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Relationship between fibroblast growth factor and arrhythmogenesis in normotensive patients with polycystic kidney disease

Year 2015, Volume: 1 Issue: 3, 106 - 112, 04.11.2015
https://doi.org/10.18621/eurj.2015.1.3.106

Abstract

Objectives. Autosomal dominant polycystic kidney disease (ADPKD) is the most common life-threatening genetic disease. Recent prospective studies showed a powerful and dose dependent association between increasing FGF-23 levels and greater risk of mortality among chronic kidney disease patients. In this study, our aim is to evaluate electrocardiogram derived arrhythmogenesis markers such as Tp-e, Tp-e/QT and Tpe/QTc ratio ADPKD. Methods. Data of 31 patients with ADPKD and age-sex matched 26 healthy were gained for study. Electrocardiogram and echocardiogram measurements, various serum markers were compared between groups. Results. FGF-23 was significantly higher, and eGFR was significantly lower in the ADPKD patients. Myocardial thickness was also higher in ADPKD group. Corrected QT dispersion, Tpe, Tp-e/QT and Tp-e/QTc were also compared between groups. All indicators were significantly worse in ADPKD group. In the correlation analyzes, FGF-23 was significantly correlated with Tp-e, Tp-e/QT and Tp-e/QTc (r=0.388, p=0.003; r=0.472, p<0.0001; r=0.442, p=0.001, respectively). Conclusions. In this occasion, we suggest that FGF-23, which probably accumulates ventricular electrical remodeling, may be helpful for risk stratification in patients with ADPKD when used with other indicators. Myocardial cell de-arrangement and electrical remodelling due to fibrosis are suggested mechanisms for this effect.

References

  • Perrone RD, Ruthazer R, Terrin NC. Survival after end-stage renal disease in autosomal dominant polycystic kidney disease: contribution of extrarenal complications to mortality. Am J Kidney Dis. 2001 October;38(4):777-84.
  • Ecder T, Schrier RW. Cardiovascular abnormalities in autosomal-dominant polycystic kidney disease. Nat Rev Nephrol. 2009 April;5(4):221-8.
  • Ecder T, Schrier RW. Hypertension and left ventricular hypertrophy in autosomal dominant polycystic kidney disease. Expert Rev Cardiovasc Ther. 2004 May;2(3):369-74.
  • Bardají A, Vea AM, Gutierrez C, Ridao C, Richart C, Oliver JA. Left ventricular mass and diastolic function in normotensive young adults with autosomal dominant polycystic kidney disease. Am J Kidney Dis. 1998 Dec;32(6):970-5.
  • Cadnapaphornchai MA, McFann K, Strain JD, Masoumi A, Schrier RW. Increased left ventricular mass in children with autosomal dominant polycystic kidney disease and borderline hypertension. Kidney Int. 2008 Nov;74(9):1192-6.
  • Gabow PA, Johnson AM, Kaehny WD, Kimberling WJ, Lezotte DC, Duley IT, et al. Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease. Kidney Int. 1992 May;41(5):1311-9.
  • Doulton TW, Saggar-Malik AK, He FJ, Carney C, Markandu ND, Sagnella GA, et al. The effect of sodium and angiotensin-converting enzyme inhibition on the classic circulating renin-angiotensin system in autosomal-dominant polycystic kidney disease patients. J Hypertens. 2006 May;24(5):939-45.
  • Pavik I, Jaeger P, Kistler AD, Poster D, Krauer F, Cavelti-Weder C, et al. Patients with autosomal dominant polycystic kidney disease have elevated fibroblast growth factor 23 levels and a renal leak of phosphate. Kidney Int. 2011 Jun;79(2):234-40.
  • Faul C, Amaral AP, Oskouei B, Hu MC, Sloan A, Isakova T, et al. FGF23 induces left ventricular hypertrophy. J Clin Invest. 2011 Nov;121(11):4393-408.
  • Surawicz B. Will QT dispersion play a role in clinical decision-making? J Cardiovasc Electrophysiol. 1996 Aug;7(8):777-84.
  • Schouten EG, Dekker JM, Meppelink P, Kok FJ, Vandenbroucke JP, Pool J. QT interval prolongation predicts cardiovascular mortality in an apparently healthy population. Circulation. 1991 Oct;84(4):1516-23.
  • Malhis M, Al-Bitar S, Farhood S, Zaiat KA. Changes in QT intervals in patients with end-stage renal disease before and after hemodialysis. Saudi J Kidney Dis Transpl. 2010 May;21(3):460-5.
  • Genovesi S, Dossi C, Viganò MR, Galbiati E, Prolo F, Stella A, et al. Electrolyte concentration during haemodialysis and QT interval prolongation in uraemic patients. Europace. 2008 Jun;10(6):771-7.
  • Wu VC, Lin LY, Wu KD. QT interval dispersion in dialysis patients. Nephrology (Carlton). 2005 Apr;10(2):109-12.
  • Castro Hevia J, Antzelevitch C, Tornés Bárzaga F, Dorantes Sánchez M, Dorticós Balea F, Zayas Molina, et al. Tpeak-Tend and Tpeak-Tend dispersion as risk factors for ventricular tachycardia/ventricular fibrillation in patients with the Brugada syndrome. J Am Coll Cardiol. 2006 May 2;47(9):1828-34.
  • Smetana P, Schmidt A, Zabel M, Hnatkova K, Franz M, Huber K, et al. Assessment of repolarization heterogeneity for prediction of mortality in cardiovascular disease: peak to the end of the T wave interval and nondipolar repolarization components. J Electrocardiol. 2011 May-Jun;44(3):301-8.
  • Opthof T, Coronel R, Janse MJ. Is there a significant transmural gradient in repolarization time in the intact heart?: Repolarization Gradients in the Intact Heart. Circ Arrhythm Electrophysiol. 2009 Feb 2;2(1):89-96.
  • Topilski I, Rogowski O, Rosso R, Justo D, Copperman Y, Glikson M, et al. The morphology of the QT interval predicts torsade de pointes during acquired bradyarrhythmias. J Am Coll Cardiol. 2007 Jan 23;49(3):320-8.
  • Shimizu M, Ino H, Okeie K, Yamaguchi M, Nagata M, Hayashi K, et al. T-peak to T-end interval may be a better predictor of high-risk patients with hypertrophic cardiomyopathy associated with a cardiac troponin I mutation than QT dispersion. Clin Cardiol. 2002 Jul;25(7):335-9.
  • Haarmark C, Hansen PR, Vedel-Larsen E, Pedersen SH, Graff C, Andersen MP, et al. The prognostic value of the Tpeak-Tend interval in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. J Electrocardiol. 2009 Nov-Dec;42(6):555-60.
  • Ravine D, Gibson RN, Walker RG, Sheffield LJ, Kincaid-Smith P, Danks DM. Evaluation of ultrasonographic diagnostic criteria for autosomal dominant polycystic kidney disease 1. Lancet. 1994 Apr 2;343(8901):824-7.
  • National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002 Feb;39(2 Suppl 1):S1–266.
  • Castro Hevia J, Antzelevitch C, Tornés Bárzaga F, Dorantes Sánchez M, Dorticós Balea F, Zayas Molina R, et al. Tpeak-Tend and Tpeak-Tend dispersion as risk factors for ventricular tachycardia/ventricular fibrillation in patients with the Brugada syndrome. J Am Coll Cardiol. 2006 May 2;47(9):1828-34.
  • Henry WL, DeMaria A, Gramiak R, King DL, Kisslo JA, Popp RL, et al. Report of the American Society of Echocardiography Committee on Nomenclature and Standards in Two- dimensional Echocardiography. Circulation. 1980 Aug;62(2):212-17.
  • Turkmen K, Oflaz H, Uslu B, Cimen AO, Elitok A, Kasikcioglu, et al. Coronary flow velocity reserve and carotid intima media thickness in patients with autosomal dominant polycystic kidney disease: from impaired tubules to impaired carotid and coronary arteries. Clin J Am Soc Nephrol. 2008 Jul;3(4):986-91.
  • Martinez-Vea A, Gutierrez C, Bardají A, Pastor R, García C, Peralta C, et al. Microalbuminuria in normotensive patients with autosomal-dominant polycystic kidney disease. Scand J Urol Nephrol. 1998 Sep;32(5):356-9.
  • Menon V, Rudym D, Chandra P, Miskulin D, Perrone R, Sarnak M. Inflammation, oxidative stress, and insulin resistance in polycystic kidney disease. Clin J Am Soc Nephrol. 2011 Jan;6(1):7-13.
  • Nagai R, Saito Y, Ohyama Y, Aizawa H, Suga T, Nakamura T, et al. Endothelial dysfunction in the klotho mouse and downregulation of klotho gene expression in various animal models of vascular and metabolic diseases. Cell Mol Life Sci. 2000 May;57(5):738-46.
  • Faul C. Fibroblast growth factor 23 and the heart. Curr Opin Nephrol Hypertens. 2012 Jul;21(4):369-75.
  • Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J,et al. Chronic Renal Insufficiency Cohort(CRIC) Study Group. Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA. 2011 Jun 15;305(23):2432-9.
  • Jovanovich A, Ix JH, Gottdiener J, McFann K, Katz R, Kestenbaum B, et al. Fibroblast growth factor 23, left ventricular mass, and left ventricular hypertrophy in community-dwelling older adults. Atherosclerosis. 2013 Nov;231(1):114-9.
  • Yildiz A, Gul CB, Ersoy A, Asiltas B, Ermurat S, Dogan S, et al. Arterial dysfunction in early autosomal dominant polycystic kidney disease independent of fibroblast growth factor 23. Iran J Kidney Dis. 2014 Nov;8(6):443-9.
  • Amano Y, Takeda M, Tachi M, Kitamura M, Kumita S. Myocardial fibrosis evaluated by Look-Locker and late gadolinium enhancement magnetic resonance imaging in apical hypertrophic cardiomyopathy: association with ventricular tachyarrhythmia and risk factors. J Magn Reson Imaging. 2014 Aug;40(2):407-12.
  • Voroneanu L, Covic A. Arrhythmias in hemodialysis patients. J Nephrol. 2009 Nov-Dec;22(6):716-25.
  • Herzog CA, Mangrum JA, Passman R. Sudden cardiac death and dialysis patients. Semin Dial. 2008 Jul-Aug;21(4):300-7.
  • Di Iorio B. Relevance of QT dispersion in haemodialysis patients. Nephrol Dial Transplant. 2010 Apr;25(4):1357-9.
  • Wolk R, Stec S, Kulakowski P. Extrasystolic beats affect transmural electrical dispersion during programmed electrical stimulation. Eur J Clin Invest. 2001 Apr;31(4):293-301.
  • Watanabe N, Kobayashi Y, Tanno K, Miyoshi F, Asano T, Kawamura M, et al. Transmural dispersion of repolarization and ventricular tachyarrhythmias. J Electrocardiol. 2004 Jul;37(3):191-200.
  • Sarubbi B, Pacileo G, Ducceschi V, Russo MG, Iacono C, Pisacane C, et al. Arrhythmogenic substrate in young patients with repaired tetralogy of Fallot: role of an abnormal ventricular repolarization. Int J Cardiol. 1999 Dec 15;72(1):73-82.
  • Letsas KP, Weber R, Astheimer K, Kalusche D, Arentz T. Tpeak-Tend interval and Tpeak-Tend/QT ratio as markers of ventricular tachycardia inducibility in subjects with Brugada ECG phenotype. Europace. 2010 Feb;12(2):271-4.
  • Gupta P, Patel C, Patel H, Narayanaswamy S, Malhotra B, Green JT, et al. T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol. 2008 Nov-Dec;41(6):567-74.
Year 2015, Volume: 1 Issue: 3, 106 - 112, 04.11.2015
https://doi.org/10.18621/eurj.2015.1.3.106

Abstract

References

  • Perrone RD, Ruthazer R, Terrin NC. Survival after end-stage renal disease in autosomal dominant polycystic kidney disease: contribution of extrarenal complications to mortality. Am J Kidney Dis. 2001 October;38(4):777-84.
  • Ecder T, Schrier RW. Cardiovascular abnormalities in autosomal-dominant polycystic kidney disease. Nat Rev Nephrol. 2009 April;5(4):221-8.
  • Ecder T, Schrier RW. Hypertension and left ventricular hypertrophy in autosomal dominant polycystic kidney disease. Expert Rev Cardiovasc Ther. 2004 May;2(3):369-74.
  • Bardají A, Vea AM, Gutierrez C, Ridao C, Richart C, Oliver JA. Left ventricular mass and diastolic function in normotensive young adults with autosomal dominant polycystic kidney disease. Am J Kidney Dis. 1998 Dec;32(6):970-5.
  • Cadnapaphornchai MA, McFann K, Strain JD, Masoumi A, Schrier RW. Increased left ventricular mass in children with autosomal dominant polycystic kidney disease and borderline hypertension. Kidney Int. 2008 Nov;74(9):1192-6.
  • Gabow PA, Johnson AM, Kaehny WD, Kimberling WJ, Lezotte DC, Duley IT, et al. Factors affecting the progression of renal disease in autosomal-dominant polycystic kidney disease. Kidney Int. 1992 May;41(5):1311-9.
  • Doulton TW, Saggar-Malik AK, He FJ, Carney C, Markandu ND, Sagnella GA, et al. The effect of sodium and angiotensin-converting enzyme inhibition on the classic circulating renin-angiotensin system in autosomal-dominant polycystic kidney disease patients. J Hypertens. 2006 May;24(5):939-45.
  • Pavik I, Jaeger P, Kistler AD, Poster D, Krauer F, Cavelti-Weder C, et al. Patients with autosomal dominant polycystic kidney disease have elevated fibroblast growth factor 23 levels and a renal leak of phosphate. Kidney Int. 2011 Jun;79(2):234-40.
  • Faul C, Amaral AP, Oskouei B, Hu MC, Sloan A, Isakova T, et al. FGF23 induces left ventricular hypertrophy. J Clin Invest. 2011 Nov;121(11):4393-408.
  • Surawicz B. Will QT dispersion play a role in clinical decision-making? J Cardiovasc Electrophysiol. 1996 Aug;7(8):777-84.
  • Schouten EG, Dekker JM, Meppelink P, Kok FJ, Vandenbroucke JP, Pool J. QT interval prolongation predicts cardiovascular mortality in an apparently healthy population. Circulation. 1991 Oct;84(4):1516-23.
  • Malhis M, Al-Bitar S, Farhood S, Zaiat KA. Changes in QT intervals in patients with end-stage renal disease before and after hemodialysis. Saudi J Kidney Dis Transpl. 2010 May;21(3):460-5.
  • Genovesi S, Dossi C, Viganò MR, Galbiati E, Prolo F, Stella A, et al. Electrolyte concentration during haemodialysis and QT interval prolongation in uraemic patients. Europace. 2008 Jun;10(6):771-7.
  • Wu VC, Lin LY, Wu KD. QT interval dispersion in dialysis patients. Nephrology (Carlton). 2005 Apr;10(2):109-12.
  • Castro Hevia J, Antzelevitch C, Tornés Bárzaga F, Dorantes Sánchez M, Dorticós Balea F, Zayas Molina, et al. Tpeak-Tend and Tpeak-Tend dispersion as risk factors for ventricular tachycardia/ventricular fibrillation in patients with the Brugada syndrome. J Am Coll Cardiol. 2006 May 2;47(9):1828-34.
  • Smetana P, Schmidt A, Zabel M, Hnatkova K, Franz M, Huber K, et al. Assessment of repolarization heterogeneity for prediction of mortality in cardiovascular disease: peak to the end of the T wave interval and nondipolar repolarization components. J Electrocardiol. 2011 May-Jun;44(3):301-8.
  • Opthof T, Coronel R, Janse MJ. Is there a significant transmural gradient in repolarization time in the intact heart?: Repolarization Gradients in the Intact Heart. Circ Arrhythm Electrophysiol. 2009 Feb 2;2(1):89-96.
  • Topilski I, Rogowski O, Rosso R, Justo D, Copperman Y, Glikson M, et al. The morphology of the QT interval predicts torsade de pointes during acquired bradyarrhythmias. J Am Coll Cardiol. 2007 Jan 23;49(3):320-8.
  • Shimizu M, Ino H, Okeie K, Yamaguchi M, Nagata M, Hayashi K, et al. T-peak to T-end interval may be a better predictor of high-risk patients with hypertrophic cardiomyopathy associated with a cardiac troponin I mutation than QT dispersion. Clin Cardiol. 2002 Jul;25(7):335-9.
  • Haarmark C, Hansen PR, Vedel-Larsen E, Pedersen SH, Graff C, Andersen MP, et al. The prognostic value of the Tpeak-Tend interval in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. J Electrocardiol. 2009 Nov-Dec;42(6):555-60.
  • Ravine D, Gibson RN, Walker RG, Sheffield LJ, Kincaid-Smith P, Danks DM. Evaluation of ultrasonographic diagnostic criteria for autosomal dominant polycystic kidney disease 1. Lancet. 1994 Apr 2;343(8901):824-7.
  • National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002 Feb;39(2 Suppl 1):S1–266.
  • Castro Hevia J, Antzelevitch C, Tornés Bárzaga F, Dorantes Sánchez M, Dorticós Balea F, Zayas Molina R, et al. Tpeak-Tend and Tpeak-Tend dispersion as risk factors for ventricular tachycardia/ventricular fibrillation in patients with the Brugada syndrome. J Am Coll Cardiol. 2006 May 2;47(9):1828-34.
  • Henry WL, DeMaria A, Gramiak R, King DL, Kisslo JA, Popp RL, et al. Report of the American Society of Echocardiography Committee on Nomenclature and Standards in Two- dimensional Echocardiography. Circulation. 1980 Aug;62(2):212-17.
  • Turkmen K, Oflaz H, Uslu B, Cimen AO, Elitok A, Kasikcioglu, et al. Coronary flow velocity reserve and carotid intima media thickness in patients with autosomal dominant polycystic kidney disease: from impaired tubules to impaired carotid and coronary arteries. Clin J Am Soc Nephrol. 2008 Jul;3(4):986-91.
  • Martinez-Vea A, Gutierrez C, Bardají A, Pastor R, García C, Peralta C, et al. Microalbuminuria in normotensive patients with autosomal-dominant polycystic kidney disease. Scand J Urol Nephrol. 1998 Sep;32(5):356-9.
  • Menon V, Rudym D, Chandra P, Miskulin D, Perrone R, Sarnak M. Inflammation, oxidative stress, and insulin resistance in polycystic kidney disease. Clin J Am Soc Nephrol. 2011 Jan;6(1):7-13.
  • Nagai R, Saito Y, Ohyama Y, Aizawa H, Suga T, Nakamura T, et al. Endothelial dysfunction in the klotho mouse and downregulation of klotho gene expression in various animal models of vascular and metabolic diseases. Cell Mol Life Sci. 2000 May;57(5):738-46.
  • Faul C. Fibroblast growth factor 23 and the heart. Curr Opin Nephrol Hypertens. 2012 Jul;21(4):369-75.
  • Isakova T, Xie H, Yang W, Xie D, Anderson AH, Scialla J,et al. Chronic Renal Insufficiency Cohort(CRIC) Study Group. Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA. 2011 Jun 15;305(23):2432-9.
  • Jovanovich A, Ix JH, Gottdiener J, McFann K, Katz R, Kestenbaum B, et al. Fibroblast growth factor 23, left ventricular mass, and left ventricular hypertrophy in community-dwelling older adults. Atherosclerosis. 2013 Nov;231(1):114-9.
  • Yildiz A, Gul CB, Ersoy A, Asiltas B, Ermurat S, Dogan S, et al. Arterial dysfunction in early autosomal dominant polycystic kidney disease independent of fibroblast growth factor 23. Iran J Kidney Dis. 2014 Nov;8(6):443-9.
  • Amano Y, Takeda M, Tachi M, Kitamura M, Kumita S. Myocardial fibrosis evaluated by Look-Locker and late gadolinium enhancement magnetic resonance imaging in apical hypertrophic cardiomyopathy: association with ventricular tachyarrhythmia and risk factors. J Magn Reson Imaging. 2014 Aug;40(2):407-12.
  • Voroneanu L, Covic A. Arrhythmias in hemodialysis patients. J Nephrol. 2009 Nov-Dec;22(6):716-25.
  • Herzog CA, Mangrum JA, Passman R. Sudden cardiac death and dialysis patients. Semin Dial. 2008 Jul-Aug;21(4):300-7.
  • Di Iorio B. Relevance of QT dispersion in haemodialysis patients. Nephrol Dial Transplant. 2010 Apr;25(4):1357-9.
  • Wolk R, Stec S, Kulakowski P. Extrasystolic beats affect transmural electrical dispersion during programmed electrical stimulation. Eur J Clin Invest. 2001 Apr;31(4):293-301.
  • Watanabe N, Kobayashi Y, Tanno K, Miyoshi F, Asano T, Kawamura M, et al. Transmural dispersion of repolarization and ventricular tachyarrhythmias. J Electrocardiol. 2004 Jul;37(3):191-200.
  • Sarubbi B, Pacileo G, Ducceschi V, Russo MG, Iacono C, Pisacane C, et al. Arrhythmogenic substrate in young patients with repaired tetralogy of Fallot: role of an abnormal ventricular repolarization. Int J Cardiol. 1999 Dec 15;72(1):73-82.
  • Letsas KP, Weber R, Astheimer K, Kalusche D, Arentz T. Tpeak-Tend interval and Tpeak-Tend/QT ratio as markers of ventricular tachycardia inducibility in subjects with Brugada ECG phenotype. Europace. 2010 Feb;12(2):271-4.
  • Gupta P, Patel C, Patel H, Narayanaswamy S, Malhotra B, Green JT, et al. T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol. 2008 Nov-Dec;41(6):567-74.
There are 41 citations in total.

Details

Primary Language English
Subjects Health Care Administration
Journal Section Original Articles
Authors

Kemal Karaagac

Abdulmecit Yildiz

Osman Yontar

Erhan Tenekecioglu

Fahriye Vatansever

Mehmet Demir

Publication Date November 4, 2015
Submission Date March 13, 2015
Acceptance Date August 21, 2015
Published in Issue Year 2015 Volume: 1 Issue: 3

Cite

AMA Karaagac K, Yildiz A, Yontar O, Tenekecioglu E, Vatansever F, Demir M. Relationship between fibroblast growth factor and arrhythmogenesis in normotensive patients with polycystic kidney disease. Eur Res J. November 2015;1(3):106-112. doi:10.18621/eurj.2015.1.3.106

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