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Expert Review of Pharmacoeconomics &... Jun 2019End-stage renal disease is associated with significant comorbidity and mortality. Among its implications, hyperphosphatemia constitutes a consistent and independent risk... (Comparative Study)
Comparative Study
A systematic review of the economic evaluations of non-calcium-containing phosphate binders, sevelamer and Lanthanum, in end-stage renal disease patients with hyperphosphatemia.
INTRODUCTION
End-stage renal disease is associated with significant comorbidity and mortality. Among its implications, hyperphosphatemia constitutes a consistent and independent risk factor. The use of benchmark treatment, low-cost calcium-based binders declined due to a potential calcification effect on coronary arteries.
AREAS COVERED
Given the increasing prevalence of end-stage renal disease and the high cost of hyperphosphatemia's new primary modality, the non-calcium based phosphate binders, we set-off to systematically assess the economic evaluations of non-calcium containing phosphate binders, sevelamer and lanthanum. The study was performed based on a systematic review of the economic evaluations of sevelamer and lanthanum. The cost-effectiveness profile of the two non-calcium-containing Phosphate Binders compared to calcium-based phosphate binders depends on several factors such as future dialysis costs, utility values, age, survival, and phosphorus levels.
EXPERT OPINION
The comparison between the two agents is rather inconclusive; nevertheless, current review suggests that non-calcium-based phosphate binders may yield a positive cost-effectiveness ratio in patients with inadequate phosphorus management and patient with longer life-expectancy. It is crucial that the literature is endowed with more data, specifically on survival, future dialysis costs, and calcification.
Topics: Chelating Agents; Cost-Benefit Analysis; Humans; Hyperphosphatemia; Kidney Failure, Chronic; Lanthanum; Life Expectancy; Renal Dialysis; Sevelamer
PubMed: 30664365
DOI: 10.1080/14737167.2019.1567336 -
Journal of Renal Nutrition : the... Nov 2014Metabolic bone disease (MBD) is a common complication of chronic kidney disease (CKD). The currently accepted international guidelines for treatment of CKD-MBD has been... (Meta-Analysis)
Meta-Analysis Review
Metabolic bone disease (MBD) is a common complication of chronic kidney disease (CKD). The currently accepted international guidelines for treatment of CKD-MBD has been published, unfortunately adequate control of serum markers of disorder, especially hyperphosphatemia, is poorly achieved. Whether educational intervention is an effective way for improving CKD-MBD remains controversial. A systematic review of educational intervention versus routine care to improve patients with CKD-MBD was conducted. All randomized controlled trials (RCTs) and quasi-RCTs examining the efficacy of educational intervention to improve patients with CKD-MBD were included. We performed a comprehensive search of several databases and sources to identify eligible trials. In addition, we searched unpublished studies by tracking the SIGLE (System for Information on Grey Literature) database. Finally, 8 RCTs and 2 quasi-RCTs containing 775 participants were included in our systematic review. The result of our study revealed that the educational intervention to patients with CKD-MBD led to an improvement of the serum phosphorus and calcium by phosphate product. Educational intervention is a beneficial supplement method in improving CKD-MBD and putting off deterioration of the disease.
Topics: Biomarkers; Bone Diseases, Metabolic; Calcium; Databases, Factual; Health Knowledge, Attitudes, Practice; Humans; Hyperphosphatemia; Patient Education as Topic; Phosphorus; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Treatment Outcome
PubMed: 25193107
DOI: 10.1053/j.jrn.2014.06.007 -
Lancet (London, England) Oct 2013Phosphate binders (calcium-based and calcium-free) are recommended to lower serum phosphate and prevent hyperphosphataemia in patients with chronic kidney disease, but... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Phosphate binders (calcium-based and calcium-free) are recommended to lower serum phosphate and prevent hyperphosphataemia in patients with chronic kidney disease, but their effects on mortality and cardiovascular outcomes are unknown. We aimed to update our meta-analysis on the effect of calcium-based versus non-calcium-based phosphate binders on mortality in patients with chronic kidney disease.
METHODS
We did a systematic review of articles published in any language after Aug 1, 2008, up until Oct 22, 2012, by searching Medline, Embase, International Pharmaceutical Abstracts, Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature. We included all randomised and non-randomised trials that compared outcomes between patients with chronic kidney disease taking calcium-based phosphate binders with those taking non-calcium-based binders. Eligible studies, determined by consensus with predefined criteria, were reviewed, and data were extracted onto a standard form. We combined data from randomised trials to assess the primary outcome of all-cause mortality using the DerSimonian and Laird random effects model.
FINDINGS
Our search identified 847 reports, of which eight new studies (five randomised trials) met our inclusion criteria and were added to the ten (nine randomised trials) included in our previous meta-analysis. Analysis of the 11 randomised trials (4622 patients) that reported an outcome of mortality showed that patients assigned to non-calcium-based binders had a 22% reduction in all-cause mortality compared with those assigned to calcium-based phosphate binders (risk ratio 0·78, 95% CI 0·61-0·98).
INTERPRETATION
Non-calcium-based phosphate binders are associated with a decreased risk of all-cause mortality compared with calcium-based phosphate binders in patients with chronic kidney disease. Further studies are needed to identify causes of mortality and to assess whether mortality differs by type of non-calcium-based phosphate binder.
FUNDING
None.
Topics: Acetates; Aged; Calcium Carbonate; Calcium Compounds; Cause of Death; Chelating Agents; Female; Humans; Hyperphosphatemia; Male; Middle Aged; Phosphates; Randomized Controlled Trials as Topic; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 23870817
DOI: 10.1016/S0140-6736(13)60897-1 -
Nephrology, Dialysis, Transplantation :... Oct 2007The relative effectiveness and safety of sevelamer for treatment of hyperphosphataemia in dialysis patients is uncertain, as compared with calcium-based phosphate... (Review)
Review
BACKGROUND
The relative effectiveness and safety of sevelamer for treatment of hyperphosphataemia in dialysis patients is uncertain, as compared with calcium-based phosphate binders.
METHODS
We conducted a comprehensive search to identify all randomized cross-over or parallel group studies comparing sevelamer to any other therapy or placebo in adult dialysis patients. Study quality was assessed using the Chalmers Index. Data was extracted and checked using a standardized form and combined using a random effects model.
RESULTS
We identified 14 primary publications of randomized trials (3193 participants) that were eligible for efficacy analysis. In analyses pooling, the 10 studies reporting on serum phosphate and calcium (2501 participants), serum phosphate was significantly lower with calcium-based phosphate binders by 0.12 mmol/l [95% confidence interval (CI) 0.05-0.19], compared with sevelamer. On-treatment calcium-phosphate product was not significantly lower in patients receiving calcium-based phosphate binders (0.12 mmol(2)/l(2), -0.05 to 0.29), compared with sevelamer. Overall mean difference in serum calcium was significantly lower with sevelamer therapy by 0.10 mmol/l (-0.12 to -0.07) and pooled on-treatment decrease in serum bicarbonate was significantly greater with sevelamer therapy by 2.8 mmol/l (2.2 to -3.5). In the five trials which reported all-cause mortality (2429 participants), the overall risk difference for all cause mortality in these five trials was similar between therapies (-2%, 95% CI -6-2). In the three trials which reported serious adverse events (2185 participants), there was a trend towards a lower risk in patients receiving calcium-based phosphate binders (13% lower, 95% CI -2-29).
CONCLUSIONS
Compared with calcium-based phosphate binders, use of sevelamer in dialysis patients is associated with similar to slightly higher phosphate levels, similar calcium phosphate product, and slightly lower serum calcium levels. There was no evidence that sevelamer reduced all-cause mortality, cardiovascular mortality, the frequency of symptomatic bone disease or health-related quality of life.
Topics: Calcium; Calcium Phosphates; Chelating Agents; Drug Design; Humans; Hyperphosphatemia; Kidney; Kidney Diseases; Phosphates; Polyamines; Randomized Controlled Trials as Topic; Renal Dialysis; Research Design; Safety; Sevelamer; Treatment Outcome
PubMed: 17906326
DOI: 10.1093/ndt/gfm421 -
Journal of Nephrology Jun 2016Hyperphosphatemia is common in chronic kidney disease (CKD) and is treated by dietary measures, dialysis techniques and/or phosphate binders. For the present review... (Review)
Review
Hyperphosphatemia is common in chronic kidney disease (CKD) and is treated by dietary measures, dialysis techniques and/or phosphate binders. For the present review PubMed was searched for new publications on phosphate binders appearing between January 2010 and October 2015. This review summarizes the latest information on non-pharmacological measures and their problems in lowering phosphate in CKD patients, effects of phosphate binders on morbidity and mortality, adherence to phosphate binder therapy as well as new information on specific aspects of the various phosphate binders on the market: calcium acetate, calcium carbonate, magnesium-containing phosphate binders, polymeric phosphate binders (sevelamer, bixalomer, colestilan), lanthanum carbonate, ferric citrate, sucroferric oxyhydroxide, aluminum-containing phosphate binders, and new compounds in development. The review also briefly covers the emerging field of drugs targeting intestinal phosphate transporters.
Topics: Drug Combinations; Ferric Compounds; Humans; Hyperphosphatemia; Lanthanum; Phosphates; Polyamines; Renal Insufficiency, Chronic; Sevelamer; Sucrose
PubMed: 26800972
DOI: 10.1007/s40620-016-0266-9 -
Journal of Bone and Mineral Research :... Oct 2022Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism due to activating variants of the calcium-sensing receptor gene (CASR). Inherited or...
Autosomal dominant hypocalcemia type 1 (ADH1) is a rare form of hypoparathyroidism due to activating variants of the calcium-sensing receptor gene (CASR). Inherited or de novo activating variants of the CASR alter the set point for extracellular calcium, resulting in inadequate parathyroid hormone (PTH) secretion and inappropriate renal calcium excretion leading to hypocalcemia and hypercalciuria. Conventional therapy includes calcium and activated vitamin D, which can worsen hypercalciuria, resulting in renal complications. A systematic literature review, using published reports from 1994 to 2021, was conducted to catalog CASR variants, to define the ADH1 clinical spectrum, and to determine the effect of treatment on patients with ADH1. There were 113 unique CASR variants reported, with a general lack of genotype/phenotype correlation. Clinical data were available in 191 patients; 27% lacked symptoms, 32% had mild/moderate symptoms, and 41% had severe symptoms. Seizures, the most frequent clinical presentation, occurred in 39% of patients. In patients with blood and urine chemistries available at the time of diagnosis (n = 91), hypocalcemia (99%), hyperphosphatemia (59%), low PTH levels (57%), and hypercalciuria (34%) were observed. Blood calcium levels were significantly lower in patients with severe symptoms compared with asymptomatic patients (6.8 ± 0.7 versus 7.6 ± 0.7 mg/dL [mean ± SD]; p < 0.0001), and the age of presentation was significantly lower in severely symptomatic patients (9.1 ± 15.0 versus 19.3 ± 19.4 years; p < 0.01). Assessments for complications including nephrocalcinosis, nephrolithiasis, renal impairment, and brain calcifications in 57 patients on conventional therapy showed that 75% had at least one complication. Hypercalciuria was associated with nephrocalcinosis, nephrolithiasis, renal impairment, or brain calcifications (odds ratio [OR] = 9.3; 95% confidence interval [CI] 2.4-37.2; p < 0.01). In 27 patients with urine calcium measures before and after starting conventional therapy, the incidence of hypercalciuria increased by 91% (p < 0.05) after therapy initiation. ADH1 is a condition often associated with severe symptomatology at presentation with an increase in the risk of renal complications after initiation of conventional therapy. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Hypercalciuria; Hypocalcemia; Receptors, Calcium-Sensing; Calcium; Nephrocalcinosis; Hypoparathyroidism; Parathyroid Hormone; Nephrolithiasis; Vitamin D
PubMed: 35879818
DOI: 10.1002/jbmr.4659 -
Journal of Renal Nutrition : the... Mar 2024Internet search engines and social media websites are prominent and growing sources of dietary information for people with chronic kidney disease (CKD) and their...
OBJECTIVE
Internet search engines and social media websites are prominent and growing sources of dietary information for people with chronic kidney disease (CKD) and their healthcare providers. However, nutrition therapy for CKD is undergoing a paradigm shift, which may lead to inconsistent advice for managing hyperphosphatemia. The aim of this study was to summarize and evaluate online resources for phosphorus-specific nutrition therapy.
DESIGN AND METHODS
Patient-facing resources were collected from Google, Yahoo, and Facebook in June-July 2021. Using nine independent search terms, the first 100 hits were reviewed. Dietary advice for food types, food groups, food subgroups, and individual food items was categorized as "restricted," "recommended," "mixed," and "not mentioned." Information on publication date, source, and author(s), phosphorus bioavailability, and demineralization were also collected.
RESULTS
After removing duplicates, 199 resources from Google and Yahoo and 33 from Facebook were reviewed. Resources ranged from 2005 to 2021 and were primarily authored by registered dietitians and medical doctors (65% and 31%, respectively). Dietary advice mostly focuses on restricting high-phosphorus foods and phosphorus additive-based processed foods. Dietary restrictions were generally consistent with the traditional low-phosphorus diet, which targets whole grains, dairy, and plant-based protein foods, although major inconsistencies were noted. Phosphorus bioavailability and demineralization were rarely mentioned (16% and 8%, respectively). Similar findings were found on Facebook, but the limited number of resources limited meaningful comparisons.
CONCLUSION
Results showed that online resources for phosphorus-specific nutrition therapy are highly restrictive of heart-healthy food items and contain significant inconsistencies. Given the widespread and increasing use of online resources by people with CKD and health care professionals to inform dietary choices, efforts are urgently needed to establish consensus for phosphorus-specific nutrition therapy. Until then, the findings of this study provide a basis for increasing awareness of the potential for confusion arising from online resources.
PubMed: 38485068
DOI: 10.1053/j.jrn.2024.01.005 -
PloS One 2020Paricalcitol, a new vitamin D receptor activator (VDRA), is reported to be more effective than other VDRAs in reducing calcium and phosphorus levels in patients... (Comparative Study)
Comparative Study Meta-Analysis
A comparative analysis of the efficacy and safety of paricalcitol versus other vitamin D receptor activators in patients undergoing hemodialysis: A systematic review and meta-analysis of 15 randomized controlled trials.
Paricalcitol, a new vitamin D receptor activator (VDRA), is reported to be more effective than other VDRAs in reducing calcium and phosphorus levels in patients undergoing hemodialysis. However, the efficacy and safety of paricalcitol remain controversial. This analysis compares paricalcitol with other VDRAs in patients undergoing hemodialysis. We searched the Cochrane Library, PubMed, EMBASE, Web of Science, and CNKI up to April 22, 2019. Standardized mean difference (SMD), risk ratio (RR) and 95% confidence interval (CI) values were estimated to compare the outcomes of the groups. Two reviewers extracted data and assessed trial quality independently. All statistical analyses were performed using the standard statistical procedures of RevMan 5.2 and Stata 12.0. Fifteen studies (N = 110,544) were included in this meta-analysis. Of these studies, 11 were randomized controlled trials (RCTs) and 4 were non-randomized studies of interventions (NRSIs). Patients receiving paricalcitol experienced better overall survival (OS) than patients receiving other VDRAs, with a pooled hazard ratio of 0.86 (95% CI 0.80-0.91; P < 0.00001). Intact parathyroid hormone (iPTH) levels were significantly reduced in the paricalcitol group compared to the group receiving other VDRAs, with a pooled SMD of -0.53 (95% CI -0.89- -0.16; P = 0.004). There was a significant increase in serum calcium levels from baseline in the paricalcitol group compared to the other VDRAs group when limiting the analysis to RCTs, with a pooled SMD of 2.14 (95% CI 0.90-3.38; P = 0.0007). Changes in serum calcium levels were significantly lower in the paricalcitol group when the analysis was limited to NRSIs, with a pooled SMD of -0.85 (95% CI -1.34--0.35; P = 0.0008). The NSRI analysis also showed a significant reduction in serum phosphorus levels in the paricalcitol group, with a pooled SMD of -0.57 (95% CI -1.00--0.13; P = 0.01). No significant differences were observed in the incidence of hypercalcemia, hyperphosphatemia, or adverse events. Generally, paricalcitol seems superior to other VDRAs in reducing mortality and iPTH levels in patients undergoing hemodialysis. However, the comparative effectiveness of paricalcitol in reducing serum calcium and phosphorus levels needs further exploration. No significant difference was found in the rate of adverse events.
Topics: Calcium; Disease-Free Survival; Ergocalciferols; Female; Humans; Male; Parathyroid Hormone; Phosphorus; Randomized Controlled Trials as Topic; Receptors, Calcitriol; Renal Dialysis; Survival Rate
PubMed: 32470067
DOI: 10.1371/journal.pone.0233705 -
Nephrology (Carlton, Vic.) Oct 2018As the GFR loss aggravates, the disturbed mineral metabolism worsens the bone microstructure and remodelling - scenario, which is known as CKD-mineral bone disease...
As the GFR loss aggravates, the disturbed mineral metabolism worsens the bone microstructure and remodelling - scenario, which is known as CKD-mineral bone disease (MBD). CKD-MBD is characterized by : (i) abnormal metabolism of calcium, phosphorus, parathyroid hormone (PTH), or vitamin D; (ii) abnormalities in bone turnover, mineralization, volume linear growth or strength; (iii) soft-tissue calcifications, either vascular or extra-osseous. Uremic vascular calcification and osteoporosis are the most common complications related to CKD-MBD. Disregulated bone turnover by uremic toxin or secondary hyperparathyroidism disturbed bone mineralization and makes it difficult for calcium and inorganic phosphate to enter into bone, resulting in increased serum calcium and inorganic phosphate. Vascular calcification worsens by hyperphosphatemia and systemic inflammation. Since vitamin D deficiency plays an important role in renal osteodystrophy, supplement of nutritional vitamin D is important in treating uremic osteoporosis and vascular calcification at the same time. Its pleotropic effect improves the bone remodeling initiated by osteoblast and alleviates the risk factors for vascular calcification with less hypercalcemia than vitamin D receptor analogs. Therefore, nutritional vitamin D should be considered in managing CKDMBD.
Topics: Animals; Arteries; Bone Remodeling; Chronic Kidney Disease-Mineral and Bone Disorder; Dietary Supplements; Humans; Kidney; Osteogenesis; Prognosis; Risk Factors; Vascular Calcification; Vitamin D; Vitamin D Deficiency
PubMed: 30298663
DOI: 10.1111/nep.13457 -
Clinical Toxicology (Philadelphia, Pa.) Jun 2022Enemas containing phosphate are widely prescribed and may cause important adverse effects. A systemic review published in 2007 reported the literature on the adverse...
INTRODUCTION
Enemas containing phosphate are widely prescribed and may cause important adverse effects. A systemic review published in 2007 reported the literature on the adverse effects of phosphate enemas from January 1957 to March 2007 and identified 12 deaths. These were thought due to electrolyte disturbances, heart failure and kidney injury. These data raised concerns about the use of phosphate enemas in routine practice. Newer osmotic-based enema alternatives are now available that do not contain absorbable ions. We sought to review the literature since this review and evaluate the latest data on the toxicity of phosphate-containing enemas. To gain a fuller picture we included case series and larger studies as well as case reports.
OBJECTIVES
To review the toxicity of phosphate enemas, particularly with respect to acute metabolic consequences and their associated clinical features. To identify risk factors for metabolic toxicity and consider whether phosphate enemas should be relatively contra-indicated in specific patient groups.
METHODS
A systematic literature review was conducted in PubMed, Google Scholar, and Cochrane Reviews (2005-2021) using the search terms 'phosphate enema or sodium phosphate enema' or 'phosphate-based enema' or (phosphate AND enema) or (Fleet AND enema) or 'sodium phosphate laxatives' or 'sodium phosphate catharsis' or 'sodium phosphate cathartic'. Relevant papers were read, and data were extracted.
RESULTS
The searches identified 489 papers of which 25 were relevant: seven papers were case reports or small case series of metabolic abnormalities from the use of phosphate enemas in nine children, six were case reports on 16 adults. Nine papers were large case series or clinical studies that included data on systemic metabolic effects, of varying size from 24 healthy volunteers to a cohort of 70,499 patients. Case reports identified seven adult deaths but none in children. Children most often presented with decreased consciousness (6/9), and tetany (4/9). In adults overall only five cases had clinical features reported, hypotension was seen in four and QT prolongation in two. Treatment was generally symptomatic, with intravenous fluid and calcium salts for electrolyte changes and hypocalcaemia, and vasopressors for severe hypotension. Haemodialysis was used in three children and peritoneal dialysis in one, all of whom survived. In adults, haemodialysis did not prevent death in two of four cases in whom it was used. Common factors underlying toxicity were inappropriately high phosphate dose, or enema retention, both resulting in greater absorption of phosphate. Associated pre-disposing conditions included Hirschsprung disease in children and co-morbidity and renal impairment (2/5) in older adults. Absolute reported changes in serum phosphate or calcium were not accurate indicators of outcome. Larger case series and clinical trials confirm an acute effect of phosphate enemas on serum phosphate, which was related to both dose and retention time. These effects were not seen with non-phosphate preparations. In these cases series, adverse events were rarely reported.
CONCLUSION
Phosphate enemas are potentially toxic, particularly in young children with Hirschsprung disease and in the elderly with co-morbidity. Raised awareness of the risk of phosphate enemas is still required. Other less toxic enema preparations are available and should be considered in patients at extremes of age. If phosphate enemas are the only clinical option careful monitoring of biochemical sequelae should be undertaken.
Topics: Aged; Calcium; Child; Child, Preschool; Enema; Hirschsprung Disease; Humans; Hypotension; Laxatives; Phosphates
PubMed: 35510830
DOI: 10.1080/15563650.2022.2054424