Circulating Osteoprotegerin in Chronic Kidney Disease and All-Cause Mortality

Joanna Kamińska,1,* Marek Stopiński,1,* Krzysztof Mucha,2,3 Michał Pac,2 Marek Gołębiowski,4 Monika A Niewczas,5,6 Leszek Pączek,2,3 Bartosz Foroncewicz2 1Department of Internal Diseases and Dialysis Unit, West Hospital of Saint John Paul II, Grodzisk Mazowiecki, Poland; 2Department of Immunology, Transplantology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland; 3Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland; 4Department of Clinical Radiology, Medical University of Warsaw, Warsaw, Poland; 5Research Division, Joslin Diabetes Center, Boston, MA, USA; 6Department of Medicine, Harvard Medical School, Boston, MA, USA*These authors contributed equally to this workCorrespondence: Bartosz ForoncewiczDepartment of Immunology, Transplantology and Internal Diseases, Medical University of Warsaw, Nowogrodzka 59, Warsaw, 02-006, PolandTel +48-22-502 1641Fax +48-22-502 2127Email bartosz.foroncewicz@wum.edu.plBackground: 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 Blood was withdrawn once to perform the measurements and cardiac computed tomography was used to evaluate coronary calcium score (CS).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, osteoprotegeri