Małgorzata Marchelek-Myśliwiec

Glucose metabolism parameters during an oral glucose tolerance test in patients with autosomal dominant polycystic kidney disease.

Abstract Objective. The aim of the study was to estimate the pancreatic beta cell function and insulin resistance indexes in a group of Autosomal Dominant Polycystic Kidney Disease (ADPKD) patients with normal kidney function and no previous diabetes mellitus diagnosis. Methods. A total of 49 adult patients with ADPKD aged 36 ± 11 years, and 50 healthy controls, all of Caucasian origin, were included in the study. Blood glucose, insulin and C-peptide concentrations were measured during an oral glucose tolerance test (OGTT with 75 g glucose) performed according to WHO recommendations in all subjects. Results. The insulin/glucose ratio at the 30th and 120th minute of the OGTT and the insulinogenic index [(insulin at 30 min – insulin at 0 min)/glucose at 30 min] were significantly lower (p = 0.018, p = 0.031 and p = 0.013, respectively) in the ADPKD group. Four other indexes of beta cell function were lower with the borderline statistical significance (p = 0.054–0.076) than in controls. None of the calculated insulin sensitivity indexes differed between the study and control groups. Conclusions. Presence of ADPKD in patients with normal kidney function is associated with impaired beta cell function after an oral glucose load, without a significant decrease in insulin sensitivity.

Insulin resistance and brain-derived neurotrophic factor levels in chronic kidney disease

Introduction: Insulin resistance is a frequent abnormality in chronic kidney disease (CKD) appearing in early stages. Factors known to promote insulin resistance in CKD patients include disorders of ion and acid–base equilibrium and circulating uremia toxins. Recent research has focused on the central nervous system as the source of the brain-derived neurotrophic factor (BDNF). The aim of our work was to study plasma BDNF concentrations in stage 3 and 4 CKD patients in relationship with insulin resistance and distribution of adipose tissue. Method: Plasma BDNF concentrations were measured in a study group of 31 patients, including a subgroup of 20 non-diabetic subjects. Additionally dual-energy X-ray absorptiometry (DXA) was performed. Homeostatic model assessment of insulin resistance (HOMA-IR) and homeostatic model assessment of B-cell function (HOMA-beta) indices were calculated. Results: Two separate analyses were performed. In the first analysis performed in all 31 CKD patients, there were no correlations between BDNF and: body mass index (BMI), android, gynoid fat distribution, HOMA-IR and HOMA-beta. In the second analysis performed in 20 CKD patients without diabetes, BDNF was negatively related to gynoid fat (Rs = −0.47, P = 0.034) and women revealed significantly lower levels of BDNF than men (P = 0.046). Normotensive patients disclosed significantly higher BDNF levels than hypertensive patients in the whole CKD group (P = 0.039) and in the non-diabetic subgroup (P = 0.028). No correlations between BDNF and eGFR were found. Conclusions: Female sex and arterial hypertension are associated with lower BDNF plasma concentration in CKD patients.

Prooxidative-Antioxidative Balance of Cells in Different Types of Renal Replacement Therapy

Background: Patients suffering from chronic kidney disease (CKD) are exposed to increased oxidative stress and disturbances manifesting in the enzymatic and non-enzymatic antioxidative defence system. The object of the research was to assess the differences between conservative treatment, peritoneal dialysis and haemodialysis in moderating cellular antioxidative agents. Methods: The group examined comprised 145 patients. The activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase were obtained using kinetic methods. The spectrophotometric method established the concentrations of reduced glutathione, albumin, uric acid, glucose, total protein and lipids. Results: The type of treatment determined significant changes in antioxidative enzyme activities and concentrations of non-enzymatic antioxidative compounds. Conclusions: Peritoneal dialysis provides better antioxidant protection than other types of therapy in CKD and should be considered as first-choice treatment despite more metabolic disorders.

Successful pregnancy in the patient with Fanconi‐Bickel syndrome undergoing daily hemodialysis

Successful Pregnancy in the Patient With Fanconi-Bickel Syndrome Undergoing Daily Hemodialysis Karolina Kędzierska, Sebastian Kwiatkowski, Andrzej Torb e,* Mal-gorzata Marchelek-Myśliwiec, Oliwia Marcinkiewicz, Katarzyna Bobrek-Lesiakowska, Edyta Gol-embiewska, Ewa Kwiatkowska, RafalRzepka, Kazimierz Ciechanowski, Ryszard Czajka, and Ren e Santer Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Szczecin, Poland Department of Obstetrics and Gynecology, Pomeranian Medical University, Szczecin, Poland Department of Children Diseases, University Hospital of Hamburg, Hamburg, Germany

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.

Association of kidney and cysts dimensions with anthropometric and biochemical parameters in patients with ADPKD.

Abstract The aim of the study was to evaluate an association between kidney and cyst dimensions and anthropometric, clinical and biochemical parameters of autosomal dominant polycystic kidney disease (ADPKD) patients. Forty-nine adults, ADPKD-diagnosed patients aged 36 ± 11 years, and 50 healthy controls were included in the study. Oral glucose tolerance test (OGTT with 75 g of glucose) was performed and venous blood was collected to measure biochemical parameters and various ion concentrations. Ultrasound abdominal examinations were performed with special emphasis on kidney and cysts parameters. In the ADPKD group, mean kidney length correlated positively with age, systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose and glucose and C-peptide concentrations after 120 min of glucose intake and negatively with Mg2+ concentration and glomerular filtration rate (eGFR). Multivariate analyses adjusted for age and gender showed that higher mean kidney length and maximal cyst diameter were significant predictors of higher SBP (p = 0.034 and 0.046, respectively) and DBP (p = 0.024 and 0.034, respectively), higher maximal cyst diameter was a significant predictor of higher OGTT 2-h C-peptide concentration (p = 0.033), higher mean cyst diameter was a significant predictor of lower eGFR (p = 0.039) and higher mean kidney length was a significant predictor of lower serum magnesium concentration (p = 0.043). In the ADPKD patients with normal GFR, mean kidney length and mean cyst diameter measured by ultrasonography are associated negatively with GFR and positively with blood pressure. Higher mean kidney length and cyst diameter might be indicators of disorders of glucose and magnesium metabolism which precede renal failure in patients with ADPKD.

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.

Three clinical cases of nonrespiratory acidosis in kidney transplant recipients receiving anti-CMV therapy.

BACKGROUND To preserve kidney graft function it is necessary to use ganciclovir or valganciclovir as a therapy for fresh CMV infection or prophylaxis in high-risk kidney transplant recipients. Ganciclovir-induced lactic acidosis has thus far not been reported. CASE REPORT Three cases of nonrespiratory acidosis in kidney transplant recipients receiving ganciclovir or valganciclovir as anti-CMV therapy or prophylaxis are presented. Lactic acidosis developed in 2 patients, and the other patient had nonrespiratory acidosis of unknown origin. The possible mechanism of the development of lactic acidosis in presented cases is explored. CONCLUSIONS The analysis of the described cases cannot eliminate the potential negative influence of anti-CMV therapy on acid-base equilibrium, especially with coexisting active viral infection.

Platelet - derived CD154 antigen in patients with chronic kidney disease

INTRODUCTION CD154 is a surface glycoprotein present on activated platelets, lymphocytes and mast cells. It mediates the transmission of information between cells and initiates an inflammatory response. The interaction of CD154 with its receptor CD40 leads to increase in concentrations of soluble forms of both molecules (sCD154, sCD40), which has an important prognostic value in cardiovascular complications. The metabolic disorders in chronic kidney disease (CKD), chronic inflammation, increased oxidative stress and type of renal replacement therapy may influence on the balance of sCD154/sCD40 in plasma and blood platelets. The purpose of the reasearch was to analyse the concentrations of sCD154 antigen and sCD40 receptor in platelet pure plasma (PPP) and platelet rich plasma (PRP) of patients with CKD treated conservatively, haemodialysed and on petitoneal dialysis. METHODS The group examined comprised 141 patients with chronic kidney disease: in pre-dialysis stage (n = 68), haemodialysed (n = 38) and on peritoneal dialysis (n = 35). The concentrations of sCD154 and sCD40 in PRP and PPP were determined with an ELISA method. The biochemical parameters were obtained using colorimetric method. RESULTS The concentrations of sCD154 and sCD40 in PPP and PRP in examined group were significantly different depending on the method of renal replacement therapy. The haemodialysis procedure caused a significant increase in sCD40 concentration in PRP. The concentrations of sCD40 and sCD154 were correlated with lipid parameters. CONCLUSIONS The type of renal replacement therapy influences on platelet activation which may be a factor contributing to increased cardiovascular complications in patients suffering from CKD.