Calcium-based Phosphate Binders Research Articles

#586 Effects of nursing facility residency on mortality in incident HD patients

Abstract Background and Aims As the elderly population increases and nuclear families are formed, the number of elderly people who are managed in nursing facility is increasing. We investigated whether dialysis performed while residing in a nursing facility before dialysis affects the mortality rate of dialysis patients. Method We enrolled 2,597 patients who visited the hemodialysis clinics of 17 teaching hospitals and surveyed the characteristics of underlying diseases, laboratory findings, and medication between patients who started dialysis while admitted to a nursing facility and those who did not. Then, multivariate survival analysis was performed to see if starting dialysis after entering a nursing facility increased mortality. Results 9.1% (n=237) of the subjects underwent dialysis while admitted to a nursing facility. This group was predominantly female and older. Also the prevalence of diabetes, dementia, heart failure and atrial fibrillation was higher. There were many users of anti-platelet agents, warfarin, dementia drugs, and antidepressants. Additionally this group showed lower weight, lymphocyte, iPTH, albumin, phosphorus, and total cholesterol and higher duration of diabetes, and alkaline phosphatase. In multivariate analysis controlling for age, sex, access type, dementia, malignancy, ischemic heart disease, cerebrovascular accident, heart failure, atrial fibrillation, liver cirrhosis, fracture, coronary artery disease, ejection fraction, lymphocyte, platelet, BUN, Cr, albumin, phosphorus, total cholesterol, RAS blockade, B-blocker, calcium channel blocker, warfarin, hyperlipidemia drugs, Calcium-based phosphate binder, sevelamer, anti-depressant, and dementia medication, the HR of group receiving dialysis after being admitted to a nursing facility was 1.658 [1.309, 2.100]. Conclusion In summary, the current study suggests a correlation between starting dialysis in a nursing facility and a higher mortality rate among dialysis patients.

#2296 Time to get calciphylaxis on clinicians’ RaDaR?—a multicentre case series

Abstract Background and Aims Calciphylaxis is a rare, severe complication of chronic kidney disease mineral bone disorder. It is hosphorzed by arteriolar calcification of the subcutaneous fat and dermis, and associated with a mortality rate of approximately 50% within a year of diagnosis. The reported prevalence of calciphylaxis in dialysis patients ranges from 1–4%. Between March 2012 and March 2020 the UK calciphylaxis study (UKCS) recruited 139 patients from 36 enrolled renal centres; an average of 1 case every 2.6 years per centre. The multicentre case series presented here includes patients from two NHS Hospital Trusts in the UK. The aim is to raise awareness of i) calciphylaxis and possible risk factors and ii) the role of registry data in rare kidney diseases. Method Patients were included if they had a diagnosis of calciphylaxis between 01.02.2020 and 01.02.2022. Data regarding demographics, dialysis modality, BMI, medications, and mineral bone parameters were collected from clinical databases. A representative sample of results was recorded from initiation of renal replacement therapy through to diagnosis of calciphylaxis. Data regarding calciphylaxis lesions, treatments and current vital status are hosphorz. Results 17 patients with end stage kidney failure (ESKF) and clinical features of calciphylaxis were included; 8 of 17 (47%) had a skin biopsy of which 6 reported evidence of calcification. Median age was 57 years (IQR: 50-74), BMI 26.8 kg/m2 (IQR: 22.9-31.1), 100% were white, 53% female and 59% had diabetes. Median time from onset of ESKF to calciphylaxis diagnosis was 5.5 years (IQR: 1-16). 53% (9 of 17) had history of recurrent hypercalcaemia (corrected calcium >2.55 mmol/L) and 82% (14 of 17) recurrent hyperphosphatemia (phosphate >1.5 mmol/L). 41% (7 of 17) had refractory secondary hyperparathyroidism. Warfarin therapy exposure was recorded in 47% (8 of 17) patients; a finding consistent with the literature. 76% (13 of 17) had received active vitamin D and 76% (13 of 17) a calcium-based phosphate binder. 76% (13 of 17) had lower leg lesions; 2 of whom also had upper leg lesions. 1 patient had a thigh lesion and 2 patients had an abdominal wound. Median follow up time was 8.5 months (range 1-24). 9 of the 17 patients remain alive, of whom lesions have completely healed in 6 patients. All patients received sodium thiosulphate and 1 (transplant patient) received hyperbaric oxygen therapy and sodium thiosulphate. Only 1 patient has been enrolled into the UK registry of rare kidney diseases (RaDaR). Conclusion Calciphylaxis is a devastating condition for which there are no proven treatments. In this case series a history of hyperphosphataemia, calcium-based binder, alfacalcidol, and warfarin use were common. It remains unknown why some patients develop calciphylaxis and others do not. National registry data, such as RaDaR, plays a crucial role in furthering knowledge and understanding of rare diseases; it helps to determine calciphylaxis incidence, and inform possible prevention and treatment strategies. Yet, in reality, few patients maybe being recruited into RaDaR. The opportunity exists for an international calciphylaxis registry; for this to offer maximum impact individual countries need to explore, and where possible address, barriers to recruitment.

#849 Association between types of phosphate binders and fragility fractures in patients on hemodialysis

Abstract Background and Aims Fractures that affect life expectancy and quality of life are an important outcome in patients undergoing hemodialysis. In older patients on dialysis, osteoporosis is particularly associated with fractures. Therefore, management of calcium, parathyroid hormone and phosphorus is essential to promote bone health. However, no effective treatment against osteoporosis has been established in patients with advanced chronic kidney disease Some reports have suggested that the use of calcium-based phosphate binder was favorable in bone metabolism; however, its effect on fragile fractures remains unclear. In this study, we aimed to investigate the relationship between the use of Ca-containing phosphate binders (CPB) or non-Ca-containing phosphate binders (NCPB) and fractures in patients on hemodialysis. Method A retrospective cohort study was conducted including 556 patients who started hemodialysis at our hospital between March 2004 and March 2023, and could be followed up for at least 3 months. To assess the association of the use of phosphate binders CPB or NCPB with fragile fractures, a multivariate analysis was performed using the Cox proportional hazard model with factors related to fractures as covariates. Results The mean age of the patients was 66 years, with women accounting for 28%. For up to 3 years from hemodialysis initiation, CPB, NCPB, vitamin D receptor activators (VDRA), and calcimimetics were prescribed in 35%, 52%, 72%, and 18% of patients, respectively. Of the 556 patients, 72 developed fragile fractures. A univariate analysis of factors associated with fractures revealed that the hazard ratio (HR) for fragile fractures was 0.39 [0.22-0.64] in CBP users and 0.81 [0.31-0.81] in NCPB users and both were statistically significant fracture suppressors. Multivariate analysis adjusted for significant factors in univariate analysis (age; history of fractures; BMI; levels of serum phosphorus, C-reactive protein, serum magnesium, and hemoglobin; and use or non-use of VDRA) as the covariates, demonstrated that the use of CPB and NCPB was not significantly associated with fractures (HR: 0.58 [0.31–1.05], HR: 0.58 [0.33–1.03]). However, the use of any phosphate binders was a significant fracture preventive factor with an HR of 0.43 [0.24-0.77]. Conclusion Regarding fragile fractures in patients on hemodialysis, no superiority was observed among CPB and NCPB; however, the use of either phosphate binders could reduce the risk of fragility fracture occurrence.

Calcium-based phosphate binders and bone mineral density in patients undergoing hemodialysis: a retrospective cohort study.

Calcium supplements are commonly prescribed to prevent fractures in patients with osteoporosis. Nonetheless, they are generally eschewed in hemodialysis patients because they increase vascular calcification and induce cardiovascular disease. This retrospective cohort study aimed to investigate the effect of calcium-based phosphate binders (CBPB) on bone mineral density (BMD) in hemodialysis patients. Outpatients on dialysis who underwent BMD measurement from January to December 2017, whose data on BMD trends and CBPB administration were recorded over the next 4years, were enrolled. Patients receiving anti-osteoporotic medications were excluded. The association between the presence and duration of CBPB administration and changes in BMD was evaluated. The femoral neck's BMD decreased from 0.836g/cm2 (0.702-0.952) to 0.764g/cm2 (0.636-0.896) (P < 0.001) in the non-CBPB group (patients who never received CBPB over 4years, n = 32). The CBPB group (n = 56) exhibited only a minute decrease from 0.833g/cm2 (0.736-0.965) to 0.824g/cm2 (0.706-0.939) (P = 0.004). Multivariate linear regression analysis revealed better BMD maintenance in the CBPB group [β-coefficient (95% CI): 0.033 (0.001-0.065); P = 0.046] than in the non-CBPB group. Additionally, the prolonged-CBPB administration group showed superior BMD preservation [β-coefficient (95% CI): 0.038 (0.001-0.076); P = 0.042]. CBPB administration may be associated with BMD maintenance.

Longitudinal Assessment of Health-Related Quality of Life in Three Different Hyperphosphatemia Management Groups of Stage III and IV Chronic Kidney Disease Patients.

Health-related quality of life (HRQoL) has emerged as an important outcome measure inpatients with CKD. The lack of prospective studies on HRQoL and its relation with hyperphosphatemia control measures among pre-dialysis patients necessitated the need for this study. This is a prospective, randomized, controlled, open-labelled studythat was conducted for one year on 120 CKD stages III and IV patients divided equally into three groups: Group 1, in which patients under went dietary phosphorus modification; Group 2, in which they were administered calcium-based phosphate binders; and Group 3, in which they were administered non-calcium-based phosphate binders. Patients were assessed for HRQoL, fibroblast growth factor 23 (FGF 23), intact parathyroid hormone (iPTH), phosphorus, and nutritional status, and dietary phosphorus control strategies at 0, 6, and 12 months. HRQoL was measured by using the 36-item Short Form Survey (SF-36) that included a physical component score (PCS) and mental component score (MCS). The scores is ranging from 0 to 100. Higher scores indicate better health status. Usingthe two-wayand one-way repeated measure ANOVA, we analyzed equality of group means, time intervals, and interactions. At baseline, the mean PCS and MCS were equal in three groups. PCS improved significantly (P < 0.00) from baseline to one year in all the three groups: ingroup 1, the PCS score was 66.5 ± 13.5to 75.1 ± 9.76; in group 2, it was 68.9 ± 11.80 to 77.2 ± 7.50; and in group 3, it was 66.2 ± 12.16 to 73.8 ± 9.27. Initially, MCS declined substantially on the sixth month but recovered afterone year. Multiple regression analysis in 13 associated parameters yielded R2 of 13.7% and 18.1% in PCS and MCS, respectively, indicating little contribution of various parameters. There has been a significant positive change in PCSs in three hyperphosphatemia management groups over a period of 12 months. Among the three study groups, the incremental changes in PCS and MCS scores were insignificant.

Multimodality approach to treat calciphylaxis in end-stage kidney disease patients

A multimodality approach has been proposed as an effective treatment for calciphylaxis in patients with end-stage kidney disease. In this retrospective study, we report the cases of 12 end-stage kidney disease patients from l’Hôtel-Dieu de Québec hospital (Canada) who were diagnosed with calciphylaxis between 2004 and 2012 and treated with a multimodality clinical approach including sodium thiosulfate (STS). Statistical analyses were performed to evaluate the impacts of patients characteristics, the different interventions as well as therapy regimen on the therapeutic response. The majority of patients (n = 9) were hemodialyzed. The patients-associated comorbidities were consistent with previously reported risk factors for calciphylaxis: Diabetes (n = 11), calcium-based phosphate binders use (n = 10), warfarin use (n = 9), obesity (n = 7), female gender (n = 8) and intravenous iron use (n = 8). STS was given for a median duration of 81 days. 75% of the patients had a response (total or partial) including a complete response in 42% of patients. One-year mortality rate was low (25%). STS was used during a mean duration of 83.33 ± 41.52 days and with a total cumulating dose of 1129.00 ± 490.58 g. The recorded mean time before a complete response was 102.20 days (51–143). Pain improvement occurred after a mean time of 8.67 ± 10.06 days. None of the studied factors was statistically associated with a complete or a partial response to the multimodality approach. Although our data have a limited statistical power, they support treating calciphylaxis with a multimodality approach including STS as its effects are independent from important clinical variables.

Recommended calcium intake in adults and children with chronic kidney disease-a European consensus statement.

Mineral and bone disorders (MBD) are common in patients with chronic kidney disease (CKD), contributing to significant morbidity and mortality. For several decades, the first-line approach to controlling hyperparathyroidism in CKD was by exogenous calcium loading. Since the turn of the millennium, however, a growing awareness of vascular calcification risk has led to a paradigm shift in management and a move away from calcium-based phosphate binders. As a consequence, contemporary CKD patients may be at risk of a negative calcium balance, which, in turn, may compromise bone health, contributing to renal bone disease and increased fracture risk. A calcium intake below a certain threshold may be as problematic as a high intake, worsening the MBD syndrome of CKD, but is not addressed in current clinical practice guidelines. The CKD-MBD and European Renal Nutrition working groups of the European Renal Association (ERA), together with the CKD-MBD and Dialysis working groups of the European Society for Pediatric Nephrology (ESPN), developed key evidence points and clinical practice points on calcium management in children and adults with CKD across stages of disease. These were reviewed by a Delphi panel consisting of ERA and ESPN working groups members. The main clinical practice points include a suggested total calcium intake from diet and medications of 800-1000mg/day and not exceeding 1500mg/day to maintain a neutral calcium balance in adults with CKD. In children with CKD, total calcium intake should be kept within the age-appropriate normal range. These statements provide information and may assist in decision-making, but in the absence of high-level evidence must be carefully considered and adapted to individual patient needs.

Journal of Pharmaceutical Negative Results ¦ Volume 13 ¦ Special Issue 9 ¦ 2022 1734 PHOSPHATE BINDERS AS A SUPPLEMENT-ASSESSMENT OF KNOWLEDGE, ATTITUDE AND PRACTICE AMONG ESRD PATIENTS ON MAINTENANCE HEMODIALYSIS IN A TERTIARY CARE TEACHING HOSPITAL IN S

Objectives: To assess the Knowledge, Attitude and Practice regarding phosphate binders among ESRD patients on maintenance hemodialysis in South India. And also, to assess its adverse effects and the impact on the gastrointestinal system. Methods: We conducted a cross sectional prospective study at nephroplus and vakula dialysis center in SVIMS, Tirupati for a period of 6 months. A total 226 patients were included in the study, who are on hemodialysis between November 2021 to April 2022. The study involved interviewing the patients, reviewing their medical records to assess the patients Knowledge, Attitude, Practice regarding these phosphate binders and to understand the impact of these binders on the GI system. Results: We included 226 patients in our study. 73:27 was the male and female ratio. The prevalence of prescribing calcium phosphate binders was 37%, non-calcium phosphate binders was 14% and combination of both binders was 49%. Most patients showed adequate to good attitudes towards phosphate balance. Calcium based phosphate binders had more effect on GI system when compared to the patients using non-calcium-based phosphate binders. Conclusion: Patients receiving hemodialysis mostly use phosphate binders. Binders negative impact on GI system is more due to low awareness level. Additionally, they claimed that nutrition restrictions during dialysis were not implemented with sufficient care and had poor compliance procedures. Further, we recommend efficacious patient counseling programs need to carried out to improve the awareness and knowledge of these phosphate binders among hemodialysis patients to minimize adverse effects.

Hyperphosphatemia in Chronic Kidney Disease: Drug Treatment and Effects on Metabolic Acidosis. A Mini Review

Hyperphosphatemia is a highly prevalent component of CKD and chronic kidney disease mineral bone disease (CKD-MBD). Its association with metabolic acidosis, hypertension, cardiovascular disease and chronic inflammation is common. Treatment is commonly with calcium based phosphate binder (PB) as the high cost of sevelamer makes it readily unavailable particularly in low income settings. Sevelamer has several comparative advantage over calcium based PBs, many of which, in addition to its non-worsening of tissue calcification contributes significantly to positive treatment outcome. The ability of sevelamer to reduce many cytokines and inflammatory mediators such as TNF-α, IL-1, IL-6, FGF-23 and high sensitivity CRP among others, contributes significantly to its renoprotection prowess.

412.11: New-Onset Osteoporotic Fracture After Kidney Transplantation: A Matched Comparative Nationwide Cohort Study

Background: Successful kidney transplantation (KT) has brought better survival and quality of life to patients with end-stage kidney disease (ESKD), although long-term immunosuppressive agent-related side effects such as osteoporosis remain unresolved. We aim to explore the incidence risk of de novo osteoporotic fractures after KT compared with matched dialysis patients. Method: We constructed a nation-wide retrospective cohort consist of 141,674 ESKD patients from 2008 to 2020 using the National Health Insurance System database of Korea. After 1-year of wash out periods, patients younger than 18-year-old, having previous history of any kind of cancer, experiencing parathyroidectomy, re-transplantation, osteoporotic fracture, or taking osteoporosis-treating medication were excluded. Then, we extracted KT recipients and 1:1-matched dialysis patients according to the age, sex, era, and the presence of hypertension or diabetes. Osteoporotic fractures are defined as fractures associated with low bone mineral density including hip, spine, forearm, and humerus. We compared the de novo osteoporotic fracture incidence between the two groups. Result: After exclusion of 26883 patients in wash-out periods, 483 children, 6953 having cancers, 336 experiencing parathyroidectomy, 8907 preexisting osteoporotic fractures, 3755 established osteoporosis medications, and 110 re-transplantations, we finally identified 12760 matched KT-dialysis pairs. Their average age was 51.0 ± (10.1) (standard deviation (SD)) years and 7951 (62.3%) were male. Patients with having hypertension and diabetes were 11800 (92.5%) and 4548 (35.6%), respectively. About 30.5% KT patients received their graft preemptively. New-onset osteoporotic fractures after inclusion occurred in 631 (4.9%) of dialysis patients and 588 (4.6%) of KT recipients, respectively. The most common fracture site was forearm in both groups. During overall 4.7 ± 3.1 years of follow up, KT recipients showed similar risk for the development of new-onset osteoporotic fracture compared with matched dialysis controls even after adjustment of matching variables, previous use of steroid or anti-depressants, vitamin D or its analog, calcium-based phosphate binders. In subgroup analysis, they showed a lower risk of hip fracture (adjusted hazard ratio 0.51, 95% CI 0.38-0.67, p <0.001), but similar risks of other types of osteoporotic fractures including spine, forearm, or humerus compared to dialysis controls. Conclusion: In this study, overall new-onset osteoporotic fracture risk of KT recipients was not different from matched dialysis controls except a lower risk of hip fractures.

MO813: The Validity of Combined Urea and Phosphate Kinetic Modelling in Estimation of Daily Protein and Phosphate Intake in Haemodialysis Patients

Abstract BACKGROUND AND AIMS The interpretation of patient dietary records, laboratory results in haemodialysis units to manage their phosphate and nutritional status is time and effort consuming and needs strictly compliant patients. This justifies the need of estimates of these parameters with accepted validity and applicability. METHOD In 100 haemodialysis patients [50 with residual kidney function (RKF) and 50 anuric patients], Daugirdas [1, 2] supposed urea and phosphate kinetic models’ estimates were extracted and correlated with the actual dietary records, phosphate binder dosage and dialysis prescription parameters. The estimates of interest were, daily ingested phosphorus (DIP), estimated phosphorus removed, intradialytic time averaged phosphate level, normalized protein catabolic ratio (nPCR) and dialysis estimated kt/v. RESULTS Modeled DIP is significantly correlated to calculated phosphate intake from average 3-day dietary records in both anuric and RKF patients (r = 0.89 and r = 91, respectively; P &amp;lt; .001). Also, the nPCR is significantly correlated with daily protein intake/kg in both study groups (r = 0.85 in anuric, r = 0.78 in RKF; P &amp;lt; .001). Estimated phosphorus removed is positively correlated to dialysis kt/v in both study groups (r = 0.51 in anuric, r = 0.52 in RKF; P &amp;lt; .001). Patients with RKF had significantly lower pre-dialysis serum phosphate (5.78 ± 1.05 versus 4.39 ± 0.78; P &amp;lt; .001), calcium-based phosphate binders’ dosage (2616.28 ± 390.93 mg/day versus 1937.5 ± 395.29 mg/day; P &amp;lt; .001), estimated phosphate removed in haemodialysis (1271.86 ± 274.5 mg/day versus 1016.82 ± 198.42 mg/day; P &amp;lt; .001) and intradialytic average phosphate levels (4.052 ± 0.87 mg/dL versus 3.26 ± 0.61 mg/dL; P &amp;lt; 0.001) than the anuric group. CONCLUSION Modeled DIP and nPCR can be used as estimates for phosphate and protein intake in haemodialysis patients with or without RKF. RKF has a positive impact on the phosphate measures and decreases the need for phosphate binders. For each patient is shown the mean result after CC treatment and after SO treatment. The red bold line represents mean values. (A) Bone turnover estimated from whole-body 18F-NaF PET/CT as Ki at lumbar vertebrae 1–5 in 20 participants. (B) Bone volume estimated as CT-derived HU at lumbar vertebrae 1–5 in 21 participants. * Significance level &amp;lt; 0.05.

MO814: Sucroferric Oxyhydroxide versus Calcium Carbonate in the Treatment Bone Metabolism in Patients with Ckd3–5 Evaluated by 18F-NA Fluoride PET/CT and Biomarkers: A Randomized Crossover Study

Abstract BACKGROUND AND AIMS Non-invasive methods for assessing bone metabolism have been lacking in chronic kidney disease (CKD), and the effects of different treatments on bone metabolism are mostly unknown. However, fluorine-18 labeled sodium fluoride (18F-NaF) PET/CT scanning can assess bone turnover as skeletal plasma clearance of tracer (Ki) and bone volume/tissue volume (BV/TV) in CKD. In a randomized crossover study, we aimed to compare the 8-week treatment effects of a non-calcium-based phosphate binder, sucroferric oxyhydroxide (SO), with 8 weeks of treatment with a calcium-based phosphate binder, calcium carbonate (CC), on bone turnover and BV/TV. METHOD Whole body 18F-NaF PET/CT scans were performed at the end of the CC and SO treatment periods in each participant. Ki was determined by the single-point Patlak method with semi-population input functions. A recently established CKD-MDB population residual curve was applied. Estimation of BV/TV was made by CT-derived Hounsfield units (HU) in specified volumes of interest. Paired t-tests were used or non-parametric tests (Wilcoxon signed-ranks test) when data were not normally distributed. Statistical analyses were performed using SPSS 20. RESULTS Ki assessed by the 18F-NaF scan was not significantly different at the lumbar spine (CC: 0.030 ± 0.014 mL min–1 mL–1; SO: 0.031 ± 0.014 mL min–1 mL–1; P = .75) or any other site after short-term treatment with SO or CC. However, HU was significantly higher after CC treatment. CONCLUSION 18F-NaF PET/CT is a practical tool with which to evaluate bone metabolism in CKD. Short-term SO treatment did not affect Ki (turnover) differently than CC treatment, but BV/TV (volume) was significantly lower after SO treatment than after CC treatment.

MO544: Outcomes Associated With use of Phosphate Binders in Persons With Chronic Kidney Disease Stages 4 and 5 in Spain

Abstract BACKGROUND AND AIMS Use of phosphate binders among non-dialysis chronic kidney disease (ND-CKD) patients remains controversial, since clinically relevant benefits have not been fully demonstrated. The goal of this study was to determine patterns of phosphate binders use and its associated outcomes in ND-CKD patients. METHOD PECERA (Collaborative Study Project in Patients with Advanced CKD) is a 3-year, prospective multicentre, open-cohort study of 966 adult patients with non-dialysed CKD stages 4–5 enrolled from 12 centres in Spain. The end of the follow-up was December 2012. At baseline and every 6 months, demographics, comorbidities, treatments and serum biochemical parameters were collected. Patients who received treatment with calcium-based and calcium-free phosphate binders were compared with those who had not. In a prespecified statistical approach, we assessed the association of phosphate binders use with all-cause mortality using time-dependent Cox proportional hazards models. RESULTS Sevelamer was the only calcium-free based binder prescribed during the study. Overall, 515 (53%) patients received some form of binder, with most of them using calcium-based binders (n = 360, 37%) and a minority (n = 111, 11%) using exclusively sevelamer (n = 111, 11%) or a combination of the two (n = 44, 5%). After a median follow-up of 29 months (IQR 13–36 months) there were 181 deaths (19%). Crude overall all-cause mortality was significantly lower in patients receiving sevelamer, but not in those receiving calcium-based binders (Figure). After multivariate adjustment for age, weight, blood pressure, diabetes, comorbidity, vitamin D treatment, renal function and levels of albumin, calcium, phosphorous and PTH, treatment with sevelamer was independently associated with lower mortality [adjusted hazard ratio (HR), 0.44 (95% confidence interval (95% CI), 0.22–0.88); P = 0.02]. Use of calcium-based phosphate binders did not predict death. CONCLUSION The administration of sevelamer is associated with lower all-cause mortality in advanced ND-CKD patient. Clinical trials are warranted to clarify the risks and benefits of phosphate binders in this population.

MO730: Markers of Vitamin K Deficiency in Haemodialysis Patients

Abstract BACKGROUND AND AIMS Vitamin K deficiency is a common feature of CKD, leading to impaired bone quality and an increased risk of vascular calcifications. A method to indirectly measure vitamin K status is measuring the blood level of vitamin K dependent proteins (VKDP)- osteocalcin (OC) and matrix GLA protein (MGP). The aim of this study is to correlate the level of OC and MGP with markers of CKD mineral bone disorder (CKD-MBD). METHOD We conducted a single-centre cross-sectional study that included 45 CKD G5D patients (haemodialysis for 6 months–10 years). All patients have been assessed regarding their dialysis status (medical history), we performed analysis before the dialysis session using standard methods blood biochemistry, complete blood count and intact osteocalcin and matrix GLA protein. RESULTS In the studied haemodialysis patients mean OC was 169.06 ± 128.28 ng/mL, while mean MGP was 3285.93 ± 2092.85 pmol/L. No statistically significant correlation has been found between OC and MGP. We found a strong statistically significant correlation of OC with the markers of CKD-MBD such as: iPTH (r = 0.48, P = 0.0007), serum calcium (r = 0.49, P = 0.0005) and serum phosphorus (r = 0.29, P = 0.04). No statistically significant correlation has been found between MGP and the above- mentioned markers. Only 2 out of 45 patients recorded a past history of bone fractures. Regarding the relationship with the nutritional status of the patients, no statistically significant correlations of the assessed VKDP with BMI and serum albumin have been found. However, a strong indirect statistically significant correlation of OC with abdominal circumference was observed (r = –0.43, P = 0.003). There was also a statistically significant correlation of MGP with markers of inflammation (CRP) (r = 0.55, P = 0.004). No statistically significant differences have been found regarding the level of VKDP between patients with and without a history of diabetes mellitus (13/45), coronary heart disease (18/45) stroke (5/45). The group of patients that are currently under treatment with vitamin K antagonists (13 out of 45) showed significantly higher levels of MGP (5693.0 ± 1728.64 versus 2276.5 ± 1232.54 pmol/L; P &amp;lt; 0.01). Treatment with non-calcium-based phosphate binders (20 patients) was associated to significantly higher levels of MGP compared with treatment with calcium-based phosphate binders (15 patients) (4089.2 ± 2045.79 versus 2134.86 ± 1944.63 pmol/L; P = 0.019). Treatment with vitamin D receptor activator-paricalcitol (20 patients) was associated to significantly increased levels of MGP (4224.55 ± 2162.32 versus 2503.75 ± 1709.31 pmol/L; P = 0.005). CONCLUSION In our study, we found that vitamin K deficiency, measured indirectly using the level of VKDP is associated to CKD-MBD, could be influenced by features of malnutrition-inflammation. The use of medications such as phosphate binders that reduce vitamin K absorbtion, vitamin D that increases vitamin K requirements and also vitamin K antagonists, seems to have an influence on the blood level of VKDPs.

Effects of phosphate binders on bone biomarkers and bone density in haemodialysis patients.

The incidences of osteoporosis, fracture and vascular calcification increase concordantly with the progression of chronic kidney disease (CKD). CKD-mineral bone disease (CKD-MBD) induced by hyperphosphatemia is a major pathophysiologic mechanism. The effects of phosphate binders on bone turnover biomarkers and bone mineral density (BMD) in haemodialysis patients are still inconclusive. Our aim is to demonstrate the effects of these phosphate binders on different aspects of CKD-MBD. We conducted a prospective cohort of 65 haemodialysis patients to investigate the effect of 12-month monotherapy of phosphate binders composing calcium-based phosphate binders (CPB) or non-calcium-based phosphate binders (NCPB), including sevelamer and lanthanum, on bone turnover biomarkers and BMD changes. The performance of bone turnover biomarkers to predict low BMD was attentively determined. When compared with CPB, NCPB use was associated with higher levels of bone turnover biomarkers. NCPB was also associated with lower BMD at lumbar and distal radius. Total procollagen type 1N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (BALP), and tartrate-resistant acid phosphatase 5b (TRAP5b) provided the best performance for diagnosing low BMD in haemodialysis patients. Switching from CPB to NCPB might increase bone biomarkers and prevent the development of adynamic bone disease. On the contrary, NCPB should be cautiously used in haemodialysis patients who already had low BMD. P1NP, BALP and TRAP5b could be used to guide the appropriate management, including anti-resorptive and anabolic medications, and predict low BMD in haemodialysis patients treated with phosphate binders.

Phosphate Intake and Removal in Predominantly Vegetarian Patients on Twice-Weekly Hemodialysis.

Hyperphosphatemia is linked to increased mortality and morbidity in patients on hemodialysis. Currently, the phosphate intake and dialytic removal in predominantly vegetarian patients on twice-weekly dialysis is not well studied. This prospective, study recruited patients on twice-weekly dialysis of at least 3 months duration. Baseline clinical variables were measured. Dietary protein and phosphorus intake was assessed using a validated food frequency questionnaire. Phosphate binder use was assessed, hourly blood was collected for serum phosphorus during dialysis, and spent dialysate was collected to estimate cumulative phosphorus removal during the session. Forty (67%) of the 60 patients studied were vegetarians. Twenty-eight (48%) were hyperphosphatemic, and 15 (25%) had serum parathormone (PTH) >500 pg/ml. The mean phosphorus intake was 1247 (±312) mg/day, the mean serum phosphorus was 5.49 (±2.01) mg/dl, and the mean dialytic phosphorus removal was 910 (±383) mg/session. Up to 67% of the study population took calcium-based phosphate binders, 25% took sevelamer carbonate, and 40% took activated vitamin D preparation. The lowest tertiles of phosphorus intake correlated with low energy-adjusted protein intake and hypoalbuminemia. Hyperphosphatemic subjects had better nutritional indices (mid-upper arm circumference and body mass index). Dietary intake and serum phosphorus levels were not mutually associated, but both were strongly correlated with total phosphorus removal in the spent dialysate. Serum phosphorus levels fell by 32% by thefirst hour of hemodialysis. Twice-weekly dialysis is often practised in resource-limited Asian countries. However, due to a predominantly vegetarian diet, hyperphosphatemia was noted only in up to half of the patients, despite twice-weekly hemodialysis schedules. This reinforces the fact that plant-based dietary phosphate is less well absorbed.

Longitudinal Study to Find the Association of Serum Phosphorus Level with FGF23 in Three Different Hyperphosphatemia Management Groups of Stage 3 and 4 Chronic Kidney Disease (CKD) Patients.

There is paucity of clinical evidence on target serum phosphorus levels in early chronic kidney disease (CKD). Present longitudinal study was done to find target phosphorus level and its association with fibroblast growth factor (FGF23) in three different hyperphosphatemia management groups. This 1-year, prospective, randomized controlled, open-labelled study was conducted among three equally allocated treatment groups that consisted of 120 screened early CKD patients totally. Group 1 patients were given dietary phosphorus modification (n = 40), group 2 patients were administered calcium-based phosphate binders (n = 40), and group 3 patients were given non-calcium-based phosphate binders (n = 40). Three-monthly dietary assessment, MDRD estimated glomerular filtration rate (eGFR), phosphorus, calcium, iPTH, alkaline phosphatase, and six-monthly FGF23, 2D echocardiography, and X-ray of chest and abdomen were performed. Association of three categories of phosphorus level up to 3.9, 4-5, and >5mg/dl, rate of progression of all parameters, and correlation with FGF23 were studied among all three groups. At baseline, all clinical and biochemical parameters were equally distributed with a controlled nutritional phosphate among all groups. There was no significant difference of FGF23 levels from all the three categories of phosphorus level among all groups. Serum phosphorus at the level of 5 mg/dl was associated with iPTH and eGFR at 1 year. Over 1 year, there was a significant decline in serum phosphorus levels in group 1 (P 0.02), group 2 (P 0.00), and group 3 (P 0.05). FGF23 declined significantly only in group 3 (P 0.00). There was no correlation of FGF23 with serum phosphorus levels (P 0.13). However, FGF23 correlated positively with iPTH (P 0.03, r = 0.19). Serum phosphorus levels upto 5mg/dl had no effect on FGF23 at early CKD stages. Although different treatment groups showed significant phosphorus reduction, non-calcium phosphate binder had a major impact on FGF23 reduction.

Effect of lanthanum carbonate on the progression of coronary artery calcification in hemodialysis patients: A meta-analysis of randomized controlled trials.

Coronary artery calcification and cardiac abnormalities are common in hemodialysis patients. The value of lanthanum carbonate over calcium-based phosphate binders in managing the progression of coronary artery calcification is debated. We reviewed all randomized controlled trials (RCTs) comparing the two strategies in these patients. RCTs comparing lanthanum carbonate with calcium-based phosphate binders used in adult hemodialysis patients were identified in the PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure, China Science and Technology Journal, and Wanfang databases. Ten RCTs involving 687 patients were suitable for inclusion. Compared with calcium-based phosphate binders, lanthanum carbonate yielded lower coronary artery calcium scores (weighted mean difference, WMD: -74.28, 95% CI: -149.89, 1.33), change in coronary artery calcium scores (WMD: -105.18, 95% CI: -113.83, -96.53), and left ventricular mass index (WMD: -29.95, 95% CI: -54.25, -7.45). Lanthanum carbonate was significantly associated with lower levels of serum phosphate (WMD: -0.18, 95% CI: -0.26, -0.10), calcium (WMD: -0.22, 95% CI: -0.25, -0.20), and fibroblast growth factor 23 (FGF23) (standard mean difference: -3.78, 95% CI: -5.60, -1.96) but not intact parathyroid hormone (WMD: -4.23, 95% CI: -64.12, 55.65). Moreover, a reduced risk of nonfatal cardiovascular events (OR: 0.31, 95% CI: 0.10-0.97) but not all-cause mortality (OR: 1.08, 95% CI: 0.39-3.01) in lanthanum carbonate therapy was observed. In hemodialysis patients, lanthanum carbonate therapy may impede the progression of coronary artery calcification and left ventricular mass index and lead to reduced serum phosphate, calcium, FGF23, and nonfatal cardiovascular events compared with calcium-based phosphate binders. However, more well-designed RCTs are required for confirmation.

Effect of Citrate-Acidified Dialysate on Intact Parathyroid Hormone in Prevalent Hemodialysis Patients: A Matched Retrospective Cohort Study.

BackgroundIt has been proposed that substituting citrate-acidified dialysate (CAD) solutions for acetate-acidified dialysate (AAD) could improve hemodynamics and dialysis tolerance and reduce the requirement for systemic anticoagulation. Citrate chelates ionized calcium, but long-term effects of CAD use during maintenance hemodialysis have not been well studied. While many studies of the effects of CAD on serum calcium and intact parathyroid hormone (iPTH) have been short-term or have been limited by sample size, we aimed to determine if there are any long-term (i.e., 6-month) changes from pre-dialysis iPTH levels when patients are switched from AAD to CAD.MethodsThis retrospective cohort study compared various clinical parameters, including pre-dialysis iPTH and serum calcium as well as single pool Kt/V, from eligible patients who received in-center hemodialysis thrice-weekly in geographically matched CAD (n=3) or AAD clinics (n=12). CAD clinics were defined as clinics converting from AAD to CAD if >85% of the patients were prescribed CAD after implementation of CAD within the clinic.ResultsPre-dialysis iPTH was not significantly different from baseline to 6-month follow-up within either CAD or AAD clinics. Moreover, the mean change from baseline to month 6 in iPTH between patients (n=142) in CAD clinics (−17 pg/mL) and patients (n=671) in AAD clinics (13 pg/mL) was similar (p = 0.24). Likewise, the differences in the mean change in serum calcium concentrations and dialysis adequacy (single pool Kt/V) were not significant between CAD and AAD clinics. For subgroups of patients who were never prescribed cinacalcet or calcium-based phosphate binders, there were no significantly different categorical shifts in iPTH between CAD and AAD clinics.ConclusionSimilar trends in single pool Kt/V, iPTH, and serum calcium levels were observed in clinics that switched from AAD to CAD versus the geographically matched AAD clinics. These results support CAD as a potential alternative to AAD in hemodialysis.

Calcium-Based Phosphate Binders and the Regulation of FGF-23

Calcium-Based Phosphate Binders and the Regulation of FGF-23