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      Effects of Hemodiafiltration versus Conventional Hemodialysis in Children with ESKD: The HDF, Heart and Height Study

      , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ,
      Journal of the American Society of Nephrology
      Ovid Technologies (Wolters Kluwer Health)

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          Abstract

          Although studies suggest that hemodiafiltration (HDF) may reduce cardiovascular mortality in adults, data in children are sparse. In this observational multicenter study, the authors compared HDF and hemodialysis (HD) in children with ESKD, finding that annualized changes in well validated subclinical markers of cardiovascular disease, including carotid intima-media thickness SD scores, were lower in HDF and associated with lower 24-hour ambulatory BP and intradialytic weight gain. Height increased only in the HDF cohort. Compared with the HD cohort, the HDF cohort also had better self-reported outcomes, with fewer headaches, less dizziness or cramps, and shorter recovery time after dialysis sessions. The study provides proof-of-concept data that HDF is a safe treatment that may have benefits over conventional HD in children. A randomized trial is required to confirm these findings. Hypertension and cardiovascular disease are common in children undergoing dialysis. Studies suggest that hemodiafiltration (HDF) may reduce cardiovascular mortality in adults, but data for children are scarce. The HDF, Heart and Height study is a nonrandomized observational study comparing outcomes on conventional hemodialysis (HD) versus postdilution online HDF in children. Primary outcome measures were annualized changes in carotid intima-media thickness (cIMT) SD score and height SD score. We enrolled 190 children from 28 centers; 78 on HD and 55 on HDF completed 1-year follow-up. The groups were comparable for age, dialysis vintage, access type, dialysis frequency, blood flow, and residual renal function. At 1 year, cIMT SD score increased significantly in children on HD but remained static in the HDF cohort. On propensity score analysis, HD was associated with a +0.47 higher annualized cIMT SD score compared with HDF. Height SD score increased in HDF but remained static in HD. Mean arterial pressure SD score increased with HD only. Factors associated with higher cIMT and mean arterial pressure SD-scores were HD group, higher ultrafiltration rate, and higher β 2-microglobulin. The HDF cohort had lower β 2-microglobulin, parathyroid hormone, and high-sensitivity C-reactive protein at 1 year; fewer headaches, dizziness, or cramps; and shorter postdialysis recovery time. HDF is associated with a lack of progression in vascular measures versus progression with HD, as well as an increase in height not seen in the HD cohort. Patient-related outcomes improved among children on HDF correlating with improved BP control and clearances. Confirmation through randomized trials is required.

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          Most cited references55

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          Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis.

          Carotid intima-media thickness (IMT) is increasingly used as a surrogate marker for atherosclerosis. Its use relies on its ability to predict future clinical cardiovascular end points. We performed a systematic review and meta-analysis of data to examine this association. Using a prespecified search strategy, we identified 8 relevant studies and compared study design, measurement protocols, and reported data. We identified sources of heterogeneity between studies. The assumption of a linear relationship between IMT and risk was challenged by use of a graphical technique. To obtain a pooled estimate of the relative risk per IMT difference, we performed a meta-analysis based on random effects models. The age- and sex-adjusted overall estimates of the relative risk of myocardial infarction were 1.26 (95% CI, 1.21 to 1.30) per 1-standard deviation common carotid artery IMT difference and 1.15 (95% CI, 1.12 to 1.17) per 0.10-mm common carotid artery IMT difference. The age- and sex-adjusted relative risks of stroke were 1.32 (95% CI, 1.27 to 1.38) per 1-standard deviation common carotid artery IMT difference and 1.18 (95% CI, 1.16 to 1.21) per 0.10-mm common carotid artery IMT difference. Major sources of heterogeneity were age distribution, carotid segment definition, and IMT measurement protocol. The relationship between IMT and risk was nonlinear, but the linear models fitted relatively well for moderate to high IMT values. Carotid IMT is a strong predictor of future vascular events. The relative risk per IMT difference is slightly higher for the end point stroke than for myocardial infarction. In future IMT studies, ultrasound protocols should be aligned with published studies. Data for younger individuals are limited and more studies are required.
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            Dialysis accelerates medial vascular calcification in part by triggering smooth muscle cell apoptosis.

            Vascular calcification is associated with increased morbidity and mortality in stage V chronic kidney disease, yet its early pathogenesis and initiating mechanisms in vivo remain poorly understood. To address this, we quantified the calcium (Ca) load in arteries from children (10 predialysis, 24 dialysis) and correlated it with clinical, biochemical, and vascular measures. Vessel Ca load was significantly elevated in both predialysis and dialysis and was correlated with the patients' mean serum Ca x phosphate product. However, only dialysis patients showed increased carotid intima-media thickness and increased aortic stiffness, and calcification on computed tomography was present in only the 2 patients with the highest Ca loads. Importantly, predialysis vessels appeared histologically intact, whereas dialysis vessels exhibited evidence of extensive vascular smooth muscle cell (VSMC) loss owing to apoptosis. Dialysis vessels also showed increased alkaline phosphatase activity and Runx2 and osterix expression, indicative of VSMC osteogenic transformation. Deposition of the vesicle membrane marker annexin VI and vesicle component mineralization inhibitors fetuin-A and matrix Gla-protein increased in dialysis vessels and preceded von Kossa positive overt calcification. Electron microscopy showed hydroxyapatite nanocrystals within vesicles released from damaged/dead VSMCs, indicative of their role in initiating calcification. Taken together, this study shows that Ca accumulation begins predialysis, but it is the induction of VSMC apoptosis in dialysis that is the key event in disabling VSMC defense mechanisms and leading to overt calcification, eventually with clinically detectable vascular damage. Thus the identification of factors that lead to VSMC death in dialysis will be of prime importance in preventing vascular calcification.
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              Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis.

              Cardiovascular disease is common in older adults with end-stage renal disease who are undergoing regular dialysis, but little is known about the prevalence and extent of cardiovascular disease in children and young adults with end-stage renal disease. We used electron-beam computed tomography (CT) to screen for coronary-artery calcification in 39 young patients with end-stage renal disease who were undergoing dialysis (mean [+/-SD] age, 19+/-7 years; range, 7 to 30) and 60 normal subjects 20 to 30 years of age. In those with evidence of calcification on CT scanning, we determined its extent. The results were correlated with the patients' clinical characteristics, serum calcium and phosphorus concentrations, and other biochemical variables. None of the 23 patients who were younger than 20 years of age had evidence of coronary-artery calcification, but it was present in 14 of the 16 patients who were 20 to 30 years old. Among those with calcification, the mean calcification score was 1157+/-1996, and the median score was 297. By contrast, only 3 of the 60 normal subjects had calcification. As compared with the patients without coronary-artery calcification, those with calcification were older (26+/-3 vs. 15+/-5 years, P<0.001) and had been undergoing dialysis for a longer period (14+/-5 vs. 4+/-4 years, P< 0.001). The mean serum phosphorus concentration, the mean calcium-phosphorus ion product in serum, and the daily intake of calcium were higher among the patients with coronary-artery calcification. Among 10 patients with calcification who underwent follow-up CT scanning, the calcification score nearly doubled (from 125+/-104 to 249+/-216, P=0.02) over a mean period of 20+/-3 months. Coronary-artery calcification is common and progressive in young adults with end-stage renal disease who are undergoing dialysis.
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                Author and article information

                Journal
                Journal of the American Society of Nephrology
                JASN
                Ovid Technologies (Wolters Kluwer Health)
                1046-6673
                1533-3450
                2019
                April 2019
                March 07 2019
                : 30
                : 4
                : 678-691
                Article
                10.1681/ASN.2018100990
                6442347
                30846560
                b269fe86-a73b-4921-bdee-7168489f36b1
                © 2019
                History

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