Skeletal muscle expression of creatine kinase-B in end-stage renal disease

Abstract

The tissue specificity of creatine kinase (CK-MB) has been shown not to be absolute for the myocardium. Unexplained increases of plasma creatine kinase (CK-MB) occur in patients with skeletal muscle disease, confounding the diagnosis of myocardial injury. The purpose of this study was to examine the expression of CK-B as well as of the nuclear regulatory factor MyoD by Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR) techniques in skeletal muscle biopsies obtained from end-stage renal disease (ESRD) patients. Quantitation of CKMB mass demonstrated a 35-fold greater concentration in skeletal muscle from ESRD patients (n=45) vs normal skeletal muscles (n=10), (p<0.01). In 22 of 45 ESRD skeletal muscles, CK-B expression was detected by Western blot analysis, molecular weight 46 kDa. In the seven CK-B Western blot positive tissues studied, one demonstrated a RT-PCR amplification product at 111 bp. In contrast, no CK-B expression was detected by either Western blot or RT-PCR in normal skeletal muscles. MyoD expression (98 bp) was found in all ESRD and normal skeletal muscles. The intensity of the MyoD expression was greatest in tissues that demonstrated a higher CKMB mass concentration. Our findings demonstrate an increase in CK-B protein expression in human skeletal muscle obtained from patients with ESRD, that may in part be controlled by an increase in expression of mRNA for CK-B. The resulting increase in CKMB mass in skeletal muscle from ESRD patients may also be regulated by alterations in expression of the nuclear regulatory protein MyD.