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Uric Acid Lowering to Prevent Kidney Function Loss in Diabetes: The Preventing Early Renal Function Loss (PERL) Allopurinol Study

Current Diabetes Reports volume 13, pages 550–559 (2013)Cite this article

Abstract

Diabetic kidney disease causes significant morbidity and mortality among people with type 1 diabetes (T1D). Intensive glucose and blood pressure control have thus far failed to adequately curb this problem and therefore a major need for novel treatment approaches exists. Multiple observations link serum uric acid levels to kidney disease development and progression in diabetes and strongly argue that uric acid lowering should be tested as one such novel intervention. A pilot of such a trial, using allopurinol, is currently being conducted by the Preventing Early Renal Function Loss (PERL) Consortium. Although the PERL trial targets T1D individuals at highest risk of kidney function decline, the use of allopurinol as a renoprotective agent may also be relevant to a larger segment of the population with diabetes. As allopurinol is inexpensive and safe, it could be cost-effective even for relatively low-risk patients, pending the completion of appropriate trials at earlier stages.

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Acknowledgments

Dr. Maahs was supported by a grant from NIDDK (DK075360). Dr. Caramori is supported by a Career Development Award from the Juvenile Diabetes Research Foundation. This project was supported by NIH grants R03 DK094484 and R34 DK097808, and by grant 17-2012-377 from the Juvenile Diabetes Research Foundation (JDRF). Its contents are the authors’ sole responsibility and do not necessarily represent official NIH or JDRF views.

Other PERL Consortium members

University of Colorado: Marian Rewers, Richard Johnson, Satish Garg.

University of Michigan: Frank Brosius.

Steno Diabetes Center: Maria Lajer, Morten Kofod Lindhardt, and Bernt Johan Illum Horten von Scholten.

University of Minnesota: John Eckfeldt, Trudy Strand.

Joslin Diabetes Center: Andrzej Krolewski, Robert Stanton, Allison Goldfine.

Conflicts of Interest

David M. Maahs declares that he has no conflict of interest.

M. Luiza Caramori declares that she has no conflict of interest.

David Z.I. Cherney declares that he has no conflict of interest.

Andrzej T. Galecki declares that he has no conflict of interest.

Chuanyun Gao declares that she has no conflict of interest.

Diana Jalal has received ASN honoraria for speaking on the role of uric acid in kidney and cardiac disease in the elderly.

Bruce A. Perkins is a Senior Advisory Board Member for Neurometrix Inc.; and has been a Site investigator for a sponsored clinical trial for Medtronic Inc.; a Co-PI for a sponsored clinical trial by Boehringer Ingelheim; and has received speaker honoraria from Medtronic Inc., Roche, GlaxoSmithKline, Johnson & Johnson, Novo Nordisk, and Eli Lilly.

Rodica Pop-Busui declares that she has no conflict of interest.

Peter Rossing serves on the board for Astra Zeneca/BMS, Eli Lilly, Janssen, Novo Nordisk, and Astellas; has received grant support from Novo Nordisk, Novartis, and Abbott; has received payment for lectures including service on speaker’s bureaus from Astra Zeneca/BMS, Novartis, and Sanofi-Aventis; and has stock/stock options with Novo Nordisk.

Michael Mauer declares that he has no conflict of interest.

Alessandro Doria has received research grant support from Sanofi-Aventis; has received travel/accommodations expenses covered or reimbursed from the American Society of Nephrology and the Italian Society of Diabetology.

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Affiliations

  1. Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, CO, USA

    David M. Maahs

  2. Division of Renal Diseases and Hypertension, University of Colorado Denver, Aurora, CO, USA

    David M. Maahs & Diana Jalal

  3. Departments of Pediatrics and Medicine, University of Minnesota, Minneapolis, MN, USA

    Luiza Caramori & Michael Mauer

  4. Department of Medicine and Division of Nephrology, University of Toronto, Toronto, ON, Canada

    David Z. I. Cherney

  5. Division of Geriatrics/Institute of Gerontology, Medical School, and Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA

    Andrzej T. Galecki

  6. Joslin Clinic, Joslin Diabetes Center, Boston, MA, USA

    Chuanyun Gao

  7. Department of Medicine and Division of Endocrinology, University of Toronto, Toronto, ON, Canada

    Bruce A. Perkins

  8. Department of Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI, USA

    Rodica Pop-Busui

  9. Steno Diabetes Center, Gentofte, Denmark

    Peter Rossing

  10. HEALTH, University of Aarhus, Aarhus, Denmark

    Peter Rossing

  11. NNF CBMR University of Copenhagen, Copenhagen, Denmark

    Peter Rossing

  12. Section on Genetics and Epidemiology, Joslin Diabetes Center, One Joslin Place, Boston, MA, 02215, USA

    Alessandro Doria

  13. Department of Medicine, Harvard Medical School, Boston, MA, USA

    Alessandro Doria

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  1. David M. Maahs
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  2. Luiza Caramori
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  6. Diana Jalal
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  8. Rodica Pop-Busui
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  9. Peter Rossing
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  10. Michael Mauer
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  11. Alessandro Doria
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Correspondence to Alessandro Doria.

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Maahs, D.M., Caramori, L., Cherney, D.Z.I. et al. Uric Acid Lowering to Prevent Kidney Function Loss in Diabetes: The Preventing Early Renal Function Loss (PERL) Allopurinol Study. Curr Diab Rep 13, 550–559 (2013). https://doi.org/10.1007/s11892-013-0381-0

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Keywords

  • Uric acid
  • Kidney disease
  • Diabetes
  • Diabetic kidney disease
  • Glomerular filtration rate
  • Allopurinol
  • Diabetic nephropathy
  • Randomized clinical trial
  • Type 1 diabetes
  • PERL trial