Preventing Early Renal Loss in Diabetes (PERL) Study: A Randomized Double-Blinded Trial of Allopurinol-Rationale, Design, and Baseline Data

PERL Study Group

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23 Scopus citations

Abstract

OBJECTIVE: Higher serum uric acid (SUA) is associated with diabetic kidney disease (DKD). Preventing Early Renal Loss in Diabetes (PERL) evaluates whether lowering SUA with allopurinol slows glomerular filtration rate (GFR) loss in people with type 1 diabetes (T1D) and mild to moderate DKD. We present the PERL rationale, design, and baseline characteristics.

RESEARCH DESIGN AND METHODS: This double-blind, placebo-controlled, multicenter trial randomized 530 participants with T1D, estimated GFR (eGFR) of 40-99.9 mL/min/1.73 m2, SUA ≥4.5 m/dL, and micro- to macroalbuminuric DKD or normoalbuminuria with declining kidney function (NDKF) (defined as historical eGFR decline ≥3 mL/min/1.73 m2/year) to allopurinol or placebo. The primary outcome is baseline-adjusted iohexol GFR (iGFR) after 3 years of treatment plus a 2-month washout period.

RESULTS: Participants are 66% male and 84% white. At baseline, median age was 52 years and diabetes duration was 35 years, 93% of participants had hypertension, and 90% were treated with renin-angiotensin system inhibitors (median blood pressure 127/71 mmHg). Median HbA1c was 8%, SUA 5.9 mg/dL, iGFR 68 mL/min/1.73 m2, and historical eGFR slope -3.5 mL/min/1.73 m2/year. Compared with participants with albuminuria (n = 419), those with NDKF (n = 94) were significantly older (56 vs. 52 years), had lower HbA1c (7.7 vs. 8.1%) and SUA (5.4 vs. 6.0 mg/dL), and had higher eGFR (82 vs. 74 mL/min/1.73 m2) and historical eGFR loss (-4.7 vs. -2.5 mL/min/1.73 m2/year). These differences persisted when comparing groups with similar rates of historical eGFR loss.

CONCLUSIONS: PERL will determine the effect of allopurinol on mild to moderate DKD in T1D, with or without albuminuria. Participants with normoalbuminuria and rapid GFR loss manifested many DKD risk factors of those with albuminuria, but with less severity.

Original languageEnglish (US)
Pages (from-to)1454-1463
Number of pages10
JournalDiabetes care
Volume42
Issue number8
DOIs
StatePublished - Aug 2019

Bibliographical note

Funding Information:
Acknowledgments. The PERL study investigators thank all the study participants for enormous contributions made to this long and demanding trial. They are also grateful to the PERL data safety and monitoring board (Linda Fried, Ananda Basu, Melanie Blank, Tom Greene, Lawrence Holzman, Charity G. Moore Patterson, and John Sedor) and the National Institutes of Health officer Dr. Teresa Jones for guidance and to Green Mountain Pharmaceuticals and Belmar Pharmacy (Lakewood, CO) for the skilled preparation and distribution of the study drug. The PERL investigators also acknowledge all the PERL research coordinators whose daily commitment and effort has made this study possible (alphabetically): Daphne Adelman, Gayatri Anupindi, Cathy Bagne, Mary Bates, Karen Belanger, Emily Boone, Jane Bulger, Leslie Cham, Jing H. Chao, Theresa Christiansen, Mary Ann Clearwaters, Mary Jane Clifton, Hector Com, Debra Conboy, Kristie DeHaan, Tineke Dineen, Amy Dunlop, Sara Eischen, C. Marcelo Falappa, Lestat Feliciano, Birgit Fink, Benjamin Flagg, Victoria Gage, Jason Gensler, Anne Goodling, Vasundhara Goplani, Monica Hartmuller, Eric Henricks, Jessie Arman Hermann, Madeleine Hermans, Xinli Huang, Karen Hyams, Marla Inducil, Lone Jelstrup, Florence John, Yvette Kowalski, Vesta Lai, Lee-Ann Langkaas, Diane Larsen, Catherine Leiendecker Foster, Virginia Leone, Camilla Levister, Annie Lukkari, Dawn Lum, Caroline Lyster, Maria Maione, Elaine Massaro, Jennifer McCance, Christine Mendonca, Sara R. Meyers, Joan Milton, Cindy A. Murphy, Ariane Nguyen, Andrej Orszag, Cynthia Plunkett, Carmyn Polk, Laurentiu Pop, Danielle Powell, Chinmaya Rajderkar, Clementina Ramos Garrido, Carol Recklein, Marilyn Richardson, Nicole Robinson, Lauri Schafer, Michelle Smith, Trudy Strand, Anna-Kay Thompson, Lindsey Towers, Josephine Tse, Joanie Tsougrianis, Victoria Tully, Sara Vecchi, Katherine Wilder, Tanisha Wilma, and Brittany Williams. Funding. The PERL study is funded by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (R03-DK-094484, R34-DK-097808, and UC4-DK-101108) and JDRF (17-2012-377). The iohexol used for the iGFR measurements was a generous gift of GE Healthcare. Research reported in this publication was supported by the National Center for Advancing Translational Sciences, the NIDDK, and the National Institute on Aging (Claude Pepper Center grants) under award numbers P30-DK-036836, UL1-TR-002494, P30-DK-020572, UL1-TR-001422, UL1-TR-002556, UL1-TR-002319, UL1-TR-001105, UL1-TR-002319-02, P30-AG-08808, and P30-AG-024824.

Publisher Copyright:
© 2019 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.

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  • Journal Article

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