Smoking increases the risk of ESRF in men with inflammatory and non-inflammatory renal disease.

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Background: We evaluated the impact of the three major genetic polymorphisms of the renin-angiotensin system [angiotensinogen (AGT) gene M235T, angiotensin-converting enzyme (ACE) gene-I/D and angiotensin II-type 1 receptor (AT₁R) gene A1166C polymorphisms] as risk factors in IgA nephropathy. Methods: The clinical course of 107 patients with biopsy proven IgA nephropathy followed up for 6.6 ± 5.8 years was examined. The genetic polymorphisms were determined by PCR amplification. Results: The allele frequencies of the polymorphisms studied were similar in patients and control subjects. AGT-M235T genotype was associated with the presence of nephrotic syndrome (p < 0.05), correlated to the number of antihypertensive drugs agents taken (p < 0.01) and influenced the rate of deterioration of renal function (p < 0.05). Combined analysis of AGT-M235T and ACE-I/D polymorphisms detected an interaction on affecting progression (p < 0.05). ACE-inhibition had a more pronounced effect in certain AGT-M235T and ACE-I/D genotypes (p < 0.05) and their combined analysis showed a synergistic effect (p < 0.01). No association between AT₁R-A1166C polymorphism and any of the parameters studied was observed. Conclusions: Our results suggest that angiotensinogen-M235T polymorphism is an important marker of progression in IgA nephropathy in Caucasian patients, especially when analyzed in combination with ACE-I/D polymorphism.

In parotid saliva of normal subjects the pH, pCO2 and concentrations of sodium, potassium, calcium, magnesium, bicarbonate and inorganic phosphate were determined continuously after stimulation of salivary secretion by pilocarpine. The electrolyte concentrations showed a marked dependence on salivary flow rate. Sodium, calcium and bicarbonate concentrations and pH increased with increasing flow rate but the concentrations of potassium, magnesium and inorganic phosphate decreased with increasing flow rate. In general salivary electrolyte concentrations showed a tendency to approach plasma concentrations with increasing flow rate with the exception of the salivary magnesium concentration, which fell below its plasma level and bicarbonate which exceeded the plasma concentration. The results will be considered as a basis of further investigations on electrolyte excretion patterns in patients with hormonal and metabolic disturbances.

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Background. A number of studies suggested that the type of dialysis membrane is associated with differences in long-term outcome of patients undergoing haemodialysis, both in terms of morbidity and mortality. In the majority of dialysis units, synthetic membranes are being used. However, no studies are available so far for comparison between different biocompatible membranes. Therefore, we studied the influence of high- and low-flux polysulphone membranes (PS) in comparison with polymethylmethacrylate (PMMA) membranes on mortality and morbidity on the basis of various laboratory parameters.Methods. In a cohort study, data of 260 consecutive haemodialysis patients entering our dialysis unit in the years 2003–07 were collected, comparing 435 PS patient-years and 85 PMMA patient-years. PMMA membranes (n = 33) were used for those patients who did not tolerate (e.g. for pruritus) PS membranes (n = 227). Low-flux dialysers (n = 233) were compared with high-flux (n = 37). Laboratory values were evaluated by unpaired t-test, and mortality was evaluated by log-rank test and Cox regression analysis adjusted for age, diabetes and laboratory parameters.Results. Patients in our dialysis unit had a high cardiovascular risk as demonstrated by a proportion of 63% of peripheral arterial disease. Despite this, cumulative survival was almost 60% after 5 years on dialysis. It was slightly but not significantly higher in patients on PMMA (68%) compared with PS dialysers (54%) and on high-flux (61%) versus low-flux membranes (54%). After accounting for the confounding effect of age and diabetes in the multivariate Cox regression analysis, there was no impact of the membranes used (high- or low-flux, PMMA or PS) on survival. Only age at the onset of dialysis showed a significant influence on survival (P ≤ 0.001). Independent predictors of mortality in all patients in the multivariate Cox regression analysis were age, haemoglobin, leucocytes, C-reactive protein (CRP) and creatinine. Laboratory parameters between the high- and low- flux groups were not different. PS-treated patients showed significantly (P ≤ 0.05) higher values for leucocytes, thrombocytes, ferritin, and CRP and lower values for haemoglobin, transferrin, creatinine, uric acid, creatine kinase (CK), and sodium than PMMA-treated patients. Irrespective of the membrane used, in deceased patients, the following laboratory values were higher than for patients alive: leucocytes, thrombocytes, ferritin and CRP; the following were lower: haemoglobin, iron, total protein, urea, creatinine, uric acid and CK.Conclusions. The data of 260 severely ill haemodialysis patients showed a slightly, but not significantly, reduced mortality in patients treated with PMMA membranes in comparison with PS and with high-flux membranes compared with low-flux. High- or low-flux membranes exhibited no difference in laboratory values. However, in PMMA patients, laboratory data with respect to inflammation, anaemia and nutrition were significantly improved compared with the PS group. A similarly positi...

Defective luteinizing-hormone-mediated cAMP generation in rat testis was previously demonstrated by us in acute and chronic uremia. This defect was abolished by administration of 1,25-dihydroxycholecalciferol (1,25-dihydroxycalciol). In the present study, we furnish evidence for a cytosolic 1,25-dihydroxycalciol receptor in the rat testis.Testes of non-rachitic, rachitic or acutely uremic male Sprague-Dawley rats were homogenized in 0. [I91 and uterus [20].In previous studies, we could show diminished luteinizinghormone-mediated cAMP generation in Leydig cells [21] and ovaries [22] of rats with acute and chronic uremia. This defect was completely restored by administration of 1,25-dihydroxycalciol. This finding prompted us to examine whether testis possesses a receptor for 1,25-dihydroxycalciol. MATERIALS A N D METHODS AnimalsNon-rachitic Sprague-Dawley rats (Fa. Ivanovas, Kisslegg/ Allgiiu) were raised on normal diet [Fa. Altromin, Lage/Lippe: Altromin C 1000: 500 IU calciol/kg; 0.95 calcium, 0.65 7; phosphorus (w/w)] for 3 weeks. In a separate experiment, animals were either bilaterally nephrectomized or shamoperated 24 h before sacrifice. In a third series, rats were weaned from vitamin-D-deficient mothers and raised on commercial vitamin-D-deficient diet (Altromin 101 7 : no calciol; 1.3 % calcium; no phosphorus). The animals were kept in the dark and handled with gloves. (68 Ci/mmol) were obtained from Amersham/Buchler Co (Braunschweig) with a radiochemical purity by high-performance liquid chromatography between 93 -98 and essentially free of other metabolites. Specific radioactive reduction was achieved by addition of the appropriate concentration of non-radioactive sterol. Radioinert chromatographically pure 1,25-dihydroxycalciol, 25-hydroxycalciol, 24(R),25-dihydroxycalciol and 1 a-hydroxycalciol were a kind gift of Dr Schmidt-Gayk (Heidelberg). The following I4C-labeled materials were purchased

A B S T R A C T The effects of phosphate depletion on magniesiumni (NMg) homeostasis were evaluated in rats fed a diet containing 0.03% phosphorus for periods up to 8 wk. Plasma phosphorus fell signiificantly (P < 0.01) from 10.1+0.27 (SE) to 5.0±0.54 mgIl00 ml within 1 day and conitiniued to fall gradually to a level of 1.2±0.21 mg/100 ml by the end of the 8th wk. A signiificant (P < 0.01) increment in urinary Mg excretion (UMgV) from 46±2.7 to 126±24 ,ueq/24 h occurred during the 1st day of phosphate depletion; UMgV reached a peak of 300±+24 pieq/24 h by the 3rd day and remained high ranging between 150-300 ,ueq/24 h, thereafter. The magnittude of the magnesuria was related to the degree of hypophosphatemia and was not affected by lowering the calcium intake and reducing the hypercalciuria. The concentration of plasma Mg fell significantly (P < 0.01) from 1.2±0.02 to 0.79±0.10 meq/liter by the 1st day of the study and remained low throughout.Mg balance became negative during the 1st day of phosphate depletion and remained so during the entire study. This occurred despite a significant increment in the fraction of ingested Mg absorbed which becarmie evident by the 3rd wk of phosphate depletion. Mg contenit of muscle, kidney, and liver were not affected but bone Mg was reduced significantly. The change in bone Mg was not due to an overall reduction in bone mineral contenit because bone calcium content was not affected. Supplementation of large amounts of Mg (800-1,000 ,ueq/day) in the drinking water produced a normalization of serum Mg but did not bring about restoration of bone Mg despite a positive Mg balance. The disturbances in Mg metabolism were independent of the age or veight of the animals.Our results indicate that phosphate depletion is Dr. Kreusser is a Fellow of the Deutsche Forschungsgemeinschaft.Dr. Aznar is a Fellow of the Del Amo Foundation.