Influence of Muscle Mass and Physical Activity on Serum and Urinary Creatinine and Serum Cystatin C

Influence of Muscle Mass and Physical Activity on Serum and Urinary Creatinine and Serum Cystatin C

Accurate renal function measurements are important in the diagnosis and treatment of kidney diseases, adjustment of drug dosages, and decision-making regarding when to initiate renal replacement therapy. Serum creatinine is the most commonly used indicator of renal function, but its measurement suffers from a variety of analytical interferences and significant standardization problems (1,2).

Serum creatinine can be affected by age, gender, ethnicity, dietary protein intake, and lean mass and may remain within the reference range despite marked renal impairment in patients with low muscle mass. Consequently, the sensitivity of serum creatinine for the early detection of kidney disease is poor and not a good predictor when analyzing the elderly (3,4). Conversely, theoretically, serum creatinine may be falsely increased in individuals with higher muscle mass and normal renal function.

The GFR represents the best overall assessment of kidney function, but the gold standard techniques for the measurement of GFR, such as inulin clearance, [¹²⁵I]iothalamate, ⁵¹Cr-EDTA, ^99mTc-diethylenetriaminepentaacetic acid, and iohexol are too labor-intensive and costly for routine clinical use (5,6), so creatinine clearance is used instead.

To rid the need of 24-h urine collections, several serum creatinine–based prediction formulas have been proposed to predict GFR (7–16). The equations of Cockcroft and Gault (7,8) and the one derived from the Modification of Diet in Renal Disease (MDRD) study (10) are the most widely accepted; however, the competence of such formulas to predict GFR in patients with normal values of serum creatinine is debated.

Despite the important influence of muscle mass on serum creatinine, the different equations used to predict GFR do not include parameters of body composition such as lean mass. Human body mass can be partitioned into two main compartments: Fat and lean (fat-free) mass. The latter comprises body cell mass (BCM), bone mass, and extracellular water. The gold standard techniques for the measurement of body composition include hydrodensitometry, computed tomography, magnetic resonance imaging, dual-photon absorptiometry, neutron activation analysis, total body potassium counting, and isotope dilution (17,18). Nevertheless, in clinical practice, the indirect, low-cost, noninvasive methods of determining human body composition, such as bioelectrical impedance and skinfold thickness, are used instead (17). Muscle mass is extremely variable among elderly individuals and in children (4,19–22) and can be substantially modified by physical exercise (23).

Cystatin C, a low molecular weight basic protein (13 kD) that is freely filtered and metabolized after tubular reabsorption with only small amounts excreted in the urine, is an endogenous filtration marker that is being considered as a potential replacement for serum creatinine. Unlike serum creatinine, the serum concentration of cystatin remains constant up to 50 yr of age. It is commonly accepted that cystatin is produced at a constant rate in virtually all nucleated cells and that it is unaltered by inflammatory conditions. The advantages of using cystatin C as a filtration marker are less influence by age, gender, weight, and muscle mass than serum creatinine (24–31). An overall meta-analysis based on 46 studies performed on adults and children demonstrated, by means of receiver operating characteristic analysis, that cystatin C is superior to serum creatinine as a marker of kidney function (32). To address the influence of muscle mass on serum and urinary creatinine determination and serum cystatin C, we evaluated the body composition through bioelectrical impedance and skinfold thickness in healthy individuals with distinct levels of physical activity.

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