Preventing Early Renal Loss in Diabetes (PERL) study: A randomized double-blinded trial of allopurinoldrationale, design, and baseline data

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; PERL Study Group

doi:10.2337/dc19-0342

Preventing Early Renal Loss in Diabetes (PERL) study: A randomized double-blinded trial of allopurinoldrationale, design, and baseline data

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-BusuiMarlon 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^*, PERL Study Group

^*Corresponding author for this work

Department of Clinical Medicine

21 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 HbA_1c was 8%, SUA 5.9 mg/dL, iGFR 68 mL/min/1.73 m², and historical eGFR slope 23.5 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 (24.7 vs. 22.5 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 language	English
Journal	Diabetes Care
Volume	42
Issue number	8
Pages (from-to)	1454-1463
ISSN	0149-5992
DOIs	https://doi.org/10.2337/dc19-0342
Publication status	Published - 2019

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Afkarian, M., Polsky, S., Parsa, A., Aronson, R., Caramori, M. L., Cherney, D. Z., Crandall, J. P., De Boer, I. H., Elliott, T. G., Galecki, A. T., Goldfine, A. B., Sonya Haw, J., Hirsch, I. B., Karger, A. B., Lingvay, I., Maahs, D. M., McGill, J. B., Molitch, M. E., Perkins, B. A., ... PERL Study Group (2019). Preventing Early Renal Loss in Diabetes (PERL) study: A randomized double-blinded trial of allopurinoldrationale, design, and baseline data. Diabetes Care, 42(8), 1454-1463. https://doi.org/10.2337/dc19-0342

Afkarian, M, Polsky, S, Parsa, A, Aronson, R, Caramori, ML, Cherney, DZ, Crandall, JP, De Boer, IH, Elliott, TG, Galecki, AT, Goldfine, AB, Sonya Haw, J, Hirsch, IB, Karger, AB, Lingvay, I, Maahs, DM, McGill, JB, Molitch, ME, Perkins, BA, Pop-Busui, R, Pragnell, M, Rosas, SE, Rossing, P, Senior, P, Sigal, RJ, Spino, C, Tuttle, KR, Umpierrez, GE, Wallia, A, Weinstock, RS, Wu, C, Mauer, M, Doria, A & PERL Study Group 2019, 'Preventing Early Renal Loss in Diabetes (PERL) study: A randomized double-blinded trial of allopurinoldrationale, design, and baseline data', Diabetes Care, vol. 42, no. 8, pp. 1454-1463. https://doi.org/10.2337/dc19-0342

@article{b378e65b969945e4a2625ba8ec23cb2b,

title = "Preventing Early Renal Loss in Diabetes (PERL) study: A randomized double-blinded trial of allopurinoldrationale, 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 23.5 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 (24.7 vs. 22.5 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 = "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 {Sonya Haw}, J. 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 and {PERL Study Group}",

year = "2019",

doi = "10.2337/dc19-0342",

language = "English",

volume = "42",

pages = "1454--1463",

journal = "Diabetes Care",

issn = "0149-5992",

publisher = "American Diabetes Association",

number = "8",

}

TY - JOUR

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

T2 - A randomized double-blinded trial of allopurinoldrationale, design, and baseline data

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 - Sonya Haw, J.

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

AU - PERL Study Group

PY - 2019

Y1 - 2019

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 23.5 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 (24.7 vs. 22.5 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 23.5 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 (24.7 vs. 22.5 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.

U2 - 10.2337/dc19-0342

DO - 10.2337/dc19-0342

M3 - Journal article

C2 - 31186299

AN - SCOPUS:85068889373

SN - 0149-5992

VL - 42

SP - 1454

EP - 1463

JO - Diabetes Care

JF - Diabetes Care

IS - 8

ER -

Preventing Early Renal Loss in Diabetes (PERL) study: A randomized double-blinded trial of allopurinoldrationale, design, and baseline data

Abstract

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