Serum indoxyl sulfate concentrations associate with progression of chronic kidney disease in children

The uremic toxins indoxyl sulfate (IS) and p-cresyl sulfate (pCS) accumulate in patients with chronic kidney disease (CKD) as a consequence of altered gut microbiota metabolism and a decline in renal excretion. Despite of solid experimental evidence for nephrotoxic effects, the impact of uremic toxins on the progression of CKD has not been investigated in representative patient cohorts. In this analysis, IS and pCS serum concentrations were measured in 604 pediatric participants (mean eGFR of 27 ± 11 ml/min/1.73m2) at enrolment into the prospective Cardiovascular Comorbidity in Children with CKD study. Associations with progression of CKD were analyzed by Kaplan-Meier analyses and Cox proportional hazard models. During a median follow up time of 2.2 years (IQR 4.3-0.8 years), the composite renal survival endpoint, defined as 50% loss of eGFR, or eGFR <10ml/min/1.73m2 or start of renal replacement therapy, was reached by 360 patients (60%). Median survival time was shorter in patients with IS and pCS levels in the highest versus lowest quartile for both IS (1.5 years, 95%CI [1.1,2.0] versus 6.0 years, 95%CI [5.0,8.4]) and pCS (1.8 years, 95%CI [1.5,2.8] versus 4.4 years, 95%CI [3.4,6.0]). Multivariable Cox regression disclosed a significant association of IS, but not pCS, with renal survival, which was independent of other risk factors including baseline eGFR, proteinuria and blood pressure. In this exploratory analysis we provide the first data showing a significant association of IS, but not pCS serum concentrations with the progression of CKD in children, independent of other known risk factors. In the absence of comorbidities, which interfere with serum levels of uremic toxins, such as diabetes, obesity and metabolic syndrome, these results highlight the important role of uremic toxins and accentuate the unmet need of effective elimination strategies to lower the uremic toxin burden and abate progression of CKD

Hemodiafiltration maintains a sustained improvement in blood pressure compared to conventional hemodialysis in children-the HDF, heart and height (3H) study

BACKGROUND: Hypertension is prevalent in children on dialysis and associated with cardiovascular disease. We studied the blood pressure (BP) trends and the evolution of BP over 1 year in children on conventional hemodialysis (HD) vs. hemodiafiltration (HDF). METHODS: This is a post hoc analysis of the "3H - HDF-Hearts-Height" dataset, a multicenter, parallel-arm observational study. Seventy-eight children on HD and 55 on HDF who had three 24-h ambulatory BP monitoring (ABPM) measures over 1 year were included. Mean arterial pressure (MAP) was calculated and hypertension defined as 24-h MAP standard deviation score (SDS) ≥95th percentile. RESULTS: Poor agreement between pre-dialysis systolic BP-SDS and 24-h MAP was found (mean difference - 0.6; 95% limits of agreement -4.9-3.8). At baseline, 82% on HD and 44% on HDF were hypertensive, with uncontrolled hypertension in 88% vs. 25% respectively; p < 0.001. At 12 months, children on HDF had consistently lower MAP-SDS compared to those on HD (p < 0.001). Over 1-year follow-up, the HD group had mean MAP-SDS increase of +0.98 (95%CI 0.77-1.20; p < 0.0001), whereas the HDF group had a non-significant increase of +0.15 (95%CI -0.10-0.40; p = 0.23). Significant predictors of MAP-SDS were dialysis modality (β = +0.83 [95%CI +0.51 - +1.15] HD vs. HDF, p < 0.0001) and higher inter-dialytic-weight-gain (IDWG)% (β = 0.13 [95%CI 0.06-0.19]; p = 0.0003). CONCLUSIONS: Children on HD had a significant and sustained increase in BP over 1 year compared to a stable BP in those on HDF, despite an equivalent dialysis dose. Higher IDWG% was associated with higher 24-h MAP-SDS in both groups

Hemodiafiltration Is Associated With Reduced Inflammation and Increased Bone Formation Compared With Conventional Hemodialysis in Children: The HDF, Hearts and Heights (3H) Study

BACKGROUND: Patients on dialysis have a high burden of bone-related comorbidities, including fractures. We report a post hoc analysis of the prospective cohort study HDF, Hearts and Heights (3H) to determine the prevalence and risk factors for chronic kidney disease-related bone disease in children on hemodiafiltration (HDF) and conventional hemodialysis (HD). METHODS: The baseline cross-sectional analysis included 144 children, of which 103 (61 HD, 42 HDF) completed 12-month follow-up. Circulating biomarkers of bone formation and resorption, inflammatory markers, fibroblast growth factor-23, and klotho were measured. RESULTS: Inflammatory markers interleukin-6, tumor necrosis factor-α, and high-sensitivity C-reactive protein were lower in HDF than in HD cohorts at baseline and at 12 months (P < .001). Concentrations of bone formation (bone-specific alkaline phosphatase) and resorption (tartrate-resistant acid phosphatase 5b) markers were comparable between cohorts at baseline, but after 12-months the bone-specific alkaline phosphatase/tartrate-resistant acid phosphatase 5b ratio increased in HDF (P = .004) and was unchanged in HD (P = .44). On adjusted analysis, the bone-specific alkaline phosphatase/tartrate-resistant acid phosphatase 5b ratio was 2.66-fold lower (95% confidence interval, −3.91 to −1.41; P < .0001) in HD compared with HDF. Fibroblast growth factor-23 was comparable between groups at baseline (P = .52) but increased in HD (P < .0001) and remained unchanged in HDF (P = .34) at 12 months. Klotho levels were similar between groups and unchanged during follow-up. The fibroblast growth factor-23/klotho ratio was 3.86-fold higher (95% confidence interval, 2.15–6.93; P < .0001) after 12 months of HD compared with HDF. CONCLUSION: Children on HDF have an attenuated inflammatory profile, increased bone formation, and lower fibroblast growth factor-23/klotho ratios compared with those on HD. Long-term studies are required to determine the effects of an improved bone biomarker profile on fracture risk and cardiovascular health

Visual evoked potential changes in migraine - Influence of migraine attack and aura

Objective: To assess the visual evoked potential (VEP) changes in migraines with and without aura. Study design: A clinical study in which the VEP results of 45 migraineurs (study group) and 22 healthy volunteers (control group) were compared. Of 45 migraineurs, 29 had migraine with aura (MA) and 16 had migraine without aura (MOA), and they were examined both during and between the migraine attacks. Methods: The patients and healthy controls underwent VEP assessment. On VEP recording, mono-ocular stimulation was performed by means of the pattern reversal check board. The latencies of N1, P1 and N2, and the N1-P1 amplitude were noted. The following comparisons were made between NI, P1 and N2 latencies and N1-P1 amplitudes of the migraine and control groups; during and between attack the VEP results of the patients with MA and MOA. Results: The VEP results of the migraineurs and healthy controls were similar (P>0.05). The during attack results of MA, during and between attack results of MOA, and the results of the control group were also similar (P>0.05). N2 latency significantly elongated in patients with MA in the attack free period than it was during the attack (P=0.01), and was also longer than it was in the control group (P=0.01). Conclusions: There is involvement of the visual pathway in MA rather than MOA, and differentiation between these subtypes of the migraine disease may be performed on the basis of VEP findings manifesting by the prolongation of the N2 wave latency. This contention should be confirmed by further studies. (C) 2001 Elsevier Science BN. All rights reserved

Design analysis of fluid-flow through perforated plates

The performance of the perforated plates in fluid-flow applications is evaluated by measuring the pressure drop of the working fluid. The purpose of this investigation is to determine how different parameters affect the capability of the perforated plates and modify the design by using a design of experiment analysis, namely Taguchi method for optimization. The flow characteristics, which were obtained by the CFD software package ANSYS-CFX, were used for this analysis. The design parameters which affect the pressure loss are Reynolds number (A), porosity (B), non-dimensional thickness of the plate (C), and hole pattern (D). The level of importance of the design parameters are determined by use of analysis of variance method. According to the analysis, the optimum values are obtained for the case A8B2C2D1 (Re = 15000, porosity = 50.3, t / D = 1, and staggered hole). The most effective design parameter on the results is found as porosity (92%), while the least effective is the hole pattern (0.2%). A special dividend of this work was to demonstrate the capabilities of the Taguchi method as a powerful means of increasing the effectiveness of numerical simulation

The A218C polymorphism of tryptophan hydroxylase gene and migraine

Objective: To determine the significance of the A218C polymorphism of the tryptophan hydroxylase (TPH) gene in migraine.Methods: Fifty-nine migraineurs and 62 healthy controls were included in the study, and polymerase chain reaction - restriction fragment length polymorphism assays were used to determine TPH A218C polymorphism.Results: There was no association between TPH gene polymorphism and gender, family history of migraine and epilepsy, or aura. There was no significant difference between the allele frequencies of both groups (p > 0.05). A significant difference was found between the genotypes of the migraineurs and controls regarding the AA genotype. Homozygosity for the C allele or heterozygosity for the A or C was not associated with the occurrence of migraine (p > 0.05), but homozygosity for the A allele was less frequent in the migraineurs (p = 0.02).Conclusion: Since it is unlikely that TPH polymorphism alters serotonin biosynthesis, its association with migraine may be attributed to linkage disequilibrium with a functional variant within the TPH gene or a nearby gene. (C) 2006 Elsevier Ltd. All rights reserved

Early Diagnosis of Right Ventricular Systolic Dysfunction by Tissue Doppler-Derived Isovolumic Myocardial Acceleration in Patients with Chronic Obstructive Pulmonary Disease

(ECHOCARDIOGRAPHY, Volume 26, October 2009)