Low Serum Creatine Kinase Level Predicts Mortality in Patients with a Chronic Kidney Disease.

Adrien Flahault,Marie Metzger,Jean-François Chassé,Nicolas Pallet,Nephrotest Study Group ,Jean-Philippe Haymann,Jean-Jacques Boffa,Bénédicte Stengel,Pascal Houillier,Eric Thervet,François Vrtovsnik,Martin Flamant

doi:10.1371/journal.pone.0156433

Abstract

BackgroundSerum creatine kinase (sCK) reflects CK activity from striated skeletal muscle. Muscle wasting is a risk factor for mortality in patients with chronic kidney disease (CKD). The aim of this study is to evaluate whether sCK is a predictor of mortality and end-stage renal disease (ESRD) in a CKD population.MethodsWe included 1801 non-dialysis-dependent CKD patients from the NephroTest cohort. We used time-fixed and time-dependent cause-specific Cox models to estimate hazard ratios (HRs) for the risk of death and for the risk of ESRD associated with gender-specific sCK tertiles.ResultsHigher sCK level at baseline was associated with a lower age, a higher body mass index, and a higher level of 24 h urinary creatinine excretion, serum albumin and prealbumin (p<0.001). Men, patients of sub-Saharan ancestry, smokers and statin users also experienced a higher level of sCK. In a time-fixed Cox survival model (median follow-up 6.0 years), the lowest gender-specific sCK tertile was associated with a higher risk of death before and after adjustment for confounders (Crude model: hazard ratio (HR) 1.77 (95% CI: 1.34–2.32) compared to the highest tertile; fully-adjusted model: HR 1.37 (95% CI: 1.02–1.86)). Similar results were obtained with a time-dependent Cox model. The sCK level was not associated with the risk of ESRD.ConclusionA low level of sCK is associated with an increased risk of death in a CKD population. sCK levels might reflect muscle mass and nutritional status.

Highlights

Creatine kinase (CK), referred to as creatine phosphokinase (CPK), is a cytosolic and mitochondrial enzyme that catalyzes the phosphorylation of creatine into phospho-creatinine, a rapidly mobilizable reserve of high energy phosphates: phosphocreatine donates a phosphate group to adenosine diphosphate (ADP) to generate adenosine triphosphate (ATP)
Higher serum CK (sCK) level at baseline was associated with a lower age, a higher body mass index, and a higher level of 24 h urinary creatinine excretion, serum albumin and prealbumin (p
Low Serum Creatine Kinase Predicts Mortality in Chronic Kidney Disease before and after adjustment for confounders (Crude model: hazard ratio (HR) 1.77 compared to the highest tertile; fully-adjusted model: hazard ratios (HRs) 1.37)

Summary

Introduction

Creatine kinase (CK), referred to as creatine phosphokinase (CPK), is a cytosolic and mitochondrial enzyme that catalyzes the phosphorylation of creatine into phospho-creatinine, a rapidly mobilizable reserve of high energy phosphates: phosphocreatine donates a phosphate group to adenosine diphosphate (ADP) to generate adenosine triphosphate (ATP). CK is an important enzyme in tissues that consumes ATP rapidly, including the muscles and brain [1], and serum CK (sCK) activity measurement is used as a blood test to monitor damage in CK-rich tissues, mainly in striated muscles [2]. SCK activity is currently measured in clinical practice to detect and monitor muscle-associated diseases, including rhabdomyolysis, myocardial infarction, myositis and muscle dystrophy. A moderately elevated level of sCK was shown to be associated with an increased risk of high blood pressure [8]. Serum creatine kinase (sCK) reflects CK activity from striated skeletal muscle. Muscle wasting is a risk factor for mortality in patients with chronic kidney disease (CKD). The aim of this study is to evaluate whether sCK is a predictor of mortality and end-stage renal disease (ESRD) in a CKD population

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