Dialysate Calcium Research Articles

The effects of dialysate calcium prescription on mortality outcomes in incident patients on hemodialysis.

The appropriate prescription of dialysate calcium concentration for hemodialysis is debated. We investigated the association between dialysate calcium and all-cause, cardiovascular mortality and sudden cardiac death. In this historical cohort study, we included adult incident hemodialysis patients who initiated dialysis between 1 January 2010 and 30 June 2017 who survived for at least 6 months (grace period). We evaluated the association between dialysate calcium 1.25 or 1.50mmol/l and outcomes in the 2 years after the grace period, using multivariable Cox regression models. Moreover, we examined the association between the serum dialysate to calcium gradient and outcomes. We included 12 897 patients with dialysate calcium 1.25mmol/l and 26 989 patients with dialysate calcium 1.50mmol/l. The median age was 65 years, and 61% were male. The unadjusted risk of all-cause mortality was higher for dialysate calcium 1.50mmol/l [hazard ratio (HR) 1.07, 95% confidence intervals (CI) 1.01-1.12]. However, in the fully adjusted model, no significant differences were noted (HR 1.05, 95% CI 0.99-1.12). Similar results were observed for the risk of cardiovascular mortality (HR 1.03, 95% CI 0.94-1.13). Adjusted risk of sudden cardiac death was lower for dialysate calcium 1.50mmol/l (HR 0.81, 95% CI 0.67-0.97). Significant and positive associations with all outcomes were observed with larger serum-to-dialysate calcium gradients, primarily mediated by the serum calcium level. In contrast to the unadjusted analysis that showed a higher risk for dialysate calcium of 1.50mmol/l, after adjusting for confounders, there were no significant differences in the risk of all-cause and cardiovascular mortality between dialysate calcium concentrations of 1.50 and 1.25mmol/l. After adjustment, a lower risk of sudden cardiac death was observed in patients with dialysate calcium 1.50mmol/l. A higher serum-to-dialysate calcium gradient is associated with an increased risk for adverse outcomes.

Deciphering simplified regional anticoagulation with citrate in intermittent hemodialysis: a clinical and computational study

Regional citrate anticoagulation use in intermittent hemodialysis is limited by the increased risk of metabolic complications due to faster solute exchanges than with continuous renal replacement therapies. Several simplifications have been proposed. The objective of this study was to validate a mathematical model of hemodialysis anticoagulated with citrate that was then used to evaluate different prescription scenarios on anticoagulant effectiveness (free calcium concentration in dialysis filter) and calcium balance. A study was conducted in hemodialyzed patients with a citrate infusion into the arterial line and a 1.25 mmol/L calcium dialysate. Calcium and citrate concentrations were measured upstream and downstream of the citrate infusion site and in the venous line. The values measured in the venous lines were compared with those predicted by the model using Bland and Altman diagrams. The model was then used with 22 patients to make simulations. The model can predict the concentration of free calcium, bound to citrate or albumin, accurately. Irrespective of the prescription scenario a decrease in free calcium below 0.4 mmol/L was obtained only in a fraction of the dialysis filter. A zero or slightly negative calcium balance was observed, and should be taken into account in case of prolonged use.

The Role of Daily Dialysate Calcium Exposure in Phosphaturic Hormones in Dialysis Patients.

Managing mineral bone disease (MBD) could reduce cardiovascular risk and improve the survival of dialysis patients. Our study focuses on the impact of calcium bath exposure in dialysis patients by comparing peritoneal dialysis patients (PD, intervention group) and hemodialysis patients (HD, control group). We assessed various factors, including calcium, phosphorus, magnesium, PTH, vitamin D 25-OH, C-terminal telopeptide (CTX), and FGF-23 levels, as well as the calcium bath six hours before the blood sample and the length of daily calcium exposure. We enrolled 40 PD and 31 HD patients with a mean age of 68.7 ± 13.6 years. Our cohort had median PTH and FGF-23 levels of 194 ng/L (Interquartile range [IQR] 130-316) and 1296 pg/mL (IQR 396-2698), respectively. We identified the length of exposure to a 1.25 mmol/L calcium bath, phosphate levels, and CTX as independent predictors of PTH (OR 0.279, p = 0.011; OR 0.277, p = 0.012; OR 0.11, p = 0.01, respectively). In contrast, independent predictors of FGF-23 were phosphate levels (OR 0.48, p < 0.001) and serum calcium levels (OR 0.25, p = 0.015), which were affected by the calcium bath. These findings suggest that managing dialysate calcium baths impacts phosphaturic hormones and could be a critical factor in optimizing CKD-MBD treatment in PD patients, sparking a new avenue of research and potential interventions.

Calcium mass balance in adults during single hemodialysis and hemodiafiltration treatments using lower calcium dialysate concentrations.

Debate continues as to the optimum hemodialysis (HD) dialysate calcium concentration. Although current guidelines advocate 1.25-1.5 mmol/L, some investigators have suggested these may cause calcium gains. As such we investigated whether using dialysate calcium of 1.25 mmol/L risked calcium gains, and whether there were differences between hemodiafiltration and high flux HD. We continuously collect an aliquot of effluent dialysate during dialysis sessions, and calculated dialysis calcium mass balance by the difference between the amount of calcium delivered as fresh dialysate and that lost in effluent dialysate. We studied 106 stable outpatients, 64% male, mean age 64.4 ± 16.2 years, median dialysis vintage 32 (22-60) months. Most sessions (69%) used a 1.0 mmol/L calcium dialysate, with a median sessional loss of 13.7 (11.5-17.1) mmol, whereas using 1.25 mmol/L the median loss was 7.4 (4.9-10.1) mmol, but with 6.9% had a positive balance (p = 0.031 vs dialysate calcium 1.0 mmol/L). Most patients (85.8%) were treated by hemodiafiltration, but there was no difference in sessional losses (11.7 (8.4-15.8) vs 13.5 (8.1-16.8)) with high flux HD. Dialysis sessional calcium balance was associated with the use of lower dialysate calcium concentration (β -19.5, 95% confidence limits (95%CL) -27.7 to -11.3, p < 0.001), and sessional duration (β 0.07 (95% CL) 0.03-012, p = 0.002). Ideally, the choice of dialysate calcium should be individualized, but clinicians should be aware, that even when using a dialysate calcium of 1.25 mmol/L, some patients are at risk of a calcium gain during hemodiafiltration and high-flux hemodialysis.

#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 &amp;lt; 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.

Real-World Experience of Using Etelcalcetide for Secondary Hyperparathyroidism in Community-Based Hemodialysis Centers in Singapore.

Introduction Chronic kidney disease-related mineral and bone disorder (CKD-MBD), characterized by abnormalities in calcium, phosphate, and parathyroid hormone metabolism, with impaired bone turnover and extravascular calcification is a known complication of advanced chronic kidney disease (CKD). Secondary hyperparathyroidism (SHPT) develops early in the disease and its prevalence gradually increases with the disease progression, becoming almost universal in patients with end-stage renal disease (ESRD).The treatment for SHPT includessynthetic vitamin D analogs, calcitriol or calcimimetics. Recently, intravenous etelcalcetide was introduced as a second-generation calcimimetic. This article provides the real-world experience of using etelcalcetide in multiethnic Asian patients receiving hemodialysis at community-based hemodialysis centers in Singapore. Methods This study was real-world evidence, generated by a retrospective clinical audit of routine clinical care of hemodialysis patients in community-based centers in Singapore who received etelcalcetide for treating SHPT.The information on the starting and maximum dose of etelcalcetide, duration of treatment on hemodialysis, parathyroid hormone (PTH) levels, dialysate calcium, concomitant medications, and reasons for discontinuation were collected from the medical records. PTH levels were collected at four-, eight-, and twelve-month intervals. Results A total of 148 patients received etelcalcetide during the study period. Ten patients died and twenty discontinued their treatment, with 118 patients remaining on treatment. Demographically, the patients included Chinese, Malay, Indians, and those belonging to other racial groups. The starting dose of etelcalcetide ranged from 2.5 mg once per week to 7.5 mg three times a week. There was a 16.8% reduction (p=<0.001) in intact-PTH after four months of therapy. Target intact-PTH level of less than 60 pmol/L, was reported as 1.4% at baseline, with 22.3% at four months (p<0.001) and 25.9% at eight months (p=0.028). Calcium and phosphate levels were also tracked as part of the safety and efficacy measures of using etelcalcetide. No symptomatic hypocalcemia was noted and phosphate levels were noted to decline significantly. Overall, the calcium-phosphate product reduced at four months (13.2%, p=<0.001) and eight months (12.7%, p<0.05). An analysis of concomitant medication usage, dialysate calcium utilized, and the side effects of etelcalcetide were also recorded. Finally, a brief descriptive analysis of the patient's subjective feedback regarding etelcalcetide was also reported, especially regarding the reduction in pill burden and overall compliance to medications. Conclusion Etelcalcetide is safe and effective for treating SHPT in multi-ethnic Asian hemodialysis patients and can be considered an alternative to oral cinacalcet. Our study showed no side effects, which was one of the key reasons for non-compliance to traditional calcimimetics. A favorable compliance profile with reduced pill burden was noted by using this intravenous calcimimetic.

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.

Formulation Optimization and Evaluation of Nanocochleate Gel of Famciclovir for the Treatment of Herpes Zoster.

Herpes zoster is a viral infection triggered due to the reactivation of the varicella- zoster virus in the posterior dorsal root ganglion. Herpes zoster infections occur mostly in the facial, cervical and thoracic regions of the body, beginning with pain and resulting in the vesicular eruption. Recently, this infection was observed during the COVID-19 pandemic and also after the induction of mRNA-based vaccine for coronavirus at an extended level. Nanocochleates are cylindrical (cigarshape) microstructure lipid-based versatile carriers for drug delivery systems. Famciclovir is an antiviral agent employed for the treatment of Herpes zoster infections. The current research patent aims to develop a novel nanocochleate gel of Famciclovir for the treatment of herpes zoster infections with higher efficacy. The interaction studies using FTIR were carried out and indicated no such interactions between the drug and lipids. The nanocochleates were developed using hydrogel, trapping, liposome before cochleate dialysis, direct calcium dialysis and binary aqueous-aqueous emulsion methods, respectively. The 32 Box-Behnken design was applied by considering the concentration of lipids (phosphatidylcholine and cholesterol) and speed of rotation as independent factors, whereas particle size and entrapment efficiency as dependable factors. The developed nanocochleates were estimated for the particle size (276.3 nm), zeta potential (-16.7 mV), polydispersity index (0.241), entrapment efficiency (73.87±0.19%) and in vitro diffusion release (>98.8% in 10 h). The optimized batch was further converted into the topical gel using carbopol 940 as a gelling agent. The prepared gel was smooth, rapidly spreadable with a viscosity (5998.72 cp), drug content (95.3%) and remained stable during stability studies. A novel nanocochleate gel of Famciclovir was successfully developed for the treatment of infections associated with Herpes Zoster with sustained release action.

Chronic kidney disease mineral bone disorder in childhood and young adulthood: a ‘growing’ understanding

Chronic kidney disease (CKD) mineral and bone disorder (MBD) comprises a triad of biochemical abnormalities (of calcium, phosphate, parathyroid hormone and vitamin D), bone abnormalities (turnover, mineralization and growth) and extra-skeletal calcification. Mineral dysregulation leads to bone demineralization causing bone pain and an increased fracture risk compared to healthy peers. Vascular calcification, with hydroxyapatite deposition in the vessel wall, is a part of the CKD-MBD spectrum and, in turn, leads to vascular stiffness, left ventricular hypertrophy and a very high cardiovascular mortality risk. While the growing bone requires calcium, excess calcium can deposit in the vessels, such that the intake of calcium, calcium- containing medications and high calcium dialysate need to be carefully regulated. Normal physiological bone mineralization continues into the third decade of life, many years beyond the rapid growth in childhood and adolescence, implying that skeletal calcium requirements are much higher in younger people compared to the elderly. Much of the research into the link between bone (de)mineralization and vascular calcification in CKD has been performed in older adults and these data must not be extrapolated to children or younger adults. In this article, we explore the physiological changes in bone turnover and mineralization in children and young adults, the pathophysiology of mineral bone disease in CKD and a potential link between bone demineralization and vascular calcification.Graphical abstractA higher resolution version of the Graphical abstract is available as Supplementary information

#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 novel calcium-binding peptide from bovine bone collagen hydrolysate and chelation mechanism and calcium absorption activity of peptide-calcium chelate

A novel calcium-binding peptide from bovine bone collagen hydrolysate was screened based on a new target—the calcium-sensing receptor (CaSR), and its chelation mechanism and calcium absorption activity were investigated. Glu-Tyr-Gly exhibited superior binding affinities to CaSR because of its interaction with the active sites of the CaSR Venus Flytrap (VFT) domain. Glu-Tyr-Gly-Ca may exist in five potential chelation modes and its potential chelation mechanism was that calcium ions were located in the center and surrounded by ionic bonds (carboxyl group) and coordination bonds (carbonyl, amino, and carboxyl group). Glu-Tyr-Gly-Ca was slightly damaged in the intestinal fluid and at different temperatures, whereas it was severely damaged in the gastric fluid and acidic conditions. The results of the calcium dialysis percentage and Caco-2 cells experiments showed that Glu-Tyr-Gly-Ca possessed good calcium transport activity and bioavailability. The findings provided theoretical basis for Glu-Tyr-Gly-Ca as potential calcium supplement to improve intestinal calcium absorption.

Study on the Effect of Low Calcium Dialysate on Biochemical Profile of Adynamic Bone Disease in Patients on Maintenance Hemodialysis.

In recent years, adynamic bone disease (ABD) has become a common skeletal lesion in adult patients with chronic kidney disease. We aimed to compare the effects of low calcium dialysate (LCD) and standard calcium dialysate of our facility [high calcium dialysate (HCD)] on the evolution of bone and mineral parameter related to ABD in dialysis patients. Forty patients with predialysis intact parathyroid hormone (iPTH) <100 pg/mL and/or bone-specific alkaline phosphatase (BAP) <27 U/L were included in this study and were equally distributed over LCD (1.25 mmol/L) or HCD (1.75 mmol/L) treatment. The duration of the study was 6 months. There was no significant difference in baseline characters and biochemical parameters related to chronic kidney disease-mineral and bone disorder in both the groups. The groups did not differ in the mean tCa before dialysis, but this parameter was significantly lower in the LCD group versus HCD at the end of the study. The mean serum levels of iPTH, total alkaline phosphatase, and BAP in the LCD group were increased at 3 months and at the end of the study compared with the baseline levels. The bone markers in the HCD group did not change significantly. At the end of the study, all bone parameters in the LCD group were significantly higher than in the HCD group. Development of measures indicating increased bone turnover in patients receiving 1.25 mmol/L of dialysate calcium, most likely as a result of inhibiting a positive calcium balance and allowing for long-term PTH secretion stimulation. Hence, LCD might be considered a valuable therapeutic option for ABD patients.

Frequency of Intradialytic Hypertension Using Kidney Disease: Improving Global Outcomes (KDIGO) Suggested Definition in a Single Hemodialysis Centre in Pakistan.

To estimate the frequency of intradialytic hypertension (IDH) in our centre as per the definition suggested by Kidney Disease: Improving Global Outcomes (KDIGO). A cross-sectional study was conducted at the dialysis department of The Kidney Centre Post Graduate Training Institute (PGTI) Karachi, Pakistan from August 2021 to October 2021 among 263 end-stage kidney disease (ESKD) patients on maintenance hemodialysis (MHD) aged ≥ 18 years of both genders. The study outcome was the frequency of IDH as per the latest KDIGO suggested definition i.e., systolic blood pressure (SBP) rise of > 10 mm Hg from pre- to post-dialysis within the hypertensive range in at least four out of six consecutive dialysis treatments. Frequencies (%) and mean (±SD) were calculated for categorical and continuous variables respectively, using SPSS version 21 (IBM Corp., Armonk, NY, USA). Among 263 patients, the mean age was 51.02 (±14.1) years and 56.3% were males. Around 30.8% of patients were dialysis-dependent for 1.1 to three years. The most common comorbidity was hypertension (88.6%). Standard dialysate calcium of 3mEq/l was received by 91.6% of study participants. About 78.7% of patients were using antihypertensive(s), out of which 85.5% were compliant and 37.6% were using a single antihypertensive. The most common antihypertensive in use was beta-blockers (78.3%). Around 16% of patients were found to have IDH. Age of the patients was significantly associated with IDH (p=0.038). The majority of the patients with IDH were those who were taking anti-hypertension medications as compared to the patients who were not taking them (p <0.004). Interdialytic weight gain was not a significant predictor for IDH. The frequency of IDH was 16% according to the latest suggested KDIGO definition. This is much lower than regional and global estimates according to earlier definitions. There is a dire need to establish a standardized definition of IDH in guidelines to diagnose, manage and compare data. Also, the association of IDH with fluid overload is not found in our study which emphasizes the need to evaluate other causative factors.

LBSAT131 Extended-release Calcifediol Reduced Ipth And Normalized 1,25-dihydroxyvitamin D In Esrd.

Abstract Background Extended-release calcifediol (ERC) has been shown in randomized clinical trials to effectively and safely treat secondary hyperparathyroidism (SHPT) in adults with stage 3-4 chronic kidney disease (CKD) and vitamin D insufficiency when administered at 210 or 420 mcg per week (30 or 60 mcg/day), doses which gradually raise serum total 25-hydroxyvitamin D (25D) to mean steady-state levels of 50-56 ng/mL. Clinical Case A 41-year-old male Caucasian with end-stage renal disease (ESRD) requiring regular hemodialysis (HD) experienced an overdose during participation in a phase 2 study of ERC for treating SHPT. Medical history included hypertension, type II diabetes, glomerulonephritis, bilateral lower extremity edema, muscle cramps, pruritus, shortness of breath, sporadic hypercalcemia and hyperphosphatemia, and iron deficiency anemia. Treatment with ERC began at an incorrect dosage of 2,700 mcg per week (900 mcg per HD) for 10 weeks as the study coordinator misunderstood the protocol-specified dose of 900 mcg per week. A 2.5% calcium dialysate was used during the study. Serum 25D gradually increased from 19 to 339 ng/mL (32-100), serum total 1,25-dihydroxyvitamin D (1,25D) increased from 6.3 to 137 pg/mL (24-86), plasma iPTH decreased from 440 to 146 pg/mL (15-65), and corrected serum calcium (Ca) decreased from 9.3 to 9.1 mg/dL (8.6-10.4). The subject remained asymptomatic throughout. Discovery of the overdose was delayed due to limited monitoring access during the pandemic and occurred when the ERC supply was prematurely exhausted. A physical exam and retrospective review of study records were promptly undertaken with no abnormalities noted. ERC administration, after a 1-dose hiatus, resumed at the correct dose (900 mcg per week). Serum 25D decreased over the next 4 weeks to 251 ng/mL, 1,25D decreased to 46. 0 pg/mL, iPTH increased to 186 pg/mL, and Ca remained stable (9. 0 mg/dL). The subject completed the full 6-month treatment period without adverse events. Clinical Lessons Gradual elevation of serum 25D and 1,25D with ERC to high levels had no impact on serum Ca or adverse events in the described subject suggesting that hypercalcemia observed with other vitamin D therapies used during HD results from abrupt increases in these metabolites. Serum 1,25D normalized with 25D elevation despite the lack of functional kidneys, indicating that extra-renal 1,25D production can become sufficient to control increased iPTH in ESRD when serum 25D is elevated well above the current clinical practice target of 30 ng/mL. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Calcific uremic arteriolopathy in a young man on intermittent hemodialysis

A 42‐year‐old man with ESKD who has been on intermittent hemodialysis for 7 years, presented with extremely painful inguinal ulcer and abdominal mass. The lesion was developed 2 weeks after repairing aneurysmal cubital AVF. At first, it was a small and painful red nodule but then its size increased and a large ulcer was developed. In addition, the physical examination revealed a palpable and painful large mass at left lower side of abdominal wall. He did not have important risk factors such as diabetes mellitus, treatment with warfarin, and use of calcium containing phosphate binders, vitamin D or calcium supplements. The patient suffered a long standing and severe secondary hyperparathyroidism. The parathyroid hormone level was too high (3100 pg/ml). In addition, serum calcium and phosphorus levels were 9.4 mg/dl and 9.8 mg/dl respectively. The SPECT-CT scan with 99 m Tc-MIBI of parathyroid glands confirmed persistence of an adenoma in right lower parathyroid gland (Figure 1, green arrow). The BMI was 32 kg/m2. He had no adherence to use of phosphate binder or calcimimetic drugs. The radiological studies showed extensive microvascular calcification in soft tissues (Figure 1, small arrow) and osteitis fibrosa cystica in long bones (Figure 1, star). The patient underwent surgical debridement of ulcer and palpable abdominal mass, wound care, intensive dialysis therapy with low calcium dialysis bath, cinacalcet, sevelamer carbonate, antibiotic and analgesic therapy. The histological sample (H&amp;E, 200X) shows Intramural calcification and obliteration of arteriole (large arrow) with extensive calcification in fat tissue (Figure 1, arrow head) which was consistent with Calcific Uremic Arteriolopathy (CUA). In addition to patient’s poor compliance to treatment of severe secondary hyperparathyroidism, the recent surgery of aneurismal AVF could also be an important trigger to development of calcific uremic arteriolopathy.

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.

Fine-tuned continuous renal replacement therapy with calcium-free dialysate to manage severe hypercalcemia refractory to medical and intermittent hemodialysis.

Malignancy-related hypercalcemia is a leading cause of hypercalcemia among hospitalized patients that carries poor prognosis. Parathyroid carcinoma is a rare form of primary hyperparathyroidism that may be associated with PTH dependent hypercalcemia. Severe hypercalcemia is life-threatening and may require management in an intensive care unit by means of medical therapy consisting of volume expansion, loop diuretics, cinacalcet, calcitonin and bisphosphonates. Renal replacement therapy such as intermittent hemodialysis has been successfully used among patients with severe hypercalcemia who become refractory to medical treatment. However, little data are available for cases of severe refractory hypercalcemia that fail to respond to both optimal medical therapy and hemodialysis. Our present case illustrates the successful use of continuous veno-venous hemodiafiltration (CVVHDF) with calcium-free dialysate calcium and markedly increased dialysate flow rate, to restore normal calcemia in a patient with metastatic parathyroid carcinoma with severe refractory hypercalcemia.

Application of simplified regional citrate anticoagulation in hemodialysis patients with high risk of bleeding.

To explore the safety, effectiveness, and dialysis adequacy of simplified regional citrate anticoagulation hemodialysis (SRCA-HD) in hemodialysis patients with high risk of bleeding. From 64 hemodialysis patients, 400 cases of low blood flow (150 mL/min, dialysate flow 300 mL/min) SRCA-HD were retrospectively analyzed and subsequently referred to as the LBF-SRCA group. Then, a prospective cross-over study was performed in 24 hemodialysis patients with normal blood flow (200 mL/min, dialysate flow 500 mL/min) SRCA-HD, which was called the NBF-SRCA group. Citrate was pumped at the artery pipeline, and calcium-containing dialysate (A group: 1.25 mmol/L, B group: 1.5 mmol/L) was used. The differences in laboratory tests, pipeline and dialyzer clotting, adequacy of dialysis, and adverse events of the groups were compared. 1) In the LBF-SRCA study, the correlation between citrate dosage and serum Ca2+ level at 2 hours post-filter during dialysis was negative (r = -0.228, p < 0.05). Compared with the LBF-SRCA and NBF-SRCA-A group, the pump speed of citrate in the NBF-SRCA-B group was the highest, with 355.0 ± 19.5 mL/h, 396.3 ± 11.9 mL/h, and 407.7 ± 13.0 mL/h, respectively, p < 0.001. 2) The serum Ca2+ at 2 and 4 hours post-filter during dialysis in the NBF-SRCA-B group was closer to the physiological level and significantly higher than in the A group, with 0.80 ± 0.06 vs. 0.68 ± 0.12 mmol/L, p < 0.001; 1.03 ± 0.11 vs. 0.93 ± 0.10 mmol/L, p = 0.005, respectively. 3) Both Kt/V of the NBF-SRCA-A (1.17 ± 0.24) and B (1.22 ± 0.23) group were significantly higher than that of the LBF-SRCA group (0.94 ± 0.02), p = 0.024 and p = 0.005, respectively. 4) The efficiency of anticoagulation was higher than 95% LBF-SRCA, NBF-SRCA-A and NBF-SRCA-B groups. The total clotting in the NBF-SRCA-B group (5/24) was significantly higher than that in the A group (3/24), p = 0.005. SRCA is safe, simple, and effective in hemodialysis. The dosage of citrate can be adjusted by monitoring serum Ca2+ at 2 hours post-filter during dialysis. BFR of 200 mL/min, dialysate flow rate of 500 mL/min, and 1.5 mmol/L calcium dialysate are much safer in hemodialysis patients with a high-risk of bleeding.