1. Preventing Early Renal Loss in Diabetes (PERL) Study: A Randomized Double-Blinded Trial of Allopurinol—Rationale, Design, and Baseline Data
- Author
-
Amisha Wallia, Irl B. Hirsch, Afshin Parsa, Alessandro Doria, J. Sonya Haw, Catherine Spino, Bruce A. Perkins, Amy B. Karger, Peter Rossing, Katherine R. Tuttle, Andrzej T. Galecki, Ruth S. Weinstock, Rodica Pop-Busui, Sylvia E. Rosas, Guillermo E. Umpierrez, Ronald J. Sigal, David M. Maahs, Ildiko Lingvay, Janet B. McGill, Maryam Afkarian, Jill P. Crandall, Mark E. Molitch, Ronnie Aronson, Peter A. Senior, Allison B. Goldfine, Sarit Polsky, Michael Mauer, Maria Luiza Caramori, David Z.I. Cherney, Chun Yi Wu, Ian H. de Boer, Marlon Pragnell, and Tom Elliott
- Subjects
Male ,medicine.medical_specialty ,Allopurinol ,Endocrinology, Diabetes and Metabolism ,Urology ,Renal function ,Blood Pressure ,030209 endocrinology & metabolism ,Placebo ,Renin-Angiotensin System ,03 medical and health sciences ,0302 clinical medicine ,Double-Blind Method ,Risk Factors ,Multicenter trial ,Diabetes mellitus ,Internal Medicine ,medicine ,Albuminuria ,Humans ,Diabetic Nephropathies ,030212 general & internal medicine ,Aged ,Advanced and Specialized Nursing ,Type 1 diabetes ,Emerging Therapies: Drugs and Regimens ,business.industry ,Middle Aged ,medicine.disease ,Uric Acid ,Diabetes Mellitus, Type 1 ,Blood pressure ,Disease Progression ,Female ,medicine.symptom ,business ,Glomerular Filtration Rate ,medicine.drug - 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.
- Published
- 2019