Association of Multiple Plasma Biomarker Concentrations with Progression of Prevalent Diabetic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study

被引：106

作者：

Schrauben, Sarah J. ^{[1
,2
]}

Shou, Haochang ^{[2
]}

Zhang, Xiaoming ^{[2
]}

Anderson, Amanda Hyre ^{[2
,3
]}

Bonventre, Joseph V. ^{[4
]}

Chen, Jing ^{[5
]}

Coca, Steven ^{[6
]}

Furth, Susan L. ^{[7
]}

Greenberg, Jason H. ^{[8
]}

Gutierrez, Orlando M. ^{[9
,10
]}

Ix, Joachim H. ^{[11
]}

Lash, James P. ^{[12
]}

Parikh, Chirag R. ^{[13
]}

Rebholz, Casey M. ^{[14
]}

Sabbisetti, Venkata ^{[4
]}

Sarnak, Mark J. ^{[15
]}

Shlipak, Michael G. ^{[16
]}

Waikar, Sushrut S. ^{[17
]}

Kimmel, Paul L. ^{[18
]}

Vasan, Ramachandran S. ^{[19
,20
,21
,22
]}

Feldman, Harold I. ^{[1
,2
]}

Schelling, Jeffrey R. ^{[23
,24
]}

机构：

[1] Univ Penn, Dept Med, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA

[2] Univ Penn, Perelman Sch Med, Dept Biostat Epidemiol & Informat, Philadelphia, PA 19104 USA

[3] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA

[4] Harvard Med Sch, Brigham & Womens Hosp, Dept Med, Div Renal Med, Boston, MA 02115 USA

[5] Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA

[6] Icahn Sch Med Mt Sinai, Dept Internal Med, Div Nephrol, New York, NY 10029 USA

[7] Univ Penn, Childrens Hosp Philadelphia, Perelman Sch Med, Div Nephrol,Dept Pediat, Philadelphia, PA 19104 USA

[8] Yale Univ, Sch Med, Dept Pediat, Sect Nephrol,Program Appl Translat Res, New Haven, CT 06510 USA

[9] Univ Alabama Birmingham, Dept Med, Birmingham, AL USA

[10] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA

[11] Univ Calif San Diego, Dept Med, Sch Med, Div Nephrol Hypertens, San Diego, CA 92103 USA

[12] Univ Illinois, Dept Med, Div Nephrol, Chicago, IL USA

[13] Johns Hopkins Sch Med, Dept Internal Med, Sect Nephrol, Baltimore, MD USA

[14] Johns Hopkins Bloomberg Sch Public Hlth, Dept Epidemiol, Baltimore, MD USA

[15] Tufts Med Ctr, Dept Med, Div Nephrol, Boston, MA 02111 USA

[16] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA

[17] Boston Med Ctr, Dept Med, Sect Nephrol, Boston, MA USA

[18] NIDDK, Bethesda, MD 20892 USA

[19] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA

[20] Boston Univ, Sch Med, Dept Epidemiol, Boston, MA 02118 USA

[21] Boston Univ, Sch Publ Hlth, Dept Med, Boston, MA USA

[22] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA

[23] MetroHlth Campus, Dept Internal Med, Div Nephrol, Cleveland, OH USA

[24] Case Western Reserve Univ, Sch Med, Dept Physiol & Biophys, Cleveland, OH 44106 USA

来源：

JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY | 2021年 / 32卷 / 01期

关键词：

diabetes; diabetic nephropathy; end stage kidney disease; epidemiology and outcomes; chronic diabetic complications; chronic kidney disease; diabetic kidney disease; biomarker; TNF RECEPTORS 1; GLOMERULAR-FILTRATION-RATE; INJURY MOLECULE-1; TRANSPLANT RECIPIENTS; FUNCTION DECLINE; ESTIMATING GFR; RISK; INFLAMMATION; MARKERS; PREDICT;

D O I：

10.1681/ASN.2020040487

中图分类号：

R5 [内科学]; R69 [泌尿科学（泌尿生殖系疾病）];

学科分类号：

1002 ; 100201 ;

摘要：

Background Although diabetic kidney disease is the leading cause of ESKD in the United States, identifying those patients who progress to ESKD is difficult. Efforts are under way to determine if plasma biomarkers can help identify these high-risk individuals. Methods In our case-cohort study of 894 Chronic Renal Insufficiency Cohort Study participants with diabetes and an eGFR of,60 ml/min per 1.73 m(2) at baseline, participants were randomly selected for the subcohort; cases were those patients who developed progressive diabetic kidney disease (ESKD or 40% eGFR decline). Using a multiplex system, we assayed plasma biomarkers related to tubular injury, inflammation, and fibrosis (KIM- 1, TNFR- 1, TNFR-2, MCP-1, suPAR, and YKL-40). Weighted Cox regression models related biomarkers to progression of diabetic kidney disease, andmixed-effectsmodels estimated biomarker relationships with rate of eGFR change. ResultsMedian follow-up was 8.7 years. Higher concentrations of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were each associated with a greater risk of progression of diabetic kidney disease, even after adjustment for established clinical risk factors. After accounting for competing biomarkers, KIM-1, TNFR2, and YKL-40 remained associated with progression of diabetic kidney disease; TNFR-2 had the highest risk (adjusted hazard ratio, 1.61; 95% CI, 1.15 to 2.26). KIM-1, TNFR-1, TNFR-2, and YKL-40 were associated with rate of eGFR decline. Conclusions Higher plasma levels of KIM-1, TNFR-1, TNFR-2, MCP-1, suPAR, and YKL-40 were associated with increased risk of progression of diabetic kidney disease; TNFR-2 had the highest risk after accounting for the other biomarkers. These findings validate previous literature on TNFR-1, TNFR- 2, and KIM-1 in patients with prevalent CKD and provide new insights into the influence of suPAR and YKL-40 as plasma biomarkers that require validation.

引用

页码：115 / 126

页数：12

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