You are here

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

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

Journal Name:

Publication Year:

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
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.
FULL TEXT (PDF): 
143-150

REFERENCES

References: 

1. Hock JM, Centralla M, Canalis E. Insulin like growth factor I has independent effects on bone matrix formation and cell replication. Endocrinology 1998; 122: 254-260.
2. Centralla M, Me Carthy T, Canalis E. (1987). Transforming growth factor beta is a bifunctional regulator of replication and collagen synthesis in osteoblast enriched cell cultures. J Biol Chem 1987;
262: 2869-2874.
3. Hiruma Y, Inoue A, Hirose S. Anjiotensin II stimulates the proliferation of osteoblast-rich populations of cells from rat calvaria. Biochem Biophys Res Comtnun 1997;
230: 176-178.
4. Hagiwara H, Hiruma Y, Inoue A. Deceleration by angiotensin II of the differentiation and bone formation of rat calvarial osteoblastic cells. J Endocrinol 1998;
156:543-550.
5. Lamparter S, Kling L, Schrader M. Effect of angiotensin
II on bone cells in vitro. J Cell Physiol 1998; 175: 89-98.
6. Pocock NA, Eisman JA, Hooper J, Yeates M, Sambrock PN, Elberl S. Genetic determinants of bone mass in
adults. J Clin Invest 1987; 80: 706-710.
7. Morrison NA, Qi JC, Tokito A. Prediction of bone density from vitamin D receptor alleles. Nature 1994;
367: 284-287.
8. Kobayashi S, Inoue S, Hosoi T, Ouchi Y, Shiraki M, Orimo H. Association of bone mineral density with polymorphism of the estrogen reseptör gene. J Bone
Miner Res 1996; 11:306-311.
9. Grant SFA, Reid DM, Blake G, Herd R, Fogelman I,
Ralston SH. Reduced bone density and osteoporosis associated with a polymorphic Spl binding site in the collagen type 1 alpha gene. Nature Genet 1996; 14: 203¬205.
10. Yoshida H, Kon V, Ichikawa I. Polymorphims of the renin angiotenin system genes in progressive renal
dieases. Kidney Int 1996; 50: 732-744.
11. Rigat B, Hubert C, Gelas F, Cambien F, Corvol P,
Soubrier F. An insertion and deletion polymorphism in the angiotensin I converting enzyme gene accounting for half variance in serum enzyme levels. .1 Clin Invest 1990;
86: 1343-1346.
12. Costerousse O, Allegrini J, Lopez M, Alhanec G, Gelas F. Angiotensin converting enzyme in human circulating mononuclear cells: Genetic polymorphism of expression
in T lymphocytes. Biochem J 1993; 290: 33-40.
13. Fletcher S, Jones RG, Rayner HC, et al. Assessment of renal osteodystrophy in dialysis patients: use of bone alkaline phosphatase, bone mineral density and paratyroid ultrasound in comparision with bone
histology. Nephron 1997; 75: 412-419.
14. Coen G, Ballanti P, Bonucci E, et al. Bone markers in the diagnosis of low turnover osteodystrophy. Neprol
Dial Transplant 1998; 13: 2294-22302.
15. Stein MS, Packham DK, Ebeling PR, Wark JD, Becker JB. Prevelance and risk factors for osteopenia in dialysis
patients. Am J Kidney Dis 1996; 28: 515-522.
16. Ghan TM, Pun KK, Cheng KP. Total and regional bone densities in dialysis patients. Nephrol Dial Transplant
1992;7:835-839.
17. Ebeling PR, Jones JD, O'Fallon WM. Janes CH. Riggs
BL. Short term effects of recombinant human insulin like growth factor I on bone turnover in normal women. J Clin Endocrinol Metab 1993; 77: 1384-1387.
18. Centralla M, Canalis E, Me Carthy T. Effects of basic-fibroblast growth factor on bone formation in vitro. J Clinlnvestl988;81: 1572-1577.
19. Zaidi M, Alam T, Bax BE, et al. Role of the endothelial
cell in osteoclast control: New perspectives. Bone 1993;
14:97-102.
20. Hatton R, Stimpel M, Chambers TJ. Angiotensin II generated from angiotensin I by bone cells and stimulates osteoclstic bone resorption in vitro. J
Endocrinol 1997; 152: 5-10.
21. Barr MJ, Cohen MMJ. ACE inhibitor fetopathy and hypocalvaria the kidney-skull connection. Teratology
1991;44:485-495.
22. Mehta N, Modt N. ACE inhibitors in pregnancy. Lancet
1989; ii: s96.
23. Tylavsky FA, Johnson KC, Wan JY, Harshtield G.
Plasma renin activity is associated with bone mineral density in premenopausal women. Osteoporosis Iftt
1998; 8: 136-140.
24. Cooper GS, Umbach DM. Are vitamin D gene polymorphism associated with bone mineral density ? A
meta analysis. J Bone Miner Res 1996; 11: 1841-1849.
25. Torres A, Salido E. Vitamin D receptor genotype its role in bone mass and turnover in non-renal and renal
patients. Nephrol Dial Transplant 1997; 12: 1811-1812.
149
26. Akiba T, Ando R, Kurihara S, Heishi M, Tazawa H, Marumo F. Is the bone mass of hemodialysis patients genetically determined ? Kidney Int Suppl 1997; 62: 69¬27. Alonso CG, Diaz MN, Corte DC, Martin FL, Andia JB.
Vitamin D receptor gene (VDR) polymorphisms: effect
on bone mass, bone loss and paratyroid hormone regulation. Nephrol Dial Transplant 1998: 13: 73-77.
A
2g Qsono E Kurihara Hayama N et al lnsertion and
deletion polymorphism in intron 16 of the ACE gene and left ventricular hypertrophy in patients with end stage renal failure. Am J Kidney Disease 1998; 32: 725-730.
150

Thank you for copying data from http://www.arastirmax.com