Association of CX3CR1 Gene Polymorphisms with Fractalkine, Fractalkine Receptor, and C-Reactive Protein Levels in Patients with Kidney Failure.

Fractalkine (CX3CL1) is a chemokine that plays a significant role in inflammation, one of the pathophysiological processes underlying end-stage renal disease (ESRD). Genetic factors are significantly involved in cytokine expression and have been studied as potential risk factors for chronic kidney disease (CKD). Objectives: We aimed to elucidate the association of CX3CR1 gene polymorphisms rs3732378 and rs3732379 with the levels of CX3CL1, CX3CL1 receptor (CX3CR1), as well as C-reactive protein (CRP). Patients and methods: We enrolled 198 participants, including 106 patients with ESRD and 92 controls. Peripheral blood samples were collected from each patient for genetic (rs3732378 and rs3732379 polymorphisms) and immunoenzymatic (fractalkine, CX3CR1, CRP) tests. Results: CX3CR1 and CRP levels were higher in patients with ESRD than in controls (p < 0.05). Fractalkine levels were significantly higher in ESRD patients who were homozygous for the G allele of the rs3732378 polymorphism and for the C allele of the rs3732379 polymorphism than in homozygous controls. Moreover, carriers of these alleles among patients with ESRD had significantly higher CX3CR1 levels than controls. Conclusions: The G allele of the rs3732378 polymorphism and the C allele of the rs3732379 polymorphism of the CX3CR1 gene are associated with higher CX3CL1 and CX3CR1 levels. Our study suggests that CX3CR1 gene polymorphisms could be potentially involved in the pathogenesis of ESRD, but the study needs to be replicated in a larger population with a longitudinal follow-up study. Identification of genetic factors associated with inflammation in ESRD may contribute to the development of targeted gene therapies in the future.

Uremic pruritus and serum brain-derived neurotrophic factor in diabetic and non-diabetic haemodialysis patients.

INTRODUCTION: Even though uremic pruritus (UP) is very troublesome for haemodialysis (HD) patients, its underlying mechanism is not fully understood. AIM: Due to the possible role of brain-derived neurotrophic factor (BDNF) and its higher serum concentration in haemodialysis diabetic patients compared to non-diabetic ones, this study is aimed to evaluate its association with UP among diabetic and non-diabetic patients on maintenance HD. MATERIAL AND METHODS: A total of 94 patients were enrolled into the study. A visual analogue scale (VAS) was used to assess pruritus. RESULTS: No differences were found between the observed study groups in terms of BDNF serum concentration, other biochemical markers, sleep disturbances, or pruritus presentation. CONCLUSIONS: BDNF serum concentration was not found to be associated with UP among HD patients, however further studies are worth performing on a larger group of individuals.

Relevance of the semi-quantitative short Food Frequency Questionnaire in assessment of calcium consumption by female inhabitants of Zabrze over the age of 55 years (the Silesia Osteo Active Study).

In the study, we compare two methods used to assess the effects of nourishment on the bone status. Statistical analysis demonstrated a moderate conformity of both methods. Short Food Frequency Questionnaires can be used as short medical screening tool for calcium intake among women over 55 years of life. INTRODUCTION: Osteoporosis is a civilisation disease, the development of which is, among others, controlled and affected by diet. The factors which promote the health of bones include calcium, vitamin D, vitamin K, phosphorus, magnesium, and protein. A number of nutritional epidemiology methods can be applied to assess the effects of nourishment on the bone status, e.g. Food Frequency Questionnaire (FFQ) in its full or short (sFFQ) version or 3-day food record (3DFR). Both methods are known and widely used tools. METHODS: In the reported study, we attempted to compare and assess the sFFQ and 3DFR tools. Both methods were employed to examine 156 women, the majority of whom presented with an overweight-indicating BMI. An analysis of sFFQ data brought an observation that most of the studied patients (33.3%) consumed milk once a day. RESULTS: Based on 3DFR and sFFQ, we compared the measured volumes of consumed calcium which were 557.8 mg/day and 880.7 mg/day, respectively. The Cohen's kappa calculator was used for a diagnostic evaluation of both tools; the kappa index was 0.5047, demonstrating a moderate conformity of both methods. In addition, sensitivity and specificity indices were calculated, revealing the values of 97% and 12%, respectively. CONCLUSIONS: sFFQ can be used as a short medical screening. It is suggested to use both the 3DFR, conducted by the patient, and sFFQ, as a complementary method. It is necessary to continue this type of studies and to standardise the methods of nutritional status assessment with regard to selected groups.

Mesenchymal Stem Cells-Potential Applications in Kidney Diseases.

Mesenchymal stem cells constitute a pool of cells present throughout the lifetime in numerous niches, characteristic of unlimited replication potential and the ability to differentiate into mature cells of mesodermal tissues in vitro. The therapeutic potential of these cells is, however, primarily associated with their capabilities of inhibiting inflammation and initiating tissue regeneration. Owing to these properties, mesenchymal stem cells (derived from the bone marrow, subcutaneous adipose tissue, and increasingly urine) are the subject of research in the settings of kidney diseases in which inflammation plays the key role. The most advanced studies, with the first clinical trials, apply to ischemic acute kidney injury, renal transplantation, lupus and diabetic nephropathies, in which beneficial clinical effects of cells themselves, as well as their culture medium, were observed. The study findings imply that mesenchymal stem cells act predominantly through secreted factors, including, above all, microRNAs contained within extracellular vesicles. Research over the coming years will focus on this secretome as a possible therapeutic agent void of the potential carcinogenicity of the cells.

Calcium supplementation from dairy products in the diet of women over the age of 55 from Zabrze (the Silesian Osteoactive Study - nutritional part).

OBJECTIVES: The primary goal of the study was to assess calcium intake among women over the age of 55. MATERIAL AND METHODS: The study participants were randomly selected from the female population of Zabrze, a town in the Upper Silesia Region in Poland, making use of the framework of the Silesia Osteoactive Study Project. The Semi-Quantitative Food Frequency Questionnaire (sFFQ) was used for nutritional assessment. A total of 388 women at the median age of 65.2 years responded to written and mailed invitations and decided to participate in the study. RESULTS: The mean calcium intake in the group of enrolled post-menopausal women was 886.9 ±615.1 mg/day. Only 32.9% of the participants met the daily calcium intake criterion of > 1000 g/day (the Estimated Average Requirement of 1000 mg according to the Nutrition Standards from 2017 for women in the age group of 51-65 years). Calcium supplementation, identified among women over the age of 55 years in Zabrze, was not sufficient and significantly differed from indicated nutrition standards. Fermented dairy products were the main source of calcium for the studied women. The quantity of calcium provided from yoghurts, kefirs and buttermilk was 338.3 mg/day. The level of consumption of fortified plant products, e.g., soy milk, was found to be very low. Some of the study participants (approximately 32%) reported the intake of calcium supplements or OTC medicinal products with calcium. CONCLUSIONS: Summing up, the studied women reported low calcium intake levels, which calls for appropriate adjustments, including either dietary modifications or proper supplementation programmes with calcium containing agents.

The role of physical activity in early adulthood and middle-age on bone health after menopause in epidemiological population from Silesia Osteo Active Study.

BACKGROUND: Osteoporosis is a growing problem in women after menopause. Among factors protecting from this disease is a physical activity (PA). AIM: The objective of the study was to evaluate the influence of PA in early adulthood and at middle-age on bone health after menopause. MATERIAL AND METHODS: The study group consisted of 362 randomly recruited postmenopausal women after menopause. Mean age was 65.2±6.9 years. Medical history was collected from all participants, and they completed questionnaires assessing PA in early adulthood and at middle-age. Physical capacity was estimated using the Duke scale. Bone status was measured with use of densitometry (DXA) for lumbar spine and hip and calcaneus quantitative ultrasound (QUS) measurements. RESULTS: Physical activity and healthy lifestyle activity in early adulthood did not correlate with bone health, but current PA did (for QUS parameters r=.11; P<.05). Physical capacity correlated with all QUS parameters (r=.2 to .22; P<.05) and femoral neck (FN) BMD and T-score (for both r=.16; P<.05). Current PA frequency at the level of several times a week has the highest positive impact on FN DXA results (P=.01). Bone mass in DXA and QUS variables is related to the type of exercises (P<.05). CONCLUSION: Physical activity, especially several times a week, at middle-age is a major factor influencing bone health in women after menopause. Further studies concerning the type of exercises are needed.

Substance P and intensity of pruritus in hemodialysis and peritoneal dialysis patients.

BACKGROUND: Uremic pruritus is a common complication in patients undergoing dialysis. The pathophysiological mechanisms of pruritus in patients with end-stage renal disease remain unknown. Neuropeptides, including substance P, are postulated to play an important role in the pathogenesis of pruritus. The aim of this study was to evaluate the role of substance P in uremic pruritus in patients on hemodialysis and peritoneal dialysis. MATERIAL/METHODS: We included 197 patients with end-stage renal disease: 54 on continuous ambulatory peritoneal dialysis and 143 on hemodialysis. Substance P, calcium, phosphorus, iron, ferritin, CRP, albumin, hemoglobin, Ca×P product, and iPTH level were determined in all participants. The correlation between these parameters and self-reported itching was evaluated in patients on hemodialysis in comparison with peritoneal dialysis patients. RESULTS: The incidence of itching was similar in hemodialysis and peritoneal dialysis patients. No differences in substance P level between the 2 groups were found. There was no correlation between substance P level and the incidence or intensity of pruritus in dialyzed patients. CONCLUSIONS: This study demonstrates that substance P does not play any important role in pruritus in hemodialysed and peritoneal dialyzed patients. However, further studies are necessary to assess the exact role of neuropeptides in uremic pruritus.

Inverse associations between androgens and renal function: the Young Men Cardiovascular Association (YMCA) study.

BACKGROUND: Men exhibit higher risk of nondiabetic renal diseases than women. This male susceptibility to renal disease may be mediated by gender-specific factors such as sex hormones. METHODS: We have undertaken a cross-sectional examination of associations between renal function (creatinine clearance estimated based on Cockcroft-Gault equation) and circulating levels of sex steroids (total testosterone, total estradiol, estrone, androstenedione, dehydroepiandrosterone sulfate (DHEA-S), and dihydrotestosterone) in 928 young (mean age: 18.5 +/- 1.2 years) men. RESULTS: Both androstenedione and DHEA-S showed inverse linear associations with renal function in the crude analysis of lean men (those with body mass index (BMI) less than median). However, only DHEA-S retained its association with renal function in lean subjects after adjustment--assuming no changes in other independent variables 1 s.d. increase in DHEA-S was associated with 13%-s.d. decrease in creatinine clearance (P = 0.004). Testosterone decreased across tertiles of creatinine clearance only in the crude analysis of nonlean (BMI greater than median) subjects (P < 0.001). The adjusted regression analysis that assumed no changes in other independent variables showed that 1 s.d. increase in total testosterone was associated with 11%-s.d. decrease in creatinine clearance of nonlean men (P = 0.006). Factor analysis confirmed an inverse association of renal function with both sex steroids and a different pattern of their loadings on glomerular filtration-related factors in lean (DHEA-S) and nonlean (testosterone) subjects. CONCLUSIONS: Our data may suggest that androgens are inversely associated with estimated renal function in apparently healthy men without history of cardiovascular disease.

Association between lipid profile and circulating concentrations of estrogens in young men.

OBJECTIVES: Men show higher rates of cardiovascular morbidity and mortality than pre-menopausal women and this sexual dimorphism may be related to sex-specific effects of sex steroids on cardiovascular risk factors. Unlike androgens, estrogens were not extensively investigated in relation to cardiovascular phenotypes in men. METHODS: We examined associations of estradiol and estrone and their precursors (total testosterone and androstenedione) with traditional cardiovascular risk factors (lipids, blood pressure, body mass) in 933 young (median age: 19 years), apparently healthy Polish men. RESULTS: Total estradiol was associated with total cholesterol (p=0.006) and high-density lipoprotein cholesterol (HDL-C) (p<0.001) and estrone showed the strongest associations with both total cholesterol (p<0.001) and low-density lipoprotein cholesterol (LDL-C) (p<0.001) in the unadjusted ANOVA analysis. In the multivariable adjusted models in which other independent variables were held as constant one standard deviation increase in estradiol level was associated with 6%-standard deviation increase in total cholesterol (standardized beta=0.06, p=0.038) and 6%-standard deviation decrease in HDL-cholesterol (standardized beta=-0.06, p=0.036). An increase in estrone levels by one standard deviation was associated with respective 12%- and 13%-standard deviation increases in total cholesterol (standardized beta=0.12, p<0.001) and LDL-cholesterol levels (standardized beta=0.12, p<0.001) after controlling for other predictors of lipids. Estrone correlated linearly with androstenedione (r=0.28, p<0.001) but there was no correlation between estradiol and testosterone. Estrogens retained their independent associations with lipids after adjustment for their biochemical precursors in the multivariable analysis. CONCLUSIONS: Increased levels of estrogens are associated with unfavourable lipid profile in men and this association is present early in life, before apparent manifestations of cardiovascular disease.

Simvastatin-induced rhabdomyolysis in a CsA-treated renal transplant recipient.

BACKGROUND: Cardiovascular disease is the most common cause of morbidity and mortality among long-term renal transplant recipients, and hyperlipidemia is an important risk factor for the development of cardiovascular and peripheral vascular disease. The prevalence of post-transplantation hyperlipidemia ranges from 16% to 78% of recipients. Lipid-lowering strategy with the use of statins has been shown shown to reduce the cardiovascular risks related to hyperlipidemia, but concomitant use of HMG-CoA reductase inhibitors and cyclosporine A may increase the risk of rhabdomyolysis or myoglobinuric acute graft failure due to drug-drug interactions with cyclosporine A. CASE REPORT: We describe the case of a 53-year-old woman, a renal transplant recipient, who developed rhabdomyolysis following simvastatin lipid-lowering therapy. Immunosuppressive treatment included cyclosporine A, azathioprine and prednisone. After 32 days of simvastatin treatment she was hospitalized for profound muscle pain and weakness with a rise in serum creatine kinase to 60.000 IU/l and serum creatinine to 147 Kmol/l. No further deterioration in renal graft function during hospitalization was observed. 10 days after simvastatin was stopped and the daily CyA dose was reduced the patient was asymptomatic, with serum creatine kinase 67 IU/l and serum creatinine level within normal range. CONCLUSIONS: Renal transplant recipients treated with cyclosporin A, and also receiving statins for postransplantational hyperlipidemia, as well as for the prophylaxis of chronic rejection, should be monitored carefully both for CyA blood levels and for possible muscle toxicity.