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HEMODİYALİZ HASTALARINDA RENİN ANJİOTENSİN SİSTEMİNİN KEMİK METABOLİZMASINDAKİ ROLÜ: ANJİOTENSİN KONVERTİNG ENZİM GEN POLİMORFİZMİNİN GENETİK BELİRLEYİCİ ETKİSİ

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

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143-150

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Abstract (Original Language): 
Amaç: Günümüzde bir büyüme faktörü olarak kabul edilen angiotensin H'nin (Ang II) tip I reseptörünün osteositler üzerinde gösterilmesi, renin anjiotensin sistemi ile kemik arasındaki ilintinin araştırılmasına neden olmuştur. Bu çalışmanın amacı hemodiyaliz hastalarında kemik metabolizması ile renin anjiotensin sistemi (RAS) arasındaki ilişkinin araştırılması idi. Metod: Bu çalışmaya 48 hemodiyaliz hastası alındı (28E, 20K). Hastaların kemik mineral dansitesi (KMD) lumbar vertebradan dual enerji X - ray absorptiometre ile ölçüldü. Ölçümler yaş cinsiyete göre Z-skoru olarak standartize edildi ve Z skoru - 2.0'den büyük değerler osteopeni olarak kabul edildi. Hastaların anjiotensin konverting enzim (ACE) genotipleri (II, ID, DD) saptandı ve hemodiyaliz öncesi ve hemodiyaliz sonrası plama renin aktiviteleri (PRA), serum ACE aktiviteleri ölçüldü. Kemik yapımının biyokimyasal belirleyicisi olan serum osteokalsin (OC), serum kemik alkalen fosfataz (bAP) ve serum karboksi terminal propeptid tip 1 kollajen (PICP) ile serum paratiroid hormon (iPTH) düzeyleri ölçüldü. Bulgular: Hemodiyaliz hastalarının ortalama Z skoru -I.21±1.46 idi ve onaltı hastada osteopeni (33 %) saptandı. (-2.75-kO.65). Osteopenik hasta grubu ile osteopenik olmayan hastaların PRA, ACE aktiviteleri benzer idi. Öte yandan, diyaliz esnasında her iki grupta aynı miktarda sıvı alınması sonucunda belirlenen ve RAS aktivasyonun göstergesi olan PRA 'deki artış oranı osteopenik olmayan grupda osteopenik hastalara göre daha yüksek idi ( % 232.6±41.9 vs. % 78.8±10.7 p<0.05). PRA'deki artış oranı ile Z skoru arasında pozitif korelasyon saptandı (r=0.48, p=0.001). Serum ACE aktivitesi 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). Serum OC (r=0.35, p=0.01) ile pozitif korelasyon göstermekte idi. KMD (0.98^0.18 g/cm vs. 0.87±0.14 g/cm,p<0.05) veZskorları (-0.6±l,5, vs-1.6±1.3 p<0,05) DD hasta grubunda II/ID grubuna güre yüksek idi. Sonuç: Hemodiyaliz hastalarında kemik yapımının biyokimyasal belirleyicilerinin ve radyolojik görüntüsünün, renin anjiotensin sisteminin aktivasyonu ile birlikteliği bu sistemin kemik metabolizmasındaki rolünün bir göstergesi olabilir.
Abstract (2. Language): 
Objectives: Recently, angiotensin II(Ang II) receptor-subtype 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+0.18g/cm vs. 0.87+0.14g/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

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