Serum Urate Lowering with Allopurinol and Kidney Function in Type 1 Diabetes

被引：240

作者：

Doria, A. ^{[1
,2
]}

Galecki, A. T. ^{[3
,4
]}

Spino, C. ^{[4
,5
]}

Pop-Busui, R. ^{[6
]}

Cherney, D. Z. ^{[7
,8
,9
,11
]}

Lingvay, I. ^{[22
,23
]}

Parsa, A. ^{[24
]}

Rossing, P. ^{[25
,26
]}

Sigal, R. J. ^{[14
,15
,16
,17
,18
,19
]}

Afkarian, M. ^{[27
]}

Aronson, R. ^{[12
]}

Caramori, M. L. ^{[30
,31
]}

Crandall, J. P. ^{[33
,34
]}

de Boer, I. H. ^{[36
]}

Elliott, T. G. ^{[20
]}

Goldfine, A. B. ^{[1
,2
]}

Haw, J. S. ^{[40
]}

Hirsch, I. B. ^{[36
]}

Karger, A. B. ^{[32
]}

Maahs, D. M. ^{[28
,29
]}

McGill, J. B. ^{[41
]}

Molitch, M. E. ^{[42
]}

Perkins, B. A. ^{[10
,13
]}

Polsky, S. ^{[43
]}

Pragnell, M. ^{[35
]}

Robiner, W. N. ^{[30
,31
]}

Rosas, S. E. ^{[1
,2
]}

Senior, P. ^{[21
]}

Tuttle, K. R. ^{[37
,38
,39
]}

Umpierrez, G. E. ^{[40
]}

Wallia, A. ^{[42
]}

Weinstock, R. S. ^{[44
]}

Wu, C. ^{[3
]}

Mauer, M. ^{[30
,31
]}

机构：

[1] Harvard Med Sch, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA

[2] Harvard Med Sch, Dept Med, Boston, MA 02215 USA

[3] Univ Michigan, Inst Gerontol, Div Geriatr, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA

[5] Univ Michigan, Stat Anal Biomed & Educ Res SABER, Ann Arbor, MI 48109 USA

[6] Univ Michigan, Dept Internal Med Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA

[7] Univ Toronto, Dept Med, Toronto, ON, Canada

[8] Univ Toronto, Dept Physiol, Toronto, ON, Canada

[9] Univ Toronto, Dept Pharmacol & Toxicol, Toronto, ON, Canada

[10] Univ Toronto, Div Endocrinol & Metab, Toronto, ON, Canada

[11] Univ Hlth Network, Div Nephrol, Toronto, ON, Canada

[12] LMC Diabet & Endocrinol, Toronto, ON, Canada

[13] Sinai Hlth Syst, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada

[14] Univ Calgary, Fac Med, Dept Med, Calgary, AB, Canada

[15] Univ Calgary, Fac Med, Dept Cardiac Sci, Calgary, AB, Canada

[16] Univ Calgary, Fac Med, Dept Community Hlth Sci, Calgary, AB, Canada

[17] Univ Calgary, Fac Kinesiol, Dept Med, Calgary, AB, Canada

[18] Univ Calgary, Fac Kinesiol, Dept Cardiac Sci, Calgary, AB, Canada

[19] Univ Calgary, Fac Kinesiol, Dept Community Hlth Sci, Calgary, AB, Canada

[20] BCDiabet, Vancouver, BC, Canada

[21] Univ Alberta, Div Endocrinol, Edmonton, AB, Canada

[22] Univ Texas Southwestern Med Ctr, Dept Med, Dallas, TX USA

[23] Univ Texas Southwestern Med Ctr, Dept Populat & Data Sci, Dallas, TX USA

[24] NIDDK, Div Kidney Urol & Hematol Dis, Bethesda, MD 20892 USA

[25] Univ Copenhagen, Steno Diabet Ctr, Copenhagen, Denmark

[26] Univ Copenhagen, Dept Clin Med, Copenhagen, Denmark

[27] Univ Calif Davis, Dept Med, Div Nephrol, Davis, CA 95616 USA

[28] Stanford Univ, Dept Pediat, Palo Alto, CA 94304 USA

[29] Stanford Univ, Stanford Diabet Res Ctr, Palo Alto, CA 94304 USA

[30] Univ Minnesota, Dept Med, Box 736 UMHC, Minneapolis, MN 55455 USA

[31] Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA

[32] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA

[33] Albert Einstein Coll Med, Div Endocrinol, New York, NY USA

[34] Albert Einstein Coll Med, Fleischer Inst Diabet & Metab, New York, NY USA

[35] JDRF Juvenile Diabet Res Fdn, New York, NY USA

[36] Univ Washington, Dept Med, Seattle, WA USA

[37] Univ Washington, Div Nephrol, Seattle, WA 98195 USA

[38] Kidney Res Inst, Inst Translat Hlth Sci, Seattle, WA USA

[39] Providence Hlth Care, Spokane, WA USA

[40] Emory Univ, Dept Med, Atlanta, GA 30322 USA

[41] Washington Univ, Sch Med, Div Endocrinol Metab & Lipid Res, St Louis, MO USA

[42] Northwestern Univ, Feinberg Sch Med, Div Endocrinol Metab & Mol Med, Chicago, IL 60611 USA

[43] Univ Colorado, Barbara Davis Ctr Diabet, Aurora, CO USA

[44] SUNY Upstate Med Univ, Dept Med, Syracuse, NY 13210 USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2020年 / 382卷 / 26期

关键词：

URIC-ACID LEVELS; FOLLOW-UP; RISK; NEPHROPATHY; DISEASE; PROGRESSION; LOSARTAN; COMPLICATIONS; CAPTOPRIL; EFFICACY;

D O I：

10.1056/NEJMoa1916624

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND Higher serum urate levels are associated with an increased risk of diabetic kidney disease. Lowering of the serum urate level with allopurinol may slow the decrease in the glomerular filtration rate (GFR) in persons with type 1 diabetes and early-to-moderate diabetic kidney disease. METHODS In a double-blind trial, we randomly assigned participants with type 1 diabetes, a serum urate level of at least 4.5 mg per deciliter, an estimated GFR of 40.0 to 99.9 ml per minute per 1.73 m(2) of body-surface area, and evidence of diabetic kidney disease to receive allopurinol or placebo. The primary outcome was the baseline-adjusted GFR, as measured with iohexol, after 3 years plus a 2-month washout period. Secondary outcomes included the decrease in the iohexol-based GFR per year and the urinary albumin excretion rate after washout. Safety was also assessed. RESULTS A total of 267 patients were assigned to receive allopurinol and 263 to receive placebo. The mean age was 51.1 years, the mean duration of diabetes 34.6 years, and the mean glycated hemoglobin level 8.2%. The mean baseline iohexol-based GFR was 68.7 ml per minute per 1.73 m(2) in the allopurinol group and 67.3 ml per minute per 1.73 m(2) in the placebo group. During the intervention period, the mean serum urate level decreased from 6.1 to 3.9 mg per deciliter with allopurinol and remained at 6.1 mg per deciliter with placebo. After washout, the between-group difference in the mean iohexol-based GFR was 0.001 ml per minute per 1.73 m(2) (95% confidence interval [CI], -1.9 to 1.9; P= 0.99). The mean decrease in the iohexolbased GFR was -3.0 ml per minute per 1.73 m(2) per year with allopurinol and -2.5 ml per minute per 1.73 m(2) per year with placebo (between-group difference, -0.6 ml per minute per 1.73 m(2) per year; 95% CI, -1.5 to 0.4). The mean urinary albumin excretion rate after washout was 40% (95% CI, 0 to 80) higher with allopurinol than with placebo. The frequency of serious adverse events was similar in the two groups. CONCLUSIONS We found no evidence of clinically meaningful benefits of serum urate reduction with allopurinol on kidney outcomes among patients with type 1 diabetes and early-to-moderate diabetic kidney disease.

引用

页码：2493 / 2503

页数：11

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