Preventing Early Renal Loss in Diabetes (PERL) Study: A Randomized Double-Blinded Trial of Allopurinol—Rationale, Design, and Baseline Data
Authors: Maryam Afkarian, Sarit Polsky, Afshin Parsa, Ronnie Aronson, Maria Luiza Caramori, David Z. Cherney, Jill P. Crandall, Ian H. de Boer, Thomas G. Elliott, Andrzej T. Galecki, Allison B. Goldfine, J. Sonya Haw, Irl B. Hirsch, Amy B. Karger, Ildiko Lingvay, David M. Maahs, Janet B. McGill, Mark E. Molitch, Bruce A. Perkins, Rodica Pop-Busui, Marlon Pragnell, Sylvia E. Rosas, Peter Rossing, Peter Senior, Ronald J. Sigal, Catherine Spino, Katherine R. Tuttle, Guillermo E. Umpierrez, Amisha Wallia, Ruth S. Weinstock, Chunyi Wu, Michael Mauer, Alessandro Doria, Alessandro Doria, Michael Mauer, Ronnie Aronson, Maria Luiza Caramori, Jill P. Crandall, Ian H. de Boer, Alessandro Doria, John H. Eckfeldt, Thomas G. Elliott, Michael Flessner, Andrzej T. Galecki, Allison B. Goldfine, Irl B. Hirsch, Amy B. Karger, Ildiko Lingvay, David M. Maahs, Michael Mauer, Janet B. McGill, Mark E. Molitch, Helen Nickerson, Afshin Parsa, Bruce A. Perkins, Sarit Polsky, Rodica Pop-Busui, Marlon Pragnell, Sylvia E. Rosas, Peter Rossing, Peter Senior, Ronald J. Sigal, Catherine Spino, Katherine R. Tuttle, Guillermo E. Umpierrez, Andrzej T. Galecki, Massimo Pietropaolo, Catherine Spino, Yi-Miau Tsai, Chunyi Wu, John H. Eckfeldt, Amy B. Karger, William Robiner, Michael Flessner, Afshin Parsa, Helen Nickerson, Marlon Pragnell, Alessandro Doria, Allison B. Goldfine, Sylvia Rosas, Enrico Cagliero, Michael Thompson, Ruth S. Weinstock, Christina Gjerlev-Poulsen, Maria Lajer, Frederik Persson, Sascha Pilemann-Lyberg, Peter Rossing, Maria Luiza Caramori, Michael Mauer, Mary Frohauer, San Thida, Peter Gottlieb, David Maahs, Sarit Polsky, Viral Shah, Emily Schroeder, Michael McDermott, Lynn Ang, Frank C. Brosius, Nazanene H. Esfandiari, Kara Mizokami-Stout, Rodica Pop-Busui, Rachel Perlman, Arti Bhan, Davida Kruger, Wenyu Huang, Mark E. Molitch, Amisha Wallia, Matthew K. Abramowitz, Valentin Anghel, Erika Brutsaert, Jill P. Crandall, Nithya Mani, Divya Rajasekaran, Carol Levy, Melissa Katz, Naina Sinha, Nobuyuki Gregory, Shayan Bill Miyawaki, Ulrich K. Shirazian, David Schubart, Bruce A. Cherney, Lorraine L. Perkins, Andrew Lipscombe, Ronnie Advani, Ronald Aronson, Janet B. Goldenberg, Amy McGill, Maamoun Riek, Julie Salam, Ronald J. McKeen, Peter Sigal, Rose Senior, J. Sonya Yeung, Guillermo E. Haw, Bruce W. Umpierrez, Darin Bode, Maryam Olson, Ian H. Afkarian, Irl B. de Boer, Dace L. Hirsch, Grace Trence, Ildiko Lee, Radica Lingvay, Katherine R. Alicic, None Tuttle, Thomas G. Elliott
Journal: Diabetes Care (2019)

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.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.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.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.