Dialysate Calcium Concentration Research Articles

#1250 Measurement of ionized calcium with a point-of-care ionometer during treatment with etelcalcetide

Abstract Background and Aims Etelcalcetide is an intravenous calcimimetic indicated for the treatment of mineral and bone disorders in hemodialysis patients by lowering parathyroid hormone (PTH), calcium and phosphorus. The assessment of ionized calcium versus total calcium has not yet been studied during treatment with etelcalcetide, and there are no real data on the occurrence of hypocalcemia as measured by ionized calcium in the pre- and post-hemodialysis period during treatment with etelcalcetide. The aim of this study was to describe the time course of ionized and total serum calcium levels during chronic treatment with etelcalcetide and to assess the occurrence of hypocalcemia in patients treated with etelcalcetide by measuring ionized calcium levels. Method This was an observational, non-interventional, prospective, single-arm phase IV study. A total of 20 chronic hemodialysis patients (15 men and 5 women) aged 55.9 ± 18.2 years undergoing dialysis for 5.5 ± 4.3 years in two hemodialysis centers of the University Medical Centre Ljubljana were enrolled in the study between January 2020 and March 2021. All patients received etelcalcetide as a bolus injection into the venous line of the dialysis circuit three times a week, immediately after each hemodialysis session. Ionized calcium levels were determined using a point-of-care ionometer (GEM Premier 3000) before starting treatment with etelcalcetide prior to dialysis, then during treatment in the first week before and after dialysis, then once a week until the maintenance phase was reached and at least once a month thereafter. Hypocalcemia was defined by a pre-dialysis ionized calcium concentration below 0.90 mmol/L. The corrected total calcium values was measured prior to dialysis at least once a month according to routine clinical practice. The data of all these patients were included in the analysis, except for one, who underwent a kidney transplantation after receiving only 4 doses of etelcalcetide. Results We demonstrated that both corrected total calcium and ionized calcium before dialysis decreased over time during treatment with etelcalcetide. Of 240 measurements of ionized calcium with a point-of-care ionometer at the bedside, the concentration of ionized calcium was below 0.90 mmol/L three times in two patients (0.81, 0.84, 0.85). In one patient, we increased a calcium level in the dialysate from 1.50 to 1.75 mmol/L and in the other from 1.25 to 1.50 mmol/L. In addition, we observed 2 further measurements of ionized calcium of 0.90 mmol/L and 18 measurements between 0.91 and 0.96 mmol/L. However, this corresponds to 1.25% of hypocalcemias with ionized calcium below 0.90 mmol/L and 8.3% of those with calcium between 0.90 and 0.96 mmol/L. As calcium concentration in the bath increased, the pre-dialysis calcium concentrations also appeared to increase. At the beginning of the study, the calcium concentration in the dialysate was 1.5 mmol/L in 16 of 20 patients. 2 patients were treated with a calcium concentration in the dialysate of 1.75 mmol/L and 2 others with 1.25 mmol/L. The proportion of patients using higher dialysate calcium concentration was higher at the end of the study, as two patients switched to 1.75 mmol/L, and one from 1.25 to 1.50 mmol/L. This probably indicates a co-intervention triggered by a reduction in serum calcium levels prior to dialysis during treatment with etelcalcetide. Visual comparisons of the time course of ionized and corrected calcium concentrations before dialysis during chronic treatment with etelcalcetide in 19 patients showed a good correlation between point-of-care ionized calcium and routinely measured total calcium. Conclusion A point-of-care ionometer for the determination of ionized calcium at the bedside has the potential to guide etelcalcetide therapy by optimizing serum calcium levels and also to prevent potentially threatening hypocalcemia.

#2524 Impact of sevelamer hydrochloride on fibroblast growth factor-23 levels in patients undergoing hemodialysis

Abstract Background and Aims Serum intact fibroblast growth factor 23 (FGF23) levels are progressively increased in relation to the severity of kidney dysfunction. High serum intact FGF23 concentration is associated with the increased cardiovascular morbidity and mortality in patients with chronic kidney disease (CKD). Clinically, phosphate binders are commonly used to reduce serum intact FGF23 levels in CKD patients by lowering serum phosphate levels. Reduction of high intact FGF23 concentration is a strategy, possibly improving the consequences of CKD. We aimed to Assessing the Impact of Sevelamer Carbonate on Fibroblast Growth Factor-23 Levels. Method This case-control study enrolled 100 pre-existing hemodialysis patients, evenly divided into two groups of 50. Group I received a specific sevelamer hydrochloride (Renagel)® dose (2 tablets every 8 hrs), while Group II served as the control group and did not receive (Renagel)®. All patients received the same modality of dialysis with a consistent dialysate calcium concentration. Additionally, they received comprehensive dietary phosphate counseling as part of the standard dietary education provided to our dialysis patients. The levels of phosphorus, calcium, alkaline phosphatase, and FGF23 were assessed in all individuals at the beginning of the study (baseline) and again following 3 months of sevelamer therapy. Results While baseline FGF-23 levels were not statistically different, a highly significant divergence emerged after 3 months of treatment. The sevelamer group experienced a remarkable 38.4% decrease in FGF-23, compared to a mere 0.5% change in the control group, highlighting the pronounced effect of sevelamer on this key protein. Analysis of PO4 levels revealed a remarkable difference between the groups following treatment. While initial PO4 measurements were statistically comparable, the sevelamer group experienced a significantly larger decrease compared to the control group (p < 0.001). Both baseline and follow-up FGF-23 levels displayed highly statistically significant positive correlations with PO4, PTH, alkaline phosphatase, and hsCRP. Conclusion This study found that non-calcium-based phosphate binders were associated with a substantial reduction in FGF-23 in hemodialysis patients. This finding suggests that utilizing such binders may offer protection against the adverse effects of high FGF-23 levels, which are prevalent in this population.

The impact of low and high dialysate calcium concentrations on cardiovascular disease and death in patients undergoing maintenance hemodialysis: a systematic review and meta-analysis.

The optimal dialysate calcium (Ca) concentration for patients undergoing hemodialysis remains inconclusive, particularly concerning cardiovascular protection. We conducted a systematic review of 19 randomized controlled trials (RCTs) and a meta-analysis of eight RCTs to determine the optimal dialysate Ca concentration for cardiovascular protection. We compared outcomes in patients receiving maintenance hemodialysis treated with either a low-Ca dialysate (LCD) (1.125 or 1.25mmol/L) or a high-Ca dialysate (HCD) (1.5 or 1.75mmol/L). The outcomes were coronary artery calcification score (CACS), all-cause and cardiovascular death, cardiovascular function and structure, and serum biochemical parameters. There was no significant difference between LCD and HCD concerning CACS (standardized mean difference [SMD] = -0.16, 95% confidence interval [CI]: [-0.38, 0.07]), the risk of all-cause death, and cardiovascular death in patients treated with chronic maintenance hemodialysis. Conversely, LCD was associated with a significantly lower intima-media thickness (SMD = -0.49, 95% CI [-0.94, -0.05]) and pulse wave velocity than HCD (SMD = -0.86, 95% CI [-1.21, -0.51]). Furthermore, LCD significantly decreased serum Ca levels (mean difference [MD] = 0.52mg/dL, 95% CI [0.19, 0.85]) and increased serum parathyroid hormone levels (MD = 44.8pg/mL, 95% CI [16.2, 73.3]) compared with HCD. Notably, most RCTs examined in our analysis did not include patients receiving calcimimetics. Our meta-analysis showed no significant differences in cardiovascular calcification and death between LCD and HCD and revealed a paucity of RCTs on dialysate Ca concentrations, including those involving patients on calcimimetics, indicating the urgent need for further studies.

Effect of low-calcium and standard-calcium dialysate on serum calcium, phosphorus and full-segment parathyroid hormone in patients on peritoneal dialysis: A retrospective observational study.

To investigate the effects of low-calcium and standard-calcium dialysate in patients with chronic kidney disease on peritoneal dialysis, and find out which dialysate has less vascular calcification effect. A total of 141 patients who had undergone peritoneal dialysis (PD) for 2 years in the PD centre from January 2012 to December 2017 were included and divided into two groups according to the calcium concentration of the PD fluid used. There were 79 cases in the low-calcium group, with a dialysate calcium concentration of 1.25 mmol/L and 62 cases in the standard-calcium group, with a dialysate calcium concentration of 1.75 mmol/L. The demographic characteristics and clinical information before initiation of PD were collected and compared between the two groups. Information on the serum calcium, phosphorus and PTH, systolic and diastolic blood pressures and the use of antihypertensive and phosphate-lowering drugs in the second year of dialysis was also collected and compared between the two groups. Vascular calcification was assessed in patients on PD treatment. The mean serum calcium concentrations before initiation of PD in the low- and standard-calcium groups were 1.94 ± 0.27 and 1.89 ± 0.28 mmol/L, respectively. The serum calcium concentrations after PD were 2.30 ± 0.21 and 2.41 ± 0.23 mmol/L, respectively. After PD, the serum calcium concentration in both groups was significantly increased (p < 0.05). The serum calcium concentration in the low-calcium group after PD treatment was lower than that in the standard-calcium group, and the difference was statistically significant (p < 0.05). Compared with the standard-calcium group, patients in the low-calcium group had significantly higher parathyroid hormone concentrations (p < 0.05). More types of phosphate-lowering drugs were used (59.49%) in the low-calcium group than that in the standard-calcium group (35.48%; p < 0.05). The number of antihypertensive drug usage were also higher in the low-calcium group, and the difference was statistically significant (p < 0.05). As for the vascular calcification effect, the two groups have shown no statistical difference in abdominal aortic calcification rate, carotid arteriosclerosis rate and aortic arch calcification rate (p < 0.05). We found that low-calcium PD fluid may increase the PTH level and the proportion of CKD patients using antihypertensive drug and phosphorus-lowering drug, but the vascular calcification effect of the low and standard calcium PD fluid needs further exploration. This paper provides new evidence for the choice of dialysate for PD, low-calcium dialysate has no outstanding advantages for long term dialysis.

#4465 NO DIFFERENCES IN ALL-CAUSE OR CARDIOVASCULAR MORTALITY BETWEEN DIALYSATE CALCIUM OF 1.25 AND 1.50 MMOL/L: RESULTS FROM A EUROPEAN HEMODIALYSIS COHORT

Abstract Background and Aims The appropriate prescription of dialysate calcium (DCa) concentration for hemodialysis (HD) patients is debated and guidelines are inconsistent. We investigated the association between DCa and all-cause, cardiovascular mortality and sudden cardiac death (SCD). Moreover, we examined the association between serum dialysate calcium gradient (SCa-DCa) and the study outcomes. Method In this historical cohort study, we included adult incident HD patients registered in the clinical database EuCliD® with dialysis initiation between January 1, 2010, and June 30, 2017 (recruitment period) who survived for at least 6 months after starting dialysis (grace period). We observed patients’ outcomes for up to 2 years after the end of the grace period (Figure 1). We categorized patients into 2 groups according to the prescribed DCa in the last 3 months of the grace period (ascertainment period): 1.25 (DCa 1.25) or 1.50 mmol/l (DCa 1.50). We calculated hazard ratio (HR) with 95% confidence intervals (CI) for all study outcomes with Cox Regression. The fully adjusted model included age, sex, ethnicity, diabetes mellitus, cardiovascular disease, liver disease, cancer, vascular access, treatment time, Kt/V, total ultrafiltered volume per session, serum hemoglobin, serum albumin, calcium containing phosphate binders, active vitamin D, Cinacalcet. We added country indicators as random effects. The SCa-DCa (in mEq/l) was calculated as (albumin-correct serum calcium (in mg⁄dl) × 0.5) – (DCa (in mmol/l) × 2) (1). Results We included 12,897 patients with DCa 1.25 and 26,989 patients with DCa 1.50 from 22 countries. The median age was 65 years and the percentage of men was 61% in both groups. In the unadjusted model, patients treated with DCa 1.50 had higher risk of all-cause mortality compared to those treated with DCa 1.25 (HR 1.07 [95% CI 1.01-1.12]. However, this association was not robust when adjusting for potential confounding (HR 1.04 [95% CI 0.97-1.10]). Similarly, we found no evidence of significant adjusted association between DCa and cardiovascular mortality (HR 1.01 [95% CI 0.92-1.11]). We observed a significant adjusted lower association between DCa 1.50 and SCD (HR 0.78 [95% CI 0.65-0.94]). We found significant associations between larger SCa-DCa gradient and all outcomes: all-cause (HR 1.16 per 1 mEq/L increase [95% CI 1.09-1.24]), cardiovascular mortality (HR 1.23 [95% CI 1.12-1.35]) and SCD (HR 1.69 [95% CI 1.41-2.03]). To explore the contribution of gradient components to patients’ risk, we included both DCa and serum calcium level (SCa) in the models. We observed significant associations with all outcomes and SCa, but not with DCa and the interaction between them. In a subgroup analysis of patients with iPTH levels below 130 pg/ml (n = 7,438), we did not find any significant association between DCa and the outcomes. Conclusion In this observational study, no differences in all-cause or cardiovascular mortality were observed with the prescription of DCa 1.50 as compared to 1.25 after adjustment for confounders, whereas the risk of SCD appeared to be lower in the group of DCa 1.50. The association between the SCa-DCa gradient and outcomes appears to be predominantly related to the effect of SCa.

A feasibility study of avoiding positive calcium balance and parathyroid hormone increase in patients on peritoneal dialysis

BackgroundThe effect of the dialysate calcium concentration (D[Ca]) on mineral and bone metabolism in patients on peritoneal dialysis (PD) is overlooked. D[Ca] of 1.75 mmol/L is still prescribed to many patients on PD around the world. Previous studies on the effects of reducing D[Ca] have been carried out before the incorporation of calcimimetics in clinical practice. We hypothesized that a reduction in D[Ca] is safe and without the risk of a rise in serum parathyroid hormone (PTH). MethodsIn this non-randomized clinical trial, the D[Ca] was reduced from 1.75 mmol/L to 1.25 mmol/L for one year in prevalent patients on PD. Demographic, clinical, and CKD-MBD-related biomarkers were evaluated at baseline, 3, 6, and 12 months of follow-up. Results20 patients completed 1-year follow-up (56 ± 16 years, 50 % male, 25 % diabetic, 55 % with baseline parathyroid hormone – PTH >300 pg/mL). Over time, there was no significant change in calcium, phosphate, total alkaline phosphatase, 25(OH)-vitamin D or PTH, although adjustments in calcitriol and sevelamer prescription were required. After 1 year, absolute and percentual change in PTH levels were 36 (−58, 139) pg/mL, and 20 % (−28, 45) respectively. The proportion of patients with PTH > 300 pg/mL did not change during the follow-up (p = 0.173). ConclusionKnowing the risk of a positive calcium balance in patients on PD, reducing the D[Ca] concentration is a safe and valuable option, although medication adjustments are needed to detain PTH rising.

Dialysate calcium, alfacalcidol, and clinical outcomes: A post-hoc analysis of the J-DAVID trial.

The selection of dialysate calcium concentration (D-Ca) is still controversial among chronic hemodialysis (HD) regimens. We examined the trajectories of CKD MBD parameters among the J-DAVID trial participants to see the effect of D-Ca and alfacalcidol. The trial was an open-label randomized clinical trial including 976 HD patients with intact PTH of 180 pg/mL or lower which compared the users of vitamin D receptor activator (oral alfacalcidol) and non-users over a median of 4 years. The main D-Ca used at baseline were 3.0 mEq/L in 70% and 2.5 mEq/L in 25%, respectively. The primary endpoint was the composite of fatal and non-fatal cardiovascular events and the secondary endpoint was all-cause mortality. Multivariable Cox proportional hazard regression analyses in which D-Ca was included as a possible effect modifier and serum laboratory data as time-varying covariates showed no significant effect modification for composite cardiovascular events or all-cause mortality. This post hoc analysis showed that the effects of alfacalcidol on cardiovascular outcomes were not significantly modified by D-Ca.

MO817: New Scenarios in Use of Calcimimetics: Could Etelcalcetide Improve Anaemia?

Abstract BACKGROUND AND AIMS Alterations of mineral metabolism in patients with chronic renal failure (MBD-CKD) are frequently found and appear in the earliest stages of the disease. If not accurately diagnosed and treated, they could lead to serious clinical complications. With the same safety and better tolerability compared with cinacalcet, etelcalcetide demonstrated greater efficacy in the control of parathyroid hormone (iPTH) with an improvement in patients' compliance. Several reports in the literature document the effect of elevated levels of iPTH on anaemia. In vitro experiments showed that elevated concentrations of PTH (comparable to those found in the blood of uraemic patients with secondary hyperparathyroidism) exert a significant inhibition on erythroid progenitors, decreasing the number of erythropoietin receptors on erythroid progenitors and making these cells insensitive to erythropoietin. High levels of iPTH could have, furthermore, a haemolytic effect on the peripheral RBCs causing disturbed calcium metabolism, increased cytosolic calcium and enhanced osmotic fragility of the cells. Aim of this study was to verify in a dialysis cohort if etelcalcetide could not only improve iPTH levels but also haemoglobin levels with a reduction in weekly doses of erythropoiesis-stimulating agents (ESA). METHOD We analysed data from 130 haemodialysis adult patients over 2 years from three different centres. A total of 24 patients treated with etelcalcetide (Image 1) were enrolled and followed at different time points (1–3–6–12–24 months). Patients were on stable doses of ferric carboxymaltose, active vitamin D analogues, phosphorus binders, supplement of oral calcium and calcium concentration in dialysate (1.25–1.50 mmol/L). RESULTS Data analysed after 24 months of treatment with etelcalcetide (Image 2) demonstrated not only a drastic improvement in iPTH values (772.53 ± 452.6 pg/mL versus 308.7 ± 207 pg/mL–60.05%) but also a statistically significant improvement of haemoglobin values ( 10.35 ± 1.45 g/dL versus 11.57 ± 0.97 g/dL; P &amp;lt; .05) in addition to a reduction in the weekly ESAs units required (193.39 ± 148 UI/kg/week versus 142.71 ± 118 UI/kg/week; P &amp;lt; .05). This effect was achieved by maintaining constant ferritin and TSAT levels and without substantial changes in iron carboxymaltose therapy. No side effects were recorded for the entire duration of the treatment. CONCLUSIONS Considering the well-known direct and indirect inhibition of parathyroid hormone on erythropoiesis, reduction of iPTH levels achieved with etelcalcetide could improve haemoglobin levels and reduce required weekly ESA units, with obvious clinical and economic advantages. Further studies, on large populations and over longer periods of time, are required.

Interventions To Attenuate Vascular Calcification Progression in Chronic Kidney Disease: A Systematic Review of Clinical Trials.

Vascular calcification is associated with cardiovascular morbidity and mortality in people with CKD. Evidence-based interventions that may attenuate its progression in CKD remain uncertain. We conducted a systematic review of prospective clinical trials of interventions to attenuate vascular calcification in people with CKD, compared with placebo, another comparator, or standard of care. We included prospective clinical trials (randomized and nonrandomized) involving participants with stage 3-5D CKD or kidney transplant recipients; the outcome was vascular calcification measured using radiologic methods. Quality of evidence was determined by the Cochrane risk of bias assessment tool and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) method. There were 77 trials (63 randomized) involving 6898 participants eligible for inclusion (median sample size, 50; median duration, 12 months); 58 involved participants on dialysis, 15 involved individuals with nondialysis CKD, and 4 involved kidney transplant recipients. Risk of bias was moderate over all. Trials involving magnesium and sodium thiosulfate consistently showed attenuation of vascular calcification. Trials involving intestinal phosphate binders, alterations in dialysate calcium concentration, vitamin K therapy, calcimimetics, and antiresorptive agents had conflicting or inconclusive outcomes. Trials involving vitamin D therapy and HMG-CoA reductase inhibitors did not demonstrate attenuation of vascular calcification. Mixed results were reported for single studies of exercise, vitamin E-coated or high-flux hemodialysis membranes, interdialytic sodium bicarbonate, SNF472, spironolactone, sotatercept, nicotinamide, and oral activated charcoal. Currently, there are insufficient or conflicting data regarding interventions evaluated in clinical trials for mitigation of vascular calcification in people with CKD. Therapy involving magnesium or sodium thiosulfate appears most promising, but evaluable studies were small and of short duration.

MO581ASSOCIATION OF ETELCALCETIDE WITH ADYNAMIC BONE DISEASE IN DIABETIC PATIENTS : A MULTI-CENTRIC STUDY

Abstract Background and Aims Several dialysis patients frequently suffer of different mineral and bone disorders (CKD-MBD) associated with secondary hyperparathyroidism (sHPT). Among CKD-MBD, adynamic bone disease (ABD) is an alteration characterized by reduced osteblasts and osteoclasts, no accumulation of osteoid and low bone turnover. The histologic pattern of ABD is generally associated to low levels of PTH. Etelcalcetide is a novel second-generation calcimimetic given intravenously after each hemodialysis session that has a longer elimination half-life than cinacalcet. Plasmatic concentration remains stable from 24 h to 48 h after injection. One potential risk of calcimimetics, such as etelcalcetide, is the dramatic and sustained PTH lowering, which could lead to the induction of adynamic bone disease (ABD). ABD and elevated serum levels of advanced glycation end products (AGEs) often are found in patients with renal failure caused by diabetic nephropathy since AGEs are involved in the pathogenesis of ABD by inhibiting osteoblastic activity and by parathyroid hormone secretion in response to hypocalcemia. So, diabetic patients treated with etelcalcetide could be considered at increased risk of developing ABD. Aim of our study was to verify the incidence of adynamic bone disease, (defined by low PTH levels) in prevalent diabetic and non-diabetic HD patient of three large community Hospital. Method Data were collected from 3 dialysis units with n = 130 patients on the charge for a period of 1 year from start of the calcimimetic. A total of 40 patients ( 23 male, 17 female) on etelcalcetide were enrolled (21 Diabetic, 19 non diabetic patients). Time points of assessment included 1-3-6-12 months. Patients were 18-years-old or older; they were on stable doses of active vitamin D analogs, phosphorus binders, a supplement of oral calcium, and calcium concentration in dialysate (1.25–1.50 mmol/L) Results Median age was 55,9 years and dialysis vintage was 4.6 year. 59,5% percent of patients switched from cinacalcet to etelcalcetide (90 days from last cinacalcet prescription); the remaining patients were calcimimetic naive. 40% of patients had a history of at least one cardiovascular event 61.5% had a starting etelcalcetide dose of 5 mg and the median weekly dose was 7.5 mg (range: 2.5-15 mg). On Diabetic Group: mean PTHi, Ca2+ and P before calcimimetic start was respectively 844±479,30 pg /mL , 9,95±0,97 mg/dl , 5,02±0,99 mg/dl. In non diabetic patients: mean PTHi, Ca2+ and P before calcimimetic start was: 793,36±534,41 150 pg /mL, 9,33±0,70 mg/dl, 5,9±1,17 mg/dl Conclusion Results of our study show that after 1 year of etelcalcetide treatment, levels of PTHi are lower more in non-diabetic patients, ( M12: 473±340,08 vs 253,13 + 98,87 p:0.042) despite scientific evidence currently supporting hypothesis that osteoblastic activity is reduced by AGES and ABD risk is increased in diabetic nephropathy. Therefore, etelcalcetide could be used safely in diabetic patients and could even protect from the risk of development ABD. However, further studies are required to validate this hypothesis. Results are shown in the following table:

Effect of citric-acid dialysate on the QTC-interval

Lower dialysate calcium (dCa) concentration and dialysate citric-acidification may positively affect calcification propensity in serum of haemodialysis (HD) patients. However, the accompanying lower ionized blood calcium concentration may lead to a prolonged cardiac action potential, which is possibly pro-arrhythmic. The aim of this study is to investigate the influence of citric-acid dialysate on the QT-interval corrected for heart rate (QTc) compared to conventional dialysate with different dCa concentrations. We conducted a four-week multicentre, randomized cross-over trial. In week one and three patients received acetic-acid dialysate with a dCa of 1.50 mmol/l (A1.5), in week two and four acetic-acid dialysate with a dCa of 1.25 mmol/l (A1.25) or citric-acid dialysate (1.0 mmol/l) with a dCa of 1.50 mmol/l (C1.5) depending on randomization. Patients had continuous ECG monitoring during one session in week one, two and four. The data of 13 patients were available for analysis. Results showed a significant though limited increase of QTc with C1.5 (from 427 to 444 ms (start to end); p = 0.007) and with A1.25 (from 431 to 449 ms; p < 0.001), but not with A1.5 (from 439 to 443 ms; p = 0.13). In conclusion, we found that the use of C1.5 or A1.25 is associated with a significant prolongation of QTc which was however relatively limited.

41. INTRADIALYTIC HYPERTENSION PROFILE IN ROUTINE HEMODIALYSIS PATIENTS: A SINGLE CENTRE EXPERIENCE

Background: Intradialytic hypertension is a common complication occuring during hemodialysis with the prevalence of 5–15%. It is a paradoxical rise in blood pressure (BP) during or immediately after dialysis, an opposite phenomenon of hemodynamic response to ultrafiltration. Intradialytic hypertension is associated with adverse cardiovascular outcome and can predict cardiovascular mortality. Aim of the study: The purpose of this study was to evaluate the intradialytic hypertension profile among maintenance hemodialysis patients. Methods: We conducted an observational study on our routine hemodialysis patients in Dr. Cipto Mangunkusumo General Hospital, Jakarta, from 1 February to 31 May 2019. We recruited 133 patients, undergone twice weekly hemodialysis at five hours per session. Intradialytic hypertension was defined as a rise in systolic blood pressure &gt;10 mmHg from pre to immediately post dialysis. Results: Among 133 subjects, the median age is 51 years old, with predominantly male (n = 68, 51.1%). Median of the dialysis vintage is 5 years and 28.6% of our patients had diabetes (n = 38). Most of our dialysis patients taking antihypertensive medications (n = 108, 81.2%) with ACE-i/ARB and CCB are the majority agents used (41.4% and 56.4%, respectively). More than half of the subjects achieved less than 5% interdialytic weight gain (IDWG) (n = 69, 51.9%) with median of IDWG is 4.91 liter. Intradialytic hypertension was found in 33.1% (44/133) subject. We identified no significant different from those experienced intradialytic hypertensions and those who did not, in terms of age and interdialytic weight gain (IDWG) although there is a trend in younger (&lt;60 years old) subject and those achieving IDWG less than 5% to have a lower chance from developing intradialytic hypertension (p = 0.09, 95% CI = 0.230–1.118, OR 0.507 and p = 0.158, 95% CI = 0.286–1.229, OR = 0.593, respectively). There is a higher risk experiencing intradialytic hypertension in those dialysis with higher dialysate calcium concentration (p = 0.075, 95% CI = 0.931–4.036, OR = 1.939), shorter dialysis vintage (p = 0.06, 95% CI = 0.964–4.394, OR = 2.058) and those with higher number of antihypertensive medication used (p = 0.158, 95% CI 1.454–33.696, OR = 7.0 [three agents compared to single agents]), although it is not statistically significant. There is a slightly lower mean ultrafiltration (UF) volume in those developing intradialytic hypertension compare to subject who did not (mean UF 3668 ml vs 3700 ml, p = 0.893). We found a significant different in hemoglobin concentration with a 2.5 times chance of developing intradialytic hypertension in subject who have lower hemoglobin concentration (p = 0.018, 95% CI 1.158–5.334, OR 2.486). Conclusion: Intradialytic hypertension is a major hemodialysis complication observed in our unit with a higher risk found in subject with lower hemoglobin concentration. Any attempt to achieving better dialysis adequacy including optimal hemoglobin level are required to lower this complication.

Skeletal and cardiovascular consequences of a positive calcium balance during hemodialysis.

Patients on hemodialysis are exposed to calcium via the dialysate at least three times a week. Changes in serum calcium vary according to calcium mass transfer during dialysis, which is dependent on the gradient between serum and dialysate calcium concentration (d[Ca]) and the skeleton turnover status that alters the ability of bone to incorporate calcium. Although underappreciated, the d[Ca] can potentially cause positive calcium balance that leads to systemic organ damage, including associations with mortality, myocardial dysfunction, hemodynamic tolerability, vascular calcification, and arrhythmias. The pathophysiology of these adverse effects includes serum calcium changes, parathyroid hormone suppression, and vascular calcification through indirect and direct effects. Some organs are more susceptible to alterations in calcium homeostasis. In this review, we discuss the existing data and potential mechanisms linking the d[Ca] to calcium balance with consequent dysfunction of the skeleton, myocardium, and arteries.

Dialysis Filter Life, Anticoagulation, and Inflammation in COVID-19 and Acute Kidney Injury.

In recent studies, 5%–20% of hospitalized patients with coronavirus disease 2019 (COVID-19) developed AKI requiring RRT (CoV-AKI-RRT) (1,2) (L. Chan et al., unpublished observations). Hypercoagulability has been recognized as a salient feature of COVID-19 in the critically ill (3,4) and there have been anecdotal accounts of unexpectedly frequent dialysis filter clotting. However, there are limited data describing the magnitude of the problem. A recent report described clotting events in 28 of 29 patients with CoV-AKI-RRT and shorter filter lifespan compared with a historical control, but no details were provided regarding anticoagulation (4). Our objective was to examine the delivery of RRT and circuit interruptions in patients with CoV-AKI-RRT in comparison with those in the pre-COVID-19 era. With approval of the Institutional Review Board, waiver of informed consent, and in accordance with the Declaration of Helsinki, we conducted a retrospective single-center study, ancillary from our previously reported cohort (2). We identified hospitalized patients with COVID-19 (positive severe acute respiratory syndrome coronavirus 2 RNA PCR by nasopharyngeal swab) and AKI, who underwent RRT by sustained low-efficiency dialysis (SLED) for ≥8 hours in an intensive care unit between March and April of 2020 (study period: 4 weeks) by either prolonged intermittent or continuous RRT modality (5,6) using Fresenius 2008K/K2 (Bad Homburg, Germany) machines. At our hospital, continuous venovenous hemodiafiltration (CVVHDF) with PrismaFlex (Deerfield, IL) machines was restricted to the neurointensive care unit and was not expanded during the pandemic due to logistics. As pre-COVID-19 control, we included consecutive patients (reverse chronological order) with AKI without COVID-19 who underwent SLED in December of 2019. Electronic medical records were accessed and RRT flowsheets were manually reviewed to extract timing of initiation and interruption, blood flow rate (BFR), dialysate flow rate, and filter transmembrane pressure (TMP). Standard BFR was 200 …

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

In patients on hemodialysis (HD), the various chemical elements in the dialysate may influence survival rates. In particular, calcium modifies mineral and bone metabolism and the vascular calcification rate. We studied the influence of the dialysate calcium concentration and the treatments prescribed for mineral bone disease (MBD) on survival. All patients in REIN having initiated HD from 2010 to 2013 were classified according to their exposure to the different dialysate calcium concentrations in their dialysis unit. Data on the individual patients' treatments for MBD were extracted from the French national health database. Cox proportional hazard models were used to estimate mortality hazard ratios (HR) associated with time-dependent exposure to dialysate calcium concentrations and MBD therapies, adjusted for comorbidities, laboratory and technical data. Dialysate calcium concentration of 1.5 mmol/L was used by 81% of the dialysis centers in 2010 and in 83% in 2014. Most centers were using several formulas in up to 78% for 3 formulas in 2010 to 86% in 2014. In full adjusted Cox survival analyses, the percentage of calcium >1.5 mmol/L and <1.5 mmol/l by center and the number of formula used per center were not associated with survival. Depending on the daily dose used, the MBD therapies were associated with survival improvement for calcium, native vitamin D, active vitamin D, sevelamer, lanthanum and cinacalcet in the second and third tertiles of dose. 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.

P1417ALTERED CATHEPSIN-K LEVELS REFLECT SEVERITY OF MINERAL BONE DISEASE AND INFLAMMATION IN CHRONIC HEMODIALYSIS PATIENTS

Abstract Background and Aims Mineral bone disease (MBD) and chronic inflammation are key triggers of the exceeding cardiovascular risk that characterizes dialysis patients. Cathepsin-K (Cts-K) is a lysosomal cysteine protease involved in bone remodeling and resorption, whose expression is promoted particularly by inflammation and whose involvement in bone and cardiovascular disorders has previously been demonstrated. We set out to undertake an exploratory, observational study to assess the possible clinical significance of Cts-K in dialysis patients. Method Eighty-five chronic HD patients (mean age 67±12, median dialysis vintage 3.2 yrs) with stable dry weight were studied. Cts-K was measured in peripheral blood samples before a mid-week dialysis session together with standard biochemical parameters. Twenty-six healthy subjects, matched with HD patients for age and gender, served as controls. Results Cts-K was statistically higher in HD patients than in controls (median 340, IQR 170-835 vs. 190 IQR 20-120 pg/mL, p&amp;lt;0.0001). At univariate analyses, Cts-K levels were significantly associated with ALP (r=0.50, p&amp;lt;0.001), CRP (r=0.46, p&amp;lt;0.001), PTH (r=0.24,p=0.02), presence of diabetes (r=0.28,p&amp;lt;0.001),peripheral vasculopathy (r=0.20, p=0.05) and dialysate calcium concentration (r=-0.28,p&amp;lt;0.001). In a multivariate model including all univariate predictors (R2=61%, p&amp;lt;0.001) only ALP (β=0.70,p&amp;lt;0.001), CRP (β=0.49,p&amp;lt;0.001) and dialysate calcium concentration (β -0.40,p=0.04) remained significantly associated with Cts-K levels. Interestingly, Cts-K levels were significantly higher among individuals who were under active calcimimetic therapy (n=28; p&amp;lt;0.001) but significantly lower among those who previously underwent parathyroidectomy (n=8; p&amp;lt;0.001) (Figure 1). Conclusion Cathepsin-K is a biomarker at the crossroads of bone and inflammatory disorders in chronic hemodialysis patients. Future research is needed to clarify the exact pathophysiological role of this protein and to test its potential usefulness as a marker for managing MBD therapy and complications.

P1427ROLE OF ETECALCETIDE IN THE MANAGEMENT OF SECUNDARY HYPERPARATHYROIDISM

Abstract Background and Aims Secondary Hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD). Etelcalcetide is the first intravenous calcimimetic authorized for the treatment of SHPT in haemodialysis (HD). It has proven to be effective in lowering parathyroid hormone (PTH), with an acceptable and comparable safety profile. The aim of this descriptive study was to evaluate the results of using etelcalcetide in patients on HD with SHPT. Method Thirty patients on HD received etelcalcetide were enrolled (figure 1). The minimum observation period was 6 months. Fifteen (50%) were previously with cinacalcet (group 1) and 15 (50%) received etelcalcetide at onset (group 2). We analyzed change of serum iPTH, calcium (Ca) and phosphorus (P) in both cohorts; as well as the dosage of calcium carbonate, non-calcium (phosphate binders) and / or vitamin D analogs. The presence of adverse effects were also recorded. Results Thirty patients on HD received etelcalcetide were enrolled (figure 1). The minimum observation period was 6 months. Fifteen (50%) were previously with cinacalcet (group 1) and 15 (50%) received etelcalcetide at onset (group 2). We analyzed change of serum iPTH, calcium (Ca) and phosphorus (P) in both cohorts; as well as the dosage of calcium carbonate, non-calcium (phosphate binders) and / or vitamin D analogs. The presence of adverse effects were also recorded. In global, serum iPTH levels were significantly decreased during therapy compared to baseline levels. When comparing both groups, we found a significant decrease of Ca, P and iPTH in group 2. However, we only found significant decrease of Ca in group 1 (figure 2). When we analyzed the reducton of PTH &amp;gt;30% in both groups, we observed that 46.6% of patients treated with etecalcetide compared to 33.3% of patients treated with cinacalcet, achieved this reduction in PTH. The dosage of calcium binders (33.3% pretreatment vs 56.7% at the end of follow-up, p 0.054), non-calcium binders (40% pretreatment vs 63.3% at the end of follow-up, p 0.02) and vitamin D analogues (56,7% pretreatment vs 66,7% at the end of follow-up, p 0,3) were increased when etelcalcetide treatment was started. No changes were made in dialysate calcium concentration. Six patients, presented hypocalcemia (Ca &amp;lt; 7.5 mEq/l). Conclusion In our cohort, etelcalcetide has shown to be effective in reducing serum iPTH. In addition, etecalcetide was noninferior to cinacalcet reducing PTH&amp;gt;30%. An increase in the use of vitamin D analogues, calcium binders and non-calcium binders has been observed, probably due to the hypocalcemia.

P1414THE PREDICTORS OF PARATHYROID HORMONE VARIABILITY IN HEMODIALYSIS PATIENTS

Abstract Background and Aims KDIGO Clinical Practice Guidelines suggest in hemodialysis (HD) patients using a dialysate calcium concentration between 1,25 and 1,5 mmol/L and maintaining serum intact parathyroid hormone (sPTH) levels in the range of approximately 2 to 9 times the upper normal limit for the assay. The aim of the study was to evaluate the predictors of PTH variability in HD patients over a 12 months period. Method The multicenter restrospective study encompassed 398 patients (256M and 142F) with the average age 59,64±13,29 years and the average HD vintage 78,63±64,26 months. Over a 12 months (M0-M12) period: serum calcium (sCa), serum phosphorus (sPi), serum alkaline phosphatase (sAPh), oral calcium-carbonate daily dose, oral calcitriol weekly dose, and dialysate Ca concentration (dCa) were monitored monthly, and sPTH at 6 months. According to PTH assay reference level (18,4-80,1 pg/ml) 3 groups of patients were categorized: patients with low sPTH&amp;lt;160, with target range sPTH =160-721, and with high sPTH&amp;gt;721. For statistical analysis chi-square test, analysis of variance with repeated measures and logistic regression analysis were performed by softver SPSS. Results Over a 12 months period the number of patients with low sPTH significantly decreased, but the number of patients with target range sPTH and high sPTH increased (Chi square=269,45; p&amp;lt;0.001). On the basis of overall pattern of sPTH fluctuation over a 12 months period six subgroups of patients were observed: consistently low in 20,6% of patients, consistently within the target range in 22,1%, consistently high in 14,07%, low-amplitude fluctuation with low and target range sPTH levels (LAL) in 31,4%, low-amplitude fluctuation with target range and high sPTH levels (LAH) in 10,55%, and high-amplitude fluctuation (HA) subgroup with low, target range and high sPTH levels in 1,25%. In 35 patients constantly hemodialyzed over a 12 months period with dCa=1,25 mmol/L due to high sCa the significant increase of sPTH (M0=797±657 vs M12=1030±740 pg/ml; p=0.001) and no significant changes of sCa (M0=2,44± vs M12=2,34± mmol/L; n.s.), sPi (M0=1,81±0,49 vs M12=1,68±0,49 mmol/L; n.s.), Ca-carbonate daily dose (M0=1,88±1,54 vs M12=2,22±1,53 g/d; n.s.) and calcitriol weekly dose (M0=0,84±1,38 vs M12=1,1±1,41 ucg/w; n.s.) were observed. In 24 patients constantly hemodialyzed with dCa=1,75 mmol/L due to low sCa the significant decrease of sPTH (M0=518±582 vs M12=391±530 pg/ml; p=0.037) and no significant changes of sCa (M0=2,17±0,19 vs M12=2,18±0,17 mmol/L; n.s.), sPi (M0=1,3±0,34 vs M12=1,36±0,52 mmol/L; n.s.), Ca-carbonate daily dose (M0=2,53±1,58 vs M12=2,1±1,91 g/d; n.s.) and calcitriol weekly dose (M0=1,33±1,23 vs M12=1,42±1,69 ucg/w; n.s.) were observed. In 195 patients constantly hemodialyzed with dCa=1,5 mmol/L no significant changes of sPTH (M0=388±421 vs M12=434±459 pg/ml; n.s.), sCa (M0=2,29±0,18 vs M12=2,27±0,15 mmol/L; n.s.), sPi (M0=1,48±0,41 vs M12=1,52±0,41 mmol/L; n.s.), Ca-carbonate daily dose (M0=2,42±1,4 vs M12=2,57±1,2 g/d; n.s.) and calcitriol weekly dose (M0=0,47±0,72 vs M12=0,38±0,68 ucg/w; n.s.) were observed. By model of logistic regression analysis dCa=1,75 (OR=8,33), increased sCa (OR=7,7), and presence of diabetes mellitus (OR=2,44) were the most significant predictors of low sPTH&amp;lt;160 (Chi square=116,27; p&amp;lt;0.001), but the increased sCa (OR=6,88), dCa=1,25 (OR=5,08), and the increased sPi (OR=2,72) were the most significant predictors of high sPTH&amp;gt;721 (Chi square=72,475; p&amp;lt;0.001). Conclusion The prolonged use of dCa=1,25 in patients with high sCa led to significant sPTH increase likely due to net negative calcium balance, but prolonged use of dCa=1,75 in patients with low sCa led to significant sPTH decrease likely due to net positive calcium balance.

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.

&lt;p&gt;Efficacy and Safety of Evocalcet Evaluated by Dialysate Calcium Concentration in Patients with Secondary Hyperparathyroidism Undergoing Hemodialysis&lt;/p&gt;

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.