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Benefits and harms of phosphate binders in CKD: a systematic review of randomized controlled trials.American Journal of Kidney Diseases :... Oct 2009Phosphate binders are widely used to control serum phosphorus levels in patients with chronic kidney disease (CKD). We analyzed the effects of phosphate binders on... (Review)
Review
BACKGROUND
Phosphate binders are widely used to control serum phosphorus levels in patients with chronic kidney disease (CKD). We analyzed the effects of phosphate binders on biochemical and patient-level end points in patients with CKD.
STUDY DESIGN
Systematic review and meta-analysis by searching MEDLINE (1966 to April 2009), EMBASE (1980 to April 2009), and the Cochrane Renal Group Specialised Register and the Cochrane Central Register of Controlled Trials (CENTRAL).
SETTING & POPULATION
Patients with CKD.
SELECTION CRITERIA FOR STUDIES
Randomized controlled trials.
INTERVENTION
Phosphate binders.
OUTCOMES
Serum phosphorus, calcium, and parathyroid hormone levels; incidence of hypercalcemia; all-cause mortality; adverse effects.
RESULTS
40 trials (6,406 patients) were included. There was no significant decrease in all-cause mortality (10 randomized controlled trials; 3,079 patients; relative risk [RR], 0.73; 95% confidence interval [CI], 0.46 to 1.16), hospitalization, or end-of-treatment serum calcium-phosphorus product levels with sevelamer compared with calcium-based agents. There was a significant decrease in end-of-treatment phosphorus and parathyroid hormone levels with calcium salts compared with sevelamer and a significant decrease in risk of hypercalcemia (RR, 0.47; 95% CI, 0.36 to 0.62) with sevelamer compared with calcium-based agents. There was a significant increase in risk of gastrointestinal adverse events with sevelamer in comparison to calcium salts (RR, 1.39; 95% CI, 1.04 to 1.87). Compared with calcium-based agents, lanthanum significantly decreased end-of-treatment serum calcium and calcium-phosphorus product levels, but with similar end-of-treatment phosphorus levels. Effects of calcium acetate on biochemical end points were similar to those of calcium carbonate. Existing data are insufficient to conclude for a differential impact of any phosphate binder on cardiovascular mortality or other patient-level outcome.
LIMITATIONS
Few long-term studies of the efficacy of phosphate binders on mortality and musculoskeletal morbidity, significant heterogeneity for many surrogate outcomes, and suboptimal reporting of study methods to determine trial quality.
CONCLUSION
Currently, there are insufficient data to establish the comparative superiority of non-calcium-binding agents over calcium-containing phosphate binders for such important patient-level outcomes as all-cause mortality and cardiovascular end points. Additional trials are still required to examine the differential effects of phosphate-binding agents on these end points and the mineral homeostasis pathway.
Topics: Acetates; Biomarkers; Bone Density Conservation Agents; Calcium; Calcium Carbonate; Calcium Compounds; Chelating Agents; Chronic Kidney Disease-Mineral and Bone Disorder; Humans; Hypercalcemia; Hyperphosphatemia; Lanthanum; Parathyroid Hormone; Phosphates; Phosphorus; Polyamines; Randomized Controlled Trials as Topic; Renal Insufficiency, Chronic; Research Design; Sevelamer
PubMed: 19692157
DOI: 10.1053/j.ajkd.2009.06.004 -
European Journal of Medical Research May 2009Poor adherence to complex multimodal therapies is a widely recognized problem in the daily care of dialysis patients, contributing to excess morbidity and mortality of... (Review)
Review
OBJECTIVE
Poor adherence to complex multimodal therapies is a widely recognized problem in the daily care of dialysis patients, contributing to excess morbidity and mortality of this population. While a few studies have been devoted to understanding patient nonadherence, their results were somewhat controversial. The goals of this review are to quantify nonadherence to certain oral medications, to raise awareness of factors that may cause problems in a patient;s adherence to this treatment, and to describe strategies that may be used to improve adherence to prescribed pharmacotherapy.
METHODS
A systematic literature review in the MEDLINE and PubMed database (1971-2008) was performed. Quantitative studies, which accurately indicated the total percentages of nonadherence to oral medication in adult patients receiving chronic hemodialysis, were identified.
RESULTS
A total of 19 studies fulfilled the search criteria. Rates of nonadherence to the oral medication ranged from 3 - 80%. More than half of the included studies reported nonadherence rates of > or = 50% (mean 67%). The use of phosphate binding therapy was the prevalent surveyed oral medication. Self reports, structured interviews, and predialysis serum phosphate levels were the most frequent assessment tools used to record adherence rates. Limitations of the reviewed studies included small patient cohorts, inconsistent definitions of adherence, and a lack of standardized methods for measuring nonadherence.
CONCLUSIONS
Nonadherence to oral medication in hemodialysis patients is still an underestimated, but life-threatening behaviour.
Topics: Administration, Oral; Adult; Aged; Antihypertensive Agents; Cooperative Behavior; Humans; Hyperphosphatemia; Kidney Failure, Chronic; Middle Aged; Patient Compliance; Renal Dialysis
PubMed: 19541573
DOI: 10.1186/2047-783x-14-5-185 -
Blood Purification 2009Due to increasing evidence suggesting a link between hyperphosphatemia and cardiovascular disease (CVD), mediated through vascular calcification in patients on dialysis,... (Review)
Review
BACKGROUND AND AIM
Due to increasing evidence suggesting a link between hyperphosphatemia and cardiovascular disease (CVD), mediated through vascular calcification in patients on dialysis, the following question arises: At what stage of chronic kidney disease (CKD) does the relationship between elevated phosphate levels, vascular calcification and increased cardiovascular mortality begin? Therefore, the purpose of the current study was to critically review the current literature regarding this issue.
METHODS
We performed a systematic search of the National Library of Medicine and the Cochrane Library databases from January 1985 to February 2008 to identify clinical studies examining the effects of plasma phosphate on cardiovascular outcome, mortality and progression of kidney disease in subjects with and without CKD who have not yet received dialysis. The primary outcome measure was the development of CVD, mortality and progression of kidney disease.
RESULTS
Twelve clinical trials investigated the role of serum phosphate levels and adverse outcome (9 studies examining CVD outcome and 3 examining progression of kidney disease). After adjustment for risk factors for mortality, adverse cardiovascular outcome and progression of kidney disease, all studies found a graded independent significant association between phosphate levels and mortality, development of CVD and progression of kidney disease. There was no such association with plasma calcium levels.
CONCLUSIONS
There is a graded independent association between serum phosphate levels and mortality, mainly cardiovascular events, and the progression of renal disease in subjects with and without definable (loss of glomerular filtration rate) CKD.
Topics: Calcium; Cardiovascular Diseases; Disease Progression; Humans; Kidney Failure, Chronic; Phosphates; Renal Insufficiency, Chronic; Risk Factors
PubMed: 19176951
DOI: 10.1159/000197562 -
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 -
Minerva Urologica E Nefrologica = the... Sep 2005Patients treated for end stage renal disease (ESRD) have a shorter life expectancy and a poorer quality of life than the general population. In an attempt to improve... (Meta-Analysis)
Meta-Analysis Review
Patients treated for end stage renal disease (ESRD) have a shorter life expectancy and a poorer quality of life than the general population. In an attempt to improve outcomes for this patient population, a few novel therapeutic approaches have been undertaken. With hemodialysis, an increase in dialysis frequency and/or time has been associated with improvements in anemia, left ventricular hypertrophy, hypertension, hyperphosphatemia, nutrition and quality of life. Yet, access to these promising hemodialysis modalities has remained limited. The reasons for this are numerous, but one concern is the potential for more frequent vascular access complications with the increased frequency of cannulation for an arteriovenous fistula/graft and connection for a central venous catheter. In this systematic review of the literature, we identified all published studies that included 10 or more patients on daily hemodialysis and reported quantitative data pertaining to vascular access complications. Twelve studies met our inclusion criteria. The overall complication rates associated with vascular access do not appear to be increased and are perhaps even decreased with daily compared to conventional thrice-weekly hemodialysis. Arteriovenous fistulas are the vascular access of choice for daily hemodialysis; however, a non-statistically significant increased complication rate for these accesses was reported in 2 North American studies. The reasons for this are unclear and require further research.
Topics: Arteriovenous Shunt, Surgical; Canada; Catheterization, Central Venous; Catheters, Indwelling; Evidence-Based Medicine; Humans; Infection Control; Infections; Kidney Failure, Chronic; Quality of Life; Renal Dialysis; Survival Analysis; Treatment Outcome
PubMed: 15986014
DOI: No ID Found