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The effectiveness of cinacalcet: a randomized, open label study in chronic hemodialysis patients with severe secondary hyperparathyroidism.
Susantitaphong, P, Vadcharavivad, S, Susomboon, T, Singhan, W, Dumrongpisutikul, N, Jakchairoongruang, K, Eiam-Ong, S, Praditpornsilpa, K
Renal failure. 2019;(1):326-333
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Abstract
BACKGROUND Secondary hyperparathyroidism (SHPT) is associated with high incidences of cardiovascular disease, bone fracture, and mortality. This study was conducted to demonstrate the effectiveness of cinacalcet treatment on chronic kidney disease-mineral bone disorder (CKD-MBD) markers in chronic hemodialysis patients with severe SHPT. METHODS In phase 1, 30 adult HD patients were randomized to cinacalcet or control groups for 12 weeks to explore the achievement of >30% reduction of iPTH. In phase 2, 45 patients were participated to further explore the effect of cinacalcet on CKD-MBD parameters for 24-week follow up and 12 additional weeks after cinacalcet discontinuation. RESULTS In phase 1, the baseline serum iPTH levels were not different [1374 (955, 1639) pg/mL in the control group vs. 1191 (1005, 1884) pg/mL in the cinacalcet group], the percentage of patients achieving iPTH target were significantly higher in the treatment group [80% vs. 13%, p = .001]. In phase 2, the significant reductions of iPTH, FGF-23, tartrate-resistant acid phosphatase 5b, and slightly decreased size of parathyroid gland and stabilized vascular calcification were observed at 24-week follow up and markedly rebounded after discontinuation of cinacalcet. CONCLUSIONS The effectiveness of cinacalcet were still obviously demonstrated even in chronic HD patients with severe SHPT. In addition, the improvements of bone markers and FGF-23, and stabilization of vascular calcification were observed. Therefore, cinacalcet can provide salutary effects on CKD-MBD in severe SHPT and might be an initially effective PTH-lowering therapy prior to surgical parathyroidectomy as well as an alternative treatment in the patients unsuitable for surgery. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov: NCT02056730. Date of registration: February 4, 2014.
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Automated individualization of dialysate sodium concentration reduces intradialytic plasma sodium changes in hemodialysis.
Ságová, M, Wojke, R, Maierhofer, A, Gross, M, Canaud, B, Gauly, A
Artificial organs. 2019;(10):1002-1013
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Abstract
In standard care, hemodialysis patients are often treated with a center-specific fixed dialysate sodium concentration, potentially resulting in diffusive sodium changes for patients with plasma sodium concentrations below or above this level. While diffusive sodium load may be associated with thirst and higher interdialytic weight gain, excessive diffusive sodium removal may cause intradialytic symptoms. In contrast, the new hemodialysis machine option "Na control" provides automated individualization of dialysate sodium during treatment with the aim to reduce such intradialytic sodium changes without the need to determine the plasma sodium concentration. This proof-of-principle study on sodium control was designed as a monocentric randomized controlled crossover trial: 32 patients with residual diuresis of ≤1000 mL/day were enrolled to be treated by high-volume post-dilution hemodiafiltration (HDF) for 2 weeks each with "Na control" (individually and automatically adjusted dialysate sodium concentration) versus "standard fixed Na" (fixed dialysate sodium 138 mmol/L), in randomized order. Pre- and post-dialytic plasma sodium concentrations were determined at bedside by direct potentiometry. The study hypothesis consisted of 2 components: the mean plasma sodium change between the start and end of the treatment being within ±1.0 mmol/L for sodium-controlled treatments, and a lower variability of the plasma sodium changes for "Na control" than for "standard fixed Na" treatments. Three hundred seventy-two treatments of 31 adult chronic hemodialysis patients (intention-to-treat population) were analyzed. The estimate for the mean plasma sodium change was -0.53 mmol/L (95% confidence interval: [-1.04; -0.02] mmol/L) for "Na control" treatments and -0.95 mmol/L (95% CI: [-1.76; -0.15] mmol/L) for "standard fixed Na" treatments. The standard deviation of the plasma sodium changes was 1.39 mmol/L for "Na control" versus 2.19 mmol/L for "standard fixed Na" treatments (P = 0.0004). Whereas the 95% CI for the estimate for the mean plasma sodium change during "Na control" treatments marginally overlapped the lower border of the predefined margin ±1.0 mmol/L, the variability of intradialytic plasma sodium changes was lower during "Na control" versus "standard fixed Na" treatments. Thus, automated dialysate sodium individualization by "Na control" approaches isonatremic dialysis in the clinical setting.
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Effect of etelcalcetide on cardiac hypertrophy in hemodialysis patients: a randomized controlled trial (ETECAR-HD).
Dörr, K, Kammer, M, Reindl-Schwaighofer, R, Lorenz, M, Loewe, C, Marculescu, R, Erben, R, Oberbauer, R
Trials. 2019;(1):601
Abstract
BACKGROUND Fibroblast growth factor 23 (FGF23) is associated with left ventricular hypertrophy (LVH) in patients with chronic kidney disease, and calcimimetic therapy reduces plasma concentrations of FGF23. It remains unknown whether treatment with the calcimimetic etelcalcetide (ETL) reduces LVH in patients on hemodialysis. METHODS/DESIGN This single-blinded randomized trial of 12 months duration will test the effects of ETL compared with alfacalcidol on LVH and cardiac fibrosis in maintenance hemodialysis patients with secondary hyperparathyroidism. Both treatment regimens will be titrated to equally suppress secondary hyperparathyroidism while alfacalcidol treatment causes an increase and ETL a decrease in FGF23, respectively. Patients treated thrice weekly with hemodialysis for ≥ 3 months and ≤ 3 years with parathyroid hormone levels ≥ 300 pg/ml and LVH will be enrolled in the study. The primary study endpoint is change from baseline to 12 months in left ventricular mass index (LVMI; g/m2) measured by cardiac magnetic resonance imaging. Sample size calculations showed that 62 randomized patients will be necessary to detect a difference in LVMI of at least 20 g/m2 between the two groups at 12 months. Due to the strong association of volume overload and LVH, randomization will be stratified by residual kidney function, and regular body composition monitoring will be performed to control the volume status of patients. Study medication will be administered intravenously by the dialysis nurses after every hemodialysis session, thus omitting adherence issues. Secondary study endpoints are cardiac parameters measured by echocardiography, biomarker concentrations of bone metabolism (FGF23, vitamin D, parathyroid hormone, calcium, phosphate, s-Klotho), cardiac markers (pro-brain natriuretic peptide, pre- and postdialysis troponin T) and metabolites of the renin-angiotensin-aldosterone cascade (angiotensin I (Ang I), Ang II, Ang-(1-7), Ang-(1-5), Ang-(1-9), and aldosterone). DISCUSSION The causal inference and pathophysiology of LVH regression by FGF23 reduction using calcimimetic treatment has not yet been shown. This intervention study has the potential to discover a new strategy for the treatment of cardiac hypertrophy and fibrosis in patients on maintenance hemodialysis. It might be speculated that successful treatment of cardiac morphology will also reduce the risk of cardiac death in this population. TRIAL REGISTRATION European Clinical Trials Database, EudraCT number 2017-000222-35; ClinicalTrials.gov, NCT03182699 . Registered on.
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Sodium and water handling during hemodialysis: new pathophysiologic insights and management approaches for improving outcomes in end-stage kidney disease.
Canaud, B, Kooman, J, Selby, NM, Taal, M, Francis, S, Kopperschmidt, P, Maierhofer, A, Kotanko, P, Titze, J
Kidney international. 2019;(2):296-309
Abstract
Space medicine and new technology such as magnetic resonance imaging of tissue sodium stores (23NaMRI) have changed our understanding of human sodium homeostasis and pathophysiology. It has become evident that body sodium comprises 3 main components. Two compartments have been traditionally recognized, namely one that is circulating and systemically active via its osmotic action, and one slowly exchangeable pool located in the bones. The third, recently described pool represents sodium stored in skin and muscle interstitium, and it is implicated in cell and biologic activities via local hypertonicity and sodium clearance mechanisms. This in-depth review provides a comprehensive view on the pathophysiology and existing knowledge gaps of systemic hemodynamic and tissue sodium accumulation in dialysis patients. Furthermore, we discuss how the combination of novel technologies to quantitate tissue salt accumulation (e.g., 23NaMRI) with devices to facilitate the precise attainment of a prescribed hemodialytic sodium mass balance (e.g., sodium and water balancing modules) will improve our therapeutic approach to sodium management in dialysis patients. While prospective studies are required, we think that these new diagnostic and sodium balancing tools will enhance our ability to pursue more personalized therapeutic interventions on sodium and water management, with the eventual goal of improving dialysis patient outcomes.
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[Dialysis monitoring: peritoneal equilibrium test, regional citrate anticoagulation and residual renal function].
Bargnoux, AS, Barguil, Y, Zaoui, E, Jean, G, Cristol, JP
Annales de biologie clinique. 2019;(4):391-396
Abstract
The SFBC working group aimed to deal with biological tests outside the French nomenclature that may be useful for the follow-up of dialysis patients. Our discussion was divided into 3 parts: 1) evaluation of peritoneal membrane characteristics; 2) monitoring of renal replacement therapy using regional citrate anticoagulation; 3) estimation of residual renal function (RRF). International recommendations underline the importance of assessing peritoneal membrane characteristics for peritoneal dialysis prescription. This peritoneal equilibrium test requires the measurement in dialysate of the following parameters: glucose, urea, creatinine and sodium. As part of the monitoring of continuous renal replacement therapy using regional citrate anticoagulation, the determination of ionized calcium assay is essential according to national and international guidelines to ensure a balance between effective anticoagulation and appropriate calcium levels. Finally, the RRF plays a key role in the dialysis adequacy and patient survival. European and international recommendations highlight the potential interest of RRF in peritoneal dialysis and hemodialysis. The RRF corresponds to the mean of urinary urea and creatinine clearance, assessed from a urine collection with measurement of urinary urea.
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The effect of intradialytic exercise twice a week on the physical capacity, inflammation, and nutritional status of dialysis patients: A randomized controlled trial.
Suhardjono, , Umami, V, Tedjasukmana, D, Setiati, S
Hemodialysis international. International Symposium on Home Hemodialysis. 2019;(4):486-493
Abstract
INTRODUCTION Inactivity, uremia, and malnutrition in dialysis patients may lead to decreased muscle mass and physical capacity. As a preventative measure, dialysis patients are provided with an intradialytic exercise program. Our study aimed to determine the role of intradialytic exercise performed 2 times per week on physical capacity, inflammation, and nutritional status in dialysis patients and to determine which exercises are more suitable for this population. METHODS A randomized clinical trial in which participants were randomly assigned to 1 of 3 groups, i.e., a group of patients performing aerobic exercise, a group of patients performing a combination of aerobic and resistance exercise and the control group. The study was conducted at the Dialysis Unit of Dr. Cipto Mangunkusumo General Hospital, Jakarta for 12 weeks from February to May 2018. The inclusion criteria were dialysis patients aged over 18 years who had undergone routine dialysis for over 3 months. FINDINGS A total of one hundred twenty patients were included in the study. There was a significant increase in lower extremity strength in the group performing aerobic exercise and in the combined exercise group compared to the lower extremity strength of the control group. There was also a significant increase in the physical component score (PCS) of the KDQOL-SF™ instrument in the aerobic training and combination exercise groups compared to the PCS of the control group. No significant differences were found between the combination exercise group and the aerobic training group in any outcome. DISCUSSION Both types of exercise programs significantly increased the lower extremity muscle strength and the PCS of the quality of life index. Combination exercise was not more effective than aerobic exercise for dialysis patients.
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Effect of extended hours dialysis on markers of chronic kidney disease-mineral and bone disorder in the ACTIVE Dialysis study.
Zhan, Z, Smyth, B, Toussaint, ND, Gray, NA, Zuo, L, de Zoysa, JR, Chan, CT, Jin, C, Scaria, A, Hawley, CM, et al
BMC nephrology. 2019;(1):258
Abstract
BACKGROUND Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD) is a significant cause of morbidity among haemodialysis patients and is associated with pathological changes in phosphate, calcium and parathyroid hormone (PTH). In the ACTIVE Dialysis study, extended hours dialysis reduced serum phosphate but did not cause important changes in PTH or serum calcium. This secondary analysis aimed to determine if changes in associated therapies may have influenced these findings and to identify differences between patient subgroups. METHODS The ACTIVE Dialysis study randomised 200 participants to extended hours haemodialysis (≥24 h/week) or conventional haemodialysis (≤18 h/week) for 12 months. Mean differences between treatment arms in serum phosphate, calcium and PTH; and among key subgroups (high vs. low baseline phosphate/PTH, region, time on dialysis, dialysis setting and frequency) were examined using mixed linear regression. RESULTS Phosphate binder use was reduced with extended hours (- 0.83 tablets per day [95% CI -1.61, - 0.04; p = 0.04]), but no differences in type of phosphate binder, use of vitamin D, dose of cinacalcet or dialysate calcium were observed. In adjusted analysis, extended hours were associated with lower phosphate (- 0.219 mmol/L [- 0.314, - 0.124; P < 0.001]), higher calcium (0.046 mmol/L [0.007, 0.086; P = 0.021]) and no change in PTH (0.025 pmol/L [- 0.107, 0.157; P = 0.713]). The reduction in phosphate with extended hours was greater in those with higher baseline PTH and dialysing at home. CONCLUSION Extended hours haemodialysis independently reduced serum phosphate levels with minimal change in serum calcium and PTH levels. With a few exceptions, these results were consistent across patient subgroups. TRIAL REGISTRATION Clinicaltrials.gov NCT00649298 . Registered 1 April 2008.
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Renin Angiotensin Aldosterone System Blockades Does Not Protect Residual Renal Function in Patients with Hemodialysis at 1 Year After Dialysis Initiation: A Prospective Observational Cohort Study.
Yoo, KD, Kim, CT, Kwon, S, Lee, J, Oh, YK, Kang, SW, Yang, CW, Kim, YL, Kim, YS, Lim, CS, et al
Scientific reports. 2019;(1):18103
Abstract
The beneficial effects of renin angiotensin aldosterone system (RAAS) blockade on residual renal function (RRF) in patients who have just initiated hemodialysis (HD) have been inconclusive. In this study, 935 patients with incident HD from a nationwide prospective observational cohort in Korea were included for analysis. The primary outcome showed that RRF as demonstrated by urine volume changes over 0, 3, and 12 months differed between the RAAS blockade and control groups. Mixed-effects linear regression was used to compare RRF between the groups. Patients in the RAAS group had a greater proportion of higher urine volume at study enrollment compared to the control group, but there was no difference in baseline characteristics, heart function, and dialysis-related indices. After adjusting for confounding factors, the RAAS group did not provide a significant benefit to RRF in a mixed-effects linear regression (p = 0.51). Male gender, high Charlson comorbidity index, diuretic use, and high weekly ultrafiltration volume were associated with faster decline in RRF. The RAAS group failed to provide a protective effect for the development of anuria 1 year after initiating dialysis based on the multivariate logistic regression (OR 0.73 95% CI 0.25-2.13, p = 0.57). In Korean patients with incident HD, RAAS blockade did not provide a protective effect for RRF after 1 year. Further research is needed to clarify the optimal treatment for preserving RRF in HD patients.
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Benefit-risk balance of native vitamin D supplementation in chronic hemodialysis: what can we learn from the major clinical trials and international guidelines?
Bentata, Y
Renal failure. 2019;(1):607-615
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Abstract
For some years, there has been a great renewal of interest in native vitamin D and its major involvement in osseous and non-osseous effects in the organism. Patients in chronic hemodialysis (CHD) constitute a specific population with different physiopathologic characteristics and needs, since morbidity and mortality are strongly correlated with vitamin D insufficiency. Vitamin D supplementation raises very pertinent questions for which we have only partial answers and we lack solid scientific proof to establish certain truths. Thus, we try through this mini-review to analyze the results of the main randomized clinical trials conducted during the last decade, and to discuss international guidelines concerning native vitamin D supplementation in CHD patients. Seven double-blind randomized clinical trials have evaluated native Vitamin D supplementation in CHD patients. These clinical trials began between 2007 and 2013 and studied relatively small samples of patients with an average of 50. All of these trials are important, but do not provide sufficient scientific proof concerning the advantages, consequences, and secondary effects of native vitamin D supplementation in CHD. None of the European, American, English, Asian, Australian, or Canadian recommendations have specified the targets, doses, duration, or the molecule of vitamin D supplementation in the patient on CHD. In 2017, the long-awaited KDIGO recommendations were published and despite the results of clinical trials conducted, the recommendations on native vitamin D supplementation in CHD were very imprecise and sparse, limited to suggesting correction of any state of vitamin D insufficiency or deficiency.
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[The different modalities of isonatric hemodialysis].
Petitclerc, T, Gaillard, F
Nephrologie & therapeutique. 2019;(1):22-28
Abstract
Setting dialysate sodium allows to adequately adjust sodium balance and plasma sodium at the end of dialysis session. In accordance with the set-point theory based on the concept of restoring cellular hydration, an adequate target for plasma sodium at the end of the session could be the value of predialysis plasma sodium concentration (isonatric hemodialysis). Some recently available dialysis monitors provide an on-line value of plasma-water conductivity usually converted in on-line natremia. There are different modalities of isonatric hemodialysis depending on whether the online value of natremia is used or not. By reviewing the few studies concerning the isonatric hemodialysis, it seems logical to set a target of postdialysis on-line natremia (or plasma-water conductivity) slightly lower than its predialysis value. However this strategy requires specifically designed software not yet available in clinical routine.