Dataset Information

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

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 HbA_1c 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 HbA_1c (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.

SUBMITTER: Afkarian M

PROVIDER: S-EPMC6647051 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Afkarian Maryam M Polsky Sarit S Parsa Afshin A Aronson Ronnie R Caramori Maria Luiza ML Cherney David Z DZ Crandall Jill P JP de Boer Ian H IH Elliott Thomas G TG Galecki Andrzej T AT Goldfine Allison B AB Haw J Sonya JS Hirsch Irl B IB Karger Amy B AB Lingvay Ildiko I Maahs David M DM McGill Janet B JB Molitch Mark E ME Perkins Bruce A BA Pop-Busui Rodica R Pragnell Marlon M Rosas Sylvia E SE Rossing Peter P Senior Peter P Sigal Ronald J RJ Spino Catherine C Tuttle Katherine R KR Umpierrez Guillermo E GE Wallia Amisha A Weinstock Ruth S RS Wu Chunyi C Mauer Michael M Doria Alessandro A

Diabetes care 20190611 8

<h4>Objective</h4>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.<h4>Research design and methods</h4>This double-blind, placebo-controlled, multicenter trial randomized 530 participants with T1D, es ...[more]

PMID: 31186299

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Project description:BackgroundGlucagon-like peptide-1 is an incretin hormone essential for normal human glucose homeostasis. Expression of the glucagon-like peptide-1 receptor in the myocardium has fuelled growing interest in the direct and indirect cardiovascular effects of native glucagon-like peptide-1, its degradation product glucagon-like peptide-1(9-36), and the synthetic glucagon-like peptide-1 receptor agonists. Preclinical studies have demonstrated cardioprotective actions of all three compounds in the setting of experimental myocardial infarction and left ventricular systolic dysfunction. This has led to Phase 2 trials of native glucagon-like peptide-1 and incretin-based therapies in humans with and without Type 2 diabetes mellitus. These studies have demonstrated the ability of glucagon-like peptide-1, independent of glycaemic control, to positively modulate the metabolic and haemodynamic parameters of individuals with coronary artery disease and left ventricular systolic dysfunction. We aim to add to this growing body of evidence by studying the effect of chronic glucagon-like peptide-1 receptor activation on exercise-induced ischaemia in patients with chronic stable angina managed conservatively or awaiting revascularisation. The hypothesis being liraglutide, a subcutaneously injectable glucagon-like peptide-1 receptor agonist, is able to improve exercise haemodynamics in patients with obstructive coronary artery disease when compared with saline placebo.Methods and designThe Liraglutide to Improve corONary haemodynamics during Exercise streSS (LIONESS) trial is an investigator-initiated single-centre randomised double-blinded placebo-controlled crossover proof-of-principle physiological study. Primary endpoints are change in rate pressure product at 0.1 mV ST-segment depression and change in degree of ST-segment depression at peak exercise during sequential exercise tolerance testing performed over a 6-week study period in which 26 patients will be randomised to either liraglutide or saline with crossover to the opposing regimen at week 3.DiscussionThe study will be conducted in accordance with the principles of Good Clinical Practice and the Declaration of Helsinki. The local Research Ethics Committee and Medicines and Healthcare Products Regulatory Agency have approved the study.Trial registrationNational Institute of Health Research Clinical Research Network (NIHR CRN) Portfolio ID 11112 and ClinicalTrials.gov Identifier NCT02315001.

Dataset Information

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

Objective

Research design and methods

Results

Conclusions

Publications

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

Similar Datasets

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