maturation of the renal tubular reabsorption system, but is also the result of increasing muscle mass with age, giving rise to increasing creatinine production. 

Because of the problems with changes in creatinine production and secretion, other endogenous compounds have been evaluated in an effort to provide a more accurate estimation of GFR. Perhaps the most promising is cystatin C, a low molecular weight protein that is a member of the cystatin super family of cysteine protease inhibitors [112]. Cystatin C is produced by all nucleated cells and its rate of production is relatively constant, being unaltered by inflammatory conditions... 

The concentration of creatinine in serum is a function of creatinine production and renal excretion. Creatinine is a product of creatine metabolism from muscle therefore its production is directly dependent on muscle mass. At steady state, the normal serum creatinine concentration is approximately 0.5 to 1.5 mg/dL for males and females. Creatinine is eliminated primarily by glomerular filtration, and as GFR declines, the serum creatinine concentration rises (Fig. 41-2). 

NKF K/DOQI National Kidney Foundation Kidney Disease Outcomes Quality Initiative NMN Al-1-methylnicotinamide PAH p-aminohippurate Per creatinine production rate Pier plasma creatinine level P-gp P-glycoprotein RBF renal blood flow RPF renal plasma flow Ser serum creatinine concentration SNGFR single nephron glomerular filtration rate SUN serum urea nitrogen (concentration)... 

Beddhu S, Samore MH, Roberts MS, et al. Creatinine production, nutri- 103. 

Leblanc M, Garred LJ, Cardinal J, et al. Catabolism in critical illness estimation from urea nitrogen appearance and creatinine production during continuous renal replacement therapy. Am J Kidney Dis 1998 32 444-453. 

Creatinine is a nitrogenous waste product derived from creatine. It is removed from the circulation by filtration through the glomeruli, and a little is secreted by the tubules. Since creatinine production is endogenous, being dependent on muscle mass, its level in the blood is usually independent of diet, unlike urea. 

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