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Losartan and enalapril are comparable in reducing proteinuria in children with Alport syndrome

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Abstract

Background

A previous subgroup analysis of a 12-week, double-blind study demonstrated that losartan significantly lowered proteinuria versus placebo and amlodipine and was well tolerated in children (1–17 years old) with proteinuria secondary to Alport syndrome. The present subgroup analysis of the open-label, extension phase of this study assessed the long-term efficacy and tolerability of losartan versus enalapril.

Methods

Patients who had completed the double-blind study were re-randomized to losartan or enalapril and followed for proteinuria and renal function for up to 3 years.

Results

Twenty-seven patients with Alport syndrome were randomized to losartan (0.44-2.23 mg/kg/day; n = 15) or enalapril (0.07-0.72 mg/kg/day; n = 12). The least-squares (LS) mean percent change from week 12 in urinary protein to creatinine ratio (UPr/Cr was +1.1 % in the losartan group versus a further 13.9 % reduction in the enalapril group (GMR [95 % CI] = 1.2 [0.7, 2.0]); the LS mean change from week 12 in estimated glomerular filtration rate (eGFR) was −6.4 ml/min/1.73 m2 in the losartan group versus −9.1 ml/min/1.73 m2 in the enalapril group. The adverse event incidence was low and comparable in both treatment groups.

Conclusions

In children with proteinuria secondary to Alport syndrome, losartan maintained proteinuria reduction, and enalapril produced a further proteinuria reduction over the 3-year study period. Both agents were generally well tolerated.

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Acknowledgments

We are grateful to Kathleen Newcomb (Merck Sharp & Dohme Corp.) for administrative and editorial support of the manuscript.

Disclosures

Dr. Nicholas Webb reports receiving consulting and/or lecture fees and participation on advisory boards alone or in some combination from Merck, Abbott, and Takeda. Dr. Thomas Wells reports receiving consulting fees from Merck and Takeda. Dr. Shahnaz Shahinfar reports receiving consulting fees from Merck. Rachid Massaad, Gilbert W. Gleim, and Christine McCrary Sisk are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, and may hold stock/stock options in the company. Chun Lam is a former employee of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, and may hold stock/stock options in the company.

Role of the funding source

Merck Sharp & Dohme Corp. a subsidiary of Merck & Co., Inc, Whitehouse Station, NJ, USA, provided all funding and study drugs for this study. The funding source was involved in the design of the study, collection of data, analysis or interpretation of the data, writing or approval of the manuscript, and the decision regarding submission of the manuscript for publication.

Contributions

Nicholas Webb participated in the planning and design of the study, interpretation of results, review and revision of the manuscript, and approved the final version.

Shahnaz Shahinfar participated in the planning and design of the study, interpretation of results, review and revision of the manuscript, and approved the final version.

Thomas Wells participated in the planning and design of the study, interpretation of results, review and revision of the manuscript, and approved the final version.

Rachid Massaad participated in the analyses, provided statistical guidance, reviewed and revised the manuscript, and approved the final version.

Gilbert Gleim participated in the planning and design of the study, review and revision of the manuscript, and approved the final version.

Christine McCrary Sisk participated in interpretation of results, wrote parts of the manuscript, reviewed and revised the manuscript, and approved the final version.

Chun Lam participated in the planning and design of the study, analyses, interpretation of results, wrote parts of the manuscript, reviewed and revised the manuscript, and approved the final version.

Author information

Authors and Affiliations

  1. Department of Paediatric Nephrology and Wellcome Trust Children’s Clinical Research Facility, Manchester Academic Health Science Centre, Royal Manchester Children’s Hospital, The University of Manchester, Manchester, M13 9WL, UK

    Nicholas J. A. Webb

  2. S. Shahinfar Consulting Inc., Newtown Square, PA, USA

    Shahnaz Shahinfar

  3. Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Shahnaz Shahinfar

  4. Arkansas Children’s Hospital, The University of Arkansas for Medical Sciences, Little Rock, AR, USA

    Thomas G. Wells

  5. MSD Belgium, Brussels, Belgium

    Rachid Massaad

  6. Merck Sharp & Dohme Corp, Whitehouse Station, NJ, USA

    Gilbert W. Gleim, Christine McCrary Sisk & Chun Lam

Authors
  1. Nicholas J. A. Webb
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  2. Shahnaz Shahinfar
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  3. Thomas G. Wells
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  4. Rachid Massaad
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  5. Gilbert W. Gleim
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  6. Christine McCrary Sisk
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  7. Chun Lam
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Corresponding author

Correspondence to Nicholas J. A. Webb.

Additional information

This study is registered on www.clinicaltrials.gov as NCT00568178.

Appendix 1

Appendix 1

Investigators

Chile: Angela Delucchi, Santiago.

Colombia: Pilar M Amado, Bucaramanga; Oscar A. Hernandez, Bogotá; Ricardo Gastelbondo, Bogotá.

Germany: Katalin Dittrich, Erlangen; Juergen Strehlau, Leipzig; Martin Pohl, Freiburg.

Guatemala: Luis F. Arroyo-Garcia, Guatemala City; Randall Lou, Guatemala City.

Hungary: György Reusz, Budapest; László Szabó, Miskolc.

India: Rajiv Aggarwal, Karnataka; Urmila Anandh, Karnataka; Shiela Bhave, Maharashtra; Padmanabha P. Maiya; Karnataka; Kishore Phadke, Karnataka.

Lithuania: Birute Pundziene, Kaunas; Augustina Jankauskiene, Vilnius.

Mexico: Silvestre Garcia, México; Froylán E. Hernández-Lara, Puebla; Ricardo López, Morelos.

Norway: Anna Bjerre, Oslo; Damien Brackman, Bergen.

Panama: Florencio A. McCarthy, Panama City.

Peru: Reyner F. Loza-Munarriz, Lima; Graciela Sakihara-Asato, Lima.

Philippines: Maria-Angeles Marbella, Quezon City; Rosario Cruz, Quezon City.

Puerto Rico: Melvin Bonilla-Felix, San Juan.

Romania: Aurel Bizo, Cluj; Gheorghe Chiriac-Babei, Cluj; Ioan Sabau, Cluj; Victor M. Nanulescu, Cluj.

Russian Federation: Yuri B. Belousov, Moscow; Vladimir V. Dlin, Moscow; Alexey N. Tsygin, Moscow.

Spain: Laura Espinosa-Román, Madrid.

Taiwan: Jeng-Daw Tsai, Taipei; Chi-Hui Cheng, Kweishan Taoyuan.

United Kingdom: William van't Hoff, London; Nicholas Webb, Manchester.

United States: Vimal Chadha, Richmond, Virginia; Vikas R. Dharnidharka, Gainesville, Florida; Robert M. Haws, Marshfield, Wisconsin; Ronald J. Hogg, Temple, Texas; Craig B. Langman, Chicago, Illinois; Kenneth V. Lieberman, Hackensack, New Jersey; Victoria Norwood, Charlottesville, VA; Cynthia G. Pan, Milwaukee, Wisconsin; Howard Trachtman, New Hyde Park, New York; Constancia Uy, Newark, New Jersey

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Webb, N.J.A., Shahinfar, S., Wells, T.G. et al. Losartan and enalapril are comparable in reducing proteinuria in children with Alport syndrome. Pediatr Nephrol 28, 737–743 (2013). https://doi.org/10.1007/s00467-012-2372-9

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  • DOI: https://doi.org/10.1007/s00467-012-2372-9

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