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Urine matrix metalloproteinase-7 and risk of kidney disease progression and mortality in type 2 diabetes.

Abstract：

AIMS:The renin-angiotensin-aldosterone system (RAAS), bone morphogenetic protein (BMP) and WNT pathways are dysregulated in diabetic kidney disease (DKD). Urine excretion of angiotensinogen, gremlin-1 and matrix metalloproteinase-7 (MMP-7), components of the RAAS, BMP and WNT pathways, respectively, is increased in DKD. We asked if this increase is associated with subsequent progression to end-stage renal disease (ESRD) or death. METHODS:Using time-to-event analyses, we examined the association of baseline urine concentration of these proteins with progression to ESRD or death in a predominantly Mexican-American cohort with type 2 diabetes and proteinuric DKD (n=141). RESULTS:Progression to ESRD occurred for 38 participants over a median follow-up of 3.0years; 39 participants died over a median follow-up of 3.6years. Urine MMP-7 and gremlin-1 were associated with increased risk of ESRD after adjustment for demographic and clinical covariates. Angiotensinogen showed a U-shaped relationship with ESRD, with the middle tertile associated with lowest risk of ESRD. After additional adjustment for glomerular filtration rate and albuminuria, all associations with ESRD lost significance. Only urine MMP-7 was associated with mortality, and this association remained robust in the fully adjusted model with a Hazard ratio of 3.59 (95% confidence interval 1.31 to 9.85) for highest vs. lowest tertile. Serum MMP-7 was not associated with mortality and did not attenuate the association of urine MMP-7 with mortality (HR 4.03 for highest vs. lowest urine MMP-7 tertile). CONCLUSIONS:Among people with type 2 diabetes and proteinuric DKD, urine MMP-7 concentration was strongly associated with subsequent mortality.

journal_name

J Diabetes Complications

journal_title

Journal of diabetes and its complications

authors

Afkarian M,Zelnick LR,Ruzinski J,Kestenbaum B,Himmelfarb J,de Boer IH,Mehrotra R

doi

10.1016/j.jdiacomp.2015.08.024

subject

Has Abstract

pub_date

2015-11-01 00:00:00

pages

1024-31

issue

eissn

1056-8727

issn

1873-460X

pii

S1056-8727(15)00370-0

journal_volume

pub_type

杂志文章,多中心研究

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Urine matrix metalloproteinase-7 and risk of kidney disease progression and mortality in type 2 diabetes.