The prognostic value of pre-procedural plasma C-reactive protein in patients undergoing elective coronary angioplasty.

AIMS: The acute phase reactant C-reactive protein is an important prognostic risk factor in patients with both stable and unstable coronary artery disease. The potential prognostic implications of an abnormal pre-procedural C-reactive protein concentration in patients undergoing elective coronary angioplasty may be relevant for subsequent treatment. METHODS AND RESULTS: Pre-procedural plasma levels of C-reactive protein were measured in 501 patients with stable coronary artery disease undergoing elective coronary angioplasty. The incidence of death or myocardial infarction during a 2-year follow-up was 10.6% (24/227) in patients with an increased C-reactive protein level (>3 mg. l(-1)) and 2.9% (8/274) in patients with a normal C-reactive protein level (RR 3.9, 95% CI 1.7-8.9). Survival without death, myocardial infarction, urgent revascularization or hospital admission for unstable angina was significantly lower in patients with an increased C-reactive protein vs patients with a normal C-reactive protein (log-rank 14.62, P<0.0001). Logistic regression analysis identified an increased C-reactive protein level as a strong independent predictor of event-free survival (RR 2.54, 95% CI: 1.44-4.47, P=0.001). CONCLUSION: Pre-procedural C-reactive protein levels are increased in 45% of patients undergoing elective coronary angioplasty. An increased C-reactive protein level is a powerful independent prognostic indicator for subsequent cardiac events, suggesting that late clinical outcome is markedly influenced by pre-procedural systemic activation of inflammation.

[Determination of cardiac troponins for diagnosis of 'acute myocardial infarct']. / Bepaling van hartspecifieke troponinen voor de diagnose 'acuut myocardinfarct'.

The diagnosis of 'myocardial infarction' was recently redefined by a commission of European and American cardiologists. The main element of the new definition is a raised serum level of heart-specific troponin (T or I). In healthy adults virtually no cardiac troponin is demonstrable, so that every rise of the level of the heart-specific troponin in the blood means that there is myocardial damage. An infarction during a coronary bypass operation and myocardial damage during skeletomuscular injury can be diagnosed almost faultlessly by a troponin assay. A raised troponin level in acute coronary ischaemia is associated with a raised mortality risk. However, even when the level is normal, a risk of cardiac complications is present. For the diagnosis of a recurrent infarction during a developing infarction, determination of the peak level of the creatine kinase muscle brain mass (CK-MBmass) is most appropriate. Also, the value of including troponin in the existing rule-out protocols has not yet been proven. Now that most Dutch hospitals shortly will be capable of troponin assays, cardiologists and clinical chemists should consider the implementation of this assay in clinical practice.

Safe discharge from the cardiac emergency room with a rapid rule-out myocardial infarction protocol using serial CK-MB(mass).

OBJECTIVE: To determine whether a new protocol, using a rapid and sensitive CK-MB(mass) assay and serial sampling, can rule out myocardial infarction in patients with chest pain and decrease their length of stay in the cardiac emergency room without increasing risk. DESIGN: The combined incidence of cardiac death and acute myocardial infarction at 30 days, six months, and 24 months of follow up were compared between patients discharged home from the cardiac emergency room after ruling out myocardial infarction with a CK-MB(activity) assay in 1994 and those discharged home after a rapid CK-MB(mass) assay in 1996. SETTING: Cardiac emergency room of a large university hospital. PATIENTS: In 1994 and 1996, 230 and 423 chest pain patients, respectively, were discharged home from the cardiac emergency room with a normal CK-MB and an uneventful observation period. RESULTS: The median length of stay in the cardiac emergency room was significantly reduced, from 16.0 hours in 1994 to 9.0 hours in 1996 (p < 0.0001). Mean event rates in patients from the 1994 and 1996 cohorts, respectively, were 0.9% (95% confidence interval (CI) -0.3% to 2.1%) v 0.7% (95% CI -0.1% to 1. 5%) at 30 days, 3.0% (95% CI 0.8% to 5.2%) v 2.8% (95% CI 1.2% to 4. 4%) at six months, and 7.0% (95% CI 3.7% to 10.3%) v 5.7% (95% CI 3. 5% to 7.9%) at 24 months. Kaplan-Meier survival analysis showed no difference in mean event-free survival at 30 days, six months, and 24 months of follow up. CONCLUSIONS: Using a rule-out myocardial infarction protocol with a rapid and sensitive CK-MB(mass) assay and serial sampling, the length of stay of patients with chest pain in the cardiac emergency room can be reduced without compromising safety.

Magnesium levels in critically ill patients. What should we measure?

We studied the relation between ionized magnesium, total magnesium, and albumin levels in serum of 115 critically ill patients and the role of extracellular and intracellular magnesium in outcome prediction. Levels of serum total and ionized magnesium, serum albumin, and magnesium in mononuclear blood cells and erythrocytes were measured and the APACHE II score and 1-month mortality recorded. Of all patients, 51.3% had a serum total magnesium concentration below the reference range. In 71% of these hypomagnesemic patients, a normal serum ionized magnesium concentration was measured. None of the patients had an intracellular magnesium concentration below the reference limit. Except for serum total and ionized magnesium, none of the magnesium parameters correlated significantly with each other. A significantly negative correlation was found between serum albumin and the fraction ionized magnesium. There was no association between low extracellular or intracellular magnesium and clinical outcome. The observation of hypomagnesemia in critically ill patients depends on which magnesium fraction is measured. The lack of correlation with clinical outcome suggests hypomagnesemia to be merely an epiphenomenon. Reliable concentrations of serum ionized magnesium can be obtained only by direct measurement and not by calculation from serum total magnesium and albumin.

C-Reactive protein and cardiac troponin T in risk stratification: differences in optimal timing of tests early after the onset of chest pain.

BACKGROUND: Increased C-reactive protein (CRP) is an important prognostic indicator for early risk stratification in patients with an acute coronary syndrome (ACS), independent of, and in combination with, increased cardiac troponin T (cTnT). However, increases in both cTnT and CRP also occur secondary to myocardial damage. METHODS AND RESULTS: In 156 consecutive patients, early release kinetics of CRP and cTnT were analyzed. The cutoff values were 3.0 mg/L for CRP and 0.1 microgram/L for cTnT. In the 75 patients with a CRP below the cutoff on admission, there was little change in CRP until 8 h after the onset of symptoms. At 12 h after the onset of symptoms, the cumulative proportions of abnormal CRP and cTnT in non-ST elevation ACS patients were 27% and 89%, respectively (P <0.01). During the first 24 h after the onset of symptoms, the median time above the cutoff was 20 h for CRP and 5 h for cTnT (P <0.0001). CRP was below the cutoff on admission significantly more often among patients receiving thrombolytic therapy than in patients without an indication for reperfusion therapy (51% vs 28%; P = 0.004). CONCLUSIONS: Increased CRP as an early independent risk indicator should be measured as soon as possible after the onset of symptoms, whereas increased cTnT is most reliable at 12 or more hours after the onset of symptoms.

Diagnostic value of the mean corpuscular volume in the detection of vitamin B12 deficiency.

In clinical practice, the finding of an elevated mean corpuscular volume (MCV), macrocytic anaemia or specific neurological symptoms is often the reason to test for vitamin B12 (B12) deficiency. Use of the MCV as a test for the detection or exclusion of B12 deficiency is only justified if the diagnostic accuracy is sufficiently high. However, the sensitivity and specificity are not well known. We performed a systematic review of the diagnostic value of an elevated MCV for B12 deficiency in both anaemic and non-anaemic patients. Of approximately 3500 titles and/or abstracts that were screened, 37 original papers contained usable data. The population under study proved to be the characteristic of major influence on the study outcome. Pooling of data from different studies was performed in subsets of the data corresponding to the different populations studied. The cut-off levels of both MCV and serum B12 had a significant influence on the study outcomes. The data, however, were pooled without taking these cut-off levels into account. The pooled estimates should be interpreted with this limitation in mind. The reference standards were (1) a low serum B12 concentration and (2) a B12 deficiency confirmed by low serum B12 combined with additional diagnostic investigations. In the population that was randomly screened for low serum B12, the sensitivity of the MCV for B12 deficiency was 17%, whereas the sensitivity was 30% for B12 deficiency in patients with anaemia. When measurement of serum B12 was ordered to exclude B12 deficiency as part of the patients' treatment, the sensitivity was 30% for low serum B12 concentration, 58% for B12 deficiency and 75% for B12 deficiency in patients with anaemia. In the population with pernicious anaemia, the sensitivity was far from perfect (77%). In the five studies that reported data on the positive predictive value of the MCV for B12 deficiency, this ranged from 0% (0/6) to 55% (11/20). This systematic review shows that a considerable number of B12-deficient patients will remain unnoticed when the MCV is used to rule in patients for further evaluation. Depending on the population studied, up to 84% of cases will than be missed. The MCV can be used to make the diagnosis of B12 deficiency more--or less--probable. An elevated MCV justifies the measurement of serum B12. The MCV should not be used as the only parameter ruling out the diagnosis of B12 deficiency.

Diagnostic accuracy of myoglobin concentration for the early diagnosis of acute myocardial infarction.

STUDY OBJECTIVE: We evaluated the diagnostic accuracy of myoglobin determination for the early diagnosis of acute myocardial infarction (AMI). METHODS: Consecutive patients with chest pain were included in the study. Receiver operating characteristic (ROC) analysis was used to assess optimal timing of blood sampling and cutoff values. RESULTS: A total of 309 patients were included, of whom 162 patients had a diagnosis of AMI. ROC analysis revealed that the diagnostic accuracy of myoglobin concentration as indicated by the area under the ROC curve (AUC) increased significantly from 3 (0.89+/-0.026) and 4 hours (0.93+/-0.019) to 5 hours after onset of symptoms (0. 96+/-0.014; P=.0040 and.035, respectively). At 5 hours (the earliest time point with maximal AUC), sensitivity was 87% and specificity was 97% using a myoglobin cutoff value of 90 microg/L. With a myoglobin cutoff value of 50 microg/L, sensitivity was 95% (95% confidence interval 90% to 98%), but specificity was 86% (95% confidence interval 80% to 93%). CONCLUSION: Myoglobin has maximal diagnostic accuracy for the diagnosis of AMI at 5 hours after the onset of symptoms, using a cutoff value of 50 microg/L. In combination with the measurement of other biochemical markers, myoglobin determination could be particularly useful for triage of patients with AMI at an early stage.

Different time frames for the occurrence of elevated levels of cardiac troponin T and C-reactive protein in patients with acute myocardial infarction.

The baseline plasma level of C-reactive protein (CRP) is considered to be a parameter for risk stratification in patients with an acute coronary syndrome, independent of the level of cardiac troponin T (cTnT) or cardiac troponin I. However, myocardial tissue necrosis following prolonged arterial occlusion also induces release of CRP. Both phenomena may have their own kinetic behaviour with respect to changes in concentration of CRP. Therefore, in this study the time frame after onset of symptoms for measurement of CRP as an independent parameter is established. For this purpose, we evaluated patients with proven myocardial damage due to acute myocardial infarction (AMI) with respect to changes of creatine kinase (CK)-MB mass, cTnT and CRP during 24 hours after onset of symptoms. Our results show that two subgroups can be discerned in patients with AMI: those with initially normal and those with already elevated concentration CRP on admission. Furthermore, based on the results of this study we conclude that for use of CRP as an independent prognostic parameter in patients with acute coronary syndrome, CRP should be measured in blood samples drawn as early as possible after the onset of symptoms to avoid contribution of a process of myocardial tissue necrosis, whereas estimation of cTnT should be performed at 6-12 hours.

Influence of repetitive finger puncturing on skin perfusion and capillary blood analysis in patients with diabetes mellitus.

BACKGROUND: Frequent puncturing of fingers to check blood glucose in patients with type 1 diabetes might alter skin perfusion and, hence, influence the representativeness of the blood sample. We investigated the influence of repetitive puncturing on skin microcirculatory perfusion using laser Doppler fluxmetry and on the preanalytical phase of capillary blood analysis for small molecules (glucose) and large particles (cholesterol). METHODS: In 49 patients with long-standing (mean, 21 years) type 1 diabetes, with a mean puncture frequency of three times daily for a mean duration of 13 years, laser Doppler skin perfusion was measured in a finger at a frequently punctured site and compared with a similar site of another finger of the same hand, which was never punctured. In the supine position with the hand level with the heart, resting flux (RF), peak flux (PF), and the microcirculatory reserve capacity (MRC; PF - RF) were assessed. Subsequently, blood samples for capillary whole blood glucose and cholesterol analyses were taken from the same sites. RESULTS: No significant differences were found between the puncture and control sites in mean RF (2.3 vs 2.0 V; P = 0.14, paired-samples t-test), PF (3.3 vs 3.1 V; P = 0.24), MRC (1.0 vs 1.0 V; P = 0.65), glucose (10.2 vs 10.2 mmol/L; P = 0.69), or cholesterol (5.1 vs 5.2 mmol/L; P = 0.26). Power calculation for a RF of 2.0 V and the SD and n of this study indicate a power (beta) of 80% to detect a 25% change in RF at P <0.05. CONCLUSIONS: Repetitive finger puncturing in diabetics appears not to injure local skin microcirculatory perfusion nor to influence results of capillary blood analysis for glucose and cholesterol.

Independent prognostic value of C-reactive protein and troponin I in patients with unstable angina or non-Q-wave myocardial infarction.

OBJECTIVES: Elevated concentrations of C-reactive protein (CRP), a non-specific acute phase reactant, and troponin I (TnI), a cardiac-specific marker of myocardial damage, have been found to be associated with a higher risk for cardiac events in patients with an acute coronary syndrome. We evaluated CRP alone and in combination with TnI for predicting the incidence of major cardiac complications within 6 months in patients with unstable angina or non-Q-wave infarction (NQMI). METHODS: CRP and TnI was measured on admission in patients with unstable angina or NQMI, but results were kept blinded. Patients were treated according to a conservative management strategy, and the incidence of major cardiac events within 6 months was assessed. RESULTS: An abnormal CRP (> 5 mg/l) and an abnormal TnI (> 0.4 microgram/l) were more frequent in patients that suffered a major cardiac event (CRP: 93 vs. 35%, P < 0.0001; TnI: 73 vs. 26%, P < 0.001). The incidence of major cardiac events was higher in patients with an abnormal CRP than in patients with a normal CRP, both when TnI was abnormal (42 vs. 4.5%, P = 0.003) and when TnI was normal (11 vs. 0%, P = 0.014). Mean event-free survival was excellent in patients with both a normal CRP and TnI, whereas survival was poorest in patients with both an abnormal CRP and TnI (121 +/- 16 vs. 180 days, P < 0.0001). CONCLUSIONS: An abnormal CRP on admission in patients with unstable angina or NQMI is associated with increased incidence of major cardiac events within 6 months, both in patients with normal and abnormal TnI. CRP and TnI have independent and additive prognostic value in this patient group, and the combination may be useful for early risk stratification.

Serum ionized magnesium: comparison of results obtained with three ion-selective analyzers.

In a two-center (Academic Medical Center, The Netherlands, and National Institutes of Health, USA) study, we compared ionized magnesium (iMg2+) results in serum determined with the AVL 988/4, KONE Microlyte 6 and NOVA CRT, which are the currently available analyzers equipped with a magnesium ion-selective electrode. The comparison was performed with frozen serum samples from normal individuals and patients. Imprecision and reference intervals were established. We found the best agreement between the KONE(x) and AVL(y) magnesium ion-selective electrodes (y= 0.972x-0.013; n=138) with samples from patients. With samples from normals, all three analyzers reported significantly different results (p<0.05). Best precision was found using the NOVA; coefficients of variation established at three levels were all < 4.0%. Coefficients of variation for the AVL and KONE were <5% at normal and high iMg2+, but 10.7 and 9.4%, respectively, at iMg2+ approximately 0.30 mmol/l. The reference intervals (mean+/-standard deviation) based on measurements in fresh serum samples were different for each analyzer: 0.55-0.63 mmol/l for AVL, 0.470.57 mmol/l for KONE and 0.43-0.55 mmol/l for NOVA. Thus, significant differences among the ionized magnesium concentration obtained with the three analyzers, limit comparison of results in clinical practice, and need to be resolved (e.g. by improvement of specificity and standardization of calibrators).

Recent activities of EC4 in the harmonization of clinical chemistry in the European Union.

This article describes the recent activities of the European Communities Confederation of Clinical Chemistry (EC4). Main goal of EC4 is harmonization of clinical chemistry in the European Union and Europe. EC4's actions connected to that are training and registration of professionals, and accreditation of laboratories. The 35000 professionals practising clinical chemistry in the EU have different backgrounds (medical, pharmaceutical, science-oriented, veterinary, or microbiological). Thus, for the harmonization of training of clinical chemists, EC4 has published a European Syllabus for Postgraduate Training, and instituted a European Union Register for Clinical Chemists. The Syllabus is an indication of the level of requirements in postgraduate training. The EC4 initiative to implement the European Register for Clinical Chemists is based on the 8 years vocational training necessary to obtain sufficient knowledge in clinical chemistry according to the European Syllabus. A guide to the EC4 Register has been published; registration leads to the title European Clinical Chemist (EurClinChem). The accreditation of laboratories must be based on a total quality management system. EC4 has described guidelines (essential criteria) which it judges appropriate for establishing the quality of medical laboratory service; it does not wish to fulfil the role of an accrediting body. Moreover, a working group has been set up to seek to harmonize the work of national accrediting bodies. Therefore, it is logical that EC4 monitors the activities of the different standardizing bodies that might influence the practice of clinical chemistry in the EU. Finally, some aspects concerning the future strategy of EC4 are brought forward.

Ruling out acute myocardial infarction early with two serial creatine kinase-MBmass determinations.

AIMS: We studied the diagnostic value for acute myocardial infarction of serial creatine kinase-MBmass measurements on admission and at 7 h after the onset of symptoms. METHODS AND RESULTS: Patients presenting to our chest pain unit with symptoms of <5-h duration were eligible. Patients were kept under observation at least until 12 h after onset of symptoms. Blood samples were drawn on admission and 7 and 10 h after onset of symptoms. Creatine kinase-MBmass>7.0 microg x 1(-1) (upper reference limit for acute myocardial infarction), or an increase >2.0 microg x 1(-1) (reference change value) between admission and at 7 h was considered abnormal. Of a total of 470 patients, 248 patients had acute myocardial infarction: 100 out of the 248 patients had a single creatine kinase-MBmass>7.0 microg x 1(-1) on admission (sensitivity 40%, 95% CI:34-46%), 234/248 patients at 7 h (sensitivity 94%, 95% CI:91-97%), and 240/248 at 10 h (sensitivity 97%, 95% CI:94-99%). At 7 h, 246/248 patients had either a single creatine kinase-MB >7.0 microg x 1(-1) or a significant increase between admission and 7 h (sensitivity 99%, 95% CI:98-100%). Of 222 patients without acute myocardial infarction, 214 had a normal serial creatine kinase-MBmass (specificity 96%, 95% CI:93-98%). CONCLUSION: In patients with symptoms of <5-h duration, acute myocardial infarction can be ruled out using serial creatine kinase-MBmass taken on admission and at 7 h.

Intracellular and extracellular, ionized and total magnesium in pre-eclampsia and uncomplicated pregnancy.

Magnesium (Mg) and calcium (CA) concentrations in women with pre-eclampsia, women with an uncomplicated pregnancy and non-pregnant women were compared. Ionized serum magnesium and calcium concentrations and intracellular magnesium concentrations were measured in 15 pregnant women with severe pre-eclampsia, 34 uncomplicated pregnant women early, at midterm and preterm in their pregnancy and 24 non-pregnant women. The ionized calcium concentration did not chance during normal pregnancy or during pre-eclampsia relative to non-pregnant women. In contrast, elevated total and ionized magnesium serum concentrations were found in women with severe pre-eclampsia (total Mg = 0.85+/-0.11 mM, ionized Mg = 0.61+/-0.06 mM) relative to uncomplicated pregnant women (total Mg = 0.72+/-0.06 mM, ionized Mg = 0.53+/-0.03 mM). Total magnesium in pre-eclamptic women were similar to non-pregnant women. Intracellular ionized and total magnesium concentrations in mononuclear blood cells and erythrocytes were similar in pre-eclamptic women and women with uncomplicated pregnancy. Serum magnesium concentrations are elevated in severe pre-eclamptic women relative to women with uncomplicated pregnancy and are related to birth weight and gestational age at delivery. There may be a causal relationship since magnesium is involved in blood pressure regulation through an intracellular inhibition of NO synthase in endothelial cells.

Magnesium in disease: a review with special emphasis on the serum ionized magnesium.

This review deals with the six main clinical situations related to magnesium or one of its fractions, including ionized magnesium: renal disease, hypertension, pre-eclampsia, diabetes mellitus, cardiac disease, and the administration of therapeutic drugs. Issues addressed are the physiological role of magnesium, eventual changes in its levels, and how these best can be monitored. In renal disease mostly moderate hypermagnesemia is seen; measuring ionized magnesium offers minimal advantage. In hypertension magnesium might be lowered but its measurement does not seem relevant. In the prediction of severe pre-eclampsia, elevated ionized magnesium concentration may play a role, but no unequivocal picture emerges. Low magnesium in blood may be cause for, or consequence of, diabetes mellitus. No special fraction clearly indicates magnesium deficiency leading to insulin resistance. Cardiac diseases are related to diminished magnesium levels. During myocardial infarction, serum magnesium drops. Total magnesium concentration in cardiac cells can be predicted from levels in sublingual or skeletal muscle cells. Most therapeutic drugs (diuretics, chemotherapeutics, immunosuppressive agents, antibiotics) cause hypomagnesemia due to increased urinary loss. It is concluded that most of the clinical situations studied show hypomagnesemia due to renal loss, with exception of renal disease. Keeping in mind that only 1% of the total body magnesium pool is extracellular, no simple measurement of the real intracellular situation has emerged; measuring ionized magnesium in serum has little added value at present.

Clinical evaluation of the CARDIAC STATus, a rapid immunochromatographic assay for simultaneous detection of elevated concentrations of CK-MB and myoglobin in whole blood.

We studied the performance of the CARDIAC STATus, a new rapid, easy to perform qualitative whole blood bedside test for detection of elevated CK-MB and myoglobin in the emergency room. Blood samples from 182 consecutive patients with chest pain were drawn on admission and at five and seven hours after the onset of symptoms. The CARDIAC STATus tests were performed by coronary care unit nurses and, independently, by a trained laboratory technician. The results were compared with quantitative assays for CK-MB mass and myoglobin. At the end of the study, a second test series using a new lot number of cartridges was performed on the same blood samples because of possible elution buffer contamination. Nurses produced more false negative results than the technician (CK-MB 43 vs. 27 %, p=0.01, myoglobin 31 vs. 13%, p<0.0001), but the technician produced more false positive myoglobin results (9.3 vs. 5.5%, p=0.0001). In the second test series, the nurses produced significantly fewer false negative tests both for CK-MB (19%, p<0.0001) and myoglobin (13%, p=0.0002). The false negative rate for the technician was not different between the first and the second test series. The CARDIAC STATus yields a substantial number of false negative results both for CK-MB and myoglobin when compared to a quantitative assay, and therefore at present has limited value for ruling out an acute myocardial infarction.

[Early exclusion of ischemic myocardial damage made possible by new biochemical cardiac markers]. / Vroege uitsluiting van ischemische myocardschade met behulp van nieuwe biochemische hartmerkstoffen.

New immunochemical assay methods for the cardiac markers creatine kinase (CK) MB mass, myoglobin, troponin T (TnT), troponin I (TnI), fatty acid binding protein (FABP) necessitate re-evaluation of their usefulness in the early diagnosis of myocardial damage. Cardiac markers play an important part in the exclusion of myocardial damage in patients with chest pain and an inconclusive ECG at admission. A serial CK-MB mass determination is particularly suitable for this exclusion of myocardial damage. The sensitivity of TnT shortly after an infarction is comparable with that of CK-MB mass; a single determination on admission is insufficient. The marker myoglobin is of limited value owing to the brief duration of myoglobin rise and insufficient heart specificity. An increased TnT or TnI value in patients with unstable angina pectoris is a prognostically negative sign. It is still not clear how this prognosis can be improved. A negative troponin finding appears not to exclude early complications. The department of Emergency Cardiac Care of the Academic Medical Centre, Amsterdam, the Netherlands, currently prefers the serial measurement of the CK-MB mass, in the future possibly to be supplemented by a troponin determination.

Intracellular and extracellular blood magnesium fractions in hemodialysis patients; is the ionized fraction a measure of magnesium excess?

To establish the best measure for determining magnesium overload, we measured ionized and total magnesium in serum and mononuclear blood cells and total magnesium in erythrocytes in blood of 23 hemodialysis patients, known for their disturbed magnesium homeostasis. When comparing the mean magnesium values obtained in the patient population with those of a control population, all of these magnesium markers, including the biologically active fractions, were significantly (P < 0.05) increased. Because serum total magnesium was not increased in all dialysis patients studied, the population was divided into two groups, according to total serum magnesium > 1.0 mmol/L or less than that. Results in these two populations showed that ionized serum magnesium and ionized magnesium in mononuclear blood cells might give a better indication about the magnesium status of the tested patients than the currently used total serum magnesium data. However, neither of the two markers, especially ionized serum magnesium, was able to discriminate fully between normal magnesium homeostasis and magnesium excess. We therefore conclude that the two ionized magnesium markers offer minimal advantage for this discrimination, and that the total magnesium concentration in serum remains the measurement of choice.