Dialysate Calcium Research Articles

SO070THE SPECTRUM OF RENAL OSTEODYSTROPHY IN PREVALENT PERITONEAL DIALYSIS PATIENTS IN 21ST CENTURY - A HISTOMORPHOMETRIC ANALYSIS OF BONE BIOPSIES

Abstract Background and Aims The spectrum of renal osteodystrophy (ROD) in peritoneal dialysis (PD) patients remains to be clarified. Most studies are old and the results inconsistent. Also there were changes in clinical practice that may have influenced the bone histology in PD patients. Method In order to characterize ROD in prevalent PD population, we performed tetracycline-labelled bone biopsies in 49 PD patients with histomorphometric analysis according KDIGO guidelines. Exclusion criteria: history of kidney transplant, hemodialysis, treatment with agents interfering in bone metabolism (for example bisphosphonates). Hands and pelvis x-ray were performed to evaluate vascular calcification (VC) and to calculate the Adragão score. All patients were treated with biocompatible PD solutions, with calcium concentration of 1.25 mmol/L. Results Forty-nine patients participated in the study, with 32 biopsies analyzed so far. Mean age was 52.4±10.9 years, 16 male, 6 with diabetes mellitus, 23 on manual PD, median time on PD was 22.1 (3-61) months. Mean calcium, phosphate and PTH were 9.2±0.5 mg/dL, 4.9±1.0 mg/dL and 489.87±227.8 pg/mL, respectively. Vascular calcification was detected in 29% of patients and mean Adragão score was 1.13. Essential histomorphometric and selected data is represented in table 1: Bone volume (BV) tended to be lower in diabetics - 17.1% (10.1-23.1) compared with non-diabetics – 22.6% (12.7-41.4) (p=0.07). Median bone formation rate (BFR) tended to be lower - 21.39 µm3/µm2/y (8.2-53.2) in diabetic patients than in non-diabetics - 28.63 µm3/µm2/y (3.5-89.77) (p=0.80). PTH levels also tended to be lower in diabetics – 384.8 pg/mL compared to non-diabetics – 514.1 pg/mL (p=0.14). BV tended to be lower in patients with VC – 19.1% (10.1-27) compared with patients without VC - 22.6% (12.7-41.4) (p=0.23). VC was detected on x-ray in all 6 patients with diabetes and only in 11.5% (3 in 26) of non-diabetic patients. Conclusion Similar to previous reports, the most frequent ROD pattern was ABD. However, PD patients with ABD had mean PTH of 405 pg/mL, a value well within the recommended KDIGO targets. This reinforces PTH as a far from ideal marker of bone turnover and suggests different targets for PTH levels in this seemingly highly susceptible population to ABD even when treated with low calcium dialysate. The proportion of patients with normal bone was higher than previously published. This finding can be explained by differences in the classification of ROD and prescription of biocompatible PD solutions in all patients. Diabetic patients tended to have lower BV and BFR. This finding is not surprising considering osteoblastic toxicity caused by advanced glycation end products. Also diabetic patients have a state of relative hypoparathyroidism. In conclusion, the most frequent pattern was ABD. Diabetic patients on PD may be a different subgroup.

P0160HOW TO MANAGE INTRADIALYTIC HYPERTENSION?

Abstract Background and Aims Hypertension in subjects on long term dialysis is frequent. Intradialytic hypertension affects up to 20% of hemodialysis patients and occurs more frequently in patients who are older, have lower dry weights, are prescribed more antihypertensive medications. Elevated BP detected by home or ambulatory BP monitoring is clearly associated with shorter survival. Method We realized a cross sectional study in two hemodialysis center patients during october 2019. We compared two groups of patients: group 1 with HTA (HTA+) and the second without (HTA-). Prevalence of hypertension intra dialysis (increase in systolic BP > 15mmHg during dialysis) was determined by blood pressure recordings every thirty minutes during hemodialysis. We collect information about prescription patients (bolus dose of IV nicardipine or administration of captopril orally) after HTA inicident. We collected and analyzed datas of 1476 hemodialysis sessions for 123 patients. Results The mean age of your patients was 46 ± 26,3 years with a female predominance. The mean duration of hemodialysis was 9,8 years. The initial nephropathy was hypertensive in 14,6%. 44,7% (n=55) patients used at least one antihypertensive treatment (HTA+ group), in 72,7% calcic inhibitor. Hypertension crisis in HTA+ group was higher than HTA- group, respectively 37,9% and 4,7% (p=0,0002). Concerning HTA+ group, in 9,35% of cases patients receveid IV bolus of nicardipine, 7,9% captopril and 17,9% of cases have not receveid any antihypertensive medication. In HTA- group they receveid IV nicardipine on only 2,5% cases and no drugs in half of all cases. Patients who were older and receive erythropoietin-stimulating agents were more likely to exhibit an increase in SPB despite similar amounts of ultrafiltration in each groups. It appears HTA- group had better control of hypertension crisis in 77,5% versus 65,5% in HTA+ group, at 20minutes of crisis (p= 0,004). Administration of captopril in the both group allowed better control of hypertension 90% (HTA+ group) and 84,2%(HTA- group). Hypertension crisis was more controlled in group with high ultrafiltration rate with administration of captopril . Conclusion Use of ACE inhibitors during dialysis to manage hypertension crisis appears a great solution and confirm hypothesis of activation of the renin–angiotensin–aldosterone system. Treatment of intradialytic hypertension may include careful attention to dry weight, avoidance of dialyzable antihypertensive medications, limiting the use of high calcium dialysate, achieving adequate sodium solute removal during hemodialysis, and using medications which inhibit the rennin-angiotensin-aldosterone system or which lower endothelin 1.

Pattern of Laboratory Parameters and Management of Secondary Hyperparathyroidism in Countries of Europe, Asia, the Middle East, and North America.

IntroductionThis analysis explored laboratory mineral and bone disorder parameters and management of secondary hyperparathyroidism in patients undergoing hemodialysis in Belgium, Canada, China, France, Germany, Italy, Japan, Russia, Saudi Arabia, Spain, Sweden, the UK, and the USA.MethodsAnalyses used demographic, medication, and laboratory data collected in the prospective Dialysis Outcomes and Practice Patterns Study (2012–2015). The analysis included 20,612 patients in 543 facilities. Descriptive data are presented as regional mean (standard deviation), median (interquartile range), or prevalence, weighted for facility sampling fraction. No testing of statistical hypotheses was conducted.ResultsThe frequency of serum intact parathyroid hormone levels > 600 pg/mL was lowest in Japan (1%) and highest in Russia (30%) and Saudi Arabia (27%). The frequency of serum phosphorus levels > 7.0 mg/dL was lowest in France (4%), the UK (6%), and Spain (6%), and highest in China (27%). The frequency of serum calcium levels > 10.0 mg/dL was highest in the UK (14%) and China (13%) versus 2% to 9% elsewhere. Dialysate calcium concentrations of 2.5 mEq/mL were common in the USA (78%) and Canada (71%); concentrations of 3.0–3.5 mEq/L were almost universal at facilities in Italy, France, and Saudi Arabia (each ≥ 99%).ConclusionsWide international variation in mineral and bone disorder laboratory parameters and management practices related to secondary hyperparathyroidism suggests opportunities for optimizing care.

<p>Efficacy and Safety of Evocalcet Evaluated by Dialysate Calcium Concentration in Patients with Secondary Hyperparathyroidism Undergoing Hemodialysis</p>

PurposeEvocalcet is a novel oral calcimimetic drug that has demonstrated similar efficacy to cinacalcet in regulating serum parathyroid hormone (PTH), calcium, and phosphate levels, with fewer upper gastrointestinal tract-related adverse drug reactions (ADRs) in patients with secondary hyperparathyroidism undergoing hemodialysis in Japan. We investigated the efficacy and safety of once-daily oral evocalcet under different dialysate calcium concentrations.Patients and MethodsA post hoc analysis by dialysate calcium concentration (2.5, 2.75, and 3.0 mEq/L) was performed using data from a previous Phase 3 study that included cinacalcet as an active control. Efficacy endpoints were the proportion of patients who achieved the target intact PTH levels of ≥60 and ≤240 pg/mL between Week 28 and Week 30; time-course changes in serum intact PTH; calcium and phosphorus levels, bone turnover markers, and fibroblast growth factor 23 (FGF23) over the 30-week study period. Safety endpoints were overall ADRs and hypocalcemia- and upper gastrointestinal tract-related ADRs.ResultsA total of 634 patients were included in the analysis. Levels of intact PTH, calcium, phosphate, bone turnover markers, and FGF23 showed improvement in all sub-groups, irrespective of dialysate calcium concentration. The incidence of upper gastrointestinal tract-related ADRs was significantly lower in the evocalcet group than the cinacalcet group with dialysate calcium concentrations of 2.75 and 3.0 mEq/L (p<0.05 for both concentrations).ConclusionEvocalcet was effective and safe in regulating the levels of serum intact PTH, calcium, and phosphate in patients with secondary hyperparathyroidism undergoing hemodialysis, irrespective of dialysate calcium concentration.

Heart failure management in dialysis patients: Many treatment options with no clear evidence.

Heart failure with reduced ejection fraction (HFrEF) impacts approximately 20% of dialysis patients and is associated with high mortality rates. Key issues discussed in this review of HFrEF management in dialysis include dialysis modality choice, vascular access, dialysate composition, pharmacological therapies, and strategies to reduce sudden cardiac death, including the use of cardiac devices. Peritoneal dialysis and more frequent or longer duration of hemodialysis may be better tolerated due to slower ultrafiltration rates, leading to less intradialytic hypotension and better volume control; dialysate cooling and higher dialysate calcium may also have benefits. While high-quality evidence exists for many drug classes in the non-dialysis population, dialysis patients were excluded from major trials, and only limited data exist for many medications in kidney failure patients. Despite limited evidence, beta blocker and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use is common in dialysis. Similarly, devices such as implantable cardiac defibrillators (ICDs) and cardiac resynchronization therapy that have proven benefits in non-dialysis HFrEF patients have not consistently been beneficial in the limited dialysis studies. The use of leadless pacemakers and subcutaneous ICDs can mitigate future hemodialysis access limitations. Additional research is critical to address knowledge gaps in treating maintenance dialysis patients with HFrEF.

Effects of the dialysate calcium concentrations and mineral bone disease treatments on mortality in The French Renal Epidemiology and Information Network (REIN) registry

Effects of the dialysate calcium concentrations and mineral bone disease treatments on mortality in The French Renal Epidemiology and Information Network (REIN) registry

Dialysis-specific factors and incident atrial fibrillation in hemodialysis patients

Background Atrial fibrillation (AF) is common in end-stage renal disease patients. Besides the traditional risk factors, we aimed to find dialysis-specific factors for developing incident AF. Methods From March 2017 to August 2018, we retrospectively reviewed all outpatient-based prevalent hemodialysis patients in our artificial kidney room, and they were followed up until August 2019. Dialysate calcium concentration (3 versus 2.5 mEq/L), time length (4 versus 3.5 h), frequency (thrice weekly versus twice weekly), dialyzer size (effective surface area of 1.4 m2 versus 1.8 m2), membrane permeability (high flux versus low flux), ultrafiltration rate (mL/kg/hour), and blood flow rate (mL/min) were evaluated. Results Among a total of 84 patients, 15 (17.9%) had newly detected AF with a follow-up period of 21 (13.3–24) months. By performing multivariate Cox regression analysis, blood flow rate (mL/min) and ultrafiltration rate (mL/kg/h) were considered significant factors for developing incident AF (adjusted hazard ratio [HR], 0.977; p = 0.011 and adjusted HR, 1.176; p = 0.013, respectively), while dialysis bath, time length, and frequency, dialyzer size, and membrane type were not considered significant factors. Ultrafiltration cutoff rate of 8.6 mL/kg/h was the best predictive factor for incident AF (area under the curve-receiver operating characteristic [AUC-ROC], 0.746; p < 0.005), while blood flow rate was not considered a significant factor for incident AF in ROC analysis (AUC-ROC, 0.623; p = 0.126). Ultrafiltration rate was largely dependent on interdialytic weight gain (p < 0.005, linear-by-linear association). Conclusion Higher ultrafiltration rate was associated with incident AF in hemodialysis patients.

Citric-acid dialysate improves the calcification propensity of hemodialysis patients: A multicenter prospective randomized cross-over trial.

IntroductionThe concentration of dialysate calcium (dCa) has been suggested to affect vascular calcification, but evidence is scarce. Calcification propensity reflects the intrinsic capacity of serum to prevent calcium and phosphate to precipitate.The use of citric-acid dialysate may have a beneficial effect on the calcification propensity due to the chelating effect on calcium and magnesium. The aim of this study was to compare the intradialytic and short-term effects of haemodialysis with either standard acetic-acid dialysate with dCa1.50 (A1.5) or dCa1.25 (A1.25), as well as citric-acid dialysate with dCa1.50 (C1.5) in bicarbonate dialysis on the calcification propensity of serum.MethodsChronic stable hemodialysis patients were included. This multicenter randomized cross-over study consisted out of a baseline week (A1.5), followed by the randomized sequence of A1.25 or C1.5 for one week after which the alternate treatment was provided after a washout week with A1.5. Calcification propensity of serum was assessed by time-resolved nephelometry where the T50 reflects the transition time between formation of primary and secondary calciprotein particles.ResultsEighteen patients (median age 70 years) completed the study. Intradialytic change in T50 was increased with C1.5 (121 [90–152]min) compared to A1.25 (83 [43–108]min, p<0.001) and A1.5 (66 [18–102]min, p<0.001). During the treatment week, predialysis T50 increased significantly from the first to the third session with C1.5 (271 [234–291] to 280 [262–339]min, p = 0.002) and with A1.25 (274 [213–308] to 307 [256–337]min, p<0.001), but not with A1.5 (284 [235–346] to 300 [247–335]min, p = 0.33).ConclusionCalcification propensity, as measured by the change in T50, improved significantly during treatment in C1.5 compared to A1.25 and A1.5. Long-term studies are needed to investigate the effects of different dialysate compositions concentrations on vascular calcification and bone mineral disorders.

A hemodialysis patient with bone disease after pregnancy: a case report

BackgroundPregnancy is rare in women on hemodialysis. Recommendations for the treatment of secondary hyperparathyroidism (sHPT) and preservation of bone health in pregnant dialysis patients are lacking.Case presentationWe present the case of a young woman with end-stage kidney disease (ESKD) due to lupus nephritis, who developed multiple brown tumors while on hemodialysis during her second pregnancy. During her first pregnancy sHPT was well controlled and no skeletal complications occurred. Before the second pregnancy she developed severe sHPT. During pregnancy, dialysis time was increased to 24 h per week, the patient was given oral calcitriol, and the dialysate calcium concentration was set at 1.5 mmol/l. In week 20 the patient complained about bone pain in her left hip. Magnetic resonance imaging revealed a cystic lesion compatible with a brown tumor. The baby was delivered in the 36th week by cesarean section. Further assessment identified multiple brown tumors of her skeleton, including the acetabulum, tibia, ribs, skull, thoracic spine and thumb. She required multiple orthopedic surgeries. Three months after pregnancy, etelcalcetide was started, which brought about a gradual improvement in her sHPT.ConclusionsThis case demonstrates that the combination of pregnancy and severe sHPT in dialysis patients can have deleterious consequences for bone health.

Short- and Long-term Effects of Dialysate Calcium Concentrations on Mineral and Bone Metabolism in Hemodialysis Patients: The K4 Study

Rationale & ObjectiveThe short- and long-term impact of conversion of dialysate calcium concentration from either 2.5 or 3.0 mEq/L to 2.75 mEq/L on mineral and bone metabolism remains unknown in hemodialysis patients.Study DesignNonrandomized intervention study.Setting & Population12 hemodialysis patients treated at baseline with a 2.5-mEq/L dialysate calcium concentration and another 12 hemodialysis patients treated with a 3.0-mEq/L dialysate calcium concentration.InterventionUse of 2.75-mEq/L dialysate calcium concentration.OutcomesChanges in intradialytic calcium and phosphate clearance and changes in predialysis and intradialytic serum and ionized mineral and biochemical parameters over the 24 weeks following dialysate calcium conversion.ResultsConversion of dialysate calcium concentration from 2.5 to 2.75 mEq/L increased intradialytic calcium loading and serum total and ionized calcium levels, whereas conversion of dialysate calcium from 3.0 to 2.75 mEq/L decreased intradialytic calcium loading and serum total and ionized calcium levels. Dialysate calcium concentration conversion did not affect intradialytic serum parathyroid hormone level, intradialytic phosphate elimination, or predialysis serum calcium, phosphate, parathyroid hormone, and fibroblast growth factor 23 levels. Intradialytic calcium influx was determined by dialysate calcium concentration and predialysis serum calcium levels, whereas intradialytic phosphate elimination was determined by predialysis serum phosphate levels.LimitationsSmall sample size and no control groups treated with 2.5- and 3.0-mEq/L dialysate calcium concentrations during the 24 weeks of the observation period.ConclusionsConversion of dialysate calcium concentration from either 3.0 or 2.5 to 2.75 mEq/L results in expected changes in calcium loading based on predialysis calcium concentration. The dialysate calcium concentration should be personalized based on clinical factors.FundingNone.Trial RegistrationUniversity Hospital Medical Information Network, www.umin.ac.jp/english/, R000040105, UMIN000035184.

Effect of extended hours dialysis on markers of chronic kidney disease-mineral and bone disorder in the ACTIVE Dialysis study

BackgroundChronic 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.MethodsThe 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.ResultsPhosphate 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.ConclusionExtended 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 registrationClinicaltrials.gov NCT00649298. Registered 1 April 2008.

MON-111 Effect of the dialysate calcium concentration and of the mineral bone disease therapies on mortality in the REIN registry

The different chemical elements of the dialysate could influence survival and calcium especially modifies the mineral and bone metabolism and the vascular calcification rate. Having garnered both the dialysate calcium concentration and the mineral bone disease (MBD) therapies, we studied the influence of these prescriptions on survival. Data from the national Renal Epidemiology Information Network registry were extracted for all the subjects having started hemodialysis from 2010 to 2013. Their exposure to the different dialysate calcium concentrations was established by center and classified by tertiles of the percentage of use of calcium <1.5mmol/l and >1.5mmol/L., updated yearly. Drug therapies involved in the MBD metabolism were extracted at the patient level from the SNIIRAM (Service National d'Information Inter régime de l'Assurance Maladie) and converted in a daily dose updated monthly. Cox survival analysis was performed on 25,629 incident patients being alive after 3 months of dialysis, adjusted for 14 baseline co-morbidities, biological data, 4 technical data and the acid of the dialysate and accounting for patient clustering within facilities. Dialysate exposure and MBD therapies were analyzed as time-dependent variables. Analysis was censored at Dec 31, 2014, or at kidney transplantation, loss to follow-up, dialysis weaning and transfer to peritoneal dialysis or home hemodialysis. The 1.5 mmol/L dialysate calcium concentration was the main dialysate in 81% of the dialysis centers in 2010 to 83% in 2014 followed by the >1.5mmol/L used as the main dialysate in 19% of the centers in 2010 to 14% in 2014. Most centers were using several formulas in up to 78% for 3 formulas in 2010 to 86% in 2014. The dialysate calcium <1.5mmol/L was scarcely used at a median level of 2.5% by center in 2010 to 4.4% in 2014. In full adjusted Cox survival analyses, all-cause mortality HRs of dialysate calcium >1.5 mmol/L and <1.5mmol/l by tertile of use by center were not associated with survival. The number of formula used by center was also not significantly associated with survival. Sole the cardiovascular mortality HR of the use of dialysate calcium >1.5mmol/L in all tertiles was significantly lowered to about 0.75 [0.57;0.91] compared to no use. The MBD therapies were broadly associated with survival improvement for calcium, native vitamine D, active vitamine D, sevelamer, lanthanum and cinacalcet and depending of the daily dose used. No influence of the dialysate calcium concentration was evidenced on survival whereas all MBD therapies were associated with a survival improvement depending on the daily dose used. More information towards HD subjects is needed.

MON-110 Effect of the acid of dialysate on survival in the French REIN registry

We previously found a reduced mortality associated with the use of acetate free dialysate (AFD) in subjects older than 70 years old. As the use of these dialysates made with hydrochloric (HCl) or citric acid steadily increases since 2010, we wonder whether this result can be reproduced in the last recent years. All patients who started HD from 2010 to 2013 were classified according to their exposure to the different types of dialysate in their dialysis unit. Cox survival analysis was performed in 25,629 incident patients being alive after 3 months of dialysis, adjusted for 14 baseline co-morbidities, biological data and 4 technical data and accounting for patient clustering within facilities. Dialysate exposure was analyzed as a time-dependent variable taking into account the changes of dialysate in the dialysis unit and the changes of dialysis center of each patient. Analysis was censored at Dec 31, 2014, or at kidney transplantation, loss to follow-up, dialysis weaning and transfer to peritoneal dialysis or home hemodialysis. Among the 25 629 included subjects, 17 747 started dialysis in centers using standard dialysate, 7358 in centers using both standard and AFD and 524 in centers using only AFD. The percentage of dialysis centers using exclusively standard dialysate dwindled from 74% in 2010 to 25% in 2014. Overall mortality HR of being dialyzed in a unit using both acetate and HCl was estimated to 0.86 [0.76 - 0.98] compared to the standard centers. On the contrary, during exposition in a mixed unit using both acetate and citrate, the all-cause mortality risk was multiply by 1.44 [1.33 -1.55]. The calcium dialysate load also varies between the different dialysates, citrate dialysate bringing calcium similarly to an acetate dialysate having a 0.15 mmol/L higher calcium concentration. We additionally adjusted the all-cause mortality Cox models for the calcium dialysate concentration after reclassifying calcium concentration of citrate dialysate and found similar results. Using an entirely new data set of subjects exposed to AFD in the REIN registry, we confirm that being dialyzed with HCl dialysate is associated with a reduced mortality risk but being dialyzed with citrate dialysate seemed deleterious. The difference in calcium load between citrate and acetate dialysate didn't explain this result.

Long-term effects on PTH and mineral metabolism of 1.25 versus 1.75\u2009mmol/L dialysate calcium in peritoneal dialysis patients: a meta-analysis

BackgroundThis study aimed to compare 1.25 and 1.75 mmol/L dialysate calcium for their effects on parathyroid hormone (PTH) and mineral metabolism in peritoneal dialysis (PD).MethodsThe PubMed, Cochrane Library, and EmBase databases were searched from inception to October 2016. Methodological quality assessment of the included studies was performed using the risk of bias tool of the Review Manager software. The meta-analysis was carried out with the Stata12.0 software. Subgroup analysis was performed by study design [randomized controlled trial (RCT) and non-RCT]. Odds ratios or standardized mean differences were used to assess the outcome measures, including intact parathyroid hormone (i-PTH) levels, serum total calcium amounts, ionized calcium levels, phosphate concentrations, and peritonitis episodes.ResultsSeven studies were enrolled in the synthesized analysis, including 4 RCTs and 3 non-RCTs. All studies compared 1.25 mmol/L and 1.75 mmol/L dialysate calcium for PD. Pooled analysis revealed that 1.75 mmol/L dialysate calcium significantly reduced i-PTH levels compared with the 1.25 mmol/L dose in PD patients. However, 1.25 mmol/L dialysate calcium was superior to the 1.75 mmol/L dose in decreasing the levels of serum total calcium and ionized calcium in PD patients. No significant differences in phosphate amounts and peritonitis episodes were observed between the two groups.ConclusionThese findings indicated that 1.75 mmol/L dialysate calcium is more appropriate for PD patients with secondary hyperparathyroidism. Meanwhile, 1.25 mmol/L dialysate calcium is more favorable to PD patients with secondary hypercalcemia. However, further well-designed and high-quality studies are required to validate these findings.

FP709Impact of pre- and post-dialysis serum calcium fluctuations and dialysate calcium levels on all-cause mortality in Japanese haemodialysis patients: The Miyazaki Dialysis Cohort study

FP709Impact of pre- and post-dialysis serum calcium fluctuations and dialysate calcium levels on all-cause mortality in Japanese haemodialysis patients: The Miyazaki Dialysis Cohort study

A Systematic Review and Meta-analysis of Nonpharmacologic-based Interventions for Aortic Stiffness in End-Stage Renal Disease

IntroductionIncreased carotid-femoral pulse wave velocity (cf-PWV) in end-stage renal disease (ESRD) indicates enhanced aortic stiffness and mortality risk. We conducted a systematic review and meta-analysis of nonpharmacologic interventions in adults with ESRD to determine their effects on cf-PWV, systolic blood pressure (SBP), and intervention-associated adverse events.MethodsMEDLINE, EMBASE, and EBM databases were searched. Study screening, selection, data collection, and methodological quality assessments were performed by 2 independent reviewers. Pooled-effect estimates from mean differences and 95% confidence intervals (CIs) were calculated using random effect models.ResultsA total of 2166 subjects with ESRD from 33 studies (17 randomized; 16 nonrandomized) were included. Four intervention-comparator pairs were meta-analyzed. Quality of evidence ranged from very low to moderate. Kidney transplantation decreased cf-PWV (−0.70 m/s; CI: –1.3 to −0.11; P = 0.02) and SBP (−8.3 mm Hg; CI: −13.2 to −3.3; P < 0.001) over pretransplantation. In randomized trials, control of fluid overload by bio-impedance reduced cf-PWV (−1.90 m/s; CI: −3.3 to −0.5); P = 0.02) and SBP (−4.3 mm Hg; CI: −7.7 to −0.93); P = 0.01) compared with clinical assessment alone. Cross-sectional studies also demonstrated significantly lower cf-PWV and SBP in normovolemia compared with hypervolemia (P ≤ 0.01). Low calcium dialysate decreased cf-PWV (−1.70 m/s; CI: −2.4 to −1.0; P < 0.00001) without affecting SBP (−1.6 mm Hg; CI: −8.9 to 5.8; P = 0.61). Intradialytic exercise compared with no exercise reduced cf-PWV (−1.13 m/s; CI: −2.2 to −0.03; P = 0.04), but not SBP (+0.5 mm Hg; CI: −9.5 to 10.4); P = 0.93).ConclusionsSeveral nonpharmacologic interventions effectively decrease aortic stiffness in ESRD. The impact of these interventions on cardiovascular outcomes and mortality risk reduction in ESRD requires further study.

Effects of etelcalcetide on fibroblast growth factor 23 in patients with secondary hyperparathyroidism receiving hemodialysis.

BackgroundEtelcalcetide is an intravenous calcimimetic approved for treatment of secondary hyperparathyroidism (sHPT) in patients receiving hemodialysis. Besides lowering parathyroid hormone (PTH), etelcalcetide also significantly reduces fibroblast growth factor 23 (FGF23), but the mechanisms are unknown.MethodsTo investigate potential mediators of etelcalcetide-induced FGF23 reduction, we performed secondary analyses of the 26-week randomized trials that compared the effects on PTH of etelcalcetide (n = 509) versus placebo (n = 514) and etelcalcetide (n = 340) versus cinacalcet (n = 343) in adults with sHPT receiving hemodialysis. We analyzed changes in FGF23 in relation to changes in PTH, calcium, phosphate and bone turnover markers. We also investigated how concomitant treatments aimed at mitigating hypocalcemia altered the FGF23-lowering effects of etelcalcetide.ResultsEtelcalcetide reduced FGF23 [median % change (quartile 1–quartile 3)] from baseline to the end of the trial significantly more than placebo [–56% (–85 to –7) versus +2% (–40 to +65); P < 0.001] and cinacalcet [–68% (–87 to –26) versus –41% (–76 to +25); P < 0.001]. Reductions in FGF23 correlated strongly with reductions in calcium and phosphate, but not with PTH; correlations with bone turnover markers were inconsistent and of borderline significance. Increases in concomitant vitamin D administration partially attenuated the FGF23-lowering effect of etelcalcetide, but increased dialysate calcium concentration versus no increase and increased dose of calcium supplementation versus no increase did not attenuate the FGF23-lowering effects of etelcalcetide.ConclusionThese data suggest that etelcalcetide potently lowers FGF23 in patients with sHPT receiving hemodialysis and that the effect remains detectable among patients who receive concomitant treatments aimed at mitigating treatment-associated decreases in serum calcium.

Cholecalciferol supplementation increases FGF23 in peritoneal dialysis patients with hypovitaminosis D: a randomized clinical trial.

Vitamin D deficiency is common in peritoneal dialysis (PD) patients, so its supplementation has been advocated as potentially beneficial. Double-blind, placebo-controlled, randomized clinical trial. Subjects on PD treated with high calcium peritoneal dialysate (Ca 3.5mEq/l) and serum levels of 25-hydroxi vitamin D (25D) < 20ng/ml were randomized to receive cholecalciferol (4800IU/daily) or placebo for 16 weeks. The outcome measures were the effects on the osteogenic biomarkers osteoprotegerin (primary endpoint), intact fibroblast growth factor-23 (iFGF23), osteocalcin, osteopontin, iPTH, 1,25-dyhydroxivitamin D (1,25D), and interleukin-6. Fifty-eight subjects were randomly assigned. Baseline characteristics were similar in both groups. Cholecalciferol supplemented subjects had a significant increase in serum 25D (from 11.4 ± 5.0 to 28.3 ± 10.3ng/ml), 1,25D and iFGF23 compared with placebo group. iFGF23 levels increased an average of 10,875pg/ml per month (95% CI 11,778-88,414) in the cholecalciferol group and was unchanged in the placebo group (2829pg/ml, 95% CI - 2181 to 14,972). Extremely high iFGF23 levels (> 30,000pg/ml) were observed in 74% of subjects receiving cholecalciferol although iFGF23 returned to baseline values after 32 weeks of withdrawal. The observed changes in iFGF23 correlated with 1,25D levels and were not modified by other variables. No difference was observed between groups in osteoprotegerin or other osteogenic biomarkers levels. Cholecalciferol supplementation increases serum 25D levels in subjects on PD exposed to high calcium dialysate, yet it induces an exponential increase of iFGF23 in most patients, which disappear after withdrawal of supplementation and may be a major concern for this maneuver.

Relationship between dialytic parameters and reviewer confirmed arrhythmias in hemodialysis patients in the monitoring in dialysis study

BackgroundHemodialysis patients have high rates of sudden death, but relationships between serum electrolytes, the dialysis prescription, and intra-dialytic shifts in fluid and electrolyte with arrhythmia are uncertain.MethodsWe analyzed sixty-six hemodialysis patients who underwent loop recorder implantation with continuous electrocardiographic monitoring, weekly to bi-weekly testing of pre- and post-dialysis electrolytes, and detailed capture of dialysis prescription and flow sheet data for 6 months. The incidence rate ratio (IRR) of reviewer confirmed arrhythmias (RCA) during dialysis through 8 h after dialysis and associations with serum chemistries and dialytic parameters were assessed using adjusted, negative-binomial regression.ResultsAmong 66 individuals with a mean age of 56 years, 12,480 events were detected in 64 (97%) patients. RCA nadired 12–24 h after dialysis and increased during the final 12 h of the inter-dialytic interval through the first 8 h after dialysis. Higher pre-dialysis serum magnesium concentration was associated with lower incidence rate ratio for arrythmia (IRR per 1 mg/dL increase 0.49, 95% CI; 0.25, 0.94), as was dialysate calcium concentration > 2.5 mEq/L vs. 2.5 mEq/L (IRR 0.52, 95% CI: 0.39, 0.70). Neither intradialytic serum potassium nor weight change were significantly associated with RCA rate. However, there was effect modification such that arrhythmia rate was maximal with concurrently high intradialytic volume and potassium removal (Pinteraction = 0.01).ConclusionsIntra and post-dialytic arrhythmias are common in hemodialysis. Additional studies designed to further elucidate whether modification of the serum magnesium concentration, dialysate calcium concentration, and the extent of intradialytic potassium and fluid removal reduces the risk of per-dialytic arrhythmia are warranted.Trial registrationClinicaltrials.gov NCT01779856. Prospectively registered on January 22, 2013.

High Dialysate Calcium Concentration is Associated with Worsening Left Ventricular Function

Dialysate calcium concentration (d[Ca]) might have a cardiovascular impact in patients on haemodialysis (HD) since a higher d[Ca] determines better hemodynamic tolerability. We have assessed the influence of d[Ca] on global longitudinal strain (GLS) by two-dimensional echocardiography using speckle-tracking imaging before and in the last hour of HD. This is an observational crossover study using d[Ca] 1.75 mmol/L and 1.25 mmol/L. Ultrafiltration was the same between interventions; patients aged 44 ± 13 years (N = 19). The 1.75 mmol/L d[Ca] was associated with lighter drop of blood pressure. Post HD serum total calcium was higher with d[Ca] 1.75 than with 1.25 mmol/L (11.5 ± 0.8 vs. 9.1 ± 0.5 mg/dL, respectively, p < 0.01). In almost all segments strain values were significantly worse in the peak HD with 1.75 mmol/L d[Ca] than with 1.25 mmol/L d[Ca]. GLS decreased from −19.8 ± 3.7% at baseline to −17.3 ± 2.9% and −16.1 ± 2.6% with 1.25 d[Ca] and 1.75 d[Ca] mmol/L, respectively (p < 0.05 for both d[Ca] vs. baseline and 1.25 d[Ca] vs. 1.75 d[Ca] mmol/L). Factors associated with a worse GLS included transferrin, C-reactive protein, weight lost, and post dialysis serum total calcium. We concluded that d[Ca] of 1.75 mmol/L was associated with higher post dialysis serum calcium, which contributed to a worse ventricular performance. Whether this finding would lead to myocardial stunning needs further investigation.