Is Cystatin C more sensitive than creatinine in detecting early chronic allograft nephropathy?

BACKGROUND: Cystatin C (CyC) has been suggested as a more accurate indicator of renal function than creatinine (Crea). CyC performance against graft histopathology has not been investigated. AIM: To compare CyC and Crea-based methods as predictors of chronic allograft damage index (CADI). MATERIAL AND METHODS: 105 protocol biopsies obtained at 6 months post-transplantation were classified with Banff'97 and CADI. CyC and Crea were measured concomitantly. Histology was correlated to CyC, Crea, their reciprocals, CyC-estimated GFR (Larsson), Cockroft and Gault (C&G) and abbreviated MDRD using Kendall's Tau. The area under ROC curve (ROC-auc),sensitivity/specificity, positive and negative predictive values were calculated at CADI cut-off of 2. RESULTS: Mild histological changes were best revealed by Crea, although with modest sensitivity/ specificity. A Crea threshold of 111 micromol/l distinguished 74% of the patients with CADI > 2 and excluded this condition in 66%. For Crea, ROC-auc was 0.72 (p < 0.001). Crea and 1/Crea correlated best to CADI, chronic allograft nephropathy, chronic inflammation, tubular atrophy, vascular changes and glomerulopathy. Neither C&G nor MDRD improved Crea performance alone. CyC and Larsson formula performed the same (ROC-auc 0.67). A CyC threshold of 1.12 mg/l distinguished 69% of the patients with CADI > 2 and excluded it in 60%. Significant Tau correlation was found between CyC, 1/CyC and Larsson with CADI, chronic inflammation, tubular atrophy and chronic vascular changes. CONCLUSIONS: CyC, 1/CyC and Larsson-estimated GFR did not offer significant advantages over Crea in predicting mild histological allograft changes. Protocol biopsy provides information that cannot be sensitively predicted by biochemical measurements used in clinical practice.

Reference intervals for the markers of proteinuria with a standardised bed-rest collection of urine.

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.

Renal follow up of premature infants with and without perinatal indomethacin exposure.

AIMS: To evaluate early childhood renal growth, structure, and function in children born at less than 33 weeks gestation and to investigate possible independent effects of perinatal indomethacin exposure. METHODS: A total of 66 children born at less than 33 weeks gestation, 31 of them with perinatal indomethacin exposure (study group) and 35 without (control group), were examined at 2-4 years of age. Serum cystatin C and protein; plasma creatinine, sodium, and potassium; urine protein, calcium:creatinine ratios, and alpha(1) microglobulin; and glomerular filtration rate (GFR) were determined. Renal sonography examinations were performed. RESULTS: The mean serum cystatin C concentrations were slightly higher in the control group than in the study group. Mean values of serum protein, and plasma creatinine and sodium did not differ between the groups, neither did median plasma potassium concentrations and urine protein:creatinine and calcium:creatinine ratios. None had tubular proteinuria. Abnormal GFR (<89 ml/min/1.73 m(2)) was found in one case in each group and renal structural abnormalities in five in each group. In logistic regression analysis the duration of umbilical artery catheter (UAC) use and furosemide treatment emerged as the significant independent risk factors for renal structural abnormalities. Furosemide treatment and assisted ventilation remained the risk factors associated with renal abnormalities in general-that is, functional and/or structural abnormal findings. CONCLUSION: Perinatal indomethacin does not seem to affect long term renal growth, structure, or function in children born at less than 33 weeks gestation. Duration of UAC use, furosemide treatment, and assisted ventilation may be correlated with later renal structural and functional abnormalities.

Effects on endogenous acetaldehyde production by disulfiram and ethanol feeding on rat pancreas.

Exogenous acetaldehyde infusion can induce pancreatitis-like injury of the pancreas in some isolated pancreas models, whereas in vivo such treatment has failed to induce pancreatitis. In vivo exogenous acetaldehyde may not be effective because it is rapidly metabolized. The aim of this study was to investigate whether endogenous acetaldehyde accumulates in the pancreas after ethanol feeding when acetaldehyde metabolism is blocked by disulfiram, and whether this treatment can induce pancreatitis-like injury in the rat. The liver was studied for comparison. In part I of the experiment, adult male Wistar rats were given water (n = 24), ethanol (n = 24), disulfiram (n = 24), and ethanol plus disulfiram for 1 week (n = 24) or 3 weeks (n = 24) and for 3 weeks with (n = 6) and without (n = 6) hypovolemia. In part II of the experiment, rats were given water (n = 6), ethanol (n = 6), and high-dose disulfiram (n = 6) and ethanol plus high-dose disulfiram (n = 6). Ethanol and acetaldehyde concentrations in blood, liver, and pancreas were measured. Animal behavior was monitored, and weight changes, plasma amylase activity, water content, and histomorphology of the pancreas and liver were studied without knowing the group. No increases in plasma amylase activity and no histomorphologic changes in the pancreas were observed under light or electron microscopy in part I of the experiment. In part II, treatment with ethanol induced acetaldehyde accumulation in the liver (33.6 +/- 2.6 micromol/L), but to a lesser degree in the blood (9.6 +/- micromol/L) and pancreas (5.0 +/-.2 micromol/L). Ethanol plus disulfiram induced marked accumulation of acetaldehyde in the liver (83.2 +/- 15.9 micromol/L), blood (280.0 +/- 47.4 micromol/L), and pancreas (43.6 +/- 4.7 micromol/L). When tissue acetaldehyde levels reached 30 to 40 micromol/L, we found a decrease in zymogen granules along with formation of small intracytoplasmic vacuolizations in the acinar cells and accumulation of lipid droplets in the hepatocytes, whereas physiologic signs of pancreatitis (hyperamylasemia, edema) or increases in liver enzymes did not develop. High levels of acetaldehyde accumulate in the liver and pancreas with the treatment described. Although this was accompanied by lipid degeneration of the hepatocytes and some subcellular changes in the acinar cells, physiologic signs of pancreatitis did not develop. Thus acetaldehyde accumulation alone, or in combination with hypovolemia, is not responsible for the induction of acute pancreatitis.

Reference intervals for cystatin C in pre- and full-term infants and children.

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 (<1 year: 0.75-1.87 mg/l; 1-3 years: 0.68-1.60 mg/l) had slightly, but significantly, higher plasma cystatin C levels.

A new biodegradable stent for the pancreaticojejunal anastomosis after pancreaticoduodenal resection: in vitro examination and pilot experiences in humans.

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.

Esmolol cardioplegia in unstable coronary revascularisation patients. A randomised clinical trial.

BACKGROUND: Esmolol has been studied and applied to control hypertension and tachycardia during open heart surgery. Esmolol has been used on a minor scale as a single cardioplegic agent. Little information is available on esmolol as a component of blood cardioplegia. In this prospective, randomised, double-blind clinical study we investigated whether esmolol improves cardioprotection in patients scheduled for an urgent coronary operation. METHODS: Forty patients with unstable angina were operated using cold blood cardioplegia as the basic cardioprotective method. Cardioplegia was infused intermittently, and esmolol was given into the cardioplegia line (15 mg/min) during cold infusions. Patients with ongoing myocardial infarction were excluded. RESULTS: The arrest time during the cardioplegic induction or the rate of spontaneous resumption of the heart rhythm did not differ significantly between the groups. The serial measurements of plasma creatine kinase MB-fraction activity (P=0.27), serum creatine kinase MB-fraction mass assay (P=0.16), troponin I (P=0.41) and myoglobin (P=0.14) similarly did not differ between the groups, nor did myocardial lactate extraction (P= 0.12). CONCLUSION: Esmolol addition to blood cardioplegia did not increase the efficacy of cardioprotection in the present study setting in unstable patients during urgent coronary revascularisation.

Potency of propofol, thiopentone and ketamine at various endpoints in New Zealand White rabbits.

Effective plasma concentrations of propofol, thiopentone and ketamine were determined at different endpoints in a study with randomized, crossover design in nine New Zealand White rabbits. A continuous infusion was used (30 ml/h) with concentrations of 10 mg/ml for propofol, 25 mg/ml for thiopentone and 20 mg/ml for ketamine. The endpoints were loss of the righting reflex, loss of purposeful reactions to tail clamping (as an example of a peripheral pain stimulus) or to intranostril insufflation of ammonia vapour (as an example of a central reflex stimulus), and the recovery of these reflexes and reactions. According to the ED50 values the potency ratios of propofol, thiopentone and ketamine were at the loss of righting reflex 1:1.8:1.2, at the loss of reaction to ammonia vapour 1:1.5:1.6, and at the loss of reaction to tail clamping 1:1.5:3.9, respectively. Recovery was significantly faster after propofol than after thiopentone and ketamine. Measuring the effective plasma concentrations of intravenous anaesthetics provides a method of relating dose to effect, but there still remains a variable gap between plasma concentration and effect.

Ultrathin cutting needle biopsy histology in the tissue diagnosis of acute pancreatitis--experimental study and application in a human case.

BACKGROUND AND AIMS: This study was to assess whether the tissue obtained with an ultrathin cutting needle, that is as thin as used for aspiration cytology and bacteriology, can give enough material to diagnose acute pancreatitis in rat model and in a human case. METHODS: Wistar rats were randomly allocated into control group (n = 6), cerulein group (n = 6), ligation group (n = 6) and bile salt group (n = 6). In the cerulein, ligation and bile salt groups acute pancreatitis was induced by cerulein intraperitoneal injections, low ligation of common biliopancreatic duct and sodium taurodeoxycholate intraductal injection, respectively. Serum amylase activity was measured and a large cut specimen and two ultrathin needle biopsy specimens were obtained from the pancreas for light microscopic histology. Oedema, acinar cell necrosis, haemorrhage or fat necrosis, and leukocyte infiltration were evaluated semiquantitatively and compared with large cut specimens. RESULTS: The pancreatitis groups revealed different severity in oedema, acinar cell necrosis, haemorrhage or fat necrosis, and leukocyte infiltration. The needle biopsy showed 100% sensitivity and 100% specificity in the diagnosis of acute pancreatitis. The histopathologic scores showed a good and significant correlation between ultrathin biopsy and large cut specimens in all the four histologic parameters, especially in oedema and acinar cell necrosis. A human case is presented, whose percutaneous ultrathin needle biopsy histology was successfully applied for diagnosing acute pancreatitis. CONCLUSIONS: The ultrathin needle biopsy histology can give enough material for the diagnosis of acute pancreatitis. Further studies with ultrasonography guided percutanous or endosonography guided transduodenal technique will be needed to assess the role of tissue sampling in acute pancreatitis.

Evaluation of plasma cystatin C as a marker for glomerular filtration rate in patients with type 2 diabetes.

AIM: To evaluate plasma cystatin C as a marker of the glomerular filtration rate in patients with type 2 diabetes and their age and sex-matched controls. MATERIALS AND METHODS: Forty-seven patients with one decade of type 2 diabetes and 51 non-diabetic control subjects were studied. Plasma cystatin C was measured by particle-enhanced turbidimetric immunoassay in a new application for the Hitachi 704 analyzer. For comparison, plasma creatinine and creatinine clearance were measured. The plasma clearance of 51Cr-EDTA by the single injection method was utilized as reference. RESULTS: In patients with type 2 diabetes the correlation coefficient between plasma cystatin C and the plasma clearance of 51Cr-EDTA was 0.774 (Spearman's coefficient) and that between plasma creatinine and the plasma clearance of 51Cr-EDTA was 0.556 (p = 0.001 for the difference). The correlation between creatinine clearance and the plasma clearance of 51Cr-EDTA was 0.411. In receiver operating characteristic (ROC) curve analysis the diagnostic accuracy of plasma cystatin C was significantly better than that of plasma creatinine (p = 0.047) or creatinine clearance (p = 0.001). The best diagnostic efficiency (98%) for cystatin C was obtained when the cut-off limit was set at 1.32 mg/l. In the control group the correlation coefficients were: between cystatin C and the plasma clearance of 51Cr-EDTA 0.627, between creatinine and the plasma clearance of 51Cr-EDTA 0.466 and between creatinine clearance and the plasma clearance of 51Cr-EDTA 0.416. The area under the ROC plot curve of cystatin C was also greatest in the control group, but the diagnostic accuracy of cystatin C was marginally better than that of either plasma creatinine (p = 0.05) or creatinine clearance (p = 0.08). Among the control subjects various non-renal causes may have interfered with cystatin C concentrations reducing the correlations. CONCLUSIONS: Cystatin C measurement is a more sensitive and specific test for GFR in patients with type 2 diabetes than plasma creatinine or its clearance, when GFR is normal or only slightly reduced. If an elevated cystatin C concentration is found, non-renal factors have to be excluded. The turbidimetric application described here can easily be applied for most clinical chemistry analyzers and is therefore useful in daily clinical practice.

Cholecystokinin in the early course of acute post-ERCP pancreatitis.

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, Malmö, 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.

Cystatin C as a marker for glomerular filtration rate in pediatric patients.

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 (

Extrapancreatic organ impairment in caerulein induced pancreatitis.

BACKGROUND AND AIMS: Multiorgan function failures are the major fatal complications in acute pancreatitis. In this experiment, we studied 1) the manifestation and time course of extrapancreatic organ damage in an acute pancreatitis model and 2) whether the obstructive liver damage in this model is caused by the obstruction of common biliopancreatic duct compressed by oedematous pancreas. MATERIAL AND METHODS: 80 male Wistar rats were divided into two groups: control and caerulein groups (five subgroups in each group). In the caerulein group, the acute pancreatitis was induced by caerulein intraperitoneal injections. In the controls equal volume of saline was injected. Two subgroups, one in caerulein and one in control groups, had an intrapancreatic bile duct stent inserted transduodenally before the injections. The pancreas, liver, lung and kidney tissues and blood samples were obtained for the measurement or analysis of interstitial oedema, plasma amylase, alanine aminotransferase, bilirubin, urea, creatinine, alkaline phosphatase, lactate dehydrogenase, blood gas and electron microscopy at 1, 6, 12 and 24 hours after the last injection in unstented animals, and at 6 hours in stented animals. RESULTS: Lungs and kidney remained unchanged. Liver damage was found during the first 6-12 hours, manifest as increased plasma alanine aminotransferase and bilirubin and dilatation of bile canaliculi and hepatocyte damage in electron microscopy. The intrapancreatic bile duct stent did not resolve these changes. CONCLUSIONS: The liver may be the first evolved extrapancreatic organ in the early stage in this mild oedematous pancreatitis model and the hepatocyte damage is not caused by the obstruction of common biliopancreatic duct compressed by the oedematous pancreas.

Extrapancreatic multiorgan injury in a severe sublethal acute pancreatitis model.

In order to develop a new severe but sublethal acute pancreatitis model for the study of clinically relevant extrapancreatic multiorgan injury, we have induced acute pancreatitis in a rat model by intraductal injection with low dose and moderate concentration of bile acid under low pressure. We examined the structural and functional features in the pancreas, lung, liver and kidney. The animals were divided into two groups: the bile acid injection group and the control group. In the bile acid injection group, acute necrotizing pancreatitis was induced by intraductal administration of 0.2 ml of 2.0% bile acid under 30 cm H2O pressure, while the controls underwent the sham operation. The two groups were divided into six subgroups (8 rats for each) and sacrificed at 12, 24, 36, 48, 72 and 144 h, respectively. The pancreatitis induced hyperamylasemia, ascites, pancreatic oedema, haemorrhage, acinar cell necrosis and extensive fat necrosis without early mortality. Accompanied with the pancreatic injury, the function and histologic changes have developed continuously in the kidney and liver for 72 and 144 h in the bile acid injection animals respectively. No pancreatitis associated pulmonary changes were found. Taking into account the results with the two previously developed models of pancreatitis, we conclude that the extrapancreatic injury in acute pancreatitis is found in the liver, kidney and lung, in that order, depending on the severity of pancreatitis. The present sublethal pancreatitis model, in comparison with the two previously studied acute pancreatitis models, is perfect for pathogenetic and therapeutic study of liver and renal changes in acute necrotizing pancreatitis.

Extrapancreatic organ manifestations in a moderately severe acute pancreatitis model.

In order to study the extent of clinically relevant extrapancreatic organ injury in a moderately severe pancreatitis model, we examined the structural and functional features of the pancreas, lung, liver and kidney in a rat model simulating gallstone pancreatitis. The animals were divided into three groups: the low-ligation group, the high-ligation group and the control group, and sacrificed at 6, 24, 42, 60 and 96 h. In the low-ligation group, moderately severe acute pancreatitis was induced by the ligation of the common biliopancreatic duct plus intralipid intragastric injection, while controls underwent the ligation of the bile duct above the pancreas (the high-ligation group) or only sham operation (the control group) with fat injection. The pancreatitis induced hyperamylasemia, pancreatic oedema, haemorrhage, acinar cell necrosis and extensive fat necrosis. Accompanied with a peak value of serum amylase activity 24 h after the induction, the kidney changes developed, characterized by decrease in urine output, increase in serum urea and creatinine, and proximal convoluted tubular damage under electron microscope. There were no pancreatitis associated lung or liver changes. These results suggest that this model can be used to study the pathogenesis and therapy of renal injury during acute moderately severe pancreatitis.

Long-term effects of transduodenal sphincterotomy: symptoms and hepatobiliary function.

BACKGROUND/AIMS: Endoscopic sphincterotomy is widely used in treating common bile duct stones, but the long-term effects of destroying the sphincter of Oddi are not known. This study investigated the long-term (15-20 years) effects of transduodenal sphincterotomy on gastrointestinal symptoms and hepatobiliary function in a retrospective controlled study. METHODOLOGY: Between 1974 and 1977, choledocholithotomy was performed in 131 patients either transduodenally (60 patients) or via choledochotomy (71 patients). For the retrospective part of the study, all hospital records, death certificates and autopsy reports were reviewed. Twenty-seven patients who could be reached and volunteered to participate (12 and 15, respectively) were re-examined. In the re-examination part of the study, a standard questionnaire interview, laboratory tests, quantitative cholescintigraphy and ultrasonography were performed. RESULTS: The hospital mortality for the primary operations was 0.8%, 0% for the transduodenal sphinterotomies and 2% for the choledochotomies; the difference was not significant. During the follow-up period, no significant differences could be seen in the death rate or in the causes of death between the study groups. During re-examination, flatulence was found to be more common in the choledochotomy subgroup (7/15 vs 2/12, p<0.05). In the laboratory tests, conjugated bilirubin and serum aspartate amino transferase levels were higher in the transduodenal subgroup than in the choledochotomy subgroup (3.3 umol/L, SD 0.4 vs 2.2 umol/L, SD 0.2, p<0.02; and 25 U/L, SD 12.6 vs 18.6 U/L, SD 5.0, p<0.05, respectively). Furthermore, 6/12 (50%) of the transduodenal subgroup had elevated serum alanine aminotransferase, aspartate aminotransferase or amylase levels, as compared to 1/15 (7%) in the choledochotomy subgroup (p<0.02). In terms of ultrasonography, in the choledochotomy subgroup, the common bile duct diameter was larger than 8 mm in 8/15 (53%) patients, as compared to 1/12 (8%) in the transduodenal subgroup (p<0.02). In terms of quantitative cholescintigraphy, in 9/12 (75%) patients of the transduodenal subgroup, the hilum-duodenum transit time was less than 10 minutes, as compared to 4/12 (47%) of the choledochotomy subgroup. CONCLUSIONS: Transduodenal sphincterotomy results in decreased flatulence and enhanced common bile duct drainage, even in the long-term period, but slightly higher serum liver funtion tests, when compared to supraduodenal choledochotomy.

Serum ionized versus total magnesium in patients with intestinal or liver disease.

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<0.001) in the patients, and r=0.75 (p<0.001) in the controls. In the patient group the fraction of ionized magnesium in the total was negatively related to the serum albumin level (r=-0.41, p<0.001). Serum total magnesium was below the reference range in 30 out of 150 measurements, serum ionized magnesium in only 9 out of 150 measurements, respectively. Thus, 21 cases with low total but normal ionized magnesium (two thirds of hypomagnesemia according to serum total magnesium) were false positive. Total magnesium measurement may overestimate the incidence of hypomagnesemia when significant hypoalbuminemia is present. Measurement of serum ionized magnesium instead of total magnesium may therefore be of advantage in evaluating patients with hypoalbuminemia and when hypomagnesemia is expected.

Unaltered antioxidant activity of plasma in subjects at increased risk for IDDM.

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.

Serum ionized versus total magnesium in patients with chronic renal disease.

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 (p<0.001) in control subjects. Serum tMg was below the reference range in 15 of 69 measurements. However, serum Mg2+ 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.