Total creatine kinase and isoenzyme fractions in ...

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We measured total serum creatine kinase (CK) and serum creatine kinase MB fraction (CK-MB) in 53 pa- tients on continuous ambulatory peritoneal dialysis.
The International Journal Of Artificial Organs I Vol. 10 I no. 2, 1987 I pp. 72-76

Artificial Kidney and Dialysis

Total creatine kinase and isoenzyme fractions in chronic dialysis patients KEYWORDS -

Creatine kinase Hemodialysis CAPO Chronic renal failure Myocardial infarction

ABSTRACT We measured total serum creatine kinase (CK) and serum creatine kinase MB fraction (CK-MB) in 53 patients on continuous ambulatory peritoneal dialysis (CAPO) and 52 patients on maintenance hemodialysis (HO), using Scalva UV methodology for CK and electrophoresis for CK-MB. Seven of the 53 CAPO patients (13%) had an elevated total CK, and only one of these 7 patients had an elevated CK-MB > 5%. In contrast 22 HO patients (42%) had increased total CK values, and 6 of these 22 HO patients (27%) showed elevated CK-MB isoenzyme > 5%. For each sex, blacks had higher mean CK values than whites. Twenty-one out of the 43 HO patients who received intramuscular injections had elevated total CK values and 6 of these 21 patients had elevated CK-MB isoenzyme independent of the timing of injection. The increased frequency of higher total CK values in HO patients appears to be related to race and androgen administration. The modest elevations in CK-MB fraction (5 to 8%) in these patients require careful interpretation.

INTRODUCTION Creatine kinase (CK) is an enzyme found predominantly in cardiac muscle, skeletal muscle and brain. Elevation of total CK enzyme is seen following acute myocardial infarction, strenuous physical activity,

S.M. Lal, K.D. Nolph, H. Hain1, H.L. Moore, R. Khanna, J.C. Van Stone, Z.J. Twardowski Division of Nephrology Department of Medicine University of Missouri Health Sciences Center, VA Hospital and Dalton Research Center Columbia, Missouri, U.S.A. 1Abteilung fur lnnere Medizin, mit Schwerpunkt Nephrologie, Klinikum Westend der Freien Universitat Berlin, Berlin, F.R.G.

rhabdomyolysis and intramuscular injections (1-5). An elevated concentration of CK-MB isoenzyme fraction is considered to be a sensitive indicator of acute myocardial injury (6-11). However, elevations in CK-MB isoenzyme levels have been observed in chronic renal failure (CRF) patients in the absence of known myocardial injury (12-16). We prospectively studied total CK and CK-MB isoenzyme elevations in CRF patients on maintenance hemodialysis (HD) and on continuous ambulatory peritoneal dialysis (CAPO).

MATERIAL AND METHODS We studied 105 patients. Fifty-two patients had been on maintenance hemodialysis for 5 to 132 months (mean 40 ± 29 SD). Fifty-three patients had been on CAPO from 4 to 87 months (mean 23 ± 18 SD). The mean age of patients on HD was 55 years (± 16 SD) with a range of 22 to 84; 27 were males and 25 were females; 34 of them were white and 18 were black. Among the 53 patients on CAPO, the mean age was 56 years (+ 13 SD) with a range of 25 to 77; all but one were white; 29 were male and 24 female. In the HD patients 9 patients received no intramuscular injections, 13 patients received an intramuscular injection of androgens 3 days before drawing blood for CK and 30 patients had an intramuscular androgen injection 5 days or longer (range 5-30 days) before blood sampling. CAPO patients received neither androgens nor other injections. Patients with chest pain, angina pectoris or a cerebrovascular accident in the past 6 months were excluded. No patient was receiving clofibrate therapy.

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Blood was drawn from CAPO patients during routine visits and in HD patients before the first hemodialysis of the week. Blood samples for total CK estimation were allowed to clot for 30 minutes at room temperature, then centrifuged. The sera were kept at 4° C until assay, done on the same day. Total CK activity was determined spectrophotometrically in an ABA200 Bichromatic analyzer (Abbott Laboratories, North Chicago, IL) by the Sclavo UV methodology. Enzyme activity was expressed as lUlL at 37° C. The Sclavo method uses AMP and fluoride together to reduce the adenylate kinase interference to very low levels without loss of CK activity. Patients whose sera showed elevated values of total CK had their sera analyzed for CK isoenzymes by an electrophoretic method within 2 weeks of collecting the blood samples (18). Mean creatine kinase and CK isoenzyme concentrations in CAPO and HD patient populations were compared by using a non-paired 't' test. Ratiosns of abnormal to normal patient levels in CAPO and HD patient populations were compared by the chi-square test. P value< 0.05 was considered to be significant.



'l'//. Normal range (1-173 IU/1) -----Mean HD

• • • • •

-Mean CAPO

CK (IU/1)

I •I

. • --- ---t--------- ---- -- ----""!------ ------



HD

CAPO

(Hemodialysis)

Fig. 1 Individual CK values the mean values in CAPO and HD

patient population.

RESULTS TABLE 1CK values in CAPO and HD patients are shown in Figure 1. The mean total CK value in CAPO patients was 107.1 ± 9.9 IU/L (range 22- 364) and in HD patients 268.7 ± 42.6 IU/L (range 24 - 1,606), (p < 0.0003). Only seven of 53 CAPO patients (Tab. 1) had elevated total CK and only 1 of these 7 patients had an elevated CK-MB ~ 5%. In contrast, 22 out of 52 HD patients (42%) had increased CK values, and six of these 22 HD patients had elevated CK-MB isoenzyme ~ 5%. The CK-MM made up most of the enzyme in both groups. None of the dialysis patients had detectable CK-BB isoenzyme. As shown in Table 2, black male hemodialysis patients showed higher mean CK concentration than white men. The black female patients on HD likewise showed a higher mean CK concentration compared to white women. Among the white patients there were no differences in the mean CK values with regard to sex or mode of dialysis therapy. The effect of intramuscular injection on CK and CK-MB isoenzyme in HD patients is shown in Table Ill. There were no significant

CREATINE KINASE ISOENZYMES IN PATIENTS WITH ELEVATED TOTAL CK VALUES CAPO

HD

Pts with elevated total CK

7/53

22/52

Total CK (lUlL)

261.3 ± 20

531.5 ± 68*

Range

212-364

230-1606

Pts with CK MB < 5%

1

8

98.7±0.8

97.2 ± 0.6

Pts with CK MB ;;:;. 5% CKMM% Mean ± SEM *P < 0.004

6

Non-Paired T Test

differences between the timing of intramuscular injection and its effect on CK, and no significant correlations with a battery of serum biochemistry values.

DISCUSSION Serum CK-MB is considered to be released from the heart and elevated concentrations are thought to be diagnostic of acute myocardial infarction (6-11).

73

Creatine kinase in dialysis patients

TABLE 2-

TOTAL CK IN DIALYSIS PATIENTS: SEX AND RACE RELATED HD

CAPO Male Black

517 ± 100* (10)

Caucasian

113 ± 14

200± 46

(29)

(17)

143

494 ± 199**

Female Black Caucasian

(1)

(7)

98± 15

108 ± 23

(23)

(18)

CK (IU/L); Mean± SEM; ( ) Denotes Number of Patients. • P < 0.003 (Male: Black vs Caucasian) •• P < 0.005 (Female: Black vs Caucasian)

TABLE 3-

CK (lUlL) Range Pts with CK

EFFECT OF INTRA MUSCULAR INJECTION ON CK AND CK M8 IN HD PATIENTS NoiNJ

INJ