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Looking for Sarcopenia Biomarkers

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Sarcopenia, defined as age-associated loss of skeletal muscle mass and function, has emerged as an important public health issue. It is associated with higher mortality, morbidity, physical disability, and health care cost.12While sarcopenia should be diagnosed with measurements of muscle mass and function, serum biomarkers are needed for screening of sarcopenia in a large population. Serum creatinine is a known biomarker for muscle mass and kidney function because 90% of its precursor, creatine phosphate, is stored in the muscle, its production is mostly constant, and its excretion is completely via the kidney.3 For patients with normal renal function, serum creatinine is a reasonable biomarker for sarcopenia. In this issue, Thongprayoon et al4 reported that a low serum creatinine level, most likely due to sarcopenia, is associated with a higher mortality rate.

They found that the association between admission creatinine values and in-hospital and 1-year mortalities is a U-shaped distribution, suggesting that low muscle mass and poor kidney function account for the higher mortality for each end, respectively. Importantly, because males usually have larger muscle mass, the cut-off for low serum creatinine level is sex dependent. From the U curves, the nadir serum creatinine level for males is 0.9-1.0 mg/dL, and for females is 0.7-0.8 mg/dL. Male patients with serum creatinine level <0.6 mg/dL, and females <0.4 mg/dL, had increased in-hospital and 1-year mortality by about two- to threefold. For patients with a low serum creatinine level, the chance to die during the admission is about 1 in 50, and to die within 1 year after discharge would be 1 in 5.4 These results suggest that we should pay more attention to patients with low serum creatinine levels and follow them more closely after discharge.

In this study, sarcopenia is probably the main cause of low admission serum creatinine levels.4 However, there are many conditions that may lower serum creatinine level and result in a misdiagnosis of sarcopenia (False positive, Table).356 Among them, the augmented renal clearance is still not fully understood. It is seen in young intensive care unit patients, probably due to fluid overload, systemic inflammation, and other unknown causes.6On the other hand, many sarcopenic patients may not have low serum creatinine levels due to the conditions that raise serum creatinine levels (False negative, Table).3 In this study, 4.6% of male and 2.0% of female hospital patients may have sarcopenia based on low serum creatinine levels.4 These numbers could be significantly underestimated, most likely due to chronic kidney disease.

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-Yeong-Hau H. Lien, MD, PhD

This article originally appeared in the May 2017 issue of The American Journal of Medicine.

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