letter to the editor
http://www.kidney-international.org & 2015 International Society of Nephrology
Induction of nitric oxide release with nebivolol may improve endothelial dysfunction in polycystic kidney disease To the Editor: We read with great interest the article by Lorthioir et al.1 in which they report that polycystin deficiency induces dopamine-reversible alterations in flowmediated dilatation and vascular nitric oxide release in autosomal-dominant polycystic kidney disease (ADPKD) patients. These patients display a loss of nitric oxide release and an associated reduction in endothelium-dependent dilatation of conduit arteries during sustained blood flow increase. In addition, they suggested that the correction of these anomalies by dopamine could reduce the occurrence of cardiovascular events in ADPKD. Cardiovascular problems due to hypertension are the major cause of morbidity and mortality in patients with ADPKD.2 Recently, it has been shown that oxidative stress and early arterial stiffness are evident in normotensive ADPKD patients.3 Endothelium-dependent relaxation is impaired and endothelial nitric oxide synthase activity is decreased in patients with ADPKD, and endothelial dysfunction secondary to impaired release of nitric oxide exists in these patients. An imbalance in endothelium-derived vasoactive mediators such as nitric oxide might contribute to the pathogenesis of hypertension in ADPKD.2 Nebivolol, a beta-blocker agent, which is associated with the release of nitric oxide, might be useful in ADPKD patients in addition to its favorable effect on blood pressure and endothelial dysfunction.4 Moreover, currently there is no study to show whether nebivolol prevents endothelial dysfunction or not in ADPKD patients. Thus, we propose that it might be plausible to focus on the use of nebivolol in this population to improve endothelial dysfunction.
The Authors Reply: We agree with Drs Eroglu and Kocyigit1 that treating patients with autosomal-dominant polycystic kidney disease (ADPKD) with a betablocker, in particular nebivolol, could be useful, and this hypothesis needs to be carefully explored.1 Interestingly, the use of a betablocker may help reduce the cyclic pulsatile stress imposed by blood pressure that exerts a fatiguing effect on the load-bearing elements of the arterial wall. This may contribute to the prevention of arterial dissection, aneurysm growth, and rupture, which are devastating complications of ADPKD. This has notably been demonstrated in the vascular Ehlers–Danlos syndrome with the other vasodilating betablocker celiprolol.2 Moreover, nebivolol is a third-generation betablocker that consistently improves the endothelial function of resistance arteries, by promoting nitric oxide release and through antioxidant effect.3 However, such a beneficial impact on the endothelium of conduit arteries is more debated.3 This may be particularly the case in ADPKD inasmuch the endothelial dysfunction of conduit arteries specifically involved an impaired mechanosensation of shear stress by polycystins.4 Finally, the recent results from the HALT-PKD trial demonstrate a beneficial impact of a strict control of blood pressure, with angiotensin-converting enzyme inhibitors (ACEIs), on cyst growth in ADPKD.5 Given that ACEIs are also the most effective pharmacological class in reversing endothelial dysfunction of conduit arteries, at least in hypertensive patients,3 a combination of an ACEI with nebivolol could synergistically contribute to the prevention of the renal and cardiovascular complications of ADPKD. 1.
2. 1.
2. 3.
4.
Lorthioir A, Joannide`s R, Re´my-Jouet I et al. Polycystin deficiency induces dopamine-reversible alterations in flow-mediated dilatation and vascular nitric oxide release in humans. Kidney Int 2015; 87: 465–472. Ecder T. Cardiovascular complications in autosomal dominant polycystic kidney disease. Curr Hypertens Rev 2013; 9: 2–11. Kocyigit I, Kaya MG, Orscelik O et al. Early arterial stiffness and inflammatory bio-markers in normotensive polycystic kidney disease patients. Am J Nephrol 2012; 36: 11–18. Pasini AF, Garbin U, Stranieri C et al. Nebivolol treatment reduces serum levels of asymmetric dimethylarginine and improves endothelial dysfunction in essential hypertensive patients. Am J Hypertens 2008; 21: 1251–1257.
3. 4.
5.
Eroglu E, Kocyigit I. Induction of nitric oxide release with nebivolol may improve endothelial dysfunction in polycystic kidney disease. Kidney Int 2015; 87: 857. Ong KT, Perdu J, De Backer J et al. Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: a prospective randomised, open, blinded-endpoints trial. Lancet 2010; 376: 1476–1484. Ghiadoni L, Taddei S, Virdis A. Hypertension and endothelial dysfunction: therapeutic approach. Curr Vasc Pharmacol 2012; 10: 42–60. Lorthioir A, Joannides R, Re´my-Jouet I et al. Polycystin deficiency induces dopamine-reversible alterations in flow-mediated dilatation and vascular NO release in humans. Kidney Int 2015; 87: 465–472. Schrier RW, Abebe KZ, Perrone RD et al. Blood pressure in early autosomal dominant polycystic kidney disease. N Engl J Med 2014; 371: 2255–2266.
Eray Eroglu1 and Ismail Kocyigit2
Aure´ lien Lorthioir1 and Je´ re´ my Bellien2
1
Department of Internal Medicine, Erciyes University Medical Faculty, Kayseri, Turkey and 2Department of Nephrology, Erciyes University Medical Faculty, Kayseri, Turkey Correspondence: Eray Eroglu, Department of Internal Medicine, Erciyes University Medical Faculty, 38039 Kayseri, Turkey. E-mail: [email protected]
1
Department of Nephrology and Hypertension, Georges Pompidou European Hospital, Paris, France and 2Department of Pharmacology & INSERM U1096, Rouen University Hospital, Rouen, France Correspondence: Aure´lien Lorthioir, Department of Nephrology and Hypertension, Georges Pompidou European Hospital 75015, Paris, France. E-mail: [email protected]
Kidney International (2015) 87, 857; doi:10.1038/ki.2014.417
Kidney International (2015) 87, 857; doi:10.1038/ki.2014.421
Kidney International (2015) 87, 857–864
857
http://www.kidney-international.org & 2015 International Society of Nephrology
Induction of nitric oxide release with nebivolol may improve endothelial dysfunction in polycystic kidney disease To the Editor: We read with great interest the article by Lorthioir et al.1 in which they report that polycystin deficiency induces dopamine-reversible alterations in flowmediated dilatation and vascular nitric oxide release in autosomal-dominant polycystic kidney disease (ADPKD) patients. These patients display a loss of nitric oxide release and an associated reduction in endothelium-dependent dilatation of conduit arteries during sustained blood flow increase. In addition, they suggested that the correction of these anomalies by dopamine could reduce the occurrence of cardiovascular events in ADPKD. Cardiovascular problems due to hypertension are the major cause of morbidity and mortality in patients with ADPKD.2 Recently, it has been shown that oxidative stress and early arterial stiffness are evident in normotensive ADPKD patients.3 Endothelium-dependent relaxation is impaired and endothelial nitric oxide synthase activity is decreased in patients with ADPKD, and endothelial dysfunction secondary to impaired release of nitric oxide exists in these patients. An imbalance in endothelium-derived vasoactive mediators such as nitric oxide might contribute to the pathogenesis of hypertension in ADPKD.2 Nebivolol, a beta-blocker agent, which is associated with the release of nitric oxide, might be useful in ADPKD patients in addition to its favorable effect on blood pressure and endothelial dysfunction.4 Moreover, currently there is no study to show whether nebivolol prevents endothelial dysfunction or not in ADPKD patients. Thus, we propose that it might be plausible to focus on the use of nebivolol in this population to improve endothelial dysfunction.
The Authors Reply: We agree with Drs Eroglu and Kocyigit1 that treating patients with autosomal-dominant polycystic kidney disease (ADPKD) with a betablocker, in particular nebivolol, could be useful, and this hypothesis needs to be carefully explored.1 Interestingly, the use of a betablocker may help reduce the cyclic pulsatile stress imposed by blood pressure that exerts a fatiguing effect on the load-bearing elements of the arterial wall. This may contribute to the prevention of arterial dissection, aneurysm growth, and rupture, which are devastating complications of ADPKD. This has notably been demonstrated in the vascular Ehlers–Danlos syndrome with the other vasodilating betablocker celiprolol.2 Moreover, nebivolol is a third-generation betablocker that consistently improves the endothelial function of resistance arteries, by promoting nitric oxide release and through antioxidant effect.3 However, such a beneficial impact on the endothelium of conduit arteries is more debated.3 This may be particularly the case in ADPKD inasmuch the endothelial dysfunction of conduit arteries specifically involved an impaired mechanosensation of shear stress by polycystins.4 Finally, the recent results from the HALT-PKD trial demonstrate a beneficial impact of a strict control of blood pressure, with angiotensin-converting enzyme inhibitors (ACEIs), on cyst growth in ADPKD.5 Given that ACEIs are also the most effective pharmacological class in reversing endothelial dysfunction of conduit arteries, at least in hypertensive patients,3 a combination of an ACEI with nebivolol could synergistically contribute to the prevention of the renal and cardiovascular complications of ADPKD. 1.
2. 1.
2. 3.
4.
Lorthioir A, Joannide`s R, Re´my-Jouet I et al. Polycystin deficiency induces dopamine-reversible alterations in flow-mediated dilatation and vascular nitric oxide release in humans. Kidney Int 2015; 87: 465–472. Ecder T. Cardiovascular complications in autosomal dominant polycystic kidney disease. Curr Hypertens Rev 2013; 9: 2–11. Kocyigit I, Kaya MG, Orscelik O et al. Early arterial stiffness and inflammatory bio-markers in normotensive polycystic kidney disease patients. Am J Nephrol 2012; 36: 11–18. Pasini AF, Garbin U, Stranieri C et al. Nebivolol treatment reduces serum levels of asymmetric dimethylarginine and improves endothelial dysfunction in essential hypertensive patients. Am J Hypertens 2008; 21: 1251–1257.
3. 4.
5.
Eroglu E, Kocyigit I. Induction of nitric oxide release with nebivolol may improve endothelial dysfunction in polycystic kidney disease. Kidney Int 2015; 87: 857. Ong KT, Perdu J, De Backer J et al. Effect of celiprolol on prevention of cardiovascular events in vascular Ehlers-Danlos syndrome: a prospective randomised, open, blinded-endpoints trial. Lancet 2010; 376: 1476–1484. Ghiadoni L, Taddei S, Virdis A. Hypertension and endothelial dysfunction: therapeutic approach. Curr Vasc Pharmacol 2012; 10: 42–60. Lorthioir A, Joannides R, Re´my-Jouet I et al. Polycystin deficiency induces dopamine-reversible alterations in flow-mediated dilatation and vascular NO release in humans. Kidney Int 2015; 87: 465–472. Schrier RW, Abebe KZ, Perrone RD et al. Blood pressure in early autosomal dominant polycystic kidney disease. N Engl J Med 2014; 371: 2255–2266.
Eray Eroglu1 and Ismail Kocyigit2
Aure´ lien Lorthioir1 and Je´ re´ my Bellien2
1
Department of Internal Medicine, Erciyes University Medical Faculty, Kayseri, Turkey and 2Department of Nephrology, Erciyes University Medical Faculty, Kayseri, Turkey Correspondence: Eray Eroglu, Department of Internal Medicine, Erciyes University Medical Faculty, 38039 Kayseri, Turkey. E-mail: [email protected]
1
Department of Nephrology and Hypertension, Georges Pompidou European Hospital, Paris, France and 2Department of Pharmacology & INSERM U1096, Rouen University Hospital, Rouen, France Correspondence: Aure´lien Lorthioir, Department of Nephrology and Hypertension, Georges Pompidou European Hospital 75015, Paris, France. E-mail: [email protected]
Kidney International (2015) 87, 857; doi:10.1038/ki.2014.417
Kidney International (2015) 87, 857; doi:10.1038/ki.2014.421
Kidney International (2015) 87, 857–864
857
