Background and objectives: Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a systemic condition defined by an increase in cardiovascular calcifications and bone fragility. The condition is diagnosed by abnormal serum concentrations of calcium, phosphorus, parathyroid hormone and vitamin D. These biochemical abnormalities have been linked to abnormal bone metabolism as well as cardiovascular calcifications if left untreated.
Phosphate binders are known to cause phosphate reduction through mechanisms involve the gastrointestinal route. Their relative effects remain uncertain. Controversy arises because of concerns related to systematic effects, tolerability, costs and impact on patient important outcomes. The objective of Chapters 2 and 3 was to explore the relative effectiveness of phosphate binders on patient-important outcomes and laboratory outcomes in patients with CKD-MBD using the frequentist and Bayesian approaches, respectively. The purpose of Chapter 4 was to critically appraise clinical practice guidelines addressing CKD-MBD.
Methods and results
Chapter 2: We performed network meta-analyses for all cause-mortality for individual agents (seven-node analysis) and conventional meta-analysis of calcium vs. non-calcium based phosphate binders (NCBPB) for all-cause mortality, cardiovascular mortality and hospitalization. Our results suggested higher mortality with calcium than either sevelamer in our network meta-analysis or NCBPB in our conventional meta-analysis. Conventional meta-analysis suggested no statistically difference in cardiovascular mortality between calcium and NCBPBs.
Chapter 3: We performed Bayesian network meta-analyses to calculate the effect estimates (mean differences) and 95% credible intervals for serum levels of phosphate, calcium and parathyroid hormone. Moderate-quality evidence suggests superior effect of active treatment categories as compared to placebo for reducing serum phosphate. Our NMA results did not find statistically significant difference between active treatment categories in lowering serum phosphate.
Chapter 4: We performed a systematic survey to critically appraise clinical practice guidelines addressing CKD-MBD. Most guidelines assessing CKD-MBD suffer from serious shortcomings using the Advancing Guideline Development, Reporting and Evaluation in Health Care instrument II (AGREE) criteria; a minority, however, fulfill the criteria. Limitations with respect to AGREE criteria do not, however, necessarily lead to inappropriate recommendations.
Conclusion: Given the likely mortality reduction with sevelamer versus calcium, the results suggest that higher calcium levels associated with calcium based phosphate binders may contribute to the mortality differential. We found that most clinical practice guidelines related to CKD-MBD were not satisfactory with major problems with rigor, update and implementation. Recommendations were consistent and thus unassociated with guideline quality. In other instances, however, this may not be the case, and ensuring trustworthiness of guidelines will require adherence to methodological standards. / Thesis / Doctor of Philosophy (PhD)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/20773 |
| Date | January 2017 |
| Creators | Sekercioglu, Nigar |
| Contributors | Guyatt, Gordan, Health Research Methodology |
| Source Sets | McMaster University |
| Language | English |
| Detected Language | English |
| Type | Thesis |
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