ROLE OF RENIN ANGIOTENSIN SYSTEM IN BONE METABOLISM IN HEMODIALYSIS PATIENTS: GENETIC INFLUENCE OF ACE GENE POLYMORPHISM ON BONE MASS

OBJECTIVES: Recently, angiotensin II (Ang II) receptorsubtype I binding sites has been demonstrated on bone cell precursors and extensive area of research has been focused on the effects of renin angiotensin system (RAS) on bone formation. So the aim of this study is to address the influence of renin angiotensin system on the bone metabolism in hemodialysis patients. METHOD: Forthy - eight hemodialysis patients (28 male. 20 female) were involved in this study. Bone mineral density (BMD) was estimated at lumbar spine using dual energy X - ray bone absorptiometry and expressed as Z-scores standardized by age and gender. Z score worse than - 2.0 were considered as osteopenia. Angiotensin converting enzyme (ACE) gene polymorphism (II, ID, DD) of the hemodialysis patients were determined and plasma renin activity (PRA), serum ACE activity were measured before and after hemodialysis. Intact parathyroid hormone (iPTH) and osteocalcin (BGP), bone alkaline phosphatase (bAP) and carboxy terminal propeptide type I collagen (PICP) were measured as the markers of bone formation. RESULTS: Z score of the hemodialysis patients was -1.21+1.46 and sixteen patients (33 %) were osteopenia (- 2.75+0.65) The PRA, ACE activity were similar in the osteopenic and non-osteopenic patients. Activation of RAS by same amount of volume depletion in two groups resulted in a higher percent increment in PRA in the non-osteopenic group compared to osteopenic patients (% 232.6+41.9 vs. % 78.8+10.7p<0.05) at the end of dialysis session. Also PRA increaments in hemodialysis patients were correlated with Z score (pO.05). ACE activity was positively correlated with serum iPTH (R=0,29, p=0.02), serum OC (R=0,35, p=0.01), serum bAP (R=0,34, p=0.01), serum PCIP (R=0,36, p=0.01). Bone mass (0.98+0.18 g/cm vs. 0.87+0.14 g/cm , p<0.05) and Z scores (-0.6±l,5. vs -I.6±J.3 p<0,05).were higher in DD group compared to II/ID group CONCLUSION:Association of biochemical and radiological signs of increased bone formation with activated RAS in hemodialysis patients might be an additional evidence for the involvement of this system in the regulation of bone metebolism