Circulating Osteoprotegerin in Chronic Kidney Disease and All-Cause Mortality

Abstract

Background

Chronic kidney disease (CKD) is associated with cardiovascular disease (CKD), mineral and bone disorder (CKD-MBD) and high mortality. Bone-related factors such as osteopontin (OPN), osteocalcin (OC), osteoprotegerin (OPG) and fibroblast growth factor 23 (FGF23) were linked to cardiovascular complications of CKD and are expected to have predictive value in CKD patients.

Purpose

The aim of this study was to assess the relationship of OPN, OC, OPG and FGF23 to clinical characteristics and to evaluate their ability to predict mortality in patients with different CKD stages.

Methods

The following study groups were enrolled: subjects with end-stage renal disease (38 ESRD), CKD stages 3 and 4 (19 CKD3-4) and non-CKD controls (19), respectively. Blood was withdrawn once to perform the measurements and cardiac computed tomography was used to evaluate coronary calcium score (CS). Patients were followed for 5 years for the ascertainment of their all-cause mortality.

Results

Serum OPN, OC and OPG concentrations increased significantly along with the progression of renal disease. We found a significant positive correlation among these proteins. Additionally, OPN and OPG were significantly and positively correlated to CS. Serum OPG revealed the strongest correlation to the calcium turnover markers of GFR decline and was significantly associated with an increased risk of death in subjects with CKD3-4 or ESRD (HR 5.8, CI 95%).

Conclusion

Single measurement of osteoprotegerin is associated with 5-year all-cause mortality in patients with CKD3-4 or ESRD. We suggest assessing its concentration, preferably in combination with calcium score, to stratify mortality risks in CKD patients.

Keywords:

• calcium score
• chronic kidney disease
• osteocalcin
• osteopontin
• osteoprotegerin

Disclosure

Dr Joanna Kamińska report personal fees from Roche Poland, outside the submitted work; Dr Bartosz Foroncewicz report congress fee + travel from Astellas and Chiesi, outside the submitted work; Dr Krzysztof Mucha report congress fee + travel from Astellas, outside the submitted work; In addition, Dr Bartosz Foroncewicz, Dr Krzysztof Mucha and Dr Leszek Pączek have patents WO2018141975A1 and WO2017212463 pending. The authors report no other conflicts of interest in this work.