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The recent campaign for standardization of creatinine measurements has been promoted to allow the widespread use of formulas for estimating the glomerular filtration rate (GFR). However, studies on trueness verification and measurement interferences still show disappointing interassay variation of serum creatinine results. Creatinine recalibration has major clinical consequences. In particular, in pediatrics where reference ranges for serum and plasma creatinine are low, calculation of the GFR is problematic when based on alkaline picrate methods because of method non-specificity and the lack of appropriate GFR estimating formulas. Therefore, enzymatic creatinine assays are preferred. In the near future, cystatin C might offer an interesting alternative for GFR estimation. For the calculation of drug doses, the Modification of Diet in Renal Disease study formula generally offers reliable data. However, attention has to be paid to the elderly. Also, the calculation of the Model for End-Stage Liver Disease score, which is used to prioritize patients for liver transplantation, may significantly be influenced by recalibration of creatinine assays. Creatinine restandardization may also affect the current guidelines for referral of chronic kidney disease patients to nephrologists.

Purpose: The purpose of this study was to evaluate the accuracy of plasma cystatin C in acute impairment in renal function; plasma cystatin C was compared to plasma creatinine in two hundred patients undergoing elective CABG surgery. Methods: We performed a prospective clinical study of two hundred patients undergoing coronary bypass surgery. Plasma creatinine and cystatin C were measured preoperatively and on the first and fourth days after surgery. Estimated glomerular filtration rate (GFR) was calculated using one creatinine-based and two cystatin C-based equations. Results: There were 144 non-diabetic and 56 diabetic patients. The need for furosemide was more common among diabetics (80.4% of the patients vs. 53.9%, p = 0.024). Changes in cystatin C-based GFR with both equations were significantly greater in the group of diabetics (-14.3 ± 28.0 and -11.2 ± 19.3 ml/min/1.73 m 2 vs. -4.3 ± 26.9 and -3.1 ± 20.5 ml/min/1.73 m 2 , p = 0.025 and 0.016, respectively). Changes in creatinine-based GFR did not differ between the diabetics and the non-diabetics. Conclusion: Cystatin C and cystatin C-based estimation of GFR may be useful and more sensitive than creatinine in detecting mild acute renal insufficiency in diabetic patients.

En 1997, la Confederation des communautes europeennes de chimie clinique et de laboratoires de biologie medicale (EC4) a fonde un Registre des specialistes europeens en biologie medicale. L’etablissement du registre est pris en charge par une commission denommee EC4RC. Pendant les 10 dernieres annees, plus de 2 000 specialistes en biologie medicale se sont inscrits au registre. En 2007, l’EC4 a fusionne avec la Federation des societes europeennes de chimie clinique et de laboratoire de biologie medicale (FESCC) pour former la Federation europeenne de chimie clinique et de laboratoires de biologie medicale (EFCC). Un code de deontologie a ete adopte en 2003 et une version revisee, qui tient compte de « la declaration sur les valeurs communes » du Conseil europeen des professions liberales (CEPLIS) dont l’EFCC est membre, a ete approuvee par la Commission du registre EC4 et par le Comite de direction de l’EFCC a Paris le 6 novembre 2008.

Background/Aim: Knowledge of the usefulness of cystatin C measurement in the detection of chronic kidney disease in patients with rheumatoid arthritis (RA) is scant. The purpose of this study was to evaluate the ability of plasma cystatin C- and creatinine-based methods to predict glomerular filtration rate (GFR) and classify chronic kidney disease in RA patients. Methods: The study population consisted of 64 RA patients aged 41–86 years. Comparisons were made between measured plasma creatinine, cystatin C, creatinine clearance and GFR estimated by the Cockcroft-Gault (CG) and the Modification of Diet in Renal Disease (MDRD) formulas. The plasma clearance of 51Cr-EDTA served as a reference. Results: The Pearson correlation coefficients between plasma clearance of 51Cr-EDTA and the markers of GFR were calculated. The correlation coefficients were 0.800 for plasma creatinine, 0.863 for cystatin C, 0.866 and 0.904 for GFR values estimated by MDRD and CG and 0.922 for plasma creatinine clearance. Statistically significant differences were detected between the correlation coefficients of plasma creatinine and GFR estimated by CG (p = 0.0412) and plasma creatinine and creatinine clearance (p = 0.0099). Creatinine clearance and the MDRD and CG formulas proved to be better at identifying GFR Conclusion: We recommend using the CG formula or creatinine clearance for the estimation of the GFR of RA patients instead of solely creatinine or cystatin C in clinical work.

Calcium phosphate product (Ca x Pi) is a clinically relevant tool to estimate the cardiovascular risk of patients with renal failure. In reports, mostly total serum calcium has been used. As measurement of serum ionized calcium has some benefits and is being used increasingly, we estimated the respective levels of calcium phosphate product using both total (t-Ca x Pi) and ionized calcium (ion-Ca x Pi). Fifty-eight healthy individuals and 180 hemodialysis (HD) patients from 2 centers were studied. Diagnostic accuracies for corresponding values of the t-Ca x Pi and ion-Ca x Pi were calculated using a GraphROC program. Of HD patients, 64% had t-Ca x Pi

Background. IgA glomerulonephritis (IgAGN) composes a variable prognosis with 15-40% of the patients eventually progressing to end-stage renal failure. Known risk factors for progressive course of IgAGN include hypertension, proteinuria and renal insufficiency. Although markers of inflammation such as serum or urinary interleukin-6 (IL-6) and serum albumin have predicted progression in some studies, sensitive CRP (hs-CRP) has not been directly linked to the progression of IgAGN. Methods. A total of 174 (70 females) patients were invited for two visits 11 and 16 years (medians) after IgAGN was diagnosed in renal biopsy. All patients had been diagnosed at least 5 years before the first visit. Progressive disease was defined as cystatin-C exceeding normal limits and showing over 20% elevation between the visits, or kidney transplantation or start of dialysis. Cystatin-C and creatinine clearance, serum hs-CRP, s-albumin, s-IL-6 and white blood cell count (WBC) were available for analysis from 118 patients. Results. IgAGN was progressive in 19.5% of the patients on the second visit. Hs-CRP, s-albumin and WBC of the first visit were significantly associated with the progression of IgAGN (P = 0.014; P = 0.0001; P = 0.023, respectively). S-IL-6 was not associated with the progression. All inflammatory variables correlated significantly with the concurrent level of kidney function. Possible study limitations are the relatively low number of outcomes in the study groups, and the lack of generally accepted definitions for disease progression. Conclusions. Our results suggest that inflammatory markers hs-CRP, s-albumin and WBC are associated with the progression of IgAGN.

Background IgA glomerulonephritis (IgAGN) has a highly variable prognosis with 15-40% of patients progressing to end-stage renal disease. Hypertension, proteinuria and renal insufficiency are risk factors associated with poor prognosis. The role of insulin resistance is unclear in IgAGN. Methods From a retrospective cohort of IgAGN patients, a total of 174 patients (104 males) were invited for two visits at the clinic, 11 and 16 years (median times) after IgAGN was diagnosed in renal biopsy. Of all the patients, 63% had been diagnosed at least 10 years before the first visit. Progressive disease was defined as cystatin-C exceeding normal limits and showing over 20% elevation between the first and second visits, or kidney transplantation or start of dialysis. Plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR) index and cystatin-C were obtained for analysis from 118 patients. Results IgAGN was progressive in 19.5% of the patients on the second visit. Insulin level and HOMA-IR of the first visit showed significant association with the progression of IgAGN (P = 0.019 and 0.005, respectively). Conclusions Our results show that in addition to the known risk factors age, hypertension, proteinuria and hyperuricaemia, plasma insulin level and calculated HOMA-IR are associated with the progression of IgAGN.

Background: In experimental settings, uranium is toxic to kidneys, but effects on humans are unclear. Ingestion of water from drilled wells is a source of high uranium exposure in some populations. Methods: Uranium exposure was measured in 95 men and 98 women aged 18 to 81 years who had used drinking water from drilled wells for an average of 16 years. Urinary N-acetyl-γ-d-glucosaminidase, alkaline phosphatase, lactate dehydrogenase, γ-glutamyltransferase, and glutathione-S-transferase; serum cystatin C; and urinary and serum calcium, phosphate, glucose, and creatinine were measured to evaluate possible toxic effects of uranium on kidney cells and renal function. In addition, supine blood pressure was measured. Associations between uranium exposure and the outcome variables were modeled by using linear regression with adjustment for age, sex, body mass index, smoking, and analgesic use. Results: Median uranium concentration in drinking water was 25 μg/L (interquartile range, 5 to 148 μg/L; maximum, 1,500 μg/L). Indicators of cytotoxicity and kidney function did not show evidence of renal damage. No statistically significant associations with uranium in urine, water, hair, or toenails was found for 10 kidney toxicity indicators. Uranium exposure was associated with greater diastolic and systolic blood pressures, and cumulative uranium intake was associated with increased glucose excretion in urine. Conclusion: Continuous uranium intake from drinking water, even at relatively high exposures, was not found to have cytotoxic effects on kidneys in humans.

To evaluate whether off-pump surgery attenuates microalbuminuria and other markers of systemic inflammatory response to coronary artery bypass surgery as compared to surgery performed using cardiopulmonary bypass.Forty-three adult patients undergoing elective coronary artery bypass grafting surgery were operated on with or without cardiopulmonary bypass (CPB). Microalbuminuria, serum C-reactive protein, and oxygenation and lung function parameters were measured at several time points until the first postoperative morning.The urinary albumin/creatinine ratio was low in both groups before surgery, but reached a maximum level at the end of CPB or just after opening the last coronary artery clamp in the off-pump group (p0.05). The urinary albumin/creatinine ratio remained slightly elevated in both groups until the morning after the operation (p0.05). There were no statistical differences between groups. Serum C-reactive protein remained at the initial level the evening after the operation, but increased by the first postoperative morning in both groups (p0.001). The alveolar-arterial gradient for oxygen partial pressure rose significantly after the operation in the intensive care unit in both groups (p0.0001). The shunt fraction of the pulmonary circulation did not change in either group.Off-pump coronary artery surgery did not prevent the acute phase inflammatory response measured in the present study. The acute phase inflammatory response after coronary artery bypass surgery is more likely a response to the surgical trauma itself rather than to CPB.

Background This study was designed to evaluate the renal consequences of the treatment of brain tumor patients diagnosed in childhood. Procedure One hundred four primary brain tumor patients diagnosed before 17 years of age from 1983 to 1997 had been treated in Tampere University Hospital, Finland. Of the 80 survivors 52 (65.0%) were examined at a median age of 14.4 years (range 3.8–28.7) and median 6.0 years (range 1.2–14.8) after the last treatment. The main outcome measures were blood pressure (BP), renal function, and calcium metabolism. Results Eight patients (15.4%) were hypertensive. Elevated BP was observed especially after exposure both to cisplatin and cranial irradiation. Spinal radiation did not increase the risk of elevated BP. Other adverse effects were observed only in patients treated with cisplatin. Five out of 14 patients treated with cisplatin evinced renal glomerular dysfunction (GFR

Objective— Obesity is associated with endothelial dysfunction that may contribute to the development of atherosclerosis. We studied whether weight reduction improves endothelial function in overweight individuals. Methods and Results— Flow-mediated endothelium-dependent vasodilation of the brachial artery was measured in 67 adults (age: 46±7 years, body mass index: 35.2±5.4 kg/m 2 ) before and after a 6-week weight reduction program induced by very-low-calorie diet (daily energy: 580 kcal/2.3 MJ). Caloric restriction reduced body weight from 101±18 to 90±17 kg. Flow-mediated vasodilation increased from 5.5%±3.7 to 8.8%±3.7% ( P P =0.0003). This relationship was independent of changes in weight, serum lipids, oxidized LDL, C-reactive protein, adiponectin, blood pressure, and insulin. Conclusions— Weight reduction with very-low-calorie diet improves flow-mediated vasodilation in obese individuals. This improvement is related to the reduction in plasma glucose concentration. These observations suggest that changes in glucose metabolism may determine endothelial vasodilatory function in obesity.

Background. Nephropathia epidemica (NE) is the Scandinavian type of haemorrhagic fever with renal syndrome. Usually heavy transient proteinuria is present at the onset of the disease. Methods. We investigated glomerular permeability in eight patients with acute NE and in eight healthy controls. Six patients were followed for 1 year. The glomerular filtration rate (GFR) was determined by inulin clearance and effective renal plasma flow v (ERPF) by para-aminohippurate clearance. Results. GFR and ERPF were significantly reduced in NE patients during the acute phase compared with those in controls (P < 0.001 and P < 0.001, respectively). The filtration fraction (FF) was thus high, 0.37. The fractional clearances of albumin. IgG, and IgG 4 were markedly increased. As a sign of tubular dysfunction, increased urinary excretion of α 1 -microglobulin was observed in all patients. After 1 year, the GFR of the patients no longer differed from that of the controls. ERPF was lower and FF higher than those in controls (P = 0.014 and P = 0.009, respectively). The fractional clearances of albumin, IgG. and IgG4 remained increased. The high-molecular fractional dextran clearances in the patients were significantly increased compared with controls during the acute phase. Computed analysis of glomerular membrane-pore structure showed that the shunt-flow' was increased in the patients during the acute phase compared with the controls. There was a positive correlation between the FF and the shunt (r = 0.768, P = 0.026). In addition, fractional clearances of albumin and IgG correlated significantly with the shunt (r = 0.810, P = 0.015 and r = 0.762, P = 0.028, respectively). Conclusions. Renal involvement in the acute phase of NE is characterized by a markedly decreased GFR and ERPF. Increased glomerular permeability is associated with impairment of both the size- and charge-selectivity properties of the glomerular filter.

Background/Aims: Metabolic syndrome (MetS) may have an independent impact on the development of chronic kidney disease. This study examines the prevalence of MetS in subjects with IgA glomerulonephritis (IgAGN) and its impact on disease progression in a retrospective fashion. Patients and Methods: Altogether, 174 subjects (104 males) were examined 11 years (first visit) after IgAGN diagnosis and again after 16 years (second visit; 144 subjects responded). Different glomerular filtration markers were utilized. The MetS criteria by Alberti et al. [Circulation 2009;120:1640-1645] were applied, in which the presence of any three of five risk factors (elevated waist circumference, triglycerides, glucose, existence of hypertension, or reduced high-density lipoprotein cholesterol) constitutes the diagnosis. Results: The prevalence of MetS at the first visit was 39%, corresponding to that of the general Finnish population. In univariate analyses, MetS was significantly associated with the progression of IgAGN at the second visit. However, in multivariate analyses, the existence of MetS was not a significant prognostic determinant. Conclusion: The number of subjects with MetS among IgAGN patients and the general population is equal in Finland. MetS does not seem to be an independent prognostic variable.

Background: A high dose of cholecystokinin (CCK) agonist cerulein can induce acute pancreatitis in animals. The role of CCK in the induction of acute pancreatitis in humans is unclear. We investigated basal plasma CCK levels before and after induction of post-ERCP pancreatitis to determine CCK levels in the early course of the disease. Study Design: We determined plasma CCK concentrations in four groups of patients who underwent ERCP: (1) post-ERCP pancreatitis patients (n = 23); (2) patients with post-ERCP hyperamylasemia without pancreatitis (n = 5); (3) patients with post-ERCP abdominal pain without hyperamylasemia (n = 18); and (4) patients with an uneventful post-ERCP period (n = 43). Plasma samples were taken before ERCP, 4 to 8 hours, 10 to 16 hours, and 24 hours after ERCP. Plasma CCK concentrations were determined by a specific and sensitive radioimmunoassay using CCK antiserum (Euro-Diagnostica, Malmo, Sweden). Results: Plasma CCK levels increased five-fold early in the course in post-ERCP pancreatitis patients, but not in post-ERCP hyperamylasemia patients or in uncomplicated ERCP patients, where CCK levels temporarily decreased after ERCP. In patients with abdominal pain, CCK levels did not change. After the early increase, plasma CCK levels declined to almost unmeasurable levels one day after the onset of symptoms in post-ERCP pancreatitis. In other groups CCK levels were close to the pre-ERCP level. Conclusions: It remains to be shown whether CCK is important in the pathogenesis of post-ERCP pancreatitis or merely a secondary phenomenon. There is a rationale to test CCK antagonists in preventing post-ERCP pancreatitis.

Objective To evaluate the magnesium status of continuous ambulatory peritoneal dialysis (CAPD) patients using a new method for assessing the level of the ionized fraction a serume magnesiumy. Design Serum ionized magnesium was measured in CAPD patients using the ion-selective electrode for Mg2+. Setting The Dialysis Unit of Tampere University Hospital. Patients Twenty -six patients on CAPD (age: 21 -81 years, mean 54 ± 16 years; duration of CAPD: 3 -52 months, mean 13 months), and 26 sex and age-matched healthy controls. Results Both serum ionized magnesium (0.73 ± 0.11 mmol/L vs 0.56 ± 0.07 mmol/L, p < 0.001) and total magnesium (1.11 ± 0.22 vs 0.81 ± 0.08 mmol/L, p < 0.01) were higher in CAPD patients than in sex and agematched controls. The ionized magnesium fraction of total magnesium was slightly lower in dialysis patients in spite of the fact that 16/26 patients had serum albumin less than 36 g/L. Hypermagnesemia (mean serum ionized magnesium 0.78± 0.10 mmol/L) was observed in the 13 of 26 patients with 0.75 mmol/L Mg2+ dialysate; those with lower magnesium dialysate (Mg2+ 0.50 mmol/L in 10/26 and Mg2+ 0.25 mmol/L in 3/26) had mean serum ionized magnesium at the upper normal margin (0.69 ± 0.10 mmol/L). Conclusion In CAPD patients with Mg2+ 0.5 0.75 mmol/L in their dialysis fluid, both serum ionized and total magnesium concentrations were higher but the ionized/total magnesium ratio was lower than in healthy control subjects. Use of ion-selective electrodes to measure ionized magnesium may be a more useful methodology than measuring total magnesium in the evaluation of magnesium status of CAPD patients, because it is not infuenced by hypoalbuminemia or increased complexed fraction of magnesium often present in dialysis patients.

The mechanism of postoperative hyperamylasaemia was studied in 48 patients undergoing coronary artery bypass grafting (CABG). Mild hyperamylasaemia developed in 87% of the patients, and in 10% the serum amylase activity was > 1000 U/l. Serial measurements of serum salivary (S-) and pancreatic (P-) isoamylases indicated that hyperamylasaemia was highest 24 hours after CABG and consisted mainly of P-amylase component. Serum creatinine, creatinine clearance and urinary albumin concentration remained normal after CABG, excluding severe renal damage. The fractional clearance (i.e. relative to creatinine clearance) of P-amylase decreased more than of S-amylase (from 3.6 to 0.9% vs 1.3 to 0.8%). Decreased rate of excretion into urine, rather than pancreatic cellular damage, is the main source of hyperamylasaemia after CABG.

Oxygen-derived free radicals constitute one part of the etiologic factors for cardiac onset harmful events. Allopurinol is able to reduce the generation of free radicals. Vitamins E and C scavenge radicals after their formation. Eighty-one patients with coronary artery disease were randomized into four study groups: Group 1 (n = 20) patients had stable disease and received oral vitamin E for 4 weeks, and vitamin C and allopurinol 2 days before and 1 day after coronary artery bypass grafting. Group 2 (n = 25) consisted of their controls. Group 3 patients (n = 17) had more unstable disease and received the same medications as group 1, except that vitamin E was given only 2 days before the operation. Group 4 (n = 19) was their controls. Groups 1 and 3 had fewer ischemic electrocardiographic events and required less dopamine perioperatively than corresponding control groups 2 and 4. Group 3 had fewer perioperative infarctions and less creatine kinase-MB release than the respective controls (group 4). Plasma levels of vitamins E and C, urate, and total free radical trapping ability were considered to support the theory about the role of free radicals in reperfusion injury. Especially the unstable patients, but also patients with stable coronary artery disease requiring coronary artery bypass grafting benefit from perioperative allopurinol and vitamin E and C treatment.

Estimation of the glomerular filtration rate (GFR) is the most widely used test of renal function, reflecting the relative mass of functional renal tissue and thus the number of functioning nephrons. Methods based on measurement of exogenous substances such as inulin, 51Cr-EDTA, 99mTc-diethylenetriaminepentaacetic acid, and iohexol are accurate but too complex and laborious for routine clinical use; thus, measurement of endogenous blood substances is common practice. Plasma or serum creatinine and its renal clearance are the approaches most commonly used despite their acknowledged unreliability. Cystatin C, a small basic protein, has been proposed as a better marker than creatinine. Recently, the value of cystatin C was thoroughly reviewed in this Journal (1), and according to this review and a new metaanalysis (2), most studies have concluded that cystatin C is superior to plasma creatinine, whereas several authors have concluded that cystatin C provides no advantage. One purpose of the present study was to clarify possible reasons for the earlier, partly conflicting results. A recently published guideline from the National Kidney Foundation (3) recommended that GFR be estimated from prediction equations taking into account the serum creatinine concentration and some or all of the following variables: age, gender, race, and body size. We therefore also compared cystatin C with GFRs calculated by the Cockcroft–Gault (4) and the MDRD(5) formulas. We studied 112 patients (55 men and 57 women) for whom 51Cr-EDTA clearance had been requested. The mean age of the patients was 57.0 years (range, 17–89 years). Body mass index (BMI) was 15.2–42.4 kg/m2, and 51 …

Serum C-reactive protein rises in acute myocardial infarction, correlating positively with infarct size if thrombolytic treatment is not given. This correlation disappears if thrombolytic treatment is given, although the serum C-reactive protein concentration is still associated with the clinical outcome of the patient. We studied the effect of early coronary recanalization induced by thrombolytic treatment alone or combined with coronary angioplasty on the infarct related rise in serum C-reactive protein concentration. The C-reactive protein response caused by the myocardial infarct was lower in patients with an open infarct-related coronary artery than in patients with a closed infarct-related coronary artery, or in control patients who did not receive thrombolytic therapy. In control patients we found the expected strong positive correlation between infarct size and serum C-reactive protein (r = 0.58; P < 0.001, n = 48), which was similar to that in patients with a closed infarct-related coronary artery (r = 0.62; P < 0.001, n = 17). In patients with an open infarct-related coronary artery the correlation between infarct size and serum C-reactive protein was much weaker (r = 30; P < 0.01, n = 91). Consequently infarct size explained approximately 35% of the variation in serum C-reactive protein values in the control patients and 36% in the patients with a closed infarct-related coronary artery, but only 9% of the variation in the patients with an open infarct-related artery. Ejection fraction correlated negatively with serum C-reactive protein in both control and recanalized patients. The association was again much stronger in the control patients.(ABSTRACT TRUNCATED AT 250 WORDS)

In 1997, the European Communities Confederation of Clinical Chemistry and Laboratory Medicine (EC4) set up a Register for European Specialists in Clinical Chemistry and Laboratory Medicine. The operation of the Register is undertaken by a Register Commission (EC4RC). During the last 12 years, more than 2200 specialists in Clinical Chemistry and Laboratory Medicine have joined the Register. In 2007, EC4 merged with the Forum of European Societies of Clinical Chemistry and Laboratory Medicine (FESCC) to form the European Federation of Clinical Chemistry and Laboratory Medicine (EFCC). Two previous Guides to the Register have been published, one in 1997 and another in 2003. The third version of the Guide is presented in this article and is based on the experience gained and development of the profession since the last revision. Registration is valid for 5 years and the procedure and criteria for re-registration are presented as an Appendix at the end of the article. Clin Chem Lab Med 2010;48:999–1008.

OBJECTIVE To investigate the prognostic importance in neurologic recovery of the lumbar cerebrospinal fluid (CSF) variables creatine kinase (CK) and brain-type creatine kinase isoenzyme (CK-BB), lactate dehydrogenase (LDH) and its isoenzymes (LDH 1-5), CSF acid phosphatase, beta-D-N-acetylglucosaminidase activity, and CSF lactate, pyruvate, sodium, potassium, and calcium concentrations in patients who experienced cardiac arrest. DESIGN Prospective clinical study with blood and CSF samples collected 4, 28, 76, and 172 hrs after resuscitation. SETTING Medical ICU in a university hospital. PATIENTS Twenty consecutive victims of out-of-hospital cardiac arrest. Eight patients recovered neurologically and 12 patients remained comatose or neurologically disabled until death. MEASUREMENTS AND MAIN RESULTS CSF CK, CK-BB, LDH, and LDH isoenzyme 1-3 concentrations in all disabled patients were markedly increased at 76 hrs after the resuscitation. However, these variables were not changed in the recovered subjects. Patients (n = 7) with a mean CSF CK level of 25 +/- 33 (SD) U/L, CK-BB 23 +/- 33 U/L, and CSF lactate 3.8 +/- 0.9 mmol/L at 28 hrs after cardiac arrest remained unconscious and died. In the recovered patients, the mean CSF CK concentration was 2.0 +/- 1.5 U/L (p less than .001) and CSF lactate concentration 2.5 +/- 0.5 mmol/L (p less than .002). The lactate concentration was highest at 4 hrs after resuscitation, declining thereafter. Patients with a mean CSF total LDH level of 609 +/- 515 U/L and acid phosphatase 2.4 +/- 1.2 U/L 76 hrs after resuscitation died without regaining consciousness. In the recovered patients, the mean total CSF LDH activity was 82 +/- 58 U/L (p = .003) and CSF acid phosphatase was 0.8 +/- 0.5 U/L (p = .01) 76 hrs after resuscitation. CONCLUSIONS CSF CK, CK-BB, and CSF lactate concentrations reflect a patient's outcome most reliably when measured within 28 to 76 hrs of the cardiac arrest. Similarly, CSF LDH, its isoenzymes 1-3, and CSF acid phosphatase concentrations, when measured at 76 hrs, can be used to monitor the patient's outcome after cardiac arrest. When correlated with Glasgow Coma Scale scores, the closest negative correlation was again seen in CSF CK and CK-BB at 28 and 76 hrs, as well as in LDH, LDH1-3, and acid phosphatase values at 76 hrs. The negative correlation between CSF lactate and Glasgow Coma Scale scores was most distinct at 28 hrs.

Conventional nonsteroidal anti-inflammatory drugs (NSAIDs) have a well-documented nephrotoxic action. Still, there are only few studies that have investigated the nephrotoxicity of cyclo-oxycenase-2-inhibitors during the perioperative period. Thirty patients scheduled for elective laparoscopic hysterectomy were enrolled in this prospective, randomized double-blind study. Patients were randomized into two groups: a saline-treated control group (placebo) and 80 mg parecoxib-treated group (parecoxib). The samples for the analyses of serum and urine were collected at the induction of anesthesia, two hours thereafter, two hours from the end of anesthesia, and on the first postoperative day (POD). S-crea, S-urea, S-cystatin C, S-Na, S-K, U-1mikroglobulin/U-crea, U-GST/U-crea, and U-GST/U-crea were analyzed from the samples. Urine output was measured every hour for the first five hours, and total amount of urine was measured until the first postoperative day. There were no clinical and few statistical significant differences between the two groups in the renal measurements during the study period. The urinary output was also similar in the two groups. A single dose of 80 mg of parecoxib was well tolerated by the kidneys in the short-term perioperative use in patients undergoing laparoscopic hysterectomy with ASA physiological status I-II and age under 60 years.

The pathogenesis of IgA glomerulonephritis (IgAGN) involves intense deposition of IgAs within the glomerulus. Although previous studies have shown that heavy drinking frequently leads to the generation of IgA antibodies against neo-antigens induced by ethanol metabolites and tissue deposition of IgAs, the associations between alcohol consumption, IgA immune responses, and kidney disease have not been examined.A total of 158 IgAGN patients (96 men, 62 women) were classified as abstainers (n = 38), moderate drinkers (n = 114), and heavy drinkers (n = 6) based on self-reported alcohol consumption. The reference population included 143 individuals (99 men, 44 women) who were either apparently healthy abstainers (n = 31), moderate drinkers (n = 43), or heavy drinkers devoid of liver disease (n = 69). The assessments included various biomarkers of alcohol consumption: carbohydrate-deficient transferrin (CDT), glutamyl transferase, gamma-CDT (combination of GGR and CDT), mean corpuscular volume (MCV), tests for liver and kidney function, serum immunoglobulin A (IgA), and specific IgA antibodies against acetaldehyde-protein adducts.In male IgAGN patients, drinking status was significantly associated with MCV, p0.001; CDT, p0.01; and gamma -CDT, p0.05. In the reference population, all biomarkers and anti-adduct IgA levels were found to vary according to drinking status. In IgAGN patients, anti-adduct IgA levels were elevated in 63% of the cases but the titers did not associate with self-reported ethanol intake.These data indicate high levels of IgA antibodies against acetaldehyde-derived antigens in IgAGN patients, which may hamper the use of the immune responses as markers of alcohol consumption among such patients. Future studies on the pathogenic and prognostic significance of anti-adduct immune responses in IgAGN patients are warranted.

We examined the acute phase reaction in myocardial infarction after thrombolytic treatment by streptokinase or tissue plasminogen activator. The magnitude of the acute phase reaction as determined by measurements of serum C-reactive protein and amyloid-A protein did not correlate with infarct size (determined by serial measurements of creatine kinase-MB) in this patient population. On the other hand, the development of acute cardiac failure was more closely associated with the magnitude of the acute phase reaction than with infarct size. The peak serum values of C-reactive protein in patients with and without acute cardiac failure were 128 mg/l (95% confidence intervals 85-170) and 60 mg/l (30-89); P less than 0.01 and concentration time integrals 578 mg/l x days (368-787) and 205 mg/l x days (62-350); P less than 0.01. The corresponding creatine kinase-MB values were 310 U/l (191-429) and 207 U/l (125-289) not significant; and 319 U/l x days (201-437) and 204 U/l x days (124-286) not significant; respectively. Patients requiring medication for cardiac failure on discharge from hospital had higher C-reactive protein and serum amyloid A protein values than those who did not, although the difference did not quite reach statistical significance. The infarct sizes were similar whether the patients needed medication for cardiac failure at discharge or not. Subjectively felt morbidity due to myocardial infarction was linearly associated with serum C-reactive protein peak values (P less than 0.05) and concentration time integrals (P less than 0.05), but not with infarct size. We conclude that thrombolytic treatment of myocardial infarction may reduce hospital inpatient morbidity independently of the limitation of infarct size. This diminished morbidity seems to be associated with modest or low acute phase reaction.

This study was conducted to determine the frequency, severity and outcome of cardiac findings in patients with acute Puumala hantavirus-induced nephropathia epidemica (NE). 70 consecutive, hospital-treated patients with serologically confirmed NE were prospectively examined using serial electrocardiograms (ECG), plasma troponin I, tumour necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and echocardiography (ECHO). Examinations were repeated after 3 and 12 months. ECG changes were observed in 57% of patients. Plasma troponin I levels remained normal in all. In six patients, ECHO showed left ventricular contraction abnormalities, and 1 patient had mild pericardial effusion. There were no differences in clinical or standard laboratory findings or in plasma TNF-alpha and IL-6 concentrations between patients with and without ECG or ECHO changes. During the follow-up, all acute-phase changes in ECG and ECHO reverted to normal, which probably reflects their benign nature. We conclude that abnormal cardiac findings are surprisingly common during NE.

The European In Vitro Diagnostics (IVD) directive requires traceability to reference methods and materials of analytes. It is a task of the profession to verify the trueness of results and IVD compatibility.: The results of a trueness verification study by the European Communities Confederation of Clinical Chemistry (EC4) working group on creatinine standardization are described, in which 189 European laboratories analyzed serum creatinine in a commutable serum-based material, using analytical systems from seven companies. Values were targeted using isotope dilution gas chromatography/mass spectrometry. Results were tested on their compliance to a set of three criteria: trueness, i.e., no significant bias relative to the target value, between-laboratory variation and within-laboratory variation relative to the maximum allowable error.: For the lower and intermediate level, values differed significantly from the target value in the Jaffe and the dry chemistry methods. At the high level, dry chemistry yielded higher results. Between-laboratory coefficients of variation ranged from 4.37% to 8.74%. Total error budget was mainly consumed by the bias. Non-compensated Jaffe methods largely exceeded the total error budget. Best results were obtained for the enzymatic method. The dry chemistry method consumed a large part of its error budget due to calibration bias.: Despite the European IVD directive and the growing needs for creatinine standardization, an unacceptable inter-laboratory variation was observed, which was mainly due to calibration differences. The calibration variation has major clinical consequences, in particular in pediatrics, where reference ranges for serum and plasma creatinine are low, and in the estimation of glomerular filtration rate.Clin Chem Lab Med 2008;46:1319–25.

Peak serum C-reactive protein concentrations were measured in 146 patients randomized to receive streptokinase, alteplase, or a combination of streptokinase and alteplase in the GUSTO-I trial. Those receiving alteplase treatment had lower values than those receiving streptokinase or the combination treatment. Irrespective of treatment, complete reperfusion of the infarct-related artery (TIMI grade 3 flow) was associated with low peak serum C-reactive protein values.

The EC4 Syllabus for Postgraduate Training is the basis for the European Register of Specialists in Clinical Chemistry and Laboratory Medicine. The syllabus: Indicates the level of requirements in postgraduate training to harmonise the postgraduate education in the European Union (EU); Indicates the level of content of national training programmes to obtain adequate knowledge and experience; Is approved by all EU societies for clinical chemistry and laboratory medicine. The syllabus is not primarily meant to be a training guide, but on the basis of the overview given (common minimal programme), national societies should formulate programmes that indicate where knowledge and experience is needed. The main points of this programme are: Indicates the level of requirements in postgraduate training to harmonise the postgraduate education in the European Union (EU); Indicates the level of content of national training programmes to obtain adequate knowledge and experience; Is approved by all EU societies for clinical chemistry and laboratory medicine. Knowledge in biochemistry, haematology, immunology, etc.; Pre-analytical conditions; Evaluation of results; Interpretations (post-analytical phase); Laboratory management; and Quality insurance management. The aim of this version of the syllabus is to be in accordance with the Directive of Professional Qualifications published on 30 September 2005. To prepare the common platforms planned in this directive, the disciplines are divided into four categories: Indicates the level of requirements in postgraduate training to harmonise the postgraduate education in the European Union (EU); Indicates the level of content of national training programmes to obtain adequate knowledge and experience; Is approved by all EU societies for clinical chemistry and laboratory medicine. Knowledge in biochemistry, haematology, immunology, etc.; Pre-analytical conditions; Evaluation of results; Interpretations (post-analytical phase); Laboratory management; and Quality insurance management. General chemistry, encompassing biochemistry, endocrinology, chemical (humoral), immunology, toxicology, and therapeutic drug monitoring; Haematology, covering cells, transfusion serology, coagulation, and cellular immunology; Microbiology, involving bacteriology, virology, parasitology, and mycology; Genetics and IVF.

Predictors of tubular proteinuria (alpha 1-M/ crea ratio >10 mg/mmol) were sought in 100 infants of 24–32 weeks’ (group 1) and 69 of 34–42 weeks’ gestation (group 2). Random spot urine samples were obtained in the former group at the ages of 0–3 days, at 1–2 weeks and thereafter at 2-week intervals until the disappearance of tubular proteinuria, and in the latter one sample at a mean (SD) of 3.0 days’ (1.3) age. In group 1, gestational age correlated negatively with the first urinary alpha 1-M/ crea ratio. The highest urinary alpha 1-M/crea ratios [median (range) 39.1 mg/mmol (9.5–268.9)] occurred at a median (range) of 5 days’ (1–42) age. Low gestational age and the need for inotropes predicted tubular proteinuria early after birth, whereas low gestation and long duration of ventilator treatment predicted the highest alpha 1-M/crea ratios. Prolonged vancomycin treatment and low gestational age were associated with delayed normalization of tubular proteinuria. In group 2 no significant risk factors for tubular proteinuria were found. The urinary alpha 1-M/crea ratio seems to be a sensitive indicator of renal tubular function in neonates, with low gestational age, the need for inotropes and prolonged assisted ventilation being predictors of increased tubular proteinuria. Long vancomycin courses should be avoided in pre-term infants in view of the prolonged adverse renal effects.

The European Communities Confederation of Clinical Chemistry and Laboratory Medicine (EC4) opened a Register for European Chemists in 1997. The operation of the Register is undertaken by a Register Committee (EC4RC). During the last 5 years more than 1,400 clinical chemists entered the register. In this article an update of the first Guide to the Register is given, based on the experience of 5 years of operation and the development of the discipline. The registration is valid for 5 years. In a second part the procedure and the conditions for re-registration are presented.

Objective— Elevated serum concentration of C-reactive protein (CRP) predicts cardiovascular events in adults. Because atherosclerosis begins in childhood, we undertook a study to determine whether changes in brachial artery endothelial function and the thickness of the carotid intima-media complex, 2 markers of early atherosclerosis, are related to CRP levels in healthy children. Methods and Results— Brachial artery flow-mediated dilatation (FMD) and carotid artery intima-media thickness (IMT) were measured with ultrasound in 79 children (aged 10.5±1.1 years). Compared with the children with CRP levels under the detection limit (0.7 mg/L, n=19, group 3) had lower FMD (9.0±4.4% versus 7.8±3.3% versus 6.5±2.6%, respectively; P =0.015 for trend) and greater carotid IMT (0.45±0.03 versus 0.46±0.04 versus 0.49±0.06 mm, respectively, P =0.002 for trend). CRP level remained a statistically significant independent predictor for brachial FMD and carotid IMT in multivariate analyses. Conclusions— These data suggest that CRP affects the arteries of healthy children by disturbing endothelial function and promoting intima-media thickening. The findings support the hypothesis that CRP plays a role in the pathogenesis of early atherosclerosis.

Reference intervals for markers of proteinuria or glomerular charge selectivity were measured in 61 healthy female and 61 healthy male individuals. Timed bed-rest and daytime collections were used to assess significance of preanalytical variability of results. Bed-rest collections are advisable for research on renal damage, whereas in routine care, robust protein/creatinine ratios work as practical estimates of protein excretion rates, the correlations to excretion rates improving with increasing proteinuria. For glomerular charge selectivity, pancreatic/salivary isoamylase clearance ratio showed lower within-subject biological variation than IgG/IgG4 clearance ratio, allowing more accurate classification into normal and reduced charge selectivity. With our method, the lower 2.5% reference intervals for isoamylase clearance ratio were 1.1 in men and 1.9 in women.

Cystatin C is a non-glycated, 13-kDa basic protein produced by all nucleated cells. Recent studies have indicated that the plasma concentration of cystatin C is a better marker for glomerular filtration rate (GFR) than plasma creatinine, which is most commonly used for this purpose. We established reference values for plasma cystatin C in pre- or full-term infants and children. For comparison we also measured the creatinine concentration in the same samples. Cystatin C was measured by a commercially available immunoturbidimetric method with a Hitachi 704 analyzer in sera obtained from 58 pre-term infants, 50 full-term infants and 299 older children (132 girls, 167 boys, median age 4.17 years, range 8 days to 16 years). No sex differences were found. The pre-term infants had higher cystatin C concentrations (mean 1.88 mg/l, SD 0.36 mg/l) than the full-term (mean 1.70 mg/l, SD 0.26 mg/l, P=0.0145). The reference interval for pre-term infants calculated non-parametrically was 1.34–2.57 mg/l and for full-term infants 1.36–2.23 mg/l. The cystatin C concentration decreased rapidly after birth, and above 3 years of age did not depend on age. The reference interval for children 3–16 years of age calculated non-parametrically was 0.51–1.31 mg/l. Younger children (

We sought to develop a biodegradable pancreatic stent that could be easily placed at operation into the human pancreatic duct and the degradation of which could be easily followed up. Spiral-shaped, gamma-sterilized stents were manufactured of 0.4-mm polylactide wire in which there was added 23 weight-% barium sulfate. The biodegradability of the stents was studied in vitro at two different pH values, the first resembling that of pancreatic juice and the other that of bile. The effects of enzymoactivity in the test solution and the composition of the stents (with or without barium addition) also were tested. These kinds of stents have been experimented with in two pilot patients. Degradation of the stents occurred from 24 to 52 weeks of incubation. Alkaline milieu together with the presence of pancreatic enzyme made the stents degrade twice as fast as when either alkaline milieu or enzyme was present. In the milieu resembling pancreatic juice, barium sulfate had no effect on the degradation time. Neither of the pilot patients had any postoperative complications. Biodegradable, x-ray-positive stents degrade faster in pancreatic than in biliary milieu. Their safety and efficacy in human pancreaticojejunal anastomoses need further study.

We describe an HPLC method for quantifying creatinine, separating the analyte from other compounds in serum and urine by cation-exchange chromatography and measuring its absorbance at 234 nm. The precision of the method (CV) varied from 2.9% (mean creatinine concentration, 31 mumol/L) to 1.7% (361 mumol/L) within a series of assays and from 3.9% (34 mumol/L) to 2.4% (391 mumol/L) between series. A comparison with the Jaffé method, as performed with a Technicon SMA analyzer, gave the regression line yHPLC = 1.00xJaffé - 12.0 (n = 141, r = 0.998, and Syx = 19). Results also are comparable with those of an enzymatic method, if the enzymatic method is standardized with a serum-based standard when serum samples are measured. An aqueous standard has to be used for enzymatic determination of creatinine in urine.

Cystatin C is a non-glycated 13-kilodalton basic protein produced by all nucleated cells. The low molecular mass and the basic nature of cystatin C, in combination with its stable production rate, suggest that the glomerular filtration rate (GFR) is the major determinant of cystatin C concentration in the peripheral circulation. Recently published studies have shown that cystatin C correlates more strongly than creatinine with GFR measured using the 51Cr-EDTA clearance. The aim of this study was to evaluate serum cystatin C as a marker for GFR in children. GFR was determined on medical indications using the 51Cr-EDTA technique in pediatric patients (2-16 years) in our renal unit. Simultaneously their cystatin C and creatinine concentrations were also measured. Of our 52 patients, 19 had a reduced renal function (

In serum, magnesium exists in three fractions: protein-bound, complex-bound and free ionized form. Only the free ionized fraction is biologically active. Until recently, only the measurement of serum total magnesium has been in clinical use. Now, commercially available instruments using new ion-selective electrodes for Mg++ have made possible the reliable measurement of serum ionized magnesium in clinical practice. For the measurement of serum ionized magnesium we used a magnesium-selective electrode installed in a six-channel electrolyte analyzer. We compared the use of ionized versus total magnesium measurement in 52 patients with intestinal disease, 54 with liver disease, and in 75 healthy control subjects. In the patients with alcoholic liver disease both serum ionized and total magnesium were lower, and in those with inflammatory bowel disease slightly higher than in control subjects. The correlation coefficient between serum ionized and total magnesium was r=0.87 (p

Evidence suggests that free oxygen radicals are involved in the destruction of islet beta-cells in insulin-dependent diabetes mellitus (IDDM). Therefore, we determined the plasma antioxidant activity in 51 healthy unaffected children and adolescents randomly chosen from a study of beta-cell autoimmunity in schoolchildren in northern Finland. Twenty-two subjects tested positive for one or more IDDM-associated autoantibodies and 9 subjects had at least two of the three antibodies tested (antibodies against islet cells, ICA; glutamic acid decarboxylase, GADA; insulin, IAA). There was no significant association of total plasma antioxidant potential, plasma concentrations of alpha-tocopherol, ascorbic acid, protein thiols, or uric acid with the presence of ICA, GADA, or IAA. A reduced first-phase insulin response to intravenous glucose was also not associated with reduced plasma antioxidant activity. These results indicate that the plasma antioxidant activity is not decreased in subjects at increased risk for IDDM. Furthermore, the results suggest that the clinical onset of IDDM is not preceded by signs of increased systemic oxidative stress in plasma.

Background: Recent technology has made it possible to assess serum ionized magnesium with user-friendly ion-selective electrodes similar to measurement of the serum calcium concentration. Methods: We measured the serum ionized (Mg2+) and total magnesium (tMg) concentration in 69 patients with chronic kidney disease (38 men, 31 women, age 22–85 years) and in 75 control subjects. Results: In control subjects the reference ranges were as follows: serum Mg2+ 0.45–0.67 mmol/l, and tMg 0.67–0.96 mmol/l. In patients with chronic renal failure serum Mg2+ was 0.57 ± 0.05 mmol/l and tMg 0.80 ± 0.11 mmol/l, and in transplant recipients receiving cyclosporine 0.53 ± 0.05 and 0.71 ± 0.10 mmol/l, respectively. The correlation coefficient between serum Mg2+ and tMg was r = 0.73 (p < 0.001) in the patient group and r = 0.75 (p2+ was below the reference range in only 1 of these 15 samples. Hence, 14 of 69 cases with low tMg but normal Mg2+ were false-positive with respect to hypomagnesemia. Conclusion: We conclude that tMg may overestimate the incidence of hypomagnesemia, and the measurement of Mg2+ may be of benefit when studying patients with expected hypomagnesemia.

Background: Postoperative hyperamylasemia and even acute pancreatitis are associated with coronary artery bypass grafting (CABG). The mechanism of hyperamylasemia and pancreatic acinar cell damage was studied in 20 patients undergoing CABG. Methods: Serial blood and urine samples at eight time points before, during, and 24 hours after the CABG were collected. Salivary and pancreatic isoamylases, the fractional clearance of isoamylases (i.e., relative to creatinine clearance), pancreatic phospholipase A2 (a specific serum marker of pancreatic acinar cell injury), and cystatin C (a sensitive marker of glomerular filtration rate) were measured. Results: Mild serum hyperamylasemia (300 to 1000 units/L) was found in 11 of 20 (55%) and severe (>1000 units/L) in 6 of 20 (30%) patients with no signs of clinical acute pancreatitis. Hyperamylasemia occurred from 6 to 24 hours after the CABG and was mainly caused by pancreatic isoamylase. Serum pancreatic phospholipase A2 concentration remained unchanged, which excludes acinar cell damage. Although renal glomerular filtration was normal during CABG as measured by serum cystatin C and creatinine clearance, the fractional clearance of isoamylases decreased. Conclusions: The decreased rate of excretion into urine, rather than pancreatic cellular damage, is the major source of hyperamylasemia after CABG. (Surgery 1998;123:504-10.)

Antioxidants may reduce pancreatic cellular injury after coronary artery bypass grafting (CABG) Twenty patients (Group A) received vitamin E (600 mg/ day) for 28 days and vitamin C (2 g/day) and allopurinol (600 mg/day) 2 days before and 1 day after CABG. Seventeen patients (Group C) received all drugs for 3 days, and 25 (Group B) and 19 (Group D) patients served as corresponding controls. The pre- and postoperative pancreatic isoamylase (P-amylase), creatinine, and antioxidant concentrations were measured. Serum hyperamylasemia was highest on the first postoperative day and occurred in 73% of the patients. After surgery serum P-amylase increased in all study groups and urine P-amylase decreased. Postoperative serum hyperamylasemia, whether primarily renal or pancreatic, cannot be decreased by pretreatment with allopurinol, vitamin C, and vitamin E.