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Endothelin-1 Antagonist in the Management of Refractory Systemic Hypertension in Children with End Stage Kidney Disease: A Case Series

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DOI: 10.4236/wjcd.2014.45029    3,043 Downloads   3,939 Views  

ABSTRACT

Uncontrolled hypertension is a significant problem in children with end stage kidney disease. We studied 10 children on chronic hemodialysis who received the endothelin-1 receptor antagonist, bosentan as adjunctive therapy in refractory systemic hypertension. Data were retrospectively analyzed on systolic (SBP) and diastolic blood pressure (DBP), antihypertensive medications and hospitalization days per patient per year, at baseline and 3 months after initiation of bosentan. The standard deviation (Z) score of BP for age, height and gender was calculated. Mean age and weight of these children were 11.4 ± 4.8 years (range 1 - 17.5 years) and 32.9 ± 14.4 kg (range 7.4 - 57 kg) respectively and 90% were African American. Seven were on hemodialysis ≥4 times weekly. The average inter-dialytic weight gain was 4.7% ± 1.8%. The pre-dialysis SBP and DBP Z scores were 4.9 ± 1.8 and 4.0 ± 1.0 at baseline and decreased to 1.3 ± 0.4 and 1.3 ± 0.8, 3 months after initiation of bosentan (p < 0.0001). Similarly, anti-hypertensive medications were decreased from 5 ± 1.5 to 2.1 ± 2.6 (p < 0.01). Hospitalization days decreased from 35.6 ± 52.4 days to 1.5 ± 3.3 days (p < 0.0001). This preliminary report indicates bosentan may be beneficial in the management of children with severe refractory hypertension.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Chandar, J. , Seeherunvong, W. , Abitbol, C. , Katsoufis, C. , Edwards-Richards, A. , Cano, T. and Zilleruelo, G. (2014) Endothelin-1 Antagonist in the Management of Refractory Systemic Hypertension in Children with End Stage Kidney Disease: A Case Series. World Journal of Cardiovascular Diseases, 4, 217-224. doi: 10.4236/wjcd.2014.45029.

References

[1] Chavers, B.M., Li, S., Collins, A.J. and Herzog, C.A. (2002) Cardiovascular Disease in Pediatric Chronic Dialysis Patients. Kidney International, 62, 648-653.
http://dx.doi.org/10.1046/j.1523-1755.2002.00472.x
[2] Mitsnefes, M. and Stablein, D. (2005) Hypertension in Pediatric Patients on Long-Term Dialysis: A Report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). American Journal of Kidney Diseases, 45, 309-315.
http://dx.doi.org/10.1053/j.ajkd.2004.11.006
[3] Chavers, B.M., Solid, C.A., Daniels, F.X., Chen, S.C., Collins, A.J., Frankenfield, D.L. and Herzog, C.A. (2009) Hypertension in Pediatric Long-Term Hemodialysis Patients in the United States. Clinical Journal of the American Society of Nephrology, 4, 1363-1369.
http://dx.doi.org/10.2215/CJN.01440209
[4] Chavers, B. and Schnaper, H.W. (2001) Risk Factors for Cardiovascular Disease in Children on Maintenance Dialysis. Advances in Renal Replacement Therapy, 8, 180-190.
http://dx.doi.org/10.1053/jarr.2001.26355
[5] Foley, R.N. and Parfrey, P.S., Harnett, J.D., Kent, G.M., Murray, D.C. and Barre, P.E. (1996) Impact of Hypertension on Cardiomyopathy, Morbidity and Mortality in End-Stage Renal Disease. Kidney International, 49, 1379-1385.
http://dx.doi.org/10.1038/ki.1996.194
[6] Flynn, J.T., Mitsnefes, M., Pierce, C., Cole, S.R., Parekh, R.S., Furth, S.L. and Warady, B.A. (2008) Blood Pressure in Children with Chronic Kidney Disease: A Report from the Chronic Kidney Disease in Children Study. Hypertension, 52, 631-637.
http://dx.doi.org/10.1161/HYPERTENSIONAHA.108.110635
[7] Halbach, S.M., Martz, K., Mattoo, T. and Flynn, J. (2012) Predictors of Blood Pressure and Its Control in Pediatric Patients Receiving Dialysis. Journal of Pediatrics, 160, 621-625.
http://dx.doi.org/10.1016/j.jpeds.2011.09.046
[8] Schwarz, E.R., Heintz, B., Stefanidis, I., vom Dahl, J. and Sieberth, H.G. (2000) The Heterogeneous and Delayed Course of Blood Pressure Normalization in Hypertensive Patients after Bilateral Nephrectomy with and without Subsequent Renal Transplantation. Renal Failure, 22, 591-604.
http://dx.doi.org/10.1081/JDI-100100900
[9] Seguias, L., Zilleruelo, G., Strauss, J., Abitbol, C. and Montane, B. (2001) An-giotensin-II and Endothelin-1 Levels in Children with Renoprival Hypertension. Pediatric Nephrology, 16, 493-496.
http://dx.doi.org/10.1007/s004670100579
[10] Mailloux, L.U. and Haley, W.E. (1998) Hypertension in the ESRD Patient: Pathophysiology, Therapy, Outcomes, and Future Directions. American Journal of Kidney Diseases, 32, 705-719.
http://dx.doi.org/10.1016/S0272-6386(98)70146-5
[11] Dinh, D.T., Frauman, A.G., Johnston, C.I. and Fabiani, M.E. (2001) Angiotensin Receptors: Distribution, Signalling and Function. Clinical Science (London), 100, 481-492.
http://dx.doi.org/10.1042/CS20000263
[12] Moreau, P., D’Uscio, L.V., Shaw, S., Takase, H., Barton, M. and Lüscher, T.F. (1997) Angiotensin II Increases Tissue Endothelin and Induces Vascular Hypertrophy—Reversal by ETA-Receptor Antagonist. Circulation, 96, 1593-1597.
http://dx.doi.org/10.1161/01.CIR.96.5.1593
[13] Krum, H., Viskoper, R.J., Lacourciere, Y., Budde, M. and Charlon, V. (1998) The Effect of an Endothelin-Receptor Antagonist, Bosentan, on Blood Pressure in Patients with Essential Hypertension. Bosentan Hypertension Investigators. New England Journal of Medicine, 338, 784-790.
http://dx.doi.org/10.1056/NEJM199803193381202
[14] Henderson, L.W. (1980) Symptomatic Hypotension during Hemodi-alysis. Kidney International, 17, 571-576.
http://dx.doi.org/10.1038/ki.1980.67
[15] (2004) The Fourth Report on the Diagnosis, Evaluation, and Treatment of High Blood Pressure in Children and Adolescents. Pediatrics, 114, 555-576.
http://dx.doi.org/10.1542/peds.114.2.S2.555
[16] Chandar, J. and Zilleruelo, G. (2012) Hypertensive Crisis in Children. Pediatric Nephrology, 27, 741-751.
http://dx.doi.org/10.1007/s00467-011-1964-0
[17] National Kidney Foundation (2005) KDOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Children with Chronic Kidney Disease. American Journal of Kidney Diseases, 46, 12-100.
http://www.kidney.org/professionals/kdoqi/guidelines_pedbone/index.htm
[18] Khoury, P.R., Mitsnefes, M., Daniels, S.R. and Kimball, T.R. (2009) Age-Specific Reference Intervals for Indexed Left Ventricular Mass in Children. Journal of the American Society of Echocardiography, 22, 709-714.
http://dx.doi.org/10.1016/j.echo.2009.03.003
[19] Beghetti, M., Hoeper, M.M., Kiely, D.G., Carlsen, J., Schwierin, B., Segal, E.S. and Humbert, M. (2008) Safety Experience with Bosentan in 146 Children 2 - 11 Years Old with Pulmonary Arterial Hypertension: Results from the European Postmarketing Surveillance Program. Pediatric Research, 64, 200-204.
http://dx.doi.org/10.1203/PDR.0b013e318179954c
[20] Dhaun, N., Goddard, J. and Webb, D. (2006) The Endothelin System and Its Antagonism in Chronic Kidney Disease. Journal of the American Society of Nephrology, 17, 943-955.
http://dx.doi.org/10.1681/ASN.2005121256
[21] Schiffrin, E.L., Deng, L.Y., Sventek, P. and Day, R. (1997) Enhanced Expression of Endothelin-1 Gene in Endothelium of Resistance Arteries in Severe Human Essential Hypertension. Journal of Hypertension, 15, 57-63.
http://dx.doi.org/10.1097/00004872-199715010-00005
[22] Li, J.S., Larivière, R. and Schiffrin, E.L. (1994) Effect of a Nonselective Endothelin Antagonist on Vascular Remodeling in Deoxycorticosterone Acetate-Salt Hypertensive Rats. Evidence for a Role of Endothelin in Vascular Hypertrophy. Hypertension, 24, 183-188.
http://dx.doi.org/10.1161/01.HYP.24.2.183
[23] Larivière, R., Deng, L.Y., Day, R., Sventek, P., Thibault, G. and Schiffrin, E.L. (1995) Increased Endothelin-1 Gene Expression in the Endothelium of Coronary Arteries and Endocardium in the DOCA-Salt Hypertensive Rat. Journal of Molecular and Cellular Cardiology, 27, 2123-2131.
http://dx.doi.org/10.1016/S0022-2828(95)91263-0
[24] Ergul, S., Parish, D.C., Puett, D. and Ergul, A. (1996) Racial Differences in Plasma Endothelin-1 Concentrations in Individuals with Essential Hypertension. Hypertension, 28, 652-655.
http://dx.doi.org/10.1161/01.HYP.28.4.652
[25] Sfikakis, P.P., Papamichael, C., Stamatelopoulos, K.S., Tousoulis, D., Fragiadaki, K.G., Katsichti, P., Stefanadis, C. and Mavrikakis, M. (2007) Improvement of Vascular Endothelial Function Using the Oral Endothelin Receptor Antagonist Bosentan in Patients with Systemic Sclerosis. Arthritis & Rheumatism, 56, 1985-1993.
http://dx.doi.org/10.1002/art.22634
[26] Wolf, S.C., Sauter, G., Risler, T. and Brehm, B.R. (2005) Effects of Combined Endothelin and Angiotensin II Antagonism on Growth Factor-Induced Proliferation of Vascular Smooth Muscle Cells Isolated from Uremic Rats. Renal Failure, 27, 465-474.
http://dx.doi.org/10.1081/jdi-65421
[27] Charra, B. and Chazot, C. (2003) Volume Control, Blood Pressure and Cardiovascular Function. Lessons from Hemodialysis Treatment. Nephron Physiology, 93, 94-101.
http://dx.doi.org/10.1159/000070242
[28] Stegmayr, B.G. (2003) Ultrafiltration and Dry Weight—What Are the Cardiovascular Effects? Artificial Organs, 27, 227-229.
http://dx.doi.org/10.1046/j.1525-1594.2003.07205.x
[29] Foster, B.J. and Leonard, M.B. (2004) Measuring Nutritional Status in Children with Chronic Kidney Disease. American Journal of Clinical Nutrition, 80, 801-814.
[30] Van Buren, P.N. and Inrig, J.K. (2012) Hypertension and Hemodialysis: Pathophysiology and Outcomes in Adult and Pediatric Populations. Pediatric Nephrology, 27, 339-350.
http://dx.doi.org/10.1007/s00467-011-1775-3
[31] Carlini, R., Obialo, C.I. and Rothstein, M. (1993) Intravenous Erythropoietin (rHuEPO) Administration Increases Plasma Endothelin and Blood Pressure in Hemodialysis Patients. American Journal of Hypertension, 6, 103-107.
[32] Pearl, R.J., Papageorgiou, P.C., Goldman, M., Amfilochiadis, A.A., Boomsma, F., Rojkjaer, R., Geary, D. and Osmond, D.H. (2003) Possible Role of New Pressor Protein in Hypertensive Anephric Hemodialysis Patients. Pediatric Nephrology, 18, 1025-1031.
http://dx.doi.org/10.1007/s00467-003-1246-6
[33] Morris, S.T., McMurray, J.J., Spiers, A. and Jardine, A.G. (2001) Impaired Endothelial Function in Isolated Human Uremic Resistance Arteries. Kidney International, 60, 1077-1082.
http://dx.doi.org/10.1046/j.1523-1755.2001.0600031077.x
[34] Litwin, M., Wühl, E., Jourdan, C., Niemirska, A., Schenk, J.P., Jobs, K., Grenda, R., Wawer, Z.T., Rajszys, P., Mehls, O. and Schaefer, F. (2008) Evolution of Large-Vessel Arteriopathy in Paediatric Patients with Chronic Kidney Disease. Nephrology Dialysis Transplantation, 23, 2552-2557.
http://dx.doi.org/10.1093/ndt/gfn083
[35] Shroff, R.C., Donald, A.E., Hiorns, M.P., Watson, A., Feather, S., Milford, D., Ellins, E.A., Storry, C., Ridout, D., Deanfield, J. and Rees, L. (2007) Mineral Metabolism and Vascular Damage in Children on Dialysis. Journal of the American Society of Nephrology, 18, 2996-3003.
http://dx.doi.org/10.1681/ASN.2006121397
[36] Miltényi, G., Tory, K., Stubnya, G., Tóth-Heyn, P., Vásárhelyi, B., Sallay, P., Szabó, A., Tulassay, T., Dobos, M. and Reusz, G.S. (2001) Monitoring Cardiovascular Changes during Hemodialysis in Children. Pediatric Nephrology, 16, 19-24.
http://dx.doi.org/10.1007/s004670000497
[37] Ramasubbu, K., Deswal, A., Herdejurgen, C., Aguilar, D. and Frost, A.E. (2010) A Prospective Echocardiographic Evaluation of Pulmonary Hypertension in Chronic Hemodialysis Patients in the United States: Prevalence and Clinical Significance. International Journal of General Medicine, 5, 279-286.

  
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