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BackgroundThe ability of extrarenal tissues to convert 25(OH)D (calcidiol) into 1,25(OH)2D (calcitriol) and dependence of the conversion on substrate levels provide the rationale for supplementing vitamin D in dialysis patients who usually have severe depletion of both: 25(OH)D and 1,25(OH)2D. The primary aim of the study was to compare effects of small doses of cholecalciferol (12,000 IU/week) with frequently used in Europe, small doses of alfacalcidol (1.5 μg/week) or placebo, given for 12 weeks, on serum 1,25(OH)2D in hemodialysis patients with 25(OH)D deficiency. Secondary outcomes were changes in serum calcium, phosphate, 25(OH)D, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23) and sclerostin during the treatment.MethodsThis was a prospective, randomized, partly double-blind (cholecalciferol vs. placebo) study. Out of 522 patients dialyzed in 5 centers in the Mazovian Province, 93 gave informed consent and met the inclusion criteria: any vitamin D metabolites and calcimimetics naïve; no history of liver or intestinal disease; serum 25(OH)D 110 pg/ml, calcium ResultsTo our knowledge, this is the first study comparing head-to-head these drugs in the hemodialysis population. There were no significant differences between the groups at baseline. 81 patients completed the study. Cholecalciferol normalized serum 25(OH)D, with a mean rise from 12.9 ± 6.7 to 31.3 ± 10.1 ng/ml (p < 0.0001). This was accompanied by a marked increase of 1,25(OH)2D from 13.8 ± 9.3 to 25.1 ± 14.2 pmol/l (p < 0.0001). A rise in serum 1,25(OH)2D was also observed in alfacalcidol treated patients, however much smaller (from 13.5 ± 10.1 to 18.5 ± 11.0 pmol/l; p = 0.02). Neither cholecalciferol nor alfacalcidol treatment resulted in significant changes in serum PTH and the remaining parameters.ConclusionsIn most patients, treatment with cholecalciferol in a 12,000 IU/week dose permits safe correction of 25(OH)D deficiency and is more effective than 1.5 μg/week dose of alfacalcidol in rising serum 1,25(OH)2D. This, together with a lack of influence on circulating iPTH the usefulness of such small alfacalcidol doses in hemodialysis patients is debatable.

Genetic factors play a key role in the pathogenesis of atrial fibrillation (AF). We would like to establish an association between previously described single-nucleotide polymorphisms (SNPs) and AF in haemodialysed patients with end-stage kidney disease (ESKD-HD) as well as to assess the cumulative effect of all genotyped SNPs on AF risk. Sixteen SNPs were genotyped in 113 patients with AF-ESKD-HD and in 157 controls: without AF (NAF) and with ESKD-HD. The distribution of the risk alleles was compared in both groups and between different sub-phenotypes. The multilocus genetic risk score (GRS) was calculated to estimate the cumulative risk conferred by all SNPs. Several loci showed a trend toward an association with permanent AF (perm-AF): CAV1, Cx40 and PITX2. However, GRS was significantly higher in the AF and perm-AF groups, as compared to NAF. Three of the tested variables were independently associated with AF: male sex, history of myocardial infarction (MI) and GRS. The GRS, which combined 13 previously described SNPs, showed a significant and independent association with AF in a Polish population of patients with ESKD-HD and concomitant AF. Further studies on larger groups of patients are needed to confirm the associations.

OBJECTIVE Introduction: Mineral homeostasis is achieved through a complex interplay of several feedback processes involving primarily the bone, intestine and kidney, regulated by different proteins acting on endocrine, paracrine or autocrine levels. The dysregulation of these processes in chronic renal failure, called kidney disease (CKD) - mineral and bone disorder (CKD-MBD), although apparent, is still poorly understood. The aim: The aim of the study was an analysis of potential relationships between selected biomarkers of CKD-MBD in maintenance hemodialysis (HD) patients. PATIENTS AND METHODS Material and Methods: In the first part of this cross-sectional study, the 25(OH)D serum concentrations were measured in 115 HD vitamin D naive patients from 5 dialysis units located in central Poland. Thereafter in 81 patients (49 men, 32 women, aged 67 ± 13 years) with vitamin deficiency (25(OH)D

Purpose The usefulness of FRAX in predicting major bone fractures in patients with end-stage kidney disease on maintenance hemodialysis treatment has been confirmed in previous studies. For meaningful clinical use, the prognostic and intervention FRAX thresholds need to be established. Methods The primary aim of our study was to calculate the optimal cut-off point of FRAX for the best prediction of an increased bone fracture risk in dialysis patients and additionally, to propose its intervention threshold, indicating the need for antifracture pharmacological treatment. The study included 718 hemodialysis patients, who were followed up for two years. Thirty low-energy major bone fractures were diagnosed during the study period. We used the Polish version of FRAX (without the DXA examination) and some particular variables of the FRAX calculator. The optimal cut-off point for prediction of an increased major bone fracture risk was based on the analysis of the sensitivity and specificity curves of FRAX. Results The analysis revealed FRAX >5% (sensitivity of 70.0%, specificity of 69.8%) as the prognostic threshold for major bone fractures. Its sensitivity for bone fracture prediction was significantly higher, but specificity lower than those of FRAX ≥10%, used in general Polish population. The reason for this can be an underestimation of bone fracture risk with FRAX in dialysis patients. Conclusions We conclude that the FRAX prognostic threshold for identification of an increased risk of major bone fractures in hemodialysis patients is >5%. We propose to use this specific value of FRAX as an intervention threshold for pharmacological antifracture treatment in hemodialysis patients.

Calcineurin inhibitors added to standard-of-care induction therapy for lupus nephritis (LN) may increase complete renal remission (CRR) rates. The AURA-LV study tested the novel calcineurin inhibitor voclosporin for efficacy and safety in active LN. AURA-LV was a Phase 2, multicenter, randomized, double-blind, placebo-controlled trial of two doses of voclosporin (23.7 mg or 39.5 mg, each twice daily) versus placebo in combination with mycophenolate mofetil (2 g/d) and rapidly tapered low-dose oral corticosteroids for induction of remission in LN. The primary endpoint was CRR at 24 weeks; the secondary endpoint was CRR at 48 weeks. Two hundred sixty-five subjects from 79 centers in 20 countries were recruited and randomized to treatment for 48 weeks. CRR at week 24 was achieved by 29 (32.6%) subjects in the low-dose voclosporin group, 24 (27.3%) subjects in the high-dose voclosporin group, and 17 (19.3%) subjects in the placebo group (OR=2.03 for low-dose voclosporin versus placebo). The significantly greater CRR rate in the low-dose voclosporin group persisted at 48 weeks, and CRRs were also significantly more common in the high-dose voclosporin group compared to placebo at 48 weeks. There were more serious adverse events in both voclosporin groups, and more deaths in the low-dose group compared to placebo and high-dose voclosporin groups (11.2%, 1.1%, and 2.3%, respectively). These results suggest that the addition of low-dose voclosporin to mycophenolate mofetil and corticosteroids for induction therapy of active LN results in a superior renal response compared to mycophenolate mofetil and corticosteroids alone, but higher rates of adverse events including death were observed.

BACKGROUND Impaired sexual function is an important cause of depression in uraemic females. Hyperprolactinaemia is frequent, and often associated with decreased serum oestradiol concentration, which can significantly contribute to accelerated bone loss. The aim of the study was to evaluate the effect of hormone replacement therapy (HRT) on sexual function, serum 17beta-oestradiol and prolactin, and bone mineral density (BMD) in pre-menopausal women undergoing haemodialysis. METHODS Among 63 women on haemodialysis, aged 18-45 years, 23 with secondary amenorrhoea and serum oestradiol < 30 pg/ml were enrolled into the 1 year study. They were divided into: group I (n = 13) treated with transdermal oestradiol with cyclic addition of noretisterone acetate, and control group II (n = 10). BMD was measured with dual energy X-ray absorptiometry (DEXA). RESULTS No important changes in sexual function and hormonal profile were observed in the control group, whereas in all women from group I the treatment induced regular menses and a marked improvement of libido and sexual activity. Serum 17beta-oestradiol increased after the first month from 20.5 +/- 11.7 to 46.8 +/- 13.6 pg/ml (P < 0.001) and remained at that level until the end of the study, accompanied by a decrease of serum prolactin (from 1457 +/- 1045 to 691 +/- 116 mIU/ml after 12 months; P < 0.001). In group I, the treatment induced an increase in BMD, although significant only in L2-L4 (P < 0.05), whereas in group II a mild insignificant decrease was observed. However, a comparison of BMD values after 12 months in both groups revealed marked (P < 0.01-P < 0.05) differences at all studied sites. CONCLUSIONS Transdermal HRT allows sustained physiological serum oestradiol concentrations in pre-menopausal women with oestrogen deficiency on haemodialysis, with the restoration of regular menses and a marked improvement in their sexual function. The treatment inhibits bone demineralization and can play an important role in the prevention of early osteoporosis in this group of patients.

Brivaracetam is a novel high-affinity SV2A ligand currently in clinical development for epilepsy. The objective was to characterize its disposition in patients with renal impairment. A single oral dose of 200 mg brivaracetam was administered to 9 patients with severe renal impairment not requiring dialysis (creatinine clearance

The aim of the study was to review our three year experience with translumbar insertion of dialysis catheters.In five adult patients (4 males and one female, mean age 45 yr), requiring dialysis due to end-stage chronic renal failure, the inferior vena cava was cannulated because of the impossibility of using any other approach. All procedures were performed under fluoroscopy. After visualisation of the inferior vena cava by injection of contrast medium into a peripheral vein, the vena cava was punctured with a 20 cm long needle, at the L3 level. The position of the needle was confirmed by injection of contrast medium, and the vein was then cannulated with a peel-away cannula, using a standard Seldinger technique. Subsequently, a pre-tunneled silastic catheter was introduced and secured.The catheters were used for from 3 to 10 months. No case of permanent catheter dysfunction was noted. Three episodes of temporary thrombosis, in two patients, were successfully treated with heparin and urokinase. Three catheters became contaminated, but they were treated without the necessity for catheter removal.The described method is a safe and effective way of securing haemodialysis access in patients where a standard approach is not possible.

Background. Although disorders of the reproductive system are very common in women undergoing chronic haemodialysis, this issue remains a neglected area. The aim of the study was to evaluate the endometrial morphology and its relationship with pituitary-gonadal axis dysfunction in uraemic women of reproductive age undergoing haemodialysis. Methods. The baseline survey with determination of the sex hormones concentrations was performed in 75 haemodialysed women aged 18–45 years. The control group consisted of 33 healthy premenopausal women, aged 18–45 years, with normal menstruation. Then, 40 haemodialysis women, who met the inclusion criteria and gave their informed consent, underwent endometrium suction biopsy. Results. The pathological endometrial morphology was observed in 80% of biopsied subjects. Atrophia or subatrophia was recognized in almost half of the cases, and proliferative changes in one-third of them. Full atrophia with no mitotic figures was found in all but one non-menstruating woman. In one case, adenocarcinoma in situ was diagnosed and successfully treated. The analysis of the relationship between hormonal status and endometrial morphology revealed the substantial influence of oestradiol on endometrium as a target organ. In women with atrophic changes, oestradiol concentrations were significantly decreased, whereas in the remaining subjects, the increase of serum oestradiol seemed to be accompanied by a shift in endometrium morphology from secretional pattern, through proliferative changes to glandular hyperplasia. Mean serum 17- oestradiol was decreased in women with amenorrhoea, and increased in those with eumenorrhoea (P

The results of the studies of hypophyseal-gonadal axis in dialysis women are not uniform. Mostly the increased serum concentrations of prolactine and pituitary gonadotropins are observed; the data about ovarian secretion are much more scanty and contradictory. The aim of this crossectional study was to assess changes in sexual hormones secretion and their associations with menstrual disturbations in premenopausal women with end-stage renal failure undergoing hemodialysis. Sixty three women from six mazovian dialysis units, aged 18-45 years (mean 35 +/- 7 years) were enrolled into the study. They were divided into four groups according to their menstrual pattern: I--eumenorrhoea (n = 17), II--polymenorrhoea (n = 9), III--oligomenorrhoea (n = 16) i IV--amenorrhoea n = 21). There were no differences between both groups in respect to age, age of menarche, time on hemodialysis, and body mass index. In all subjects gynecological examination was performed and serum prolactin, FSH, LH, estradiol, progesterone and testosterone concentrations were assayed. In 49% women high serum prolactin concentrations were noted (the highest in group IV--1699 +/- 1022 vs 441 +/- 205 microIU/ml in group I; p0.05). Mean serum FSH and LH were increased in group IV only (33 +/- 59 and 22 +/- 31 mIU/ml); no significant differences among groups examined were seen. Serum estradiol was increased in groups I-III (95 +/- 46, 72 +/- 33, and 83 +/- 55 pg/ml, respectively) and decreased in group IV (27 +/- 22 pg/ml; p0.001 in respect to remaining groups). Mean serum progesterone and testosterone concentrations were normal in all four groups, but serum progesterone was significantly lower in groups II-IV than in group I (p0.05). No differences in hormonal status between patients receiving and not receiving rHuEpo were observed. Menstrual disturbances are common (73%) in premenopausal women with end-stage renal failure, with amenorrhea constituting a half of them. Hyperprolactinemia is the most frequently seen alteration in their hormonal profile with the highest concentrations in those with secondary amenorrhea. Increased serum gonadotropins and reduced serum estradiol concentrations are mostly seen in amenorrheic women, whereas in menstruating women serum estradiol is often slightly increased.