[BP.07.07] PROGNOSTIC VALUE OF BONE- AND VASCULAR DERIVED MOLECULAR BIOMARKERS IN HEMODIALYSIS AND RENAL TRANSPLANT PATIENTS: A SYSTEMATIC REVIEW AND META-ANALYSIS. (September 2017) - Pichler, G.
Abstract : Objective: Patients undergoing hemodialysis and kidney graft recipients are high-risk populations for cardiovascular and all-cause mortality. Fibroblast growth factor 23 (FGF23), osteoprotegerin (OPG), RANK ligand, osteopontin, klotho protein and bone morphogenetic protein-7 are bone- and vascular derived molecular biomarkers that have shown to be associated with cardiovascular surrogate end points, however, currently available data on the prognostic value of these biomarkers is inconsistent. The aim of the present study was to conduct a systematic review and meta-analysis in order to summarize the available evidence on the association of molecular biomarkers with mortality in individuals undergoing hemodialysis and renal transplant patients. Figure. No caption available. Design and method: Two databases (MEDLINE and Embase) were systematically searched. Studies were eligible if the association of biomarker and mortality was reported as time-to-event data (Hazard Ratio (HR)) or as effect size with a fixed time of follow-up (Odds Ratio (OR)). Abstracted HRs were converted onto a standard scale of effect and combined using a random effects model. Results: From a total of 1170 studies identified in initial searches, 21 met the inclusion criteria. In hemodialysis patients, comparing the lower third with the upper third of baseline fibroblast growth factor 23 distribution, pooled HRs were 1.94 (1.47, 2.56) for all-cause mortality and 2.4 (1.64, 3.51) for cardiovascular mortality. For the same comparison of baseline osteoprotegerin distribution, pooled HRs were 1.8 (0.95, 3.39) for all-cause mortality and 2.53 (1.29, 4.94) for cardiovascular mortality (figure 1). Reported risk estimates of RANK ligand, osteopontin, klotho protein and bone morphogenetic protein-7 were not suitable for pooling, however, only klotho protein was significantly related to mortality. For kidney graft recipients, four studies that investigated the relationship of fibroblast growth factor 23 and osteoprotegerin with mortality were identified, all of which reported a significant association. Conclusions: In hemodialysis patients, fibroblast growth factor 23 is a predictor of all-cause and cardiovascular mortality, whereas the predictive value of osteoprotegerin is restricted to cardiovascular mortality. Further studies are needed in order to gain insight into the prognostic value of these biomarkers in renal transplant recipients.