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.

[high on-treatment platelet reactivity in patients with chronic renal failure using acetylsalicylic acid].

Cardiovascular diseases (CVD) are the most common cause of mortality in the world. Acetylsalicylic acid (ASA) is a widely used medicine in primary and secondary prevention of cardiovascular diseases. About 1-60% patients taking aspirin have high platelet reactivity (HOPR) despite aspirin treatment. HOPR is significantly more frequent in patients with chronic kidney disease (CKD) and it increases the risk of adverse cardiovascular events in these patients. The cause of HOPR in patients with CKD may be oxidative stress and inflammation. To the risk factors belong diabetes, female sex or decreased HDL cholesterol level.

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.

Fabry disease - a genetically conditioned extremely rare disease with a very unusual course.

Fabry disease (FD) is a rare lysosomal storage disease. FD is caused by the presence of a deleterious mutation in the GLA gene encoding the enzyme alpha galactosidase A (αGAL A) on the X chromosome. The accumulation of Gb3 and lyso-GL-3 in nerve fiber cells, endothelium, vascular muscle cells, mesangial cells, podocytes, renal tubular epithelial cells and cardiomyocytes is the most important pathogenetic factor. The rate of disease progression depends on residual conserved enzymatic activity. In this article we present an example of a 25-year-old patient with FD with an initial asymptomatic course. The first manifestation of FD developed in the third decade of life. These include high blood pressure, urinary changes and grade V renal failure, requiring renal replacement therapy. The diagnosis was made very late, when renal failure and cerebro-cardiac complications occurred, including stroke and dangerous cardiac tamponade.

Association between Selected Polymorphisms rs12086634, rs846910, rs4844880, rs3753519 of 11ß-Hydroxysteroid Dehydrogenase Type 1 (HSD11B1) and the Presence of Insulin Resistance in the Polish Population of People Living in Upper Silesia.

BACKGROUND: Many factors influence the development of insulin resistance, among other genetic factors. Cortisol is one of the factors that has a significant impact on the development of insulin resistance. The proteins that have a substantial effect on blood cortisol levels include 11ß-hydroxysteroid dehydrogenase type 1. HSD11B1 is a microsomal enzyme that catalyzes the conversion of the stress hormone cortisol to the inactive metabolite cortisone. Gene encoding HSD11B1 is located on 1q32.2. This study was designed to assess the association between four polymorphic sides in HSD11B1 (rs12086634, rs846910, rs4844880, rs3753519) between subjects with and without insulin resistance in the Polish population of people living in Upper Silesia. METHODS: The study included a total of 507 consecutive patients, 374 (73.77%) with and 133 (26.23%) without insulin resistance. RESULTS: The results show that there were no statistically significant differences in the distribution of genotypes and alleles of the examined polymorphisms of the 11ß-hydroxysteroid dehydrogenase type 1 gene between subjects with and without insulin resistance (determined using the HOMA-IR, insulin resistance index) and that rs846910 and rs1208663 polymorphisms of the 11ß-hydroxysteroid dehydrogenase type 1 gene in the examined subjects have a significant effect on the magnitude of the HOMA-IR insulin resistance index. CONCLUSIONS: The study results suggested that genetic variation of rs846910 and rs1208663 polymorphism of the HSD11B1 gene is related to the susceptibility to insulin resistance. Our results provide a basis to begin basic research on the role of the HSD11B1 gene in the pathogenesis of insulin resistance.

Whether Prolyl Hydroxylase Blocker-Roxadustat-In the Treatment of Anemia in Patients with Chronic Kidney Disease Is the Future?

In patients with chronic kidney disease (CKD), anemia develops gradually, which is primarily due to an inadequate synthesis of erythropoietin by the kidneys, as well as to iron disorders in the body, blood loss, shortened erythrocyte survival and inflammation. The currently accepted treatment employs iron, vitamin B12, folic acid supplementation and the use of erythropoiesis stimulants, which are administered only parenterally. Research is currently underway on the new erythropoiesis drugs that can be orally administered, i.e., hypoxia-inducible factor-propyl hydroxylase inhibitor (HIF-PHI) inhibitors which temporarily block propyl hydroxylase [PHD] catalysis and promote a transient increase in the expression of genes regulated by HIF, including kidney and liver erythropoietin [EPO]. Roxadustat is the first oral drug in this class and a potent HIF-PHD inhibitor, exerted to treat anemia in patients with CKD. In phase 1, 2 and 3 studies with CKD-affected patients, roxadustat was more effective to stimulate erythropoiesis for anemia correction than previously used drugs. Roxadustat can be orally given, unlike other erythropoiesis drugs with parenteral administration only, which grants roxadustat a considerable advantage. Our paper presents the results of studies with roxadustat applied for the treatment of anemia in CKD patients with or without dialysis. We are currently not yet able to know the exact role of roxadustat in the treatment of anemia in patients with CKD, but time will tell. It is possible that roxadustat has benefits an iron metabolism and cardiovascular risk.

DIAPH2, PTPRD and HIC1 Gene Polymorphisms and Laryngeal Cancer Risk.

AIM, DIAPH2, PTPRD and HIC1 are the cell glycoprotein, which play an important role in the occurrence and development of tumors. This study was designed to assess the association between DIAPH2, PTPRD and HIC1 SNPs and laryngeal cancer risk. PATIENTS AND METHODS: This study including 267 patients with histologically confirmed laryngeal cancer and 157 controls. The relationship between genetic variations DIAPH2 (rs6620138), PTPRD (rs3765142) and HIC1 (rs9901806) and the onset of laryngeal cancer were investigated. Statistical analysis to calculate the relationship between DIAPH2, PTPRD and HIC1 genes polymorphism and pathogenesis of laryngeal cancer. RESULTS: The results showed that rs6620138 DIAPH2 polymorphism could increase the onset risk of laryngeal cancer. Statistically significant differences in allele distribution of rs6620138 DIAPH2 and rs9901806 HIC1 in the case and control groups subgroups. CONCLUSIONS: This study results suggested that genetic variation of rs6620138 DIAPH2 polymorphism is related to the susceptibility to laryngeal cancer. Our results provide a basis to begin basic research on the role of DIAPH2 gene in the pathogenesis of laryngeal cancer.

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.

Prevalence of high on-treatment platelet reactivity in patients with chronic kidney disease treated with acetylsalicylic acid for stroke prevention.

Introduction Chronic kidney disease (CKD) is one of risk factors for stroke and may be associated with impaired platelet reactivity. Objectives The aim of the study was to evaluate platelet reactivity in patients with CKD treated with acetylsalicylic acid (ASA), using 2 different laboratory methods. Moreover, we searched for factors responsible for the phenomenon of high on-treatment platelet reactivity (HOPR). Patients and methods A total of 108 patients with CKD and 41 controls without CKD using ASA were enrolled in the study. Platelet function was assessed by impedance aggregometry in whole blood, using a multi-channel platelet function analyzer (Multiplate®; ASPItest). Urinary 11-dehydrotromboxane levels were measured by the AspirinWorks® test. Results No significant differences were observed in the prevalence of HOPR between patients with and without CKD. Patients with CKD and HOPR measured by ASPItest had higher creatinine levels (P = 0.05) and were younger (P <0.01) than patients with CKD without HOPR, while patients with CKD and HOPR measured by AspirinWorks® had lower red blood cell count (P = 0.05), hemoglobin (P = 0.05), hematocrit (P = 0.05), and high-density lipoprotein levels (P = 0.05). All patients with HOPR had higher C-reactive protein levels (P <0.05) (AspirinWorks®) and white blood cells (P <0.05) (ASPItest). Conclusions The applied methods allowed to detect HOPR in more than one third of CKD patients taking ASA for stroke prevention. The compatibility of both methods for HOPR assessment was confirmed. The study revealed several potential risk factors for HOPR in CKD, including younger age, higher levels of inflammatory markers, dyslipidemia, and lower hematocrit and hemoglobin levels.

Association of rs 3807337 polymorphism of CALD1 gene with diabetic nephropathy occurrence in type 1 diabetes - preliminary results of a family-based study.

INTRODUCTION: The worldwide growing burden of diabetes and end-stage renal disease due to diabetic nephropathy has become the reason for research looking for a single marker of chronic kidney disease development and progression that can be found in the early stages of the disease, when preventive action delaying the destructive process could be performed. The aim of the study was to investigate the influence of rs3807337 polymorphism of the caldesmon 1 (CALD1) gene located on the long arm of chromosome 7 encoding for protein that is connected with physiological kidney function on development of diabetic nephropathy. MATERIAL AND METHODS: There was an association study of rs3807337 polymorphism of the CALD1 gene in parent-offspring trios by PCRRFLP method. Ninety-nine subjects: 33 patients with diabetic nephropathy due to type 1 diabetes and 66 of their biological parents, were examined. The mode of alleles transmission from heterozygous parents to affected offspring was determined using the transmission disequilibrium test. RESULTS: The allele G of rs3807337 polymorphism of the CALD1 gene was transmitted to affected offspring significantly more often than expected for no association. CONCLUSIONS: The obtained results suggest that the genetic variability of the CALD1 gene may influence the development of diabetic nephropathy in type 1 diabetes, but further studies involving larger studied groups of patients are needed. (Endokrynol Pol 2017; 68 (1): 13-17).