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Objectives Current guidelines mandate organ donation to be financially neutral such that it neither rewards nor exploits donors. This systematic review was conducted to assess the magnitude and type of costs incurred by adult living kidney donors and to identify those at risk of financial hardship. Methods We searched English-language journal articles and working papers assessing direct and indirect costs incurred by donors on PubMed, MEDLINE, Scopus, the National Institute for Health Research Economic Evaluation Database, Research Papers in Economics, and EconLit in 2005 and thereafter. Estimates of total costs, types of costs, and characteristics of donors who incurred the financial burden were extracted. Results Sixteen studies were identified involving 6158 donors. Average donor-borne costs ranged from US$900 to US$19 900 (2019 values) over the period from predonation evaluation to the end of the first postoperative year. Less than half of donors sought financial assistance and 80% had financial loss. Out-of-pocket payments for travel and health services were the most reported items where lost income accounted for the largest proportion (23.2%-83.7%) of total costs. New indirect cost items were identified to be insurance difficulty, exercise impairment, and caregiver income loss. Donors from lower-income households and those who traveled long distances reported the greatest financial hardship. Conclusions Most kidney donors are undercompensated. Our findings highlight gaps in donor compensation for predonation evaluation, long-distance donations, and lifetime insurance protection. Additional studies outside of North America are needed to gain a global prospective on how to provide for financial neutrality for kidney donors.

Previous primary studies have explored the association between blood pressure (BP) and mortality in ambulatory heart failure (HF) patients reporting varying and contrasting associations. The aim is to determine the pooled BP prognostic value and explore potential reasons for between-study inconsistency. We searched Medline, Cochrane, EMBASE and CINAHL from January 2005 to October 2018 for studies with ≥ 50 events (mortality and/or hospitalization) and included BP in a multivariable model in ambulatory HF patients. We pooled hazard ratios (random effects model) for systolic BP (SBP) or diastolic BP (DBP) effect on mortality and/or hospitalization risk. We used a priori defined sub-group analyses to explore heterogeneity and GRADE approach to assess the certainty of the evidence. Seventy-one eligible articles (239,467 screened) at low to moderate risk of bias included 235,752 participants. Higher SBP was associated with reduced all-cause mortality (HR 0.93, 95%CI 0.91–0.95, I2 = 87.13%, moderate certainty), all-cause hospitalization events (HR 0.91, 95%CI 0.88–0.93, I2 = 44.4%, high certainty) and their composite endpoint (HR 0.93 per 10 mmHg, 95%CI 0.91–0.94, I2 = 86.3%, high certainty). DBP did not demonstrate a statistically significant effect for all outcomes. The association strength was significantly weaker in studies following patients with either LVEF > 40%, higher average SBP (> 130 mmHg), increasing age and diabetes. All other a priori subgroup hypotheses did not explain between study differences. Higher ambulatory SBP is associated with reduced risk of all-cause mortality and hospitalization. Patients with lower BP and reduced LVEF are in a high-risk group of developing adverse events with moderate certainty of evidence.

Supervised machine learning (ML) is a class of algorithms that "learn" from existing input-output pairs, which is gaining popularity in pattern recognition for classification and prediction problems. In this scoping review, we examined the use of supervised ML algorithms for the prediction of long-term allograft survival in kidney transplant recipients. Data sources included PubMed, the Cumulative Index to Nursing and Allied Health Literature, and the Institute for Electrical and Electronics Engineers (IEEE) Xplore libraries from inception to November 2019. We screened titles and abstracts and potentially eligible full-text reports to select studies and subsequently abstracted the data. Eleven studies were identified. Decision trees were the most commonly used method (n = 8), followed by artificial neural networks (ANN) (n = 4) and Bayesian belief networks (n = 2). The area under receiver operating curve (AUC) was the most common measure of discrimination (n = 7), followed by sensitivity (n = 5) and specificity (n = 4). Model calibration examining the reliability in risk prediction was performed using either the Pearson r or the Hosmer-Lemeshow test in four studies. One study showed that logistic regression had comparable performance to ANN, while another study demonstrated that ANN performed better in terms of sensitivity, specificity, and accuracy, as compared with a Cox proportional hazards model. We synthesized the evidence related to the comparison of ML techniques with traditional statistical approaches for prediction of long-term allograft survival in patients with a kidney transplant. The methodological and reporting quality of included studies was poor. Our study also demonstrated mixed results in terms of the predictive potential of the models.

Aim Type 2 diabetes is a major global epidemic affecting over 400 million people worldwide. The objective of this systematic review was to provide an overview of recommendations from clinical practice guidelines (guidelines) addressing non-insulin based pharmacological management of among non-pregnant adults in an outpatient setting, and critically appraise their methodological development. Methods We systematically searched MEDLINE and Embase databases, for relevant guidelines using the Ovid interface. We scanned the bibliographies of all eligible guidelines for additional relevant citations. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility and appraised the reporting quality of guidelines using the Advancing Guideline Development, Reporting and Evaluation in Health Care instrument II (AGREE II) instrument. Results Our search yielded 11264 unique citations, of which 124 were retrieved for full-text review; 17 guidelines proved eligible. The highest scoring AGREE domain was 'clarity of presentation' (66%; range 7-92%), followed by 'scope and purpose' (58%; range 25-92%), 'editorial independence' (55%; range 0-91%), 'stakeholder involvement' (45%; range 11-90%) and 'rigour of development' (43%; range 4-92%). The poorest domain was 'applicability' (37%; range 6-84%). The guidelines authored by the World Health Organization group achieved the highest AGREE overall score. Conclusions Most of the guidelines provided recommendations with a local jurisdictional focus and showed significant variation in the quality. Nevertheless, only a small number of those scored well overall.

Objective: The objective of the study was to clarify how the Grading of Recommendations Assessment, Development and Evaluation (GRADE) concept of certainty of evidence applies to certainty ratings of test accuracy. Study Design and Setting: After initial brainstorming with GRADE Working Group members, we iteratively refined and clarified the approaches for defining ranges when assessing the certainty of evidence for test accuracy within a systematic review, health technology assessment, or guideline. Results: Ranges can be defined both for single test accuracy and for comparative accuracy of multiple tests. For systematic reviews and health technology assessments, approaches for defining ranges include some that do not require value judgments regarding downstream health outcomes. Key challenges arise in the context of a guideline that requires ranges for sensitivity and specificity that are set considering possible effects on all critical outcomes. We illustrate possible approaches and provide an example from a systematic review of a direct comparison between two test strategies. Conclusions: This GRADE concept paper provides a framework for assessing, presenting, and making decisions based on the certainty of evidence for test accuracy. More empirical research is needed to support future GRADE guidance on how to best operationalize the candidate approaches.

Objective To propose an approach for developing trustworthy recommendations as part of urgent responses (1-2 weeks) in the clinical, public health, and health systems fields. Study design and setting We conducted a review of the literature, outlined a draft approach, refined the concept through iterative discussions, a workshop by the GRADE Rapid Guidelines project group, and obtained feedback from the larger GRADE working group. Results A request for developing recommendations within two weeks is the usual trigger for an urgent response. While the approach builds on the general principles of trustworthy guideline development, we highlight the following steps: (1) assess the level of urgency; (2) assess feasibility; (3) set up the organizational logistics; (4) specify the question(s); (5) collect the information needed; (6) assess the adequacy of identified information; (7) develop the recommendations using one of four potential approaches: adopt existing recommendations; adapt existing recommendations; develop new recommendations using existing adequate systematic review; or develop new recommendations using expert panel input; and (8) consider an updating plan. Conclusion An urgent response for developing recommendations requires building a cohesive, skilled and highly motivated multidisciplinary team with the necessary clinical, scientific, and methodological expertise, adapting to shifting needs, complying with the principles of transparency and properly managing conflicts of interest., Highlights • The proposed approach for developing trustworthy recommendations as part of urgent responses (1-2 weeks) builds on the general principles of trustworthy guideline development; • The approach proposes the following steps: (1) assess the level of urgency; (2) clarify and focus the scope of question(s); (3) prioritize and collect the information needed; (4) assess the adequacy of identified information; and then (5) develop recommendations; • Developing recommendations can consist of a) adopting existing recommendations; (b) adapting existing recommendations; c) developing new recommendations using existing systematic reviews; or d) developing new recommendations using identified information and panel input.

Background Resting heart rate is a risk factor of adverse heart failure outcomes; however, studies have shown controversial results. This meta-analysis evaluates the association of resting heart rate with mortality and hospitalization and identifies factors influencing its effect. Methods and Results We systematically searched electronic databases in February 2019 for studies published in 2005 or before that evaluated the resting heart rate as a primary predictor or covariate of multivariable models of mortality and/or hospitalization in adult ambulatory patients with heart failure. Random effects inverse variance meta-analyses were performed to calculate pooled hazard ratios. The Grading of Recommendations, Assessment, Development and Evaluation approach was used to assess evidence quality. Sixty-two studies on 163,445 patients proved eligible. Median population heart rate was 74 bpm (interquartile range 72–76 bpm). A 10-bpm increase was significantly associated with increased risk of all-cause mortality (hazard ratio 1.10, 95% confidence interval 1.08–1.13, high quality). Overall, subgroup analyses related to patient characteristics showed no changes to the effect estimate; however, there was a strongly positive interaction with age showing increasing risk of all-cause mortality per 10 bpm increase in heart rate. Conclusions High-quality evidence demonstrates increasing resting heart rate is a significant predictor of all-cause mortality in ambulatory patients with heart failure on optimal medical therapy, with consistent effect across most patient factors and an increased risk trending with older age.

Objectives: Diabetic kidney disease (DKD) is an independent predictor of cardiovascular morbidity and mortality in type 1 diabetes (T1D). We aimed to explore clinical and biochemical factors, including the achievement of American Diabetes Association (ADA) recommended targets associated with DKD in people living with T1D for ≥50 years. Methods: This was a post hoc analysis of a cross-sectional study of 75 participants enrolled in the Canadian Study of Longevity in T1D. We explored diabetes-related complications, including neuropathy, retinopathy, cardiovascular disease, and DKD. Study participants were dichotomized based on the achievement of ADA recommended targets as the low-target group (achieving ≤4 targets, n = 31) and high-target group (achieving >4 targets, n = 44). The outcome of interest was DKD defined by estimated glomerular filtration rate (eGFR) values 30 mg. Multivariable logistic regression models were employed to estimate odds ratios (ORs) for DKD with 95% confidence intervals (CIs). Results: Of the 75 participants with prolonged T1D duration (45% male, mean age 66 years), 25 participants had DKD and 50 did not. There was no statistical difference between the high- and low-target groups in terms of age and body mass index. eGFR was significantly higher and the prevalence of diabetic retinopathy was significantly lower in the high-target group. Older age at diagnosis of T1D and lower frequency component to high-frequency component ratio increased the odds of having DKD. Conclusions: In adults with prolonged T1D duration, older age at diagnosis and lower heart rate variability may be associated with DKD.

Coverage decisions in publicly funded healthcare systems require a formal, systematic and transparent assessment process for policies related to distribution of resources. The process is complex and employs multiple types of information, such as clinical effectiveness, costs and health utility scores which are used to produce quality-adjusted life years. The purpose of this study was to create health utility scores for CKD patients within the Canadian population. This is a cross-sectional study of CKD patients. We administered the Short-Form 36 Quality of Life Questions to all participants and employed the Short-Form 6 Dimension index to create health utility scores which were created using a set of parametric preference weights, nonparametric preference weights and ordinal health state valuation techniques obtained from a sample of the general population. Utility values in the dialysis group were lower than in the non-dialysis group. There was a significant relationship between age and health utility scores: As age increases, health utility scores decrease. Diabetes was associated with lower health utility scores in dialysis patients, whereas other covariates did not reach levels of statistical significance in our stepwise regression models. The parametric Bayesian model and standard gamble approach yielded the same results, while the correlation between the nonparametric and parametric methods was above 0.9. Health utility scores were low relative to the general population norm in our study cohort. Longitudinal assessment of CKD patients to capture possible fluctuations in health utility scores may add useful information.

Health systems guidance (HSG) documents contain systematically developed statements or recommendations intended to address a health system challenge. The concept of HSG is fairly new and considerable effort has been undertaken to build tools to support the contextualization of recommendations. One example is the Appraisal of Guidelines for REsearch and Evaluation - Health Systems (AGREE-HS), created by international stakeholders and researchers, to assist in the development, reporting and evaluation of HSG. Here, we present the quality appraisal of 85 HSG documents published from 2012 to 2017 using the AGREE-HS. The AGREE-HS consists of five items (Topic, Participants, Methods, Recommendations, and Implementability), which are scored on a 7-point response scale (1=lowest quality; 7=highest quality). Overall, AGREE-HS item scores were highest for the 'Topic' and 'Recommendations' items (means above the mid-point of 4), while the 'Participants', 'Methods', and 'Implementability' items received lower scores. Documents without a specific health focus and those authored by the National Institute for Health and Care Excellence group, achieved higher AGREE-HS overall scores than their comparators. No statistically significant changes in overall scores were observed over time. This is the first time that the AGREE-HS has been applied, providing a current quality status report of HSG and identifying where improvements in HSG development and reporting can be made.

OBJECTIVES To explore the responsiveness of patient-reported outcomes (PROs) in interventional studies involving patients with rare lysosomal storage diseases (LSDs). STUDY DESIGN AND SETTING We searched eight databases for experimental and nonexperimental studies. Pairs of trained reviewers independently screened articles and subsequently extracted data from the eligible studies. Among studies with 10 or more patients using a valid PRO, we assessed the responsiveness of PROs based on a reanalysis of the data using minimal important difference estimates. Our analyses focused on statistically significant within-group differences in PROs for observational studies or the statistically significant between-group differences in PRO scores for controlled studies. RESULTS Of 2,679 unique records, 62 interventional studies addressing patients with Fabry (55%), Gaucher (19%), Pompe (16%), and mucopolysaccharidoses (11%) proved eligible. The most frequently used PROs were the Short-Form-36 (25 studies), Brief Pain Inventory (20 studies), EuroQoL-5D (9 studies), and the Fatigue Severity Scale (6 studies). Observational studies suggest that PROs sometimes detect significant within-group changes when present. Randomized trials raise questions regarding the responsiveness of PROs to small differences between groups. CONCLUSIONS Most studies have relied on generic PROs to evaluate quality of life and symptoms in patients with rare LSDs. PROs appear more responsive in observational studies than randomized trials.

Supplemental Digital Content is available in the text., Deceased-donor renal transplant (DDRT) is an expensive and potentially risky health intervention with the prospect of improved life and lower long-term costs compared with dialysis. Due to the increasing shortage of kidneys and the associated rise of transplantation costs, certain patient groups may not benefit from transplantation in a cost-effective manner compared with dialysis. The objective of this systematic review was to provide a comprehensive synthesis of evidence on the cost-effectiveness of DDRT relative to dialysis to treat adults with end-stage renal disease and patient-, donor-, and system-level factors that may modify the conclusion. A systematic search of articles was conducted on major databases including MEDLINE, Embase, Scopus, EconLit, and the Health Economic Evaluations Database. Eligible articles were restricted to those published in 2001 or thereafter. Two reviewers independently assessed the suitability of studies and excluded studies that focused on recipients with age

Background Chronic kidney disease-mineral and bone disorder (CKD-MBD), a complication of chronic kidney disease, has been linked to reduced quality and length of life. High serum phosphate levels that result from CKD-MBD require phosphate-lowering agents, also known as phosphate binders. The objective of this systematic review is to compare the effects of available phosphate binders on laboratory outcomes in patients with CKD-MBD. Methods Data sources included MEDLINE and EMBASE from January 1996 to April 2016, and the Cochrane Register of Controlled Trials up to April 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible randomized controlled trials (RCTs). Eligible trials enrolled patients with CKD-MBD and randomized them to receive calcium-based phosphate binders (delivered as calcium acetate, calcium citrate or calcium carbonate), non-calcium-based phosphate binders (NCBPB) (sevelamer hydrochloride, sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide and ferric citrate), phosphorus restricted diet (diet), placebo or no treatment and reported effects on serum levels of phosphate, calcium and parathyroid hormone. We performed Bayesian network meta-analyses (NMA) to calculate the effect estimates (mean differences) and 95% credible intervals for serum levels of phosphate, calcium and parathyroid hormone. We calculated direct, indirect and network meta-analysis estimates using random-effects models. We applied the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for each pairwise comparison. Results Our search yielded 1108 citations; 71 RCTs were retrieved for full review and 16 proved eligible. Including an additional 13 studies from a previous review, 29 studies that enrolled 8335 participants proved eligible; 26 trials provided data for quantitative synthesis. Sevelamer, lanthanum, calcium, iron, diet and combinations of active treatments (calcium or sevelamer or lanthanum and combination of calcium and sevelamer) resulted in significantly lower serum phosphate as compared to placebo (moderate to very low quality of evidence). We found no statistically significant differences between active treatment categories in lowering serum phosphate. Sevelamer, lanthanum and diet resulted in lower serum calcium compared to calcium (moderate quality evidence for lanthanum and diet; low quality evidence for Sevelamer). Iron, sevelamer and calcium yielded lower parathyroid hormone levels as compared to lanthanum. Meta-regression analyses did not yield a statistically significant association between treatment effect and trial duration. Discussion/Conclusions We found few differences between treatments in impact on phosphate and differences in parathyroid hormone. Relative to calcium, sevelamer, lanthanum and diet showed significant reduction in serum calcium from baseline. Treatment recommendations should be based on impact on patient-important outcomes rather than on surrogate outcomes. Systematic review registration: PROSPERO CRD-42016032945

BACKGROUND:Chronic kidney disease-mineral and bone disorder (CKD-MBD) has been linked to poor health outcomes, including diminished quality and length of life. This condition is characterized by high phosphate levels and requires phosphate-lowering agents-phosphate binders. The objective of this systematic review is to compare the effects of available phosphate binders on patient-important outcomes in patients with CKD-MBD. METHODS:Data sources included MEDLINE and EMBASE Trials from 1996 to February 2016. We also searched the Cochrane Register of Controlled Trials up to April 2016. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible randomized controlled trials (RCTs). Eligible trials enrolled patients with CKD-MBD, randomized them to receive calcium (delivered as calcium acetate, calcium citrate or calcium carbonate), non-calcium-based phosphate binders (NCBPB) (sevelamer hydrochloride, sevelamer carbonate, lanthanum carbonate, sucroferric oxyhydroxide and ferric citrate), phosphorus restricted diet, placebo or no treatment, and reported effects on all-cause mortality, cardiovascular mortality or hospitalization at ≥4 weeks follow-up. We performed network meta-analyses (NMA) for all cause-mortality for individual agents (seven-node analysis) and conventional meta-analysis of calcium vs. NCBPBs for all-cause mortality, cardiovascular mortality and hospitalization. In the NMAs, we calculated the effect estimates for direct, indirect and network meta-analysis estimates; for both NMA and conventional meta-analysis, we pooled treatment effects as risk ratios (RR) and calculated 95% confidence intervals (CIs) using random effect models. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence for each paired comparison. RESULTS:Our search yielded 1190 citations, of which 71 RCTs were retrieved for full review and 15 proved eligible. With 13 eligible studies from a prior review, we included 28 studies with 8335 participants; 25 trials provided data for our quantitative synthesis. Results suggest higher mortality with calcium than either sevelamer (NMA RR, 1.89 [95% CI, 1.02 to 3.50], moderate quality evidence) or NCBPBs (conventional meta-analysis RR, 1.76 [95% CI, 1.21 to 2.56, moderate quality evidence). Conventional meta-analysis suggested no difference in cardiovascular mortality between calcium and NCBPBs (RR, 2.54 [95% CI, 0.67 to 9.62 low quality evidence). Our results suggest higher hospitalization, although non-significant, with calcium than NCBPBs (RR, 1.293 [95% CI, 0.94 to 1.74, moderate quality evidence). DISCUSSION/CONCLUSIONS:Use of calcium results in higher mortality than either sevelamer in particular and NCBPBs in general (moderate quality evidence). Our results raise questions about whether administration of calcium as an intervention for CKD- MBD remains ethical. Further research is needed to explore the effects of different types of phosphate binders, including novel agents such as iron, on quality and quantity of life. SYSTEMATIC REVIEW REGISTRATION:PROSPERO CRD-42016032945.

Chronic kidney disease-mineral and bone disorders (CKD-MBD) have been associated with poor health outcomes, including diminished quality and length of life. Standard management for CKD-MBD includes phosphate restricted diet, vitamin D and phosphate binders. Persistently elevated parathyroid hormone levels may require the addition of cinacalcet hydrochloride (cinacalcet), which sensitizes calcium receptors in the parathyroid gland.The objective of this systematic review is to compare, in patients with CKD-MBD the effect of cinacalcet versus standard treatment on patient-important outcomes, including parathyroidectomy, fractures, hospitalizations due to cardiovascular events, cardiovascular mortality, all-cause mortality, and intermediate outcomes, in particular Kidney Disease Outcome Quality Initiative targets.Data sources included MEDLINE, EMBASE, the Cochrane Register of Controlled Trials and Web of Science from 1996 to June 2015. Teams of two reviewers, independently and in duplicate, screened titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstracted data and assessed risk of bias in eligible trials. We calculated the effect estimates (risk ratios or mean differences) and 95% confidence intervals, as well as statistical measures of variability in results across studies using random effect models. We used the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate quality of evidence about estimates of effect on an outcome-by-outcome basis for all outcomes. We presented our results with a GRADE summary table.Twenty-four trials including 8311 CKD patients proved eligible. The results left considerable uncertainty regarding the impact of cinacalcet on reducing fractures (relative risk [RR] 0.59, 95% confidence interval [CI] 0.13-2.60; heterogeneity: p = 0.03, I(2)= 78%; very low quality evidence), and indicated that cinacalcet did not reduce hospitalizations due to cardiovascular events (RR 0.93, 95% CI 0.85-1.02, moderate quality of evidence), cardiovascular mortality (RR 0.95, 95% CI 0.84-1.07; heterogeneity p= 0.61, high quality evidence) or all-cause mortality (RR 0.96, 95% CI 0.89-1.04; heterogeneity: p= 0.98, I(2)= 0%; moderate quality evidence). Cinacalcet reduced the need for parathyroidectomy (RR 0.30, 95% CI 0.22-0.42; heterogeneity: p= 0.70, I(2)= 0%; absolute effect 55 fewer per 1000 [95% CI 61 fewer to 45 fewer], high quality of evidence). The most common adverse event associated with cinacalcet therapy was gastrointestinal side effects. Cinacalcet increased nausea (RR 2.16, 95% CI 1.46-3.21, absolute effect 158 more per 1000 [95% CI 82 more to 302 more]) and vomiting (RR 2.15, 95% CI 1.66-2.80, absolute effect 63 more per 1000 [95% CI 109 more to 171 more]). Cinacalcet treatment increased the rate of hypocalcemia (RR 6.0, 95% CI 3.65-9.87; heterogeneity: p= 0.71, I(2)= 0%, absolute effect 20 more per 1000 [95% CI 11 more to 36 more], high quality of evidence).In the hands of clinicians participating in these studies, cinacalcet decreased the rate of parathyroidectomy but had no influence on mortality. Patients and clinicians can trade of the benefit of fewer parathyroidectomies against the adverse effects.

Background Chronic kidney disease-mineral and bone disorders (CKD-MBD) have been associated with poor health outcomes, including diminished quality and length of life. Standard management for CKD-MBD includes phosphate-restricted diet, active vitamin D, vitamin D analogs, and phosphate binders. Persistently elevated parathyroid hormone (PTH) levels may require the addition of Cinacalcet hydrochloride (cinacalcet) which sensitizes calcium receptors on the parathyroid glands. The objective of this systematic review is to compare the effect of cinacalcet versus standard treatment in patients with CKD-MBD. Methods/design Data sources will include MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, and Web of Science from 1996 to June 2015. Teams of two reviewers will, independently and in duplicate, screen titles and abstracts and potentially eligible full text reports to determine eligibility, and subsequently abstract data and assess risk of bias in eligible trials. We will calculate the effect estimates (risk ratios or mean differences) and 95 % confidence intervals, as well as statistical measures of variability in results across studies using random effect models for patient-important and intermediate outcomes. We will use the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach to rate the quality of evidence about estimates of effect on an outcome-by-outcome basis. We will present our results with a GRADE summary table. Discussion Our review will explore the effect of cinacalcet versus standard treatment in patients with CKD-MBD. The results of this systematic review will help guide management of this patient population, and identify targets for future research. Systematic review registration PROSPERO CRD42015020318http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42015020318.