Fracture risk in dialysis and kidney transplanted patients: a protocol for systematic review and meta-analysis

Background: Chronic kidney disease (CKD) is associated with an increased risk of fracture and cardiovascular mortality. The risk of fracture in hemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation (KT) is higher when compared to the general population. However, uncertainties remain about which group has the highest risk of fracture. We aim to identify the risk of fracture and cardiovascular mortality post-fracture in HD compared to PD or KT and in PD compared to KT population. Methods: We will conduct a systematic review of observational studies and randomized control trials on patients with CKD. Eligible studies will be searched on MEDLINE, Embase, Web of Science, Cochrane Library, and in gray literature. Two independent reviewers will screen all identified references in order to include studies reporting the risk of fracture without a comparator or comparing that risk in HD vs KT, PD vs KT, or HD vs PD. Studies comparing the risk of fracture in a renal replacement therapy group to general population or to non-dialyzed CKD patients will also be included. Data on study settings, population characteristics, intervention, comparator, and outcomes will be extracted. Study data will be summarized and analyzed in RevMan and SAS. Risk of bias in cohort design studies will be assessed with an adapted version of the ROBINS-I tool and by the Cochrane handbook tool for RCTs. The quality of evidence and strengths of recommendations will be evaluated by the Grading of Recommendations Assessment, Development and Evaluations (GRADE) tool. We will pool relative risks with random-effect models and Mantel-Haenszel methods. Subgroup and sensitive analysis are planned according to the intervention and comparator, study design, and type of fracture. Discussion: This review will provide new pooled data about fracture risk in dialysis and KT patients. Our results should guide the implementation of future preventive strategies targeting patients with the highest fracture risk. A pooled analysis of observational studies could be limited by a probable considerable heterogeneity among these studies.