Bone Metabolism and Arterial Stiffness After Renal Transplantation

Background/Aims: To assess the relationship between bone and vascular disease and its changes over time after renal transplantation. Metabolic bone disease (MBD) is common in chronic kidney disease (CKD) and is associated with cardiovascular (CV) disease. Following transplantation (Tx), improvement in CV disease has been reported; however, data regarding changes in bone disease remain controversial. Methods: Bone turnover and arterial stiffness (pulse wave velocity (PWV)) were assessed in 47 Tx patients (38 (3-191) months after Tx). Results: Bone alkaline phosphatase (BALP), osteocalcin (OC) and beta-crosslaps were significantly higher in Tx patients, and decreased significantly after one year. There was a negative correlation between BALP, OC and steroid administered (r=-0.35;r=-0.36 respectively). PWV increased in the Tx group (1.15 SD). In patients with a follow up of Conclusions: Increased bone turnover and arterial stiffness are present following kidney transplantation. While bone turnover decreases with time, arterial stiffness correlates initially with bone turnover, after which the influence of cholesterol becomes significant. Non-invasive estimation of bone metabolism and arterial stiffness may help to assess CKD-MBD following renal transplantation

Distinct axo-somato-dendritic distributions of three potassium channels in CA1 hippocampal pyramidal cells

Potassium channels comprise the most diverse family of ion channels and play critical roles in a large variety of physiological and pathological processes. In addition to their molecular diversity, variations in their distributions and densities on the axo-somato-dendritic surface of neurons are key parameters in determining their functional impact. Despite extensive electrophysiological and anatomical investigations, the exact location and densities of most K(+) channels in small subcellular compartments are still unknown. Here we aimed at providing a quantitative surface map of two delayed-rectifier (Kv1.1 and Kv2.1) and one G-protein-gated inwardly rectifying (Kir3.2) K(+) channel subunits on hippocampal CA1 pyramidal cells (PCs). Freeze-fracture replica immunogold labelling was employed to determine the relative densities of these K(+) channel subunits in 18 axo-somato-dendritic compartments. Significant densities of the Kv1.1 subunit were detected on axon initial segments (AISs) and axon terminals, with an approximately eight-fold lower density in the latter compartment. The Kv2.1 subunit was found in somatic, proximal dendritic and AIS plasma membranes at approximately the same densities. This subunit has a non-uniform plasma membrane distribution; Kv2.1 clusters are frequently adjacent to, but never overlap with, GABAergic synapses. A quasi-linear increase in the Kir3.2 subunit density along the dendrites of PCs was detected, showing no significant difference between apical dendritic shafts, oblique dendrites or dendritic spines at the same distance from the soma. Our results demonstrate that each subunit has a unique cell-surface distribution pattern, and predict their differential involvement in synaptic integration and output generation at distinct subcellular compartments

QMPSF is sensitive and specific in the detection of NPHP1 heterozygous deletions

BACKGROUND: Nephronophthisis, an autosomal recessive nephropathy, is responsible for 10% of childhood chronic renal failure. The deletion of its major gene, NPHP1, with a minor allele frequency of 0.24% in the general population, is the most common mutation leading to a monogenic form of childhood chronic renal failure. It is challenging to detect it in the heterozygous state. We aimed to evaluate the sensitivity and the specificity of the quantitative multiplex PCR of short fluorescent fragments (QMPSF) in its detection. METHODS: After setting up the protocol of QMPSF, we validated it on 39 individuals diagnosed by multiplex ligation-dependent probe amplification (MLPA) with normal NPHP1 copy number (n=17), with heterozygous deletion (n=13, seven parents and six patients), or with homozygous deletion (n=9). To assess the rate of the deletions that arise from independent events, deleted alleles were haplotyped. RESULTS: The results of QMPSF and MLPA correlated perfectly in the identification of 76 heterozygously deleted and 56 homozygously deleted exons. The inter-experimental variability of the dosage quotient obtained by QMPSF was low: control, 1.05 (median; range, 0.86-1.33, n = 102 exons); heterozygous deletion, 0.51 (0.42-0.67, n = 76 exons); homozygous deletion, 0 (0-0, n = 56 exons). All patients harboring a heterozygous deletion were found to carry a hemizygous mutation. At least 15 out of 18 deletions appeared on different haplotypes and one deletion appeared de novo. CONCLUSIONS: The cost- and time-effective QMPSF has a 100% sensitivity and specificity in the detection of NPHP1 deletion. The potential de novo appearance of NPHP1 deletions makes its segregation analysis highly recommended in clinical practice

Mayor, as the first man of the local govermant in Nyíradony

Dolgozatom célja, hogy bemutassam azt a környezetet ahol élek, és a város polgármesterének feladat- és hatáskörét, tevékenységét, és elért eredményeit. Ennek eléréséhez kutatásokat végeztem, és magát a polgármestert kérdeztem hatásköri feladatairól. Az írás során jöttem rá, hogy a polgármesteri feladat nagyon szerteágazó és rendkívül sokrétű. Nem egyszerűen csak a törvényeket kell tudni és betartani, illetve betarttatni, hanem érteni kell a politikához, pénzügyekhez, diplomáciához. A lakossággal kapcsolatos esetekben szociális érzékenységgel, és sok esetben pszichológiai rátermettséggel kell rendelkezni.Mag

Prevalence of obesity and metabolic changes after kidney transplantation: hungarian pediatric cohort study

BACKGROUND: Cardiovascular mortality rate in patients with end-stage renal disease is 3 magnitudes higher than in the general population; it remains 10-fold higher after successful renal transplantation (Tx). Among others, obesity and hypertension can exert deleterious effects on vascular structure and function after Tx. Successful kidney transplantation may induce excessive weight gain in part because of the effects of steroid treatment. METHODS: The purpose of this study was to evaluate the presence of obesity in Tx children, their obesity-related metabolic disturbances, and to assess their blood pressure and arterial stiffness in relation to obesity. Forty-one transplant children (age, 15.7 [3.5] years; 28 males) were studied. Body composition was assessed by body mass index (BMI), waist circumference, skin-fold measurements, and multifrequence bioimpedance analysis. Glucose metabolism, blood pressure, and arterial stiffness (with the use of pulse wave velocity) were studied. Age- and sex-dependent parameters were expressed as standard deviation scores (SDS). RESULTS: The prevalence of overweight (BMI >85%) increased from 3.2% to 24.4% at 49 months (3-183) (median, range); the BMI SDS increased from -0.27 (0.79) to 0.67 (1.35) after Tx. There was a close correlation between BMI SDS and the percentage of body fat and body fat mass in the Tx group (r = 0.80; r = 0.94, P = .0001). Children with disturbed glycemic control (n = 14) had higher percentage of body fat and higher blood pressure compared with those with normal glucose metabolism (P < .05). There was no difference in pulse wave velocity between the lean and obese patients. CONCLUSIONS: The prevalence of overweight or obese patients in the Hungarian pediatric renal cohort is low at transplantation and rises subsequently. Overweight is associated with disturbed glycemic control and increased blood pressure; however, these disturbances are not yet reflected by stiffening of the arteries. Strategies are needed to prevent obesity, its impact on hypertension, and cardiovascular disease in pediatric transplantation

Bone Metabolism and Arterial Stiffness After Renal Transplantation

Background/Aims: To assess the relationship between bone and vascular disease and its changes over time after renal transplantation. Metabolic bone disease (MBD) is common in chronic kidney disease (CKD) and is associated with cardiovascular (CV) disease. Following transplantation (Tx), improvement in CV disease has been reported; however, data regarding changes in bone disease remain controversial. Methods: Bone turnover and arterial stiffness (pulse wave velocity (PWV)) were assessed in 47 Tx patients (38 (3-191) months after Tx). Results: Bone alkaline phosphatase (BALP), osteocalcin (OC) and beta-crosslaps were significantly higher in Tx patients, and decreased significantly after one year. There was a negative correlation between BALP, OC and steroid administered (r=-0.35;r=-0.36 respectively). PWV increased in the Tx group (1.15 SD). In patients with a follow up of Conclusions: Increased bone turnover and arterial stiffness are present following kidney transplantation. While bone turnover decreases with time, arterial stiffness correlates initially with bone turnover, after which the influence of cholesterol becomes significant. Non-invasive estimation of bone metabolism and arterial stiffness may help to assess CKD-MBD following renal transplantation

Cardiovascular risk assessment in children with chronic kidney disease

Chronic kidney disease (CKD) is a major factor contributing to cardiovascular (CV) morbidity and mortality with the highest risk in patients on dialysis. An estimation of CV risk is important not only to identify potential modifiable risk factors but also to evaluate the effect of treatments aimed to reduce the risk. Non-invasive methods of measuring vascular changes and circulating biomarkers are available to assess the presence and severity of cardiovascular damage. These include measures of structural (carotid intima-media thickness and coronary artery calcification score) and functional (aortic pulse wave velocity, 24-h ambulatory blood pressure monitoring, ambulatory arterial stiffness index, heart rate variability and flow-mediated dilatation) changes in the vessel wall. In addition, a number of circulating biomarkers of vascular damage and its progression have been studied. Many of these tests are well validated as surrogate markers of future cardiovascular events and death in adult CKD patients, but need technical adaptation, standardization and validation for use in children. With our current state of knowledge, these are best reserved for research studies and scarce clinical resources may be better utilized for preventative strategies to reduce the modifiable risk factors for calcification from early CKD stages