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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 -
International Urology and Nephrology May 2018To evaluate the efficacy and safety of PA21 versus sevelamer in dialysis patients. (Comparative Study)
Comparative Study Meta-Analysis Review
AIM
To evaluate the efficacy and safety of PA21 versus sevelamer in dialysis patients.
METHODS
We searched Medline, Embase, Science Citation Index, Cochrane Central Register of Controlled Trials, and Clinical Trial Registries for randomized controlled trials comparing PA21 and sevelamer in dialysis patients.
RESULTS
Four studies were included. Compared with sevelamer group, PA21 needed fewer mean daily number of tablets (WMD, - 7.97 pill; 95% CI, - 11.28 to - 4.65, p < 0.00001), developed fewer all adverse events (RR = 1.05; 95% CI, 1.00 to 1.11, p = 0.05), and developed fewer gastrointestinal adverse events (RR = 1.32; 95% CI, 1.15 to 1.53, p = 0.0001). There was no significant difference in serum phosphorus between two groups (WMD, - 0.07 mmol/L; 95% CI, - 0.15 to 0.02, p = 0.12). As for serum calcium, there was also no significant difference between two groups (WMD, 0.27 mmol/L; 95% CI, - 0.63 to 1.17, p = 0.55).
CONCLUSION
PA21 can effectively control serum phosphorus with lower pill burden and less side effects than sevelamer. PA21 might be another valuable choice for dialysis patients with hyperphosphatemia when patients are unable to tolerate sevelamer.
Topics: Calcium; Chelating Agents; Ferric Compounds; Hypercalcemia; Hyperphosphatemia; Kidney Failure, Chronic; Phosphorus; Randomized Controlled Trials as Topic; Renal Dialysis; Sevelamer
PubMed: 29294216
DOI: 10.1007/s11255-017-1774-9 -
American Journal of Kidney Diseases :... Jan 2018Understanding phosphate kinetics in dialysis patients is important for the prevention of hyperphosphatemia and related complications. One approach to gain new insights...
BACKGROUND
Understanding phosphate kinetics in dialysis patients is important for the prevention of hyperphosphatemia and related complications. One approach to gain new insights into phosphate behavior is physiologic modeling. Various models that describe and quantify intra- and/or interdialytic phosphate kinetics have been proposed, but there is a dearth of comprehensive comparisons of the available models. The objective of this analysis was to provide a systematic review of existing published models of phosphate metabolism in the setting of maintenance hemodialysis therapy.
STUDY DESIGN
Systematic review.
SETTING & POPULATION
Hemodialysis patients.
SELECTION CRITERIA FOR STUDIES
Studies published in peer-reviewed journals in English about phosphate kinetic modeling in the setting of hemodialysis therapy.
PREDICTOR
Modeling equations from specific reviewed studies.
OUTCOMES
Changes in plasma phosphate or serum phosphate concentrations.
RESULTS
Of 1,964 nonduplicate studies evaluated, 11 were included, comprising 9 different phosphate models with 1-, 2-, 3-, or 4-compartment assumptions. Between 2 and 11 model parameters were included in the models studied. Quality scores of the studies using the Newcastle-Ottawa Scale ranged from 2 to 11 (scale, 0-14). 2 studies were considered low quality, 6 were considered medium quality, and 3 were considered high quality.
LIMITATIONS
Only English-language studies were included.
CONCLUSIONS
Many parameters known to influence phosphate balance are not included in existing phosphate models that do not fully reflect the physiology of phosphate metabolism in the setting of hemodialysis. Moreover, models have not been sufficiently validated for their use as a tool to simulate phosphate kinetics in hemodialysis therapy.
Topics: Humans; Hyperphosphatemia; Kidney Failure, Chronic; Kinetics; Latent Class Analysis; Phosphates; Renal Dialysis
PubMed: 29191624
DOI: 10.1053/j.ajkd.2017.07.016 -
International Urology and Nephrology Apr 2018To evaluate the efficacy and safety of the restricted protein diet supplemented with keto analogues when applied in end-stage renal disease (ESRD). (Meta-Analysis)
Meta-Analysis Review
AIM
To evaluate the efficacy and safety of the restricted protein diet supplemented with keto analogues when applied in end-stage renal disease (ESRD).
METHODS
The Cochrane Library, PubMed, Embase, CBM and CENTRAL databases were searched and reviewed up to January 2017. Clinical trials were analyzed using RevMan 5.3 software.
RESULTS
Five randomized controlled trials were selected and included in this study according to our inclusion and exclusion criteria. Changes in serum albumin, PTH, triglyceride, cholesterol, calcium, phosphorus, hemoglobin, Kt/v and CRP before and after treatment were analyzed. Meta-analysis results indicated that, compared with normal protein diet, low-protein diet (LPD) supplemented with keto analogues (sLPD) could improve serum albumin (P < 0.00001), hyperparathyroidism (P < 0.00001) and hyperphosphatemia (P = 0.008). No differences in triglyceride, cholesterol, hemoglobin, Kt/v and CRP were observed between different protein intake groups.
CONCLUSION
Restricted protein diet supplemented with keto analogues (sLPD) may improve nutritional status and prevent hyperparathyroidism in ESRD patients. The current data were mainly obtained from short-term, single-center trails with small sample sizes and limited nutritional status indexes, indicating a need for further study.
Topics: Diet, Protein-Restricted; Dietary Supplements; Humans; Hyperparathyroidism; Hyperphosphatemia; Keto Acids; Kidney Failure, Chronic; Nutritional Status; Randomized Controlled Trials as Topic; Serum Albumin
PubMed: 28975468
DOI: 10.1007/s11255-017-1713-9 -
JBI Database of Systematic Reviews and... Apr 2017People with end-stage kidney disease (ESKD) develop impaired excretion of phosphate. Hyperphosphatemia develops in ESKD as a result of the kidney's reduced ability to... (Review)
Review
BACKGROUND
People with end-stage kidney disease (ESKD) develop impaired excretion of phosphate. Hyperphosphatemia develops in ESKD as a result of the kidney's reduced ability to excrete ingested phosphate load and is characterized by high bone turnover and increased musculoskeletal morbidity including bone pain and muscle weakness. Increased serum phosphate levels are also associated with cardiovascular disease and associated mortality. These effects are significant considering that cardiovascular disease is the leading cause of death in ESKD, making phosphate control a crucial treatment goal.
OBJECTIVES
To determine the effectiveness of education or behavioral interventions on adherence to phosphate control in adults with ESKD receiving hemodialysis (HD).
INCLUSION CRITERIA TYPES OF PARTICIPANTS
Adults aged over 18 years with ESKD undergoing HD, attending dialysis facilities regardless of frequency and duration of treatment sessions per week. Studies with participants receiving hemodiafiltration were excluded.
TYPES OF INTERVENTION(S)/PHENOMENA OF INTEREST
All types of educational and behavioral interventions aimed at improving adherence to dietary phosphate restriction, phosphate binder medication and HD.
TYPES OF STUDIES
Randomized controlled trials (RCTs), non-RCTs, before and after and cohort studies.
OUTCOMES
Outcome measures included serum phosphate levels, patient knowledge and adherence to phosphate control methods, chronic kidney disease (CKD) self-management behavior and perceived self-efficacy for CKD related to phosphate control.
SEARCH STRATEGY
A search was conducted in CINAHL, MEDLINE, The Cochrane Library, Embase, Web of Science, PsycINFO and ProQuest Dissertations and Theses Global to find published studies between January 2005 and December 2015.
METHODOLOGICAL QUALITY
Risk of bias was assessed by three reviewers prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI).
DATA EXTRACTION
Data were extracted using the standardized data extraction tool from JBI-MAStARI.
DATA SYNTHESIS
Data were pooled using JBI software. Mean differences (95% confidence interval [CI]) and effect size estimates were calculated for continuous outcomes. Meta-analysis using a random-effects model was performed for serum phosphate levels, and where the findings could not be pooled using meta-analysis, results have been presented in a narrative form. Standard GRADE (Grading of Recommendations Assessment, Development and Evaluation) evidence assessment of outcomes has been reported.
RESULTS
A total of 18 studies were included in the review: seven studies focused on dietary phosphate, four studies focused on medications (phosphate binders) and six studies focused on dietary phosphate and medications. Only one study taught patients about diet, medications and HD to control phosphate. Sixteen studies showed significant improvements in phosphate levels. Meta-analysis of eight RCTs favored educational or behavioral interventions over standard care for serum phosphate control, with a weighted mean reduction of -0.23 mmol/l (95% CI -0.37, -0.08) in treatment groups.
CONCLUSION
Overall, educational or behavioral interventions increase adherence to phosphate control. Studies in this systematic review revealed improved outcomes on serum phosphate levels, patient knowledge and adherence to phosphate control methods, CKD self-management behavior and perceived self-efficacy for CKD related to phosphate control. However, there is a lack of sufficient data on how some of the studies implemented their interventions, suggesting that further research is required. Successful strategies that improve and optimize long-term adherence to phosphate control still need to be formulated.
Topics: Adult; Humans; Kidney Failure, Chronic; Patient Education as Topic; Phosphates; Renal Dialysis; Self Care
PubMed: 28398983
DOI: 10.11124/JBISRIR-2017-003360 -
American Journal of Kidney Diseases :... Aug 2017Owing to its longer treatment duration-up to 8 hours per dialysis treatment-in-center thrice-weekly nocturnal hemodialysis (HD) is receiving greater attention. To better... (Comparative Study)
Comparative Study Review
BACKGROUND
Owing to its longer treatment duration-up to 8 hours per dialysis treatment-in-center thrice-weekly nocturnal hemodialysis (HD) is receiving greater attention. To better understand the evidence for in-center nocturnal HD, we sought to systematically review the literature to determine the effects of in-center nocturnal HD versus conventional HD on clinically relevant outcomes.
STUDY DESIGN
We searched MEDLINE, Embase, Evidence-Based Medicine Reviews (EBMR), Web of Science, and Scopus from the earliest date in the database to November 2016.
SETTING & POPULATION
Adults receiving in-center nocturnal HD compared with those receiving conventional HD.
SELECTION CRITERIA FOR STUDIES
All quasi-experimental and observational studies were considered; randomized trials were sought but not found.
PREDICTOR
Nocturnal vs conventional in-center HD.
OUTCOMES
Indexes of blood pressure and left ventricular hypertrophy, markers of anemia, measures of bone mineral metabolism, nutrition, quality of life, sleep quality, episodes of intradialytic hypotension, hospitalization, and mortality.
RESULTS
Of 2,086 identified citations, 21 met the inclusion criteria, comprising a total of 1,165 in-center nocturnal HD patients and 15,865 conventional HD patients. Although there was substantial heterogeneity in reporting of outcomes, we pooled data for measures of blood pressure, anemia, and mineral metabolism. Though heterogeneity was generally high, in-center nocturnal HD was associated with improved systolic blood pressure (-3.18 [95% CI, -5.58 to -0.78) mm Hg, increased hemoglobin levels (0.53 [95% CI, 0.11-0.94] g/dL), and lower serum phosphate levels (-0.97 [95% CI, -1.48 to -0.46] mg/dL).
LIMITATIONS
No randomized trials have been conducted to address the clinical effects of in-center nocturnal HD. The quality of the observational literature contributing to the results of this review was generally poor to moderate. Confounded outcomes are a significant concern. Publication bias and outcome reporting bias remain possibilities.
CONCLUSIONS
Relative to conventional HD, in-center nocturnal HD was associated with improvements in several clinically relevant outcomes. Other benefits may not have been detected due to small sample sizes of included studies; no prespecified outcome was worse with in-center nocturnal HD.
Topics: Ambulatory Care Facilities; Hemodialysis, Home; Humans; Renal Dialysis; Treatment Outcome
PubMed: 28359656
DOI: 10.1053/j.ajkd.2017.01.047 -
Nephrology, Dialysis, Transplantation :... Jan 2017It remains unclear which phosphate binders should be preferred for hyperphosphatemia management in chronic kidney disease (CKD). (Comparative Study)
Comparative Study Meta-Analysis Review
The efficacy and safety of sevelamer and lanthanum versus calcium-containing and iron-based binders in treating hyperphosphatemia in patients with chronic kidney disease: a systematic review and meta-analysis.
BACKGROUND
It remains unclear which phosphate binders should be preferred for hyperphosphatemia management in chronic kidney disease (CKD).
METHODS
We performed a systematic review and meta-analysis of randomized trials comparing sevelamer or lanthanum with other phosphate binders in CKD.
RESULTS
Fifty-one trials (8829 patients) were reviewed. Compared with calcium-based binders, all-cause mortality was nonsignificantly lower with sevelamer {risk ratio [RR] 0.62 [95% confidence interval (CI) 0.35-1.08]} and lanthanum [RR 0.73 (95% CI 0.18-3.00)], but risk of bias was concerning. Compared with calcium-based binders, sevelamer reduced the risk of hypercalcemia [RR 0.27 (95% CI 0.17-0.42)], as did lanthanum [RR 0.12 (95% CI 0.05-0.32)]. Sevelamer reduced hospitalizations [RR 0.50 (95% CI 0.31-0.81)], but not lanthanum [RR 0.80 (95% CI 0.34-1.93)]. The presence/absence of other clinically relevant outcomes was infrequently reported. Compared with calcium-based binders, sevelamer reduced serum calcium, low-density lipoprotein and coronary artery calcification, but increased intact parathyroid hormone. The clinical relevance of these changes is unknown since corresponding clinical outcomes were not reported. Lanthanum had less favorable impact on biochemical parameters. Sevelamer hydrochloride and sevelamer carbonate were similar in three studies. Sevelamer was similar to lanthanum (three studies) and iron-based binders (three studies).
CONCLUSION
Sevelamer was associated with a nonsignificant reduction in mortality and significantly lower hospitalization rates and hypercalcemia compared with calcium-based binders. However, differences in important outcomes, such as cardiac events, fractures, calciphylaxis, hyperchloremic acidosis and health-related quality of life remain understudied. Lanthanum and iron-based binders did not show superiority for any clinically relevant outcomes. Future studies that fail to measure clinically important outcomes (the reason why phosphate binders are prescribed in the first place) will be wasteful.
Topics: Biomarkers; Calcium Compounds; Chelating Agents; Humans; Hyperphosphatemia; Lanthanum; Phosphates; Renal Insufficiency, Chronic; Safety; Sevelamer; Treatment Outcome
PubMed: 27651467
DOI: 10.1093/ndt/gfw312 -
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 -
International Urology and Nephrology Mar 2016To evaluate the efficacy and safety of the restricted protein diet (low or very low protein diet) supplemented with keto analogues in the treatment of chronic kidney... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
To evaluate the efficacy and safety of the restricted protein diet (low or very low protein diet) supplemented with keto analogues in the treatment of chronic kidney disease (CKD).
METHODS
The Cochrane library, PubMed, Embase, CBM and CENTRAL databases were searched and reviewed up to April 2015. Clinical trials were analyzed using RevMan 5.3 software.
RESULTS
Seven random control trials, one cross-over trial and one non-randomized concurrent control trial were selected and included in this study according to our inclusion and exclusion criteria. The changes of eGFR, BUN, Scr, albumin, PTH, triglyceride, cholesterol, calcium, phosphorus and nutrition indexes (BMI, lean body mass and mid-arm muscular circumference) before and after treatment were analyzed. The meta-analysis results indicated that, comparing with normal protein diet, low protein diet (LPD) or very low protein diet (vLPD) supplemented with keto analogues (s(v)LPD) could significantly prevent the deterioration of eGFR (P < 0.001), hyperparathyroidism (P = 0.04), hypertension (P < 0.01) and hyperphosphatemia (P < 0.001). No differences in BUN, Scr, Albumin, triglyceride, cholesterol, hemoglobin, calcium and nutrition indexes were observed between different protein intake groups.
CONCLUSION
Restricted protein diet supplemented with keto analogues (s(v)LPD) could delay the progression of CKD effectively without causing malnutrition.
Topics: Diet, Protein-Restricted; Dietary Supplements; Disease Progression; Humans; Ketoses; Renal Insufficiency, Chronic
PubMed: 26620578
DOI: 10.1007/s11255-015-1170-2 -
Nephrology (Carlton, Vic.) Mar 2016Managing hyperphosphataemia in haemodialysis patients is resource-intensive. A search for cost-effective interventions in this field is needed to inform decisions on the... (Review)
Review
Managing hyperphosphataemia in haemodialysis patients is resource-intensive. A search for cost-effective interventions in this field is needed to inform decisions on the allocation of healthcare resources. NHSEED, MEDLINE, EMBASE and CINAHL were searched for full economic evaluations of hyperphosphataemia-managing interventions in adult haemodialysis patients, published between 2004 and 2014, in English, French, Dutch or German. Incremental cost-effectiveness ratios of the interventions were up-rated to 2013US$ using Purchasing Power Parity conversion rates and Consumer Price Indices. The quality of included studies was assessed using the Extended Consensus on Health Economic Criteria List. Twelve out of the 1681 retrieved records fulfilled the inclusion criteria. They reported only on one aspect of hyperphosphataemia management, which is the use of phosphate binders (calcium-based and calcium-free, in first-line and sequential use). No economic evaluations of other phosphorus-lowering interventions were found. The included articles derived from five countries and most of them were funded by pharmaceutical companies. The incremental cost-effectiveness ratios of phosphate binders ranged between US$11 461 and US$157 760 per quality-adjusted life-year gained. Calcium-based binders (especially calcium acetate) appear to be the optimal cost-effective first- and second-line therapy in prevalent patients, while the calcium-free binder, lanthanum carbonate, might provide good value for money, as second-line therapy, in incident patients. The studies' overall quality was suboptimal. Drawing firm conclusions was not possible due to the quality heterogeneity and inconsistent results. Future high-quality economic evaluations are needed to confirm the findings of this review and to address other interventions to manage hyperphosphataemia in this population.
Topics: Biomarkers; Chelating Agents; Cost-Benefit Analysis; Drug Costs; Humans; Hyperphosphatemia; Models, Economic; Phosphates; Quality of Life; Quality-Adjusted Life Years; Renal Dialysis; Treatment Outcome
PubMed: 26246269
DOI: 10.1111/nep.12584