Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach.

AIMS/HYPOTHESIS: In the present study we investigated potential associations of a set of 45 single nucleotide polymorphisms (SNP) in 20 candidate genes on eight chromosomes with diabetic nephropathy (DN) in type 2 diabetes mellitus. We aimed to compare two methodological approaches suitable for analysing susceptibility to complex traits: single- and multi-locus analyses. MATERIALS AND METHODS: The study comprised a total of 647 subjects in one of three groups: diabetes with or without DN, or no diabetes. Genotypes were detected by PCR-based methodology (PCR only, PCR plus RFLP, or allele-specific PCR). Haplotypes were inferred in silico. Set association (tested using SUMSTAT software) was used for multilocus analysis. RESULTS: After correction for multiple comparisons, only one SNP, in the gene encoding the receptor of advanced glycation end products, AGER 2184A/G (gene symbol formerly known as RAGE) showed a significant association with DN (p = 0.0006) in single-locus analysis. In multi-locus analysis, six SNPs exhibited a significant association with DN: four SNPs on chromosome 6p (AGER 2184A/G, LTA 252A/G, EDN1 8002G/A and AGER -429T/C) and two SNPs on chromosome 7q (NOS3 774C/T and NOS3 E298D), omnibus p = 0.033. Haplotype analysis revealed significant differences between DN and control groups in haplotype frequencies on chromosome 6 (p = 0.0002); however, there were no significant difference in the frequencies of the NOS3 haplotypes on chromosome 7. Logistic regression analysis identified SNPs AGER 2184A/G and NOS3 774C/T, together with diabetes duration and HbA1c, as significant predictors of DN. Testing for interactions between SNPs on chromosomes 6 and 7 did not provide significant evidence for epistatic interaction. CONCLUSIONS/INTERPRETATION: Using the set-association approach we identified significant associations of several SNPs on chromosomes 6 and 7 with DN. The single- and multi-locus analyses represent complementary methods.

[Cystatin C in estimates of glomerular filtration in patients with renal disease--initial experience]. / Cystatin C v odhadu glomerulární filtrace u pacientu s nemocemi ledvin, první zkusenosti.

Cystatin is reported in the literature with increasing frequency as a new reliable parameter for estimates of glomerular filtration. The authors examined cystatin C by the PET method of DAKO Co. in 151 patients from the nephrological out-patient clinic. 91 patients had normal renal functions, 60 suffered from renal insufficiency of different severity. Between cystatin C and glomerular filtration assessed by creatinine clearance was a close correlation, R = -0.787 according to Pearson. The authors evaluated separately a group of 36 patients with glomerulonephritis, 34 diabetic patients with diabetic nephropathy, 38 patients with tubulointerstitial nephritis and 43 subjects with other kidney diseases. The groups did not differ significantly when compared with the whole group nor mutually (p = n.s.). The authors of the study confirmed that a good correlation of cystatin with creatinine filtration is not influenced by the type of basic nephrological disease. The effect of administration of insulin, antihypertensive drugs, cyclosporin A and glucocorticoids was not proved in the investigated group. The published method is accurate, not demanding from the technical aspect. The examined subject is not restricted by conditions ensuring the accuracy of assessment and seems thus useful and perspective for nephrological patients.

Safety and tolerability of a multidose formulation of epoetin beta in dialysis patients. Collaborative Study Group.

AIM: Previous studies in healthy volunteers and renal patients have demonstrated the favorable tolerability of a new multidose formulation of epoetin beta. The aim of this open, multicenter study was to further assess the safety, tolerability and efficacy of this formulation ofepoetin beta in patients with end-stage renal disease (ESRD). MATERIALS AND METHODS: 375 adult patients receiving maintenance epoetin therapy for renal anemia were switched to the multidose formulation of epoetin beta for 12 weeks, using the same dosage and route of administration. RESULTS: Adverse events were experienced by 123 patients (33%), most commonly hypertension (5.6%) and hypotension (4.5%). Few patients (2%) were prematurely withdrawn because of tolerability concerns. No clinically relevant changes in blood pressure or laboratory variables were observed. Compared with baseline, hemoglobin and hematocrit values remained essentially unchanged during treatment with this new formulation of epoetin beta. No changes in iron metabolism parameters were apparent, and nearly all patients (94%) did not require blood transfusions during the study. CONCLUSION: The results of this study indicate that the multidose formulation of epoetin beta is safe and well tolerated in patients with ESRD. Moreover, switching patients to this new formulation of epoetin beta does not compromise therapeutic efficacy.

[Levels of selenium and glutathione peroxidase in dialyzed patients]. / Hladina selenu a glutathionperoxidázy u dialyzovaných pacientu.

The authors examined in 37 patients dialyzed in a dialysis centre in Brno-Bohunice, a region with selenium deficiency in the population the serum selenium and glutathione peroxidase level before and after 4-hour standard haemodialysis across a polysulphone membrane. In 78% patients selenium deficiency was found. The mean value in the whole group was 33.4 micrograms Se/l. The reference range for the Brno population is 41.3-80.7 micrograms/l. After dialysis a rise of the serum selenium level by 15.4 micrograms/l occurred due to haemoconcentration during ultrafiltration and also due to redistribution of fluids and selenium during dialysis. In anuric patients selenium does not cumulate in serum, although it is excreted in healthy subjects mainly in the urine. Due to the closer bond with selenoproteins it is not significantly separated by dialysis. Glutathione peroxidase assessed in whole blood was in 76% patients before dialysis within the reference range and did not change significantly as a result of dialysis. Selenium deficiency participates significantly in the inadequate activity of antioxidant systems in the organism and in dialyzed patients it potentiates the development of chronic complications.

[Erythropoietin in non-specific intestinal inflammation]. / Erytropoetin u nespecifických strevních zánetu.

In 39 patients with non-specific intestinal inflammations the authors examined the erythropoietin level. They found a significantly higher level of serum erythropoietin in patients during relapse, when the organism responds to more severe anaemia by increased erythropoietin production. The idea that the reactivity of the bone marrow or effectiveness of erythropoietin is influenced by mediators of the inflammation is supported by the fact that the group comprised patients with high erythropoietin values of 102, 106.6, 109 and 445 ImU/l but their anaemia did not improve markedly. The theory on an inadequate erythropoietin secretion is supported by the fact that four patients in relapse with relatively severe anaemia had low erythropoietin levels and six patients had despite a significant drop of haemoglobin normal erythropoietin levels. Contrary to other diseases, in non-specific intestinal inflammations the erythropoietin secretion depends not only on the severity of the inflammation but probably on many other factors, incl. immunological ones.

[Anorexia nervosa--the views of the internist]. / Mentální anorexie--pohled internisty.

BACKGROUND: From the metabolic aspect anorexia nervosa is long-term incomplete starvation, sometimes interrupted by bulimic periods. Biochemical investigations reveal a differentiated protein catabolism, a decrease of protein carriers, enzymes, hormones, changes of minerals and their reserves, metabolic acidosis, a reduced plasma protein formation and other changes. As to psychic changes, behavioural abnormalities are found as well as altered attitudes and possibly also a more marked psychiatric symptomatology. The objective of the investigation was to test the extent and depth of metabolic changes and their possible improvement during intense metabolic care; permanent care of a clinical psychologist formed part of the treatment. METHODS AND RESULTS: In five patients, age 17-44 years, height 155-170 cm, body weight on admission 29-42 kg with the clinical diagnosis of anorexia nervosa the following most marked metabolic changes were revealed: a low basal energy expenditure (range 4367-5468 kJ) calculated for fasting (3057-3828 kJ), reduced energy reserves of sugars, fats and protein, reduced total protein values (48-68 g/l), serum albumin (25-39 g/l); prealbumin (0.13-0.29 g/l), transferrin (1.2-2.59 g/l) and total cholesterol (five of six values were either at the lower borderline of normal values or reduced). The urinary N output per 24 hours was increased. After complete parenteral nutrition for 3-9 days (energy load increased from 150-190 kJ/kg body weight, amino acids from 30 to 60 g/day, and 50-100 ml 20% Nutralipid/day) and possible supplements the weight increment was 1.5-1.7 kg after 18-57 days in hospital. Throughout the hospital stay the patients were looked after by a psychologist. After returning home two patients developed a relapse. CONCLUSIONS: Complete parenteral nutrition is an effective way of realimentation in anorexia nervosa. Psychological support is essential but it cannot prevent a relapse.

[A metabolic and gastroenterologic intensive care unit]. / Jednotka intenzivní péce metabolicko-gastroenterologická.

The authors analyzed the work of the metabolic intensive care unit which due to the gastroenterological orientation of the clinic deals increasingly with treatment of patients with serious gastroenterological conditions. Since 1989 995 patients were hospitalized and the ratio of gastroenterological patients increased from 15% in 1990 to 35% in 1993. The most serious course and prognosis is in patients with hepatic failure who accounted for 42% of the total number of gastroenterological patients. Another large group was formed by a total of 46 patients with acute pancreatitis and 40 patients with severe forms of non-specific inflammations of the gut. The metabolic intensive care unit possesses also two artificial kidneys. During the mentioned period a total of 2195 haemodialyses were made, incl. 613 on account of acute renal failure, 53 on account of intoxications and the remainder in chronic renal failure. Forty haemoperfusions were made on account of intoxications. The remainder of the patients suffered as a rule from serious impairment of the milieu intérieur. The authors' experience and data in the literature indicate that care of these patients concentrated in specialized departments with skilled staff and satisfactory technical equipment enhances their hope of survival and improvement of the condition. It is increasingly apparent that the development of specialized intensive care units of the non-coronary type is important.