• 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, and PERL Study Group.
• Division of Nephrology, Department of Medicine, University of California, Davis, Davis, CA.
• Diabetes Care. 2019 Aug 1; 42 (8): 1454-1463.

ObjectiveHigher 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 MethodsThis 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.ResultsParticipants 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.ConclusionsPERL 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.© 2019 by the American Diabetes Association.

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