Urinary Complement proteome strongly linked to diabetic kidney disease progression

被引：0

作者：

Md Dom, Zaipul I. ^{[1
,2
]}

Moon, Salina ^{[1
]}

Satake, Eiichiro ^{[1
,2
]}

Hirohama, Daigoro ^{[3
,4
,5
]}

Palmer, Nicholette D. ^{[6
]}

Lampert, Heather ^{[1
,2
,13
]}

Ficociello, Linda H. ^{[1
,2
,14
]}

Abedini, Amin ^{[3
,4
,5
,15
]}

Fernandez, Karen ^{[1
,7
,16
]}

Liang, Xiujie ^{[3
,4
,5
]}

Pickett, Sara ^{[1
,17
]}

Levinsohn, Jonathan ^{[3
,4
,5
]}

O'Neil, Kristina ^{[1
]}

Dillon, Simon T. ^{[2
,8
]}

Mauer, Michael ^{[9
]}

Galecki, Andrzej T. ^{[10
,11
]}

Freedman, Barry I. ^{[12
]}

Susztak, Katalin ^{[3
,4
,5
]}

Doria, Alessandro ^{[1
,2
]}

Krolewski, Andrzej S. ^{[1
,2
]}

Niewczas, Monika A. ^{[1
,2
]}

机构：

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

[2] Harvard Med Sch, Dept Med, Boston, MA 02115 USA

[3] Univ Penn, Perelman Sch Med, Dept Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA USA

[4] Univ Penn, Inst Diabet Obes & Metab, Perelman Sch Med, Philadelphia, PA USA

[5] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA USA

[6] Wake Forest Univ, Sch Med, Dept Biochem, Winston Salem, NC USA

[7] Harvard Univ, Cambridge, MA USA

[8] Beth Israel Deaconess Med Ctr, Genom Prote Bioinformat & Syst Biol Ctr, Boston, MA USA

[9] Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN USA

[10] Univ Michigan, Dept Internal Med, Ann Arbor, MI USA

[11] Univ Michigan, Dept Biostat, Ann Arbor, MI USA

[12] Wake Forest Univ, Dept Internal Med, Sect Nephrol, Sch Med, Winston Salem, NC USA

[13] One Med, Newton, MA USA

[14] Global Med Off, Fresenius Med Care, Waltham, MA USA

[15] Univ Maryland Med Syst, Baltimore, MD USA

[16] Stanford Univ, Stanford Sch Med, Stanford, CA USA

[17] Univ Texas Hlth Sci Ctr, Houston, TX USA

来源：

NATURE COMMUNICATIONS | 2025年 / 16卷 / 01期

基金：

美国国家卫生研究院;

关键词：

ACTIVATION PRODUCTS; FUNCTION DECLINE; RENAL DECLINE; NEPHROPATHY; ASSOCIATION; BIOMARKERS; AGREEMENT;

D O I：

10.1038/s41467-025-62101-5

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Diabetic kidney disease (DKD) progression is not well understood. Using high-throughput proteomics, biostatistical, pathway and machine learning tools, we examine the urinary Complement proteome in two prospective cohorts with type 1 or 2 diabetes and advanced DKD followed for 1,804 person-years. The top 5% urinary proteins representing multiple components of the Complement system (C2, C5a, CL-K1, C6, CFH and C7) are robustly associated with 10-year kidney failure risk, independent of clinical covariates. We confirm the top proteins in three early-to-moderate DKD cohorts (2,982 person-years). Associations are especially pronounced in advanced kidney disease stages, similar between the two diabetes types and far stronger for urinary than circulating proteins. We also observe increased Complement protein and single cell/spatial RNA expressions in diabetic kidney tissue. Here, our study shows Complement engagement in DKD progression and lays the groundwork for developing biomarker-guided treatments.

引用

页数：19

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