Dialysate Calcium Concentration Research Articles

<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.

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.

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

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.

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.

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.

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.

New peritoneal dialysates, for which benefits ?

The ideal peritoneal dialysis solution should allow efficient withdrawal of waste products of the metabolism and water and solutes equilibrium with minimal side effects for the patient and the peritoneal membrane. Glucose degradation products (GDP) resulting from the manufacturing process play a major toxic role and new biocompatible PD solutions with low GDP content and a more physiological bicarbonate or bicarbonate/lactate buffer have brought a clear benefit in experimental studies; however, in clinical cohorts and meta-analysis, the benefits of these solutions appear limited to better preservation of residual renal function and of diuresis. Glucose is the principal osmotic agent although hypertonic glucose solutions have a deleterious effect on PD, and their use should be restrained. Dialysate concentrations of sodium, calcium and magnesium are close to plasma; their diffusive transport is thus limited and their net peritoneal transport mainly depends on the ultrafiltration volume. A dialysate calcium concentration above 1.25 mmol/l generates a calcium load which may contribute to the high prevalence of adynamic bone disease in PD patients; this should be avoided. Low sodium dialysis solutions experimentally improve sodium diffusive transport and extraction in PD patients; the clinical benefit of this approach has to be confirmed.

Dialysate Calcium Concentration below 3.0 mEq/L Is Not Associated with Improved Outcomes in the Japanese Dialysis Outcomes and Practice Patterns Study

Background: Abnormal chronic kidney disease-mineral and bone disorder (CKD-MBD) markers have been associated with adverse outcomes in hemodialysis (HD) patients. Dialysate calcium concentration (D-Ca) likely influences serum calcium and phosphorus levels. Optimal D-Ca level remains unclear. We hypothesized that higher D-Ca is associated with cardiovascular events and mortality among Japanese HD patients. Methods: Enrollment data of chronic HD patients in the prospective observational study JDOPPS, phases 1–5 (1999–2015), provided exposures and covariates. All-cause mortality, non-arrhythmic cardiovascular events (NonAR-CVE), or their composites were analyzed by D-Ca, and divided into 2.5, 2.75, and 3.0 mEq/L. To minimize confounding by indication, analyses were restricted to facilities in which at least 90% of patients received the same D-Ca prescription. Association of D-Ca level with outcomes was evaluated in Cox models stratified by phase and accounting for facility clustering. Covariates describing patient demographics, comorbidities, laboratory values, CKD-MBD therapy, and facility attributes provided adjustment. Results: Of 9,201 patients included, 25.0% had D-Ca of 2.5 mEq/L; 6.8% D-Ca 2.75; and 68.2% D-Ca 3.0. Median follow-up time was 2.03 years. D-Ca was not associated with all-cause mortality, with hazards ratios for 2.5 vs. 3.0 mEq/L of 0.90 and 95% CI (0.73–1.11), nor with other outcomes. One effect modification occurred, protective for lower D-Ca on NonAR-CVE in the absence of cardiovascular comorbidities (p = 0.032), although corresponding D-Ca effects were not significant after multiple comparisons adjustment (p = 0.261 [D-Ca 2.5] and 0.125 [D-Ca 2.75]). Conclusion: Lowering D-Ca level below 3.0 mEq/L seems not to have a meaningful effect on patient outcomes.

Higher dialysate calcium concentration is associated with incident myocardial infarction among diabetic patients with low bone turnover: a longitudinal study

This is a longitudinal study on 53,560 hemodialysis patients from the Japan Renal Data Registry. Predictor was D[Ca] ≥3.0 vs 2.5 mEq/L. Outcomes were the first CV events during 1-year observation period. Association of D[Ca] with CV events and effect modifications were tested using multivariate logistic regression analyses. Diabetes mellitus (DM) was a significant effect modifier for association of higher D[Ca] and myocardial infarction (MI) (OR: 1.26 (1.03–1.55) among DM and 0.86 (0.72–1.03) among non-DM, p for interaction <0.01). The effect size was not affected by further adjustment for serum albumin-corrected Ca or intact parathyroid hormone (iPTH) levels, but was attenuated by adjustment for intradialytic change in serum Ca concentration (ΔCa) (1.16 [0.89–1.51]). Among DM, D[Ca] ≥3.0 mEq/L was significantly associated with MI in the first tertile of corrected Ca or iPTH ≤60 pg/ml (p for interaction 0.03 and 0.03, respectively). In conclusion, higher D[Ca] was associated with incident MI in DM, especially with low serum Ca or iPTH levels. Attenuation of the effect size by adjustment for ΔCa and stratified analyses suggest that larger Ca influx during dialysis with higher D[Ca] in patients suggestive of low bone turnover leads to vascular calcification and subsequent MI in DM.

Intradialytic alkalinization is a neglected factor affecting calcium mass balance and parathyroid hormone level during haemodiafiltration.

BackgroundThe diffusion gradient between ionized calcium (iCa) in the inlet dialysate and blood is considered to be the main driving force of calcium mass balance (CMB). The intradialytic change of parathyroid hormone (PTH) level corresponds to the change in plasma iCa. In contrast to the widely discussed calcium concentration of dialysis solution, the dialysate pH and bicarbonate concentration (DHCO3), important factors affecting the level of iCa, have not been studied with respect to the intradialytic change of plasma PTH level (ΔPTH) and CMB.MethodsWe measured ΔPTH and CMB (calcium flux from the dialysate to the patient) in 10 stable patients on haemodiafiltration. All patients underwent two treatments differing in DHCO3 (26 versus 32 mmol/L). The dialysate calcium concentration was 1.25 mmol/L for all treatments.ResultsWe found significant difference in ΔPTH, which decreased with 26_DHCO3 and slightly increased with 32_DHCO3 (−110.5 versus +19.7 pg/mL, P < 0.01). CMB was negative for both DHCO3, but with higher DHCO3 there was a trend to minor intradialytic loss of calcium (−108 versus −309 mg).ConclusionsDHCO3 increase at first glance leads to contrasting phenomena: the intradialytic rise of PTH and calcium gain. Both processes are caused by a pH-dependent decrease of plasma iCa, resulting in parathyroid stimulation and intradialytic increase of iCa diffusion gradient. We found no significant correlation between CMB and intradialytic change of plasma total Ca. With respect to plasma PTH level and CMB, the bicarbonate concentration should always be taken into account when selecting the optimal dialysis solution.

Effects of Lowering Dialysate Calcium Concentration on Bone Metabolic Markers in Hemodialysis Patients With Suppressed Serum Parathyroid Hormone: A Preliminary Study.

Although the Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend a dialysate calcium concentration between 2.5 and 3.0 mEq/L, its optimal concentration remains unclear. A total of 53 hemodialysis patients with intact parathyroid hormone (PTH) levels <150 pg/mL were enrolled in this prospective observational study. A dialysate calcium concentration was converted from 3.0 to 2.75 mEq/L and bone metabolic markers including bone alkaline phosphatase (BAP) and tartrate-resistant acid phosphatase-5b (TRACP-5b) were examined. After 3 months, serum corrected calcium levels decreased (P < 0.001), while serum intact PTH, BAP and TRACP-5b levels increased (P < 0.05, P < 0.05 and P < 0.001, respectively). Multiple regression analyses showed that the amount of change in BAP was significantly associated with dialysis vintage (P < 0.01). In conclusion, the lowering of dialysate calcium concentration stimulated parathyroid gland and bone remodeling in hemodialysis patients with suppressed PTH, particularly with longer dialysis vintage.

Impact of post-dialysis calcium level on ex vivo rat aortic wall calcification.

ObjectivesVascular calcification is a frequent complication in chronic haemodialysis patients and is associated with adverse outcomes. Serum calcium and phosphate levels and imbalances in calcification regulators are thought to contribute to the process. In this regard, the dialysate calcium concentration is a modifiable tool for modulating the risk of vascular calcification. We explored pre- and post-dialysis phosphate and calcium concentrations in stable chronic haemodialysis patients treated by dialysis with the KDIGO-suggested 1.5 mmol/L calcium dialysate to investigate the effects on ex vivo calcification of rat aortic rings.Approach and resultsAt the end of haemodialysis, mean serum calcium levels were increased in 88% of paired pre-/post-dialysis samples, while mean serum phosphate and parathyroid hormone levels were decreased. Rat aortic ring cultures grown at the same calcium and phosphate concentrations revealed that pre- and post-dialysis resulted in a similar degree of calcification. By contrast, haemodialysis with unchanged serum calcium resulted in a 5-fold reduction in calcium deposition.ConclusionDialysis with the widely prescribed 1.5 mmol/L calcium dose results in persistent high serum calcification potential in a sizable proportion of patients, driven by increased post-dialysis calcium concentration. This could potentially be mitigated by individualising dialysate calcium dosage based on pre-dialysis serum calcium levels.

An in silico method to predict net calcium transfer during hemodialysis.

International guidelines for chronic hemodialysis patients suggest a dialysate calcium concentration between 1.25 and 1.5 mmol/L. However, it is not certain if these dialysate calcium levels result in net calcium transfer into the patient. With ubiquitous prevalence of vascular calcification in hemodialysis patients, it is pertinent to model the mass balance of calcium during dialysis. To this end, we developed a two compartmental patient model and spatiotemporal representation of dialyzer model to investigate and quantify the calcium mass balance during dialysis. The model accounts for calcium-albumin binding and varying protein concentration; the latter accounts for the Gibbs-Donnan effect. The model simulations suggest that despite a lower dialysate calcium concentration of 1.25 mmol/L, some of our patients may be loaded with calcium during dialysis. This net calcium flux from dialysate to blood side may be a potential contributor to vascular calcification, a primary cause of cardiovascular mortality in hemodialysis patients.

Assessment of intradialysis calcium mass balance by a single pool variable-volume calcium kinetic model.

A reliable method of intradialysis calcium mass balance quantification is far from been established. We herein investigated the use of a single-pool variable-volume Calcium kinetic model to assess calcium mass balance in chronic and stable dialysis patients. Thirty-four patients on thrice-weekly HD were studied during 240 dialysis sessions. All patients were dialyzed with a nominal total calcium concentration of 1.50 mmol/L. The main assumption of the model is that the calcium distribution volume is equal to the extracellular volume during dialysis. This hypothesis is assumed valid if measured and predicted end dialysis plasma water ionized calcium concentrations are equal. A difference between predicted and measured end-dialysis ionized plasma water calcium concentration is a deviation on our main hypothesis, meaning that a substantial amount of calcium is exchanged between the extracellular volume and a nonmodeled compartment. The difference between predicted and measured values was 0.02 mmol/L (range -0.08:0.16 mmol/L). With a mean ionized dialysate calcium concentration of 1.25 mmol/L, calcium mass balance was on average negative (mean ± SD -0.84 ± 1.33 mmol, range -5.42:2.75). Predialysis ionized plasma water concentration and total ultrafiltrate were the most important predictors of calcium mass balance. A significant mobilization of calcium from the extracellular pool to a nonmodeled pool was calculated in a group of patients. The proposed single pool variable-volume Calcium kinetic model is adequate for prediction and quantification of intradialysis calcium mass balance, it can evaluate the eventual calcium transfer outside the extracellular pool in clinical practice.

Effects of Lowering Dialysate Calcium Concentration on Carotid Intima-Media Thickness and Aortic Stiffness in Patients Undergoing Maintenance Hemodialysis: A Prospective Study

Background and Aim: The study aimed to prospectively evaluate the effects of lowering the dialysate calcium concentration (DCa) to 1.25 mmol/l on Chinese patients undergoing maintenance hemodialysis (MHD), which are largely unknown to date. Methods: A singer-center, prospective, randomized trial was conducted for 2 years. The DCa in one group was decreased from 1.5 to 1.25 mmol/l but there was no change in the other group. The clinical outcomes, biochemical parameters, medicine treatments and markers of vascular change were compared among the 2 groups at different time intervals. Results: At baseline, the groups were similar with respect to serum levels of calcium, phosphorus, intact parathyroid hormone and fibroblast growth factor-23 as well as carotid intima-media thickness (cIMT) and carotid-femoral pulse wave velocity (cf-PWV). It was found that the serum phosphorus concentration in the lower DCa group had decreased markedly at 2-year follow-up (0-month: 7.13 ± 1.56 mg/dl; 24-month: 5.92 ± 1.73 mg/dl; p = 0.005). Serum calcium (p = 0.018), cIMT (p = 0.029) and cf-PWV (p = 0.024) in DCa 1.25 group were significantly lower than those in 1.5 group at the 24-month visit. Kaplan-Meier curve revealed that patients in DCa 1.25 group had a better rate of survival. In the multivariate Cox regression analysis, cIMT (HR 1.010; 95% CI 1.002-1.217; p = 0.015) and cf-PWV (HR 1.265; 95% CI 1.022-1.567; p = 0.031) were potential risk factors for mortality in those patients. Importantly, we showed that the average change in these 2 risk variables were both associated with the average change in levels of serum calcium and phosphorus. Conclusion: Our results indicate that lowering DCa to 1.25 mmol/l may be suitable for the MHD patients in our unit.

Acute calcium kinetics in haemodialysis patients.

To avoid excessive calcium loading in haemodialysis (HD) patients, current guidelines suggest a dialysate calcium concentration (dCa) of 2·5 mEq/L based on relatively stable intradialytic serum calcium levels. However, the latter do not account for possible calcium storage in acutely accessible pools. A rapidly exchangeable calcium pool located at the bone level has been previously proposed to be involved in acute (minute-to-minute) extracellular calcium regulation. To evaluate the contribution of this pool in the maintenance of serum calcium levels, acute calcium buffer capacity was assessed by measuring intradialytic dialysate-sided ionized calcium mass balance (iCaMB ) and change in extracellular fluid calcium mass in chronic HD patients using a dCa of 3·5 (n = 28) and 2·5 (n = 10) mEq/L. Serum osteocalcin, the most abundant noncollagenous bone protein, was measured before the HD session. iCaMB was invariably positive for both 2·5 and 3·5 mEq/L dCa, with a mean of 434 (±125) and 725 (±162) mg/HD, respectively (P < 0·001). Buffered intradialytic calcium load was 410 (±116) and 565 (±130) mg/HD, and acute calcium buffer capacity was 95 (±8)% and 78 (±7)% (mean values at 2·5 and 3·5 mEq/L dCa, respectively) (P < 0·001). Using 3·5 mEq/L dCa, an independent association of acute calcium buffer capacity with undercarboxylated osteocalcin (β = 0·512, P = 0·002) was demonstrated. Our data strongly suggest the existence of a rapidly exchangeable calcium pool that counteracts acute serum calcium deviations in HD patients. This study provides, for the first time, experimental evidence for the involvement of bone in acute extracellular calcium regulation in vivo.