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RUTİN HEMODİYALİZ HASTALARINDA SERUMDA SOLUBLE KLOTHO SEVİYESİ İLE KARDİYOVASKÜLER HASTALIKLAR VE MORTALİTE ARASINDAKİ İLİŞKİ

Year 2023, Volume: 13 Issue: 6, 1033 - 1038, 30.11.2023

Abstract

Amaç: Serum sKlotho, bazı insan populasyonlarında ve hayvan deneylerinde kardiyovasküler hastalık veya ölüm riskini belirlemede rol oynar. Bu çalışmada rutin hemodiyaliz hastalarında 18 aylık takip sonrası sKlotho düzeyleri ile ekokardiyografik parametreler ve 30 aylık takipteki mortalite arasındaki ilişki araştırıldı.
Gereç Ve Yöntem: Farklı sKlotho oranları (≥1,24 ng/ml ve <1,24 ng/ml) ve yaşları (<54 ve ≥54) olan hasta grupları karşılaştırıldı.
Bulgular: sKlotho <1,24 ve ≥1,24 grupları arasında hesaplanan sol ventrikül kütle indeksi ve sol ventrikül kütle parametreleri arasında anlamlı fark bulunmadı. İki farklı yaş (<54 yaş ve ≥54 yaş) grubu arasında hesaplanan sol ventrikül kütle indeksi ve sol ventrikül kütle parametreleri arasında anlamlı fark bulunmadı. 30 ay takip edilen 136 hastada sKlotho ile tüm nedenlere bağlı ölüm arasındaki ilişkiyi belirlemek için, ölen 34 hasta ve yaşayan 102 hastadan oluşan iki grup karşılaştırıldı. Bu iki grup arasında yaş, giriş kreatinin, sodyum bikarbonat, C-reaktif protein, albümin düzeyi ve Diabetes Mellitus varlığı açısından anlamlı fark gözlendi. Sklotho değerleri açısından iki grup arasında belirgin bir fark olmamasına rağmen, ölen grupta sKlotho düzeyi daha düşük bulundu.
Sonuç: sKlotho'nun uzun dönemde üremik kardiyomiyopatiyi öngörmede uygun bir gösterge olmadığını, ancak sKlotho düzeylerinin daha geniş hasta popülasyonlu çalışmalarda mortaliteyi öngörmede yararlı olabileceğini düşünüyoruz.

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References

  • 1. Cozzolino M, Mangano M, Stucchi A, Ciceri P, Conte F, Galassi A. Cardiovascular disease in dialysis patients. Nephrol Dial Transplant 2018;1(33):iii28-iii34.
  • 2. Kuro-O M. The Klotho proteins in health and disease. Nat Rev Nephrol 2019;15(1):27-44.
  • 3. Barker SL, Pastor J, Carranza D, et al. The demonstration of αKlotho deficiency in human chronic kidney disease with a novel synthetic antibody. Nephrol Dial Transplant 2015; 30(2):223-33.
  • 4. Xie J, Yoon J, An SW, Kuro-o M, Huang CL. Soluble Klotho Protects against Uremic Cardiomyopathy Independently of Fibroblast Growth Factor 23 and Phosphate. J Am Soc Nephrol 2015; 26(5):1150-60.
  • 5. Hu MC, Shiizaki K, Kuro-o M, Moe OW. Fibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism. Annu Rev Physiol 2013;75:503-33.
  • 6. Kuro-o M, Matsumura Y, Aizawa H, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 1997;390(6655):45-51.
  • 7. Kurosu H, Yamamoto M, Clark JD, et al. Suppression of aging in mice by the hormone Klotho. Science 2005;309(5742):1829-33.
  • 8. Semba RD, Cappola AR, Sun K, et al. Plasma klotho and cardiovascular disease in adults. J Am Geriatr Soc 2011;59(9):1596-601.
  • 9. Sun CY, Chang SC, Wu MS. Suppression of klotho expression by protein-bound uremic toxins is associated with increased DNA methyltransferase expression and DNA hypermethylation. Kidney Int 2012;81(7):640–650.
  • 10. Pavik I, Jaeger P, Ebner L, et al. Secreted Klotho and FGF23 in chronic kidney disease Stage 1 to 5: a sequence suggested from a cross-sectional study. Nephrol Dial Transplant 2013;28(2):352-9.
  • 11. Kim HR, Nam BY, Kim DW, et al. Circulating α-klotho levels in CKD and relationship to progression. Am J Kidney Dis 2013;61(6):899-909.
  • 12. Wan M, Smith C, Shah V, et al. Fibroblast growth factor 23 and soluble klotho in children with chronic kidney disease. Nephrol Dial Transplant 2013;28(1):153-61.
  • 13. Semba RD, Cappola AR, Sun K, et al. Plasma klotho and mortality risk in older community-dwelling adults. J Gerontol A Biol Sci Med Sci 2011;66(7):794-800.
  • 14. Pan HC, Chou KM, Lee CC, Yang NI, Sun CY. Circulating Klotho levels can predict long-term macrovascular outcomes in type 2 diabetic patients. Atherosclerosis 2018;276:83-90.
  • 15. Devereux RB, Dahlöf B, Gerdts E, et al. Regression of hypertensive left ventricular hypertrophy by losartan compared with atenolol: the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) trial. Circulation 2004;110(11):1456–62.
  • 16. Mosteller RD. Simplified calculation of body-surface area. N Engl J Med 1987;317(17):1098.
  • 17. Erkus E, Buyukterzı Z, Karakose S, et al. The relationship of soluble klotho level with uremic cardiomyopathy and ecocardiographic parameters in hemodialysis patients. Semin Dial 2021;34(2):157-162
  • 18. Zhang AH, Guo WK, Yu L, Liu WH. Relationship of Serum Soluble Klotho Levels and Echocardiographic Parameters in Patients on Maintenance Hemodialysis. Kidney Blood Press Res 2019;44(3):396-404.
  • 19. Seiler S, Wen M, Roth HJ, et al. Plasma Klotho is not related to kidney function and does not predict adverse outcome in patients with chronic kidney disease. Kidney Int 2013;83(1):121-8.
  • 20. Seiler S, Rogacev KS, Roth HJ, et al. Associations of FGF-23 and sKlotho with cardiovascular outcomes among patients with CKD stages 2-4. Clin J Am Soc Nephrol 2014;9(6):1049-58.
  • 21. Buiten MS, de Bie MK, Bouma-de Krijger A, et al. Soluble Klotho is not independently associated with cardiovascular disease in a population of dialysis patients. BMC Nephrol 2014;15(1):1-7.
  • 22. Nowak A, Friedrich B, Artunc F, et al. Prognostic value and link to atrial fibrillation of soluble Klotho and FGF23 in hemodialysis patients. PLoS One 2014;9(7):e100688.
  • 23. Navarro-González JF, Donate-Correa J, Muros de Fuentes M, Pérez-Hernández H, Martínez-Sanz R, Mora-Fernández C. Reduced Klotho is associated with the presence and severity of coronary artery disease. Heart 2014;100(1):34-40.
  • 24. Cai H, Zhu X, Lu J, et al. A Decreased Level of Soluble Klotho Can Predict Cardiovascular Death in No or Mild Abdominal Aortic Calcification Hemodialysis Patients. Front Med (Lausanne) 2021;8:672000.
  • 25. Otani-Takei N, Masuda T, Akimoto T, et al. Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients. Int J Endocrinol 2015;2015:406269.
  • 26. Komaba H, Koizumi M, Tanaka H, et al. Effects of cinacalcet treatment on serum soluble Klotho levels in haemodialysis patients with secondary hyperparathyroidism. Nephrol Dial Transplant 2012;27(5):1967-9.
  • 27. Takahashi H, Komaba H, Takahashi Y, et al. Impact of parathyroidectomy on serum FGF23 and soluble Klotho in hemodialysis patients with severe secondary hyperparathyroidism. J Clin Endocrinol Metab 2014;99(4):E652-8.
  • 28. Sahyoun NR, Jacques PF, Dallal G, Russell RM. Use of albumin as a predictor of mortality in community dwelling and institutionalized elderly populations. J Clin Epidemiol 1996;49(9):981-8.
  • 29. Gondo Y, Hirose N, Arai Y, et al. Functional status of centenarians in Tokyo, Japan: developing better phenotypes of exceptional longevity. J Gerontol A Biol Sci Med Sci 2006;61(3):305-10.
  • 30 Takata Y, Ansai T, Soh I, et al. Serum albumin levels as an independent predictor of 4-year mortality in a community-dwelling 80-year-old population. Aging Clin Exp Res 2010;22(1):31-5.
  • 31. Ma L, Zhao S. Risk factors for mortality in patients undergoing hemodialysis: A systematic review and meta-analysis. Int J Cardiol 2017;238:151-158.
  • 32. Ayrancı MK, Küçükceran K, Dundar ZD. NLR and CRP to albumin ratio as a predictor of in-hospital mortality in the geriatric ED patients. Am J Emerg Med 2021;44:50-55.
  • 33. Kato A, Takita T, Furuhashi M, Maruyama Y, Hishida A. Comparison of serum albumin, C-reactive protein and carotid atherosclerosis as predictors of 10-year mortality in hemodialysis patients. Hemodial Int 2010;14(2):226-32.
  • 34. Msaad R, Essadik R, Mohtadi K, et al. Predictors of mortality in hemodialysis patients. Pan Afr Med J 2019;33:61.
  • 35. Nwaneri C, Bowen-Jones D, Cooper H. Screening for type 2 diabetes and population mortality over 10 years. Lance. 2013;381(9870):901-2.

THE ASSOCIATION BETWEEN SERUM SOLUBLE KLOTHO LEVEL AND CARDIOVASCULAR DİSEASE AND MORTALİTY IN ROUTİNE HEMODIALYSIS PATIENTS

Year 2023, Volume: 13 Issue: 6, 1033 - 1038, 30.11.2023

Abstract

Aim: Serum sKlotho plays a role in identifying the risk of cardiovascular disease or death in some human populations and animal experiments. In this study, the relationship between sKlotho levels and echocardiographic parameters after 18 months of follow-up and mortality at 30 months of follow-up in routine hemodialysis patients was investigated.
Matarial and Method: Groups of patients with different sKlotho rates (≥1.24 ng/ml and <1.24 ng/ml) and ages (<54 years and ≥54 years) were compared.
Results: No significant difference was found between the left ventricular mass index and left ventricular mass parameters calculated between the sKlotho <1.24 and ≥1.24 groups. No significant difference was found between the left ventricular mass index and left ventricular mass parameters calculated between the two different age (<54 years and ≥54 years) groups. In order to determine the association between sklotho and all-reason mortality in 136 patients followed for 30 months, two groups of 34 patients who died and 102 patients who survived were compared. A significant difference was observed between these two groups in terms of age, entry creatinine, sodium bicarbonate, C-reactive protein, albumin level and existence of Diabetes Mellitus. Although there was no considerable distinction in the two groups with regards to sklotho values, the sklotho level was found to be lower in the deceased group.
Conclusion: We think that sKlotho is not an appropriate indicator to predict uremic cardiomyopathy in the long term, but sKlotho levels may be useful in predicting mortality in studies with larger patient populations.

Project Number

yok

References

  • 1. Cozzolino M, Mangano M, Stucchi A, Ciceri P, Conte F, Galassi A. Cardiovascular disease in dialysis patients. Nephrol Dial Transplant 2018;1(33):iii28-iii34.
  • 2. Kuro-O M. The Klotho proteins in health and disease. Nat Rev Nephrol 2019;15(1):27-44.
  • 3. Barker SL, Pastor J, Carranza D, et al. The demonstration of αKlotho deficiency in human chronic kidney disease with a novel synthetic antibody. Nephrol Dial Transplant 2015; 30(2):223-33.
  • 4. Xie J, Yoon J, An SW, Kuro-o M, Huang CL. Soluble Klotho Protects against Uremic Cardiomyopathy Independently of Fibroblast Growth Factor 23 and Phosphate. J Am Soc Nephrol 2015; 26(5):1150-60.
  • 5. Hu MC, Shiizaki K, Kuro-o M, Moe OW. Fibroblast growth factor 23 and Klotho: physiology and pathophysiology of an endocrine network of mineral metabolism. Annu Rev Physiol 2013;75:503-33.
  • 6. Kuro-o M, Matsumura Y, Aizawa H, et al. Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 1997;390(6655):45-51.
  • 7. Kurosu H, Yamamoto M, Clark JD, et al. Suppression of aging in mice by the hormone Klotho. Science 2005;309(5742):1829-33.
  • 8. Semba RD, Cappola AR, Sun K, et al. Plasma klotho and cardiovascular disease in adults. J Am Geriatr Soc 2011;59(9):1596-601.
  • 9. Sun CY, Chang SC, Wu MS. Suppression of klotho expression by protein-bound uremic toxins is associated with increased DNA methyltransferase expression and DNA hypermethylation. Kidney Int 2012;81(7):640–650.
  • 10. Pavik I, Jaeger P, Ebner L, et al. Secreted Klotho and FGF23 in chronic kidney disease Stage 1 to 5: a sequence suggested from a cross-sectional study. Nephrol Dial Transplant 2013;28(2):352-9.
  • 11. Kim HR, Nam BY, Kim DW, et al. Circulating α-klotho levels in CKD and relationship to progression. Am J Kidney Dis 2013;61(6):899-909.
  • 12. Wan M, Smith C, Shah V, et al. Fibroblast growth factor 23 and soluble klotho in children with chronic kidney disease. Nephrol Dial Transplant 2013;28(1):153-61.
  • 13. Semba RD, Cappola AR, Sun K, et al. Plasma klotho and mortality risk in older community-dwelling adults. J Gerontol A Biol Sci Med Sci 2011;66(7):794-800.
  • 14. Pan HC, Chou KM, Lee CC, Yang NI, Sun CY. Circulating Klotho levels can predict long-term macrovascular outcomes in type 2 diabetic patients. Atherosclerosis 2018;276:83-90.
  • 15. Devereux RB, Dahlöf B, Gerdts E, et al. Regression of hypertensive left ventricular hypertrophy by losartan compared with atenolol: the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) trial. Circulation 2004;110(11):1456–62.
  • 16. Mosteller RD. Simplified calculation of body-surface area. N Engl J Med 1987;317(17):1098.
  • 17. Erkus E, Buyukterzı Z, Karakose S, et al. The relationship of soluble klotho level with uremic cardiomyopathy and ecocardiographic parameters in hemodialysis patients. Semin Dial 2021;34(2):157-162
  • 18. Zhang AH, Guo WK, Yu L, Liu WH. Relationship of Serum Soluble Klotho Levels and Echocardiographic Parameters in Patients on Maintenance Hemodialysis. Kidney Blood Press Res 2019;44(3):396-404.
  • 19. Seiler S, Wen M, Roth HJ, et al. Plasma Klotho is not related to kidney function and does not predict adverse outcome in patients with chronic kidney disease. Kidney Int 2013;83(1):121-8.
  • 20. Seiler S, Rogacev KS, Roth HJ, et al. Associations of FGF-23 and sKlotho with cardiovascular outcomes among patients with CKD stages 2-4. Clin J Am Soc Nephrol 2014;9(6):1049-58.
  • 21. Buiten MS, de Bie MK, Bouma-de Krijger A, et al. Soluble Klotho is not independently associated with cardiovascular disease in a population of dialysis patients. BMC Nephrol 2014;15(1):1-7.
  • 22. Nowak A, Friedrich B, Artunc F, et al. Prognostic value and link to atrial fibrillation of soluble Klotho and FGF23 in hemodialysis patients. PLoS One 2014;9(7):e100688.
  • 23. Navarro-González JF, Donate-Correa J, Muros de Fuentes M, Pérez-Hernández H, Martínez-Sanz R, Mora-Fernández C. Reduced Klotho is associated with the presence and severity of coronary artery disease. Heart 2014;100(1):34-40.
  • 24. Cai H, Zhu X, Lu J, et al. A Decreased Level of Soluble Klotho Can Predict Cardiovascular Death in No or Mild Abdominal Aortic Calcification Hemodialysis Patients. Front Med (Lausanne) 2021;8:672000.
  • 25. Otani-Takei N, Masuda T, Akimoto T, et al. Association between Serum Soluble Klotho Levels and Mortality in Chronic Hemodialysis Patients. Int J Endocrinol 2015;2015:406269.
  • 26. Komaba H, Koizumi M, Tanaka H, et al. Effects of cinacalcet treatment on serum soluble Klotho levels in haemodialysis patients with secondary hyperparathyroidism. Nephrol Dial Transplant 2012;27(5):1967-9.
  • 27. Takahashi H, Komaba H, Takahashi Y, et al. Impact of parathyroidectomy on serum FGF23 and soluble Klotho in hemodialysis patients with severe secondary hyperparathyroidism. J Clin Endocrinol Metab 2014;99(4):E652-8.
  • 28. Sahyoun NR, Jacques PF, Dallal G, Russell RM. Use of albumin as a predictor of mortality in community dwelling and institutionalized elderly populations. J Clin Epidemiol 1996;49(9):981-8.
  • 29. Gondo Y, Hirose N, Arai Y, et al. Functional status of centenarians in Tokyo, Japan: developing better phenotypes of exceptional longevity. J Gerontol A Biol Sci Med Sci 2006;61(3):305-10.
  • 30 Takata Y, Ansai T, Soh I, et al. Serum albumin levels as an independent predictor of 4-year mortality in a community-dwelling 80-year-old population. Aging Clin Exp Res 2010;22(1):31-5.
  • 31. Ma L, Zhao S. Risk factors for mortality in patients undergoing hemodialysis: A systematic review and meta-analysis. Int J Cardiol 2017;238:151-158.
  • 32. Ayrancı MK, Küçükceran K, Dundar ZD. NLR and CRP to albumin ratio as a predictor of in-hospital mortality in the geriatric ED patients. Am J Emerg Med 2021;44:50-55.
  • 33. Kato A, Takita T, Furuhashi M, Maruyama Y, Hishida A. Comparison of serum albumin, C-reactive protein and carotid atherosclerosis as predictors of 10-year mortality in hemodialysis patients. Hemodial Int 2010;14(2):226-32.
  • 34. Msaad R, Essadik R, Mohtadi K, et al. Predictors of mortality in hemodialysis patients. Pan Afr Med J 2019;33:61.
  • 35. Nwaneri C, Bowen-Jones D, Cooper H. Screening for type 2 diabetes and population mortality over 10 years. Lance. 2013;381(9870):901-2.
There are 35 citations in total.

Details

Primary Language English
Subjects Nefroloji
Journal Section Original Research
Authors

Edip Erkuş 0000-0002-7821-8275

İbrahim Güney 0000-0002-1646-2811

Zafer Büyükterzi 0000-0001-9391-049X

Project Number yok
Publication Date November 30, 2023
Acceptance Date October 11, 2023
Published in Issue Year 2023 Volume: 13 Issue: 6

Cite

AMA Erkuş E, Güney İ, Büyükterzi Z. THE ASSOCIATION BETWEEN SERUM SOLUBLE KLOTHO LEVEL AND CARDIOVASCULAR DİSEASE AND MORTALİTY IN ROUTİNE HEMODIALYSIS PATIENTS. J Contemp Med. November 2023;13(6):1033-1038.