ADMA：预测1型糖尿病肾病心血管死亡率

readok2009

Plasma concentration of asymmetric dimethylarginine (ADMA) predicts cardiovascular morbidity and mortality in type 1 diabetic patients with diabetic nephropathy

ABSTRACT

Objective: To investigate whether circulating ADMA levels are predictive of cardiovascular events, decline in glomerular filtration rate (dGFR), end-stage renal disease (ESRD), and all-cause mortality in type 1 patients.

Research Design and Methods: A prospective observational follow-up study; including 397 type 1 patients with overt diabetic nephropathy (243 men; age 42.1 ± 10.5 years (mean ± SD); GFR 76 ± 34 ml/min/1.73 m2) and a control group of 175 patients with longstanding type 1 and persistent normoalbuminuria (104 men; age 42.7 ± 9.7 years; duration of diabetes 27.7 ± 8.3 years). Patients were followed for 11.3 (0.0-12.9) years (median (range)) with yearly measurements of GFR (51Cr-EDTA plasma clearance) in patients with diabetic nephropathy. Endpoints were fatal and non-fatal CVD, dGFR, ESRD, and all-cause mortality.

Results: Among patients with diabetic nephropathy, 37 (19.4 %) patients with ADMA levels below the median compared to 79 (43.4 %) patients above the median suffered a major cardiovascular event during the follow-up period (p< 0.001). This effect persisted after adjustment for conventional CVD risk factors including baseline GFR (adjusted hazard ratio (HR) for elevated ADMA of 2.05 (1.31; 3.20), p= 0.002). Furthermore, elevated ADMA levels predicted an increased rate of decline in GFR, development of ESRD, and all-cause mortality (p< 0.001). After adjustment for well known progression promoters including baseline GFR HR (adjusted) was 1.85 (0.99; 3.46); p= 0.055 for ESRD comparing upper and lower median ADMA levels.

Conclusions: Plasma ADMA levels predict fatal and non-fatal cardiovascular events in patients with type 1 nephropathy. Furthermore, increased ADMA levels tended to contribute to increased risk of progressive diabetic kidney disease.

http://care.diabetesjournals.org/cgi/content/abstract/dc07-1762v1

作者单位
1Steno Diabetes Center, Gentofte, Denmark
2Department of Clinical Chemistry, VU, University Medical Center, Amsterdam, The Netherlands
3Department of Medical Endocrinology, Rigshospitalet, University Hospital of Copenhagen, Copenhagen, Denmark
4Faculty of Health Science, University of Aarhus, Aarhus