ADMA predicts major adverse renal events in patients with mild renal impairment and/or diabetes mellitus undergoing coronary angiography

Abstract

Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of the nitric oxide (NO)-synthase and a biomarker of endothelial dysfunction (ED). ED plays an important role in the pathogenesis of contrast-induced nephropathy (CIN). The aim of our study was to evaluate serum ADMA concentration as a biomarker of an acute renal damage during the follow-up of 90 days after contrast medium (CM) application.Blood samples were obtained from 330 consecutive patients with diabetes mellitus or mild renal impairment immediately before, 24 and 48 hours after the CM application for coronary angiography. The patients were followed for 90 days. The composite endpoints were major adverse renal events (MARE) defined as occurrence of death, initiation of dialysis, or a doubling of serum creatinine concentration.Overall, ADMA concentration in plasma increased after CM application, although, there was no differences between ADMA levels in patients with and without CIN. ADMA concentration 24 hours after the CM application was predictive for dialysis with a specificity of 0.889 and sensitivity of 0.653 at values higher than 0.71 μmol/L (area under the curve: 0.854, 95% confidential interval: 0.767–0.941, P < 0.001). This association remained significant in multivariate Cox regression models adjusted for relevant factors of long-term renal outcome. 24 hours after the CM application, ADMA concentration in plasma was predictive for MARE with a specificity of 0.833 and sensitivity of 0.636 at a value of more than 0.70 μmol/L (area under the curve: 0.750, 95% confidence interval: 0.602–0.897, P = 0.004). Multivariate logistic regression analysis confirmed that ADMA and anemia were significant predictors of MARE. Further analysis revealed that increased ADMA concentration in plasma was highly significant predictor of MARE in patients with CIN. Moreover, patients with CIN and MARE had the highest plasma ADMA levels 24 hours after CM exposure in our study cohort. The impact of ADMA on MARE was independent of such known CIN risk factors as anemia, pre-existing renal failure, pre-existing heart failure, and diabetes.ADMA concentration in plasma is a promising novel biomarker of major contrast-induced nephropathy-associated events 90 days after contrast media exposure.

The Main Determinants of Diabetes Mellitus Vascular Complications: Endothelial Dysfunction and Platelet Hyperaggregation

“…Alternatively, compounds that inactivate or alter the normal precursor/product ratio have been highlighted: one of these is asymmetric dimethyl arginine (ADMA). It has recently been found that, in type 2 diabetes, ADMA increases significantly after ingestion of a fatty meal, and its levels correlate with the reduction of flow-mediated vasodilatation [ 34 ]. Regarding the second hypothesis, it has been shown that some factors are able to reduce the expression of NOS.…”

HDL in CKD—The Devil Is in the Detail

“…128,129 Several studies described ADMA and SDMA to be connected to kidney impairment, 130 as well as to the progression of CKD. [131][132][133][134][135][136][137][138][139][140] Recent data identified SDMA within HDL particles of CKD patients but not in healthy controls, and SDMA was considered to be the culprit that modifies HDL and reverts the endothelial-protective properties. This modified HDL induces endothelial dysfunction, impairs endothelial repair, increases BP, and activates endothelial TLR-2 signaling, resulting in enhanced reactive oxygen species production and inhibition of endothelial NO bioavailability.…”

Effects of remote ischemic preconditioning on contrast induced nephropathy after percutaneous coronary intervention in patients with acute coronary syndrome

“…Therefore, CIN has become a common complication of PCI, and has become the third leading cause of acute renal failure in hospital. [ 2 , 3 ] The diagnostic criteria of CIN was that the absolute value of serum creatinine (Scr) in 48 to 72 hours after the injection of contrast agent was increased by >44.2 mmol/L or above the base value of 25%, and was not associated with other renal damage. [ 4 , 5 ] In addition to hydration, there is still no effective prophylactic regimen available to prevent occurrence of CIN recently.…”