Reliability and Significance of Increased Creatine Kinase MB
Isoenzyme in the Serum of Uremic Patients
L. JEFFREY MEDEIROS, M.D., DIANA SCHOTTE, MT(ASCP), AND BENJAMIN GERSON, M.D.
The authors quantified creatine kinase MB (CK-MB) isoenzyme
activity and mass in the serum of 81 uremic and 20 nonuremic
(control) patients who had no clinical or electrocardiographic
evidence of acute myocardial infarction. CK-MB was quantified
by three methods: electrophoresis, the QuiCK-MB® (International Immunoassay Labs), and the Tandem-E® CK-MB (Hybritech, Inc.). The authors then followed all uremic patients for
subsequent hospitalization for cardiac disease. Median CK-MB
was increased in the serum of the uremic patients as compared
with the control patients by all methods. Most uremic patients
had CK-MB in serum above the median CK-MB of the control
group. Seventeen (21%) uremic patients had CK-MB in serum
elevated above the reference range by at least one method. All
control patients had CK-MB in the serum within the reference
range. Twelve of 81 (15%) uremic patients have subsequently
developed acute myocardial infarction (six patients; four died)
or angina pectoris (six patients; one died). Eleven patients were
specifically hospitalized for cardiac symptoms. One patient had
acute myocardial infarction three weeks after renal transplant.
With the use of the chi-square test and 2X2 contingency tables,
patients with CK-MB in serum above 5 U/L by electrophoresis
(x2 = 5.47; P < 0.05) or at least 2.9 EU/L by the QuiCK-MB
(x2 = 6.56; P < 0.01) appeared to be at increased risk of subsequent hospitalization. The authors conclude that a slight increase of CK-MB in serum is found in most uremic patients.
However, CK-MB elevated above reference range in the serum
of uremic patients without clinical or electrocardiographic evidence of acute myocardial infarction is not common. When found,
elevated CK-MB isoenzyme appears to be associated with an
increased risk of subsequent cardiac disease. Therefore, quantification of CK-MB in the serum of uremic patients is more
reliable than is implied in the literature. (Key words: Creatine
kinase; MB isoenzyme; Electrophoresis; immunoradiometric;
Immunoenzymometric; Uremia.) Am J Clin Pathol 1987; 87:
103-108
IN PREVIOUS STUDIES, elevated levels of creatine kinase (EC 2.7.3.2; CK) MB (CK-MB) isoenzyme were
found in the serum of uremic patients undergoing
maintenance dialysis.2'6'8,9 These patients had no clinical
or electrocardiographic evidence of acute myocardial infarction at the time their serum samples were studied.
These authors suggested that CK-MB isoenzyme might
be increased in the serum of these patients as a result of
Received December 31, 1985; received revised manuscript and accepted for publication July 14, 1986.
Address reprint requests to Dr. Medeiros: Department of Pathology,
Stanford University Medical Center, 300 Pasteur Drive, Stanford, California 94305.
Department of Pathology, New England Deaconess Hospital,
Boston, Massachusetts
renal failure itself.2,8,9 Perhaps uremia, by paralyzing the
reticuloendothelial system, decreases clearance of CK-MB
from serum, resulting in its elevation.8'9 The authors also
implied that elevated CK-MB isoenzyme in the serum of
uremic patients may not be an indicator of cardiac disease,
thereby decreasing the reliability of this laboratory test in
a group of patients known to be at increased risk of coronary atherosclerosis.7
Recently, new developments in methods have occurred
that may lead to more accurate and reliable quantification
of CK-MB isoenzyme. Corning (Corning Medical, Medfield, MA) has introduced the Model 760® fluorometer/
densitometer into their electrophoresis system. This instrument has adjustable features that allow the experienced user to avoid nonspecific background fluorescence,
which makes accurate quantification of CK-MB activity
difficult, particularly when the total serum CK is within
the reference range.10 Also, immunoradiometric 13 and
immunoenzymometric 1 methods that measure CK-MB
mass in serum have been developed. These methods do
not depend on enzyme activity and, instead, use the antigenic properties of the CK-MB isoenzyme.
In this study, we quantified CK-MB isoenzyme in the
serum of 81 uremic and 20 nonuremic (control) patients
without evidence of acute myocardial infarction by electrophoresis using the Model 760 instrument and two immunoassays: the QuiCK-MB® (International Immunoassay Labs) and the Tandem-E® CK-MB (Hybritech, Inc.).
We then followed all of the uremic patients for three to
six months. We did the study to answer the following
questions: (1) Are the quantity and prevalence of CK-MB
isoenzyme in the serum of uremic patients increased as
compared with that of a control group? (2) Are uremic
patients with CK-MB in serum above the reference range
at increased risk of hospitalization for cardiac disease?
And, by answering the first two questions, (3) are serum
CK-MB isoenzyme levels quantified by these new methods
reliable in uremic patients?
103
104
MEDEIROS, SCHOTTE, AND GERSON
Materials and Methods
Patient Population
Eight-one patients undergoing maintenance hemodialysis or peritoneal dialysis who had no clinical or electrocardiographic evidence of acute myocardial infarction
were studied. No patients had had evidence of a recent
(within one month of this study) myocardial infarction.
All patients were on dialysis for at least two months and
were dialyzed at New England Deaconess Hospital between January 1 and June 30, 1985. The median blood
urea nitrogen (BUN) of these patients were 28.0 /umol/L
(range, 12.9-72.1 jtmol/L) and the median serum creatinine, 937 /xmol/L (range, 274-1,963 /umol/L). The reference range in this laboratory for BUN is 1.8-8.6 /tmol/
L and for serum creatinine, 44-115 jmiol/L.
A control group of 20 patients without uremia was also
studied in order to compare the quantity and prevalence
of CK-MB isoenzyme in the serum of both groups. This
group was selected from the outpatients requiring laboratory studies of serum seen at New England Deaconess
Hospital on February 27, 1985.
Specimen Collection
On all patients of both groups laboratory studies were
ordered by their respective physicians. Dialysis patient
blood samples were drawn before the next dialysis treatment. Similarly, patients subsequently hospitalized for
cardiac disease had blood samples drawn as part of a protocol to rule-out acute myocardial infarction. All samples
were allowed to clot, and the serum was separated from
the cells by centrifugation within two hours. The requested
studies were performed in routine fashion. The remaining
serum was stored in the dark at -20 °C until time of
experiment.
A.J.C.P. • January 1987
enzyme fraction by automatic integration. The percent
of CK-MB isoenzyme multipled by the total serum CK
activity yielded the total serum activity of CK-MB. According to Wagner and Dillon,14 up to 5 U/L of CK-MB
is within the reference range.
With the second and third aliquots, CK-MB mass was
determined by the QuiCK-MB (International Immunoassay Labs, Santa Clara, CA) and the Tandem-E CKMB (Hybritech, Inc., San Diego, CA) immunoassays.
The QuiCK-MB assay is a solid-phase, two-site sandwich, immunoradiometric method. In the first step, patient serum is mixed with antibody specific for the CK B
unit, which is bound to a solid phase. The CK-BB and
CK-MB attached to the solid phase is then incubated with
I125-labeled antibody specific for the CK M unit. The
bound radioactivity, quantified by a Packard Auto-gamma
Scintillation Spectrometer®, Model 5130 (Packard Instrument Company, Rockville, MD), is a measure of CKMB in patient serum. The normal range of this assay as
suggested by the manufacturer is less than 2.9 equivalent
units per liter (EU/L).13 One EU/L is defined as the immunologic activity of CK-MB equivalent to 1 unit of enzymatic activity (U/L) of freshly prepared calibrators, as
measured by Calbiochem-Behring "Stat-Pack"® at 30 °C.3
The Tandem-E CK-MB assay is a solid-phase, two-site
sandwich, immunoenzymometric method. In the first
step, patient serum is mixed simultaneously with monoclonal antibody specific for the CK M unitfixedto a plastic
bead and monoclonal antibody specific for the CK B unit
linked to alkaline phosphatase. After separation of the
solid phase, p-nitrophenyl phosphate (substrate) is added,
and the p-nitrophenol cleaved by the enzyme is quantified
at 405 nm (Photon Immunoassay Analyzer®, Hybritech).
The normal range of this assay, as suggested by the manufacturer, is less than than 9 ^g/L.1
Follow-up
Laboratory Methods
At the time of experiment, the stored serum was thawed
and divided into three aliquots. With the first aliquot, we
measured total serum CK by the modified Rosalki
method" in a Multistat III® microcentrifugal analyzer
(Instrumentation Laboratory, Lexington, MA) with Statzyme® CK n-1 reagents (Worthington Diagnostics System,
Freehold, NJ). The reference range for total serum CK in
this laboratory for both sexes is up to 155 U/L. With the
same aliquot, we quantified CK-MB by agarose gel electrophoresis employing a method we have previously described.10 The Corning® (Corning Medical, Medfield, MA)
electrophoresis system, reagents, and the Model 760 fluorometer/densitometer were used. The Model 760 instrument calculated the percentage of activity of each iso-
Follow-up was obtained for all uremic patients. The
maximum follow-up was six months (range three to six
months). Eleven patients were subsequently hospitalized
at New England Deaconess Hospital for either acute
myocardial infarction or angina pectoris. Ten patients
were subsequently hospitalized at New England Deaconess
Hospital for noncardiac reasons (e.g., insertion of catheter
for peritoneal dialysis, limb amputation) and were considered to not have been hospitalized for cardiac disease.
One additional patient subsequently hospitalized for a
noncardiac reason (renal transplant) had acute myocardial
infarction develop three weeks after successful surgery and
is, therefore, included with the group of patients subsequently hospitalized for cardiac disease. Two patients
subsequently hospitalized for elective coronary artery by-
105
CREATINE KINASE MB IN UREMIC SERUM
Vol. 87 • No. 1
Table 1. Causes of Renal Failure in 81 Uremic Patients
Cause
Diabetes mellitus
Hypertension
Congenital kidney diseases
Renal artery stenosis
Glomerulonephritis
Calculi/pyelonephritis
Antiglomerular basement membrane disease
Drug induced
Hemolytic uremic syndrome
Unknown
58
9
4
3
2
Total no. patients
pass graft surgery were excluded from the statistical analysis.
The remaining uremic patients of this study were seen
in the dialysis units numerous times as part of their
maintenance dialysis treatment. These patients had no
clinical or electrocardiographic evidence of acute myocardial infarction at time of follow-up.
Specifically not followed in this study were (1) subsequent episodes of angina pectoris that occurred at home,
and (2) subsequent hospitalization of uremic patients for
cardiac disease at institutions other than the New England
Deaconess Hospital. Although we cannot completely exclude the latter possibility, all uremic patients when seen
in the dialysis units during the follow-up interval of this
study had no mention of recent hospitalization at a separate institution within their medical record.
Table 2. Uremic and Nonuremic (control) Patients:
Laboratory Data
Median
No. Patients with
Elevated Value
(range)
Total serum CK
(reference range: 0-155 U/L)
Uremic
Control
64 U/L
63 U/L
7 (167-438 U/L)
0
CM-M B/electrophoresis
(reference range: <5 U/L)*
Uremic
Control
1.8 U/L
0
13 (5.6-18.2 U/L)
0
CK-MB/QuiCK-MB (reference
range: <2.9 EU/L)t
Uremic
Control
2.1EU/L
<2 EU/L
11 (2.9-4.3 EU/L)
0
CK-MB/Tandem-E CK-MB
(reference range: <9 Mg/L)t
Uremic
Control
1.1 Mg/L
0.8 Mg/L
* Recommended by Wagner and Dillon.1
t Recommended by manufacturer.13
t Recommended by manufacturer.1
2 (11.4-14.4 Mg/L)
0
Criteria for Diagnosis of Acute Myocardial Infarction
Patients who developed acute myocardial infarction
fulfilled two of the three following criteria: (1) typical clinical history; (2) acute electrocardiographic changes; and
(3) serial total CK and CK-MB results by electrophoresis
demonstrating a characteristic peak. Patients diagnosed
as having angina pectoris had only clinical symptoms.
Statistical Analysis
The risk of subsequent hospitalization for cardiac disease of uremic patients with and without CK-MB in serum
elevated above the reference range was compared by using
the chi-square test with Yates' correction factor. Linear
regression was used to correlate BUN or serum creatinine
with total serum CK and CK-MB quantified by each
method.
Results
Eighty-one uremic patients undergoing maintenance
dialysis were studied—35 on hemodialysis and 46 on
peritoneal dialysis. The median duration of dialysis was
17.5 months (range, 2-228 months). The mean age of the
patients was 53.1 years (range, 24-94 years). Fifty-one
patients were men and 30 were women. Seventy-six patients were white, 4 were black, and 1 was oriental. The
causes of uremia are summarized in Table 1. Diabetes
mellitus was the most common cause of renal failure in
58 (72%) patients.
The mean age of the control patients was 50.3 years
old (range, 29-79 years). Nine patients were men and 11
were women. All were white. No patient was or had ever
been dialyzed. They had been seen in the gastroenterology
and gynecology clinics for reasons that did not require
hospitalization, before specimen collection, or during the
follow-up period of this study.
Laboratory Data
The laboratory data are summarized in Table 2.
Total Serum CK. The median total serum CK of the
uremic patients was 64 U/L (range, <26-438 U/L). Seven
patients (five men, two women) had a total serum CK
above normal (range, 167-438). The median total serum
CK of the control group was 63 U/L (range, 33-128 U/
L). Total serum CK did not correlate with BUN or serum
creatinine.
Serum CK-MB Activity by Electrophoresis. CK-MB
isoenzyme activity was increased in uremic patients as
compared with the control group. The median CK-MB
was 1.8 U/L, and the mean was 2.8 U/L (range, 0-18.2
U/L). Sixty-three of 81 patients were found to have CKMB in serum. Thirteen of 81 patients (16%) had greater
than 5 U/L of CK-MB in their serum. Of these 13 patients,
11 had CK-MB greater than 5% of the total CK. An additional nine patients had CK-MB greater than 5% of the
106
MEDEIROS, SCHOTTE, AND GERSON
A.J.C.P.- January 1987
Table 3. Uremic Patients Subsequently Hospitalized for Acute Myocardial Infarction (MI) or Angina Pectoris (AP)
Time of Initial Serum Study*
1
2
3t
4
5
6
7
8
9
10
11
12
Time of Hospitalization
Electrophoresis
QuiCK-MB
Tandem-E
CK-MB
Electrophoresis
QuiCKMB
Tandem-E
CK-MB
Clinical
Diagnosis
_
+
+
+
+
+
-
_
+
+
+
+
+
-
_
-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
MI
MI
MIJ
MI*
AP
AP
AP
AP*
AP
AP
MI|
MI*
+ = CK-MB in serum >5 U/L by electrophoresis, 22.9 EU/L by the QuiCK-MB, and 2:9
jig/L by the Tandem-E CK-MB.
* All patients had no clinical or electrocardiographic evidence of acute myocardial infarction
when serum was studied.
t The patient was hospitalized for renal transplant and had acute myocardial infarction develop
three weeks after surgery,
t Patient died.
total CK, but the absolute quantity of CK-MB was less
than 5 U/L. CK-MB activity did not correlate with BUN
or serum creatinine.
In the control group, the median CK-MB was 0 and
the mean was 0.4 U/L (range, 0-1.6 U/L). Two of the 20
patients were found to have CK-MB in serum. No patient
had CK-MB activity in serum greater than 5% of the
total CK.
Determination ofCK-MB Mass by Immunoassays. Using both the QuiCK-MB and Tandem-E CK-MB immunoassays, the uremic patients had slightly increased
CK-MB mass in their serum compared with the control
group. The median CK-MB of the renal failure patients
was 2.1 EU/L (range, <2-4.3 EU/L) by the QuiCK-MB
and 1.1 Mg/L (range, 0-14.4 /tg/L) by the Tandem-E CKMB. With the use of the QuiCK-MB and the Tandem-E
CK-MB, 48 and 59 patients had CK-MB in serum, respectively. According to the Tandem-E CK-MB, 47 of
these 59 patients had CK-MB in the serum above the
median CK-MB of the control group. Using the QuiCKMB, 11 uremic patients had CK-MB in serum above the
reference range, while, according to the Tandem-E CKMB, two uremic patients had CK-MB in serum above
the reference range. CK-MB mass did not correlate with
BUN or serum creatinine.
In the control group, the median CK-MB was less than
2 EU/L (range, <2-2.2 EU/L) by the QuiCK-MB and
0.8 Mg/L (range, 0-2.9 /ig/L) by the Tandem-E CK-MB.
The QuiCK-MB detected CK-MB in two patients, while
the Tandem-E CK-MB detected CK-MB in 15 patients.
(This difference is in part explained by the lower limit of
CK-MB quantified by the two methods: 2 U/L for the
QuiCK-MB and 0 /ug/L for the Tandem-E CK-MB.)
Follow-Up Data
Since the initial study of serum, 12 of 79 (15%) uremic
patients have subsequently been hospitalized for acute
myocardial infarction (6 patients; 4 died) or angina pectoris (6 patients; 1 died). Autopsy confirmed the clinical
diagnosis of acute myocardial infarction in one patient
and supported the clinical diagnosis of angina pectoris in
one patient. At time of patients' hospitalization for cardiac
disease, all laboratory methods supported the clinical diagnosis of acute myocardial infarction (i.e., CK-MB in
serum above reference range) in all six patients (Table 3).
Electrophoresis and the immunoassays disagreed on two
of the six patients diagnosed to have angina pectoris. (Both
patients had CK-MB greater than 5 U/L by electrophoresis
but within the reference range by the immunoassays.)
At the time the sera of these patients were initially studied,fivehad CK-MB above 5 U/L by electrophoresis, five
had CK-MB at least 2.9 EU/L by the QuiCK-MB, and
no patients had CK-MB above 9 /xg/L by the Tandem-E
CK-MB. Electrophoresis and the QuiCK-MB agreed on
ten of these patients, four with CK-MB above the reference
range (Table 3).
With the use of the chi-square test and 2 X 2 contingency tables, uremic patients with CK-MB in serum above
5 U/L by electrophoresis are at increased risk of subsequent hospitalization for acute myocardial infarction or
angina pectoris (x2 = 5.47; P < 0.05). Similarly, uremic
patients with CK-MB in serum at least 2.9 EU/L by the
QuiCK-MB are at increased risk of subsequent hospitalization for cardiac disease (x2 = 6.56; P < 0.01). In contrast, patients with CK-MB in serum at least 9 ^g/L by
the Tandem-E CK-MB were not at increased risk of sub-
CREATINE KINASE MB IN UREMIC SERUM
Vol. 87 • No. 1
2
sequent hospitalization by cardiac disease (x = 0.15; P
not significant).
If the chi-square test is done comparing the risk of subsequent cardiac disease of patients with CK-MB in serum
greater than 5% of the total CK with patients with CKMB less than 5% of the total CK, patients with greater
than 5% CK-MB are at a statistically significant increased
risk of subsequent hospitalization for cardiac disease (x 2
= 5.52; P < 0.05).
If the chi-square test is again done comparing the risk
of subsequent cardiac disease of patients with CK-MB in
serum greater than 5% of the total CK and greater than
5 U/L with those patients with CK-MB in serum not
meeting both criteria, patients with CK-MB greater than
5% and greater than 5 U/L are at a statistically significant
increased risk of subsequent hospitalization for cardiac
disease (x 2 = 7.97; P < 0.001).
As described above, two uremic patients who subsequently underwent elective coronary artery bypass graft
surgery were excluded from the statistical analysis. At time
of initial study of serum, one patient had CK-MB above
reference range by electrophoresis; neither patient had
abnormally elevated CK-MB according to the QuiCKMB. If these patients are included as patients subsequently
hospitalized for cardiac disease, thereby increasing the total number of patients to 81, uremic patients with CKMB above reference range by either electrophoresis (x 2
= 6.78; P < 0.01) or the QuiCK-MB (x 2 = 4.97; P < 0.05)
are at increased risk of subsequent hospitalization for cardiac disease.
If the uremic patient subsequently hospitalized for renal
transplant who then had acute myocardial infarction (described above) develop is excluded from the statistical
analysis, thereby reducing the total number of patients
followed to 78, patients with CK-MB above the reference
range by electrophresis (x 2 = 6.41; P < 0.01) and the
QuiCK-MB (x 2 = 4.97; P < 0.05) are at increased risk of
subsequent cardiac disease.
Discussion
In agreement with previous studies,2'6'8'9 we found a
slight increase of CK-MB in the serum of most uremic
patients as compared with control patients. This increase
was slight, within the reference range, and should not be
confused with the greater elevations of CK-MB seen in
the serum of patients who had an acute myocardial infarction. In this conclusion, electrophoresis, the QuiCKMB, and the Tandem-E CK-MB methods agreed. The
median CK-MB of uremic patients by electrophoresis was
1.8 U/L (reference range, <5 U/L), 14 by the QuiCK-MB
2.1 EU/L (reference range, <2.9 EU/L), 13 and by the
Tandem-E CK-MB 1.1 /xg/L (reference range, <9 Mg/L).1
The elevation of CK-MB in uremic patient sera did not
107
correlate with the BUN and serum creatinine. Sixty-three
(78%) patients by electrophoresis, 48 (59%) patients by
the QuiCK-MB, and 47 (58%) uremic patients had CKMB in the serum greater than the median CK-MB of the
control group.
The results of this study have also shown that a minority
of uremic patients without clinical or electrocardiographic
evidence of acute myocardial infarction have CK-MB
isoenzyme in their serum above the reference range. Seventeen of 81 (21%) uremic patients had elevated CK-MB
in serum by at least one method. Does the finding of increased CK-MB in the serum of these patients have any
prognostic value?
With the use of the chi-square test and 2 X 2 contingency tables, it appears that uremic patients with CK-MB
isoenzyme in serum elevated above 5 U/L by electrophoresis (x 2 = 5.47; P < 0.05) or at least 2.9 EU/L by the
QuiCK-MB immunoassay (x 2 = 6.56; P < 0.01) are at a
statistically significant increased risk of subsequent hospitalization for acute myocardial infarction or angina
pectoris. Uremic patients with CK-MB in serum greater
than 5% of the total CK (x 2 = 5.52; P < 0.05) and patients
with CK-MB both greater than 5% of the total CK and
greater than 5 U/L (x 2 = 7.97; P < 0.001) are also at a
statistically significant increased risk of subsequent cardiac
disease. The data suggest that the presence of CK-MB
isoenzyme above the reference range in the serum of
uremic patients at our institution who had no overt evidence of acute myocardial infarction is a manifestation
of low-grade myocardial injury and should not be readily
attributed to a noncardiac cause such as uremic paralysis
of the reticuloendothelial system. Perhaps the finding of
CK-MB in serum above the reference range should be
used as one criterion by which uremic patients would recieve more aggressive medical therapy or earlier surgical
intervention for cardiac disease.
We suggest that the finding of only a slight increase of
CK-MB in the serum of most uremic patients in this study,
coupled with an apparent statistically significant increased
risk of subsequent hospitalization for cardiac disease for
patients with abnormally elevated CK-MB in serum, is
evidence that CK-MB isoenzyme quantification in uremic
patients is more reliable than is implied in the literature.
Two flaws of this study relate to our methods of followup. Specifically not followed were (1) subsequent episodes
of angina pectoris that occurred at home; and (2) subsequent hospitalization of uremic patients for cardiac disease
at institutions other than New England Deaconess Hospital. We believe that the second possibility is unlikely
because all patients were followed in the dialysis clinics,
had no clinical or electrocardiographic evidence of acute
myocardial infarction during the follow-up interval, and
had no documentation of subsequent hospitalization at
a second institution within their medical record. However,
108
MEDEIROS, SCHOTTE, A N D GERSON
subsequent studies with more complete and prolonged
follow-up are needed.
Recently, Chan and associates' have suggested that two
reference ranges should be established for the Tandem-E
CK-MB immunoassay: 0-4 /ig/L for "normal" persons
and 5-9 jig/L for patients with elevated CK-MB mass in
serum, not diagnostic of acute myocardial infarction. With
the use of the 0-4 /ug/L reference range, eight uremic patients had CK-MB in serum above 4 ngJL. Two of these
patients were subsequently hospitalized for acute myocardial infarction (one patient) or angina pectoris (one
patient). Those patients with CK-MB above 4 /xg/L in
serum at time of initial study were not at increased risk
of subsequent hospitalization for cardiac disease (x2 = 0.9;
P not significant).
The median total serum CK of the uremic patients and
that of the control patients were virtually identical. Our
findings do not support previous studies,412 which suggested that total serum CK is increased in patients with
renal failure who are undergoing maintenance dialysis.
The discrepancy between our results and earlier studies
may be explained by the patient population we studied.
Soffer and colleagues12 reported that total serum CK is
increased in black as compared with white persons. Most
of the patients in this study were white. Furthermore, total
serum CK is increased in physically active patients.512
Most patients in this study were sedentary.
Acknowledgments. The authors thank Charles F. Arkin, M.D., and
Walter H. Dzik, M.D., for their critical suggestions and Marie Bassett
and Margaret Beers for secretarial assistance.
A.J.C.P. • January 1987
References
1. Chan DW, Taylor E, Frye R, Blitzer RL: Immunoenzymetric assay
for creatine kinase MB with subunit-specific monoclonal antibodies compared with an immunochemical method and electrophoresis. Clin Chem 1985; 31:465-469
2. Cohen IM, Griffiths J, Stone RA, Leech T: The creatine kinase profile
of a maintenance hemodialysis population: A possible marker of
uremic myopathy. Clin Nephrol 1980; 13:235-238
3. DePuey EG, Aessopos A, Monroe LR et al: Clinical utility of a twosite immunoradiometric assay for creatine kinase-MB in the detection of perioperative myocardial infarction. J Nucl Med 1983;
24:703-709
4. Eschar J, Zimmerman JH: Creatine phosphokinase in disease. Am
J Med Sci 1967; 253:272-282
5. Griffiths PD: Serum levels of ATP: Creatine phosphotransferase
(creatine kinase). The normal range and effect of muscular activity. Clin Chim Acta 1966; 13:413-420
6. Jaffe AS, Ritter C, Meltzer V, Harter H, Roberts R: Unmasking
artifactual increases in creatine kinase isoenzymes in patients with
renal failure. J Lab Clin Med 1984; 104:193-202
7. Linder A, Charra B, Sherrara DJ, Schribner BH: Accelerated atherosclerosis in prolonged maintenance hemodialysis. N Engl J
Med 1974; 290:697-701
8. Ma KW, Brown DC, Steele BW, From AHL: Serum creatine kinase
MB isoenzyme activity in long-term hemodialysis patients. Arch
Intern Med 1981; 141:164-166
9. Martinez-Vea A, Montoliu J, Company X, Vives A, Lopez-Pedret
J, Revert L: Elevated CK-MB with normal total creatine kinase
levels in patients undergoing maintenance hemodialysis. Arch
Intern Med 1982; 142:2346
10. Medeiros LJ, Gerson B: Creatine kinase MB isoenzyme in serum
of uremic patients: Electrophoresis and quantification by the
Corning Model 720 and 760 fluorometer densitometers. Clin
Chem 1986; 32:227-228
11. Rosalki SB: An improved procedure for serum creatine kinase phosphokinase determination. J Lab Clin Med 1967; 69:696-705
12. Soffer O, Fellner SK, Rush RL: Creatine phosphokinase in longterm dialysis patients. Arch Intern Med 1981; 141:181-183
13. Shah VD: Effect of sample dilution on creatine kinase MB measurement. Clin Chem 1983; 29:987
14. Wagner GS, Dillon MC: In reply. Arch Intern Med 1982; 142:2346