Magda Wiśniewska

Autosomal Dominant Polycystic Kidney Disease Is Not a Risk Factor for Post-transplant Diabetes Mellitus. Matched-pair Design Multicenter Study

BACKGROUND Post-transplant diabetes mellitus (PTDM) is a relatively common complication of kidney transplantation. The aim of our work was to compare the incidence of PTDM in kidney transplant recipients with and without autosomal dominant polycystic kidney disease (ADPKD) in a matched-pair design study. METHODS In total, 98 pairs of graft recipients, all of Caucasian origin and who received a kidney from the same cadaveric donor, were included in the study. The following clinical data were collected for statistical analysis: age, body mass index (BMI) before transplant, length and type of dialysis treatment, residual diuresis, and cold and warm graft ischemia time. Diabetes was diagnosed based on American Diabetes Association (ADA) criteria. RESULTS Incidence of PTDM was 19.4% in the ADPKD group and 18.4% in the non-ADPKD group, with no significant differences between groups. Multivariate logistic regression analysis of the PTDM risk in the ADPKD group including age, gender, BMI, and dialysis time as independent variables indicated that only higher residual diuresis is a significant independent risk factor (OR = 5.64 per every L/24 h, 95% CI = 1.31-24.33, p = 0.017). Similarly, logistic regression analysis adjusted for age and gender in the non-ADPKD group has shown that significant independent risk factors are BMI (OR = 1.30 per every kg/m(2), 95% CI = 1.06-1.59, p = 0.0094), longer dialysis time prior to transplant (OR = 1.036 per each month, 95% CI = 1.004-1.070, p = 0.025), and a history of arterial hypertension (OR = 9.09, 95% CI = 1.20-68.66, p = 0.030). CONCLUSIONS In this paired analysis, our results suggest that diagnosis of ADPKD does not increase risk of PTDM.

The impact of CTLA4 and PTPN22 genes polymorphisms on long-term renal allograft function and transplant outcomes

Abstract Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) downregulates the immune system. Lymphoid tyrosine phosphatase (Lyp)—PTPN22 protein—is suggested to be negative regulator of T-cell reaction. There are several polymorphisms in the CTLA4 and PTPN22 genes, which can influence the immune response and allograft function after kidney transplantation. The aim of this study was to examine the impact of CTLA4 and PTPN22 genes polymorphisms on the long-term renal transplant function and recipients’ outcomes during a 5-year follow-up observation. The study enrolled 268 Caucasian renal transplant recipients. Genotyping of the rs231775 (+49AG) CTLA4 gene polymorphism was performed using real-time PCR and rs2476601 (C1858T) PTPN22 gene polymorphism using PCR-RFLP method. The 5-year graft survival rate was 81.7%. Dialysis was necessary in 22 (8%) patients, 7 (2.6%) patients died and 20 (7.4%) switched to another transplantation center. We found no association between studied polymorphisms and graft loss/dialysis. Comparison of the distribution of the +49AG CTLA4 and C1858T PTPN22 genes polymorphisms genotypes among dead and living patients showed no statistically significant differences. Above results suggest that the rs231775 (+49AG) CTLA4 and rs2476601 (C1858T) PTPN22 genes polymorphisms are not associated with long-term allograft failure, graft loss and mortality after transplantation.

The association of the Klotho polymorphism rs9536314 with parameters of calcium-phosphate metabolism in patients on long-term hemodialysis

Abstract Background: Patients on long-term hemodialysis frequently suffer from complications, such as secondary hyperparathyroidism, bone fractures, and arteriosclerosis. The process of regulating Ca/P metabolism depends on factors, such as FGF23 and Klotho. This study aimed to answer the question of whether the Klotho polymorphism rs9536314 is associated with FGF23 plasma concentration. Methods: In 118 patients undergoing hemodialysis, blood was collected before and after hemodialysis. The following parameters were measured in plasma: FGF23, serum: Ca, P, PTH, HGB, and iron concentrations. The KL gene polymorphism rs9536314 was identified by PCR-RFLP. Results: The KL polymorphism rs9536314 was not associated with Ca, P, PTH, or FGF23. There was a negative correlation between FGF23 and blood HGB levels and positive correlation between FGF23 and ESA dose. Conclusions: The results obtained may indicate that there is no association between the KL polymorphism and FGF23 concentration in patients undergoing long-term.

Brain-derived neurotrophic factor: a new face of metabolic disorders.

Insulin resistance is a disorder of glucose homeostasis manifested by reduced sensitivity of muscles, adipose tissue and liver to insulin. Its aetiology is well understood and encompasses the polymetabolic syndrome, obesity, limited physical activity, endocrine pathology (polycystic ovary syndrome), chronic kidney disease and hereditary defects. Research continues to provide new information on the pathology and causes of insulin resistance while recent reports have focused on associations between the nervous system and metabolic disorders. It appears that the nervous system is involved in metabolic processes through production of specific compounds called neurotrophins. Thomas Willis, who noted that diabetes is often seen in patients with a stressful lifestyle, published the first work in this direction 400 years ago. In 1935, W Menninger, an American psychiatrist described what he called the diabetic personality. Today, there is little doubt that the nervous system and insulin metabolism are interrelated. Brain-derived neurotropic factor (BDNF) belongs to the neurotrophin family which regulates processes of growth and survival of neurons. The first reports on BDNF have concentrated on its role in learning and memory. Involvement of BDNF in diseases of the nervous system (Alzheimer’s disease, depression) has been demonstrated. The study of Nitta et al. showed that BDNF plays a pathogenic role in synaptic dysfunction in type 2 diabetes. BDNF acts on the tyrosine-related kinase B (TrkB) receptor present in the central nervous system (CNS), hypothalamus and in some other organs. Studies in animals have revealed that BDNF penetrates the blood–brain barrier. Progression of obesity, diabetes and cardiovascular diseases may be modified by induction or inhibition of BDNF inside and outside of the CNS. The sympathetic system has nerve endings in the white and brown adipose tissue through which it regulates energy output. This process is mediated by noradrenaline and controlled by BDNF. Genetic studies have shown that deletion of the BDNF gene is lethal in homozygotes but produces increased appetite, obesity and diabetes in heterozygotes. In animals, administration of BDNF into the CNS or subcutaneously modulates the central and peripheral nervous system. It has been shown that BDNF reduces food intake and lowers blood glucose concentration in genetically modified (db/db) obese mice. These mutants suffer from obesity, hyperinsulinaemia, hyperleptinaemia and hyperactivity. Administration of BDNF led to a decrease in food intake and had beneficial effects on glucose homeostasis and improved insulin resistance. Expression of BDNF in the hypothalamus activates the sympathetic system manifested with hypertrophy of the brown adipose tissue. Research in patients with type 2 diabetes has revealed significantly lower plasma BDNF concentrations which correlated with body mass index, high-density lipoprotein cholesterol and triglyceride concentrations. Regulation of cholesterol metabolism in the CNS neurons remains ill defined. Suzuki et al. investigated the effect of BDNF on the biosynthesis of cholesterol in cultured CNS neurons. The results suggested that BDNF regulates cholesterol biosynthesis for the development of presynaptic function. In another study it has been observed that a high fat diet impairs hippocampal neurogenesis through increased lipid peroxidation and increased lipid oxidation. Nevertheless, debate continues on the relationship between BDNF and obesity. Reduced plasma concentrations of BDNF have been found in patients with type 2 diabetes regardless of obesity. Moreover, there was an inverse correlation between BDNF and fasting glucose concentrations in this study. No correlation with insulin was found and BDNF gene polymorphism analysis has not revealed any associations with diabetes or obesity. Hyperglyacaemic and euglycaemic clamp studies in healthy individuals have demonstrated that BDNF release in the CNS is blocked only by hyperglycaemia. On the other hand, elevated concentrations of BDNF were observed in obese patients with type 2 diabetes. Physical activity not only increases BDNF concentrations, but also improves memory and insulin sensitivity of tissues. There is evidence that insulin participates in cognitive and memory processes through receptors in the CNS. Impaired glucose tolerance has a negative impact on memory and on the function of the hippocampus where concentrations of BDNF are normally high.