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

PERL Study Group

Research output: Contribution to journalArticle

9 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1454-1463
Number of pages10
JournalDiabetes care
Volume42
Issue number8
DOIs
StatePublished - Aug 1 2019

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Allopurinol
Diabetic Nephropathies
Uric Acid
Glomerular Filtration Rate
Albuminuria
Kidney
Type 1 Diabetes Mellitus
Iohexol
Serum
Placebos
Renin-Angiotensin System
Double-Blind Method
Multicenter Studies
Research Design
Randomized Controlled Trials
Blood Pressure
Hypertension

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

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

In: Diabetes care, Vol. 42, No. 8, 01.08.2019, p. 1454-1463.

Research output: Contribution to journalArticle

@article{8dcc43b627a345ff953100d87a503ef5,
title = "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 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.",
author = "{PERL Study Group} and Maryam Afkarian and Sarit Polsky and Afshin Parsa and Ronnie Aronson and Caramori, {Maria Luiza} and Cherney, {David Z.} and Crandall, {Jill P.} and {de Boer}, {Ian H.} and Elliott, {Thomas G.} and Galecki, {Andrzej T.} and Goldfine, {Allison B.} and Haw, {J. Sonya} and Hirsch, {Irl B.} and Karger, {Amy B.} and Ildiko Lingvay and Maahs, {David M.} and McGill, {Janet B.} and Molitch, {Mark E.} and Perkins, {Bruce A.} and Rodica Pop-Busui and Marlon Pragnell and Rosas, {Sylvia E.} and Peter Rossing and Peter Senior and Sigal, {Ronald J.} and Catherine Spino and Tuttle, {Katherine R.} and Umpierrez, {Guillermo E.} and Amisha Wallia and Weinstock, {Ruth S.} and Chunyi Wu and Michael Mauer and Alessandro Doria",
year = "2019",
month = "8",
day = "1",
doi = "10.2337/dc19-0342",
language = "English (US)",
volume = "42",
pages = "1454--1463",
journal = "Diabetes Care",
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TY - JOUR

T1 - Preventing Early Renal Loss in Diabetes (PERL) Study

T2 - A Randomized Double-Blinded Trial of Allopurinol-Rationale, Design, and Baseline Data

AU - PERL Study Group

AU - Afkarian, Maryam

AU - Polsky, Sarit

AU - Parsa, Afshin

AU - Aronson, Ronnie

AU - Caramori, Maria Luiza

AU - Cherney, David Z.

AU - Crandall, Jill P.

AU - de Boer, Ian H.

AU - Elliott, Thomas G.

AU - Galecki, Andrzej T.

AU - Goldfine, Allison B.

AU - Haw, J. Sonya

AU - Hirsch, Irl B.

AU - Karger, Amy B.

AU - Lingvay, Ildiko

AU - Maahs, David M.

AU - McGill, Janet B.

AU - Molitch, Mark E.

AU - Perkins, Bruce A.

AU - Pop-Busui, Rodica

AU - Pragnell, Marlon

AU - Rosas, Sylvia E.

AU - Rossing, Peter

AU - Senior, Peter

AU - Sigal, Ronald J.

AU - Spino, Catherine

AU - Tuttle, Katherine R.

AU - Umpierrez, Guillermo E.

AU - Wallia, Amisha

AU - Weinstock, Ruth S.

AU - Wu, Chunyi

AU - Mauer, Michael

AU - Doria, Alessandro

PY - 2019/8/1

Y1 - 2019/8/1

N2 - 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.

AB - 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.

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JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

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