Preventing Early Renal Loss in Diabetes (PERL) Study: A Randomized Double-Blinded Trial of Allopurinol—Rationale, Design, and Baseline Data
Authors: Afkarian Maryam , Polsky Sarit , Parsa Afshin , Aronson Ronnie , Caramori Maria Luiza , Cherney David Z. , Crandall Jill P. , de Boer Ian H. , Elliott Thomas G. , Galecki Andrzej T. , Goldfine Allison B. , Haw J. Sonya , Hirsch Irl B. , Karger Amy B. , Lingvay Ildiko , Maahs David M. , McGill Janet B. , Molitch Mark E. , Perkins Bruce A. , Pop-Busui Rodica , Pragnell Marlon , Rosas Sylvia E. , Rossing Peter , Senior Peter , Sigal Ronald J. , Spino Catherine , Tuttle Katherine R. , Umpierrez Guillermo E. , Wallia Amisha , Weinstock Ruth S. , Wu Chunyi , Mauer Michael , Doria Alessandro ,   PERL Study Group, Doria Alessandro , Mauer Michael , Aronson Ronnie , Caramori Maria Luiza , Crandall Jill P. , de Boer Ian H. , Doria Alessandro , Eckfeldt John H. , Elliott Thomas G. , Flessner Michael , Galecki Andrzej T. , Goldfine Allison B. , Hirsch Irl B. , Karger Amy B. , Lingvay Ildiko , Maahs David M. , Mauer Michael , McGill Janet B. , Molitch Mark E. , Nickerson Helen , Parsa Afshin , Perkins Bruce A. , Polsky Sarit , Pop-Busui Rodica , Pragnell Marlon , Rosas Sylvia E. , Rossing Peter , Senior Peter , Sigal Ronald J. , Spino Catherine , Tuttle Katherine R. , Umpierrez Guillermo E. , Galecki Andrzej T. , Pietropaolo Massimo , Spino Catherine , Tsai Yi-Miau , Wu Chunyi , Eckfeldt John H. , Karger Amy B. , Robiner William , Flessner Michael , Parsa Afshin , Nickerson Helen , Pragnell Marlon , Doria Alessandro , Goldfine Allison B. , Rosas Sylvia , Cagliero Enrico , Thompson Michael , Weinstock Ruth S. , Gjerlev-Poulsen Christina , Lajer Maria , Persson Frederik , Pilemann-Lyberg Sascha , Rossing Peter , Luiza Caramori Maria , Mauer Michael , Frohauer Mary , Thida San , Gottlieb Peter , Maahs David , Polsky Sarit , Shah Viral , Schroeder Emily , McDermott Michael , Ang Lynn , Brosius Frank C. , Esfandiari Nazanene H. , Mizokami-Stout Kara , Pop-Busui Rodica , Perlman Rachel , Bhan Arti , Kruger Davida , Huang Wenyu , Molitch Mark E. , Wallia Amisha , Abramowitz Matthew K. , Anghel Valentin , Brutsaert Erika , Crandall Jill P. , Mani Nithya , Rajasekaran Divya , Levy Carol , Katz Melissa , Sinha Naina , Gregory Nobuyuki , Bill Miyawaki Shayan , Shirazian Ulrich K. , Schubart David , Cherney Bruce A. , Perkins Lorraine L. , Lipscombe Andrew , Advani Ronnie , Aronson Ronald , Goldenberg Janet B. , McGill Amy , Riek Maamoun , Salam Julie , McKeen Ronald J. , Sigal Peter , Senior Rose , Yeung J. Sonya , Haw Guillermo E. , Umpierrez Bruce W. , Bode Darin , Olson Maryam , Afkarian Ian H. , de Boer Irl B. , Hirsch Dace L. , Trence Grace , Lee Ildiko , Lingvay Radica , Alicic Katherine R. , Tuttle  , Elliott Thomas G. 
Published: June 2019

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.