Methylarginines in CKD
November 02, 2017 | 10:00 AM - 10:00 AM
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Methylarginines in CKD
- CKD: Epidemiology, Outcomes - Cardiovascular - I
November 02, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Chronic Kidney Disease (Non-Dialysis)
- 303 CKD: Epidemiology, Outcomes - Cardiovascular
- Emrich, Insa E., Saarland University, Homburg, Saarland, Germany
- Zawada, Adam M., Saarland University Medical Center, Homburg, SL, Germany
- Martens-lobenhoffer, Jens, University Magdeburg, Magdeburg, Germany
- Wagenpfeil, Stefan, Saarland University, Homburg, Germany
- Fliser, Danilo, Saarland University Medical Centre, Homburg/Saar, Germany
- Heine, Gunnar H., Saarland University Faculty of Medicine, Homburg, Germany
- Bode-Böger, Stefanie M., Institute of Clinical Phamacology, Medical Faculty, Otto-von Guericke University, Magdeburg, Germany
Insa E. Emrich,
Adam M. Zawada,
Gunnar H. Heine,
Stefanie M. Bode-Böger,
Patients suffering from chronic kidney disease (CKD) have a substantial burden of cardiovascular disease, whose underlying pathophysiological mechanism cannot fully be explained by traditional risk factors. Therefore, non-traditional cardiovascular risk factors have to be taken into account.
As such potential non-traditional risk factors, asymmetric dimethylarginine (ADMA) & symmetric dimethylarginine (SDMA) have been a focus of cardiorenal research for several years. It has recently been revealed that ADMA & SDMA become acetylated during their degradation. In murine models the acetylated ADMA (Ac-ADMA) & the acetylated SDMA (Ac-SDMA) were significantly associated with kidney function.
We now hypothesize that (a) a similar accumulation of Ac-ADMA & Ac-SDMA occurs in humans & (b) Ac-ADMA & Ac-SDMA are more prominent predictors of incident cardiovascular events than ADMA & SDMA.
Blood samples of 528 CKD patients KDIGO stage G2 to G4 who participated in our CARE FOR HOMe study were analyzed. ADMA, SDMA & acetylated metabolites were measured by liquid chromatography – tandem mass spectrometry. All patients were followed annually with standardized interviews during a follow up period of 4.6 ± 2.0 years.
Mean plasma ADMA concentration was 0.49 [0.44; 0.55] µmol/l, mean plasma SDMA concentration was 0.72 [0.59; 0.98] µmol/l, mean plasma Ac-ADMA concentration was 1.24 [0.74; 2.16] nmol/l & mean plasma Ac-SDMA concentration was 8.42 [3.60; 19.12] nmol/l. All four metabolites accumulated in patients with more advanced CKD. While Ac-ADMA was more strongly correlated with eGFR than ADMA, Ac-SDMA was less strongly correlated with eGFR than SDMA.
During follow up, 144 patients suffered from a cardiovascular event. In univariate Cox-regression analyses, high plasma levels of all four metabolites were significantly associated with incident cardiovascular events. However, after adjustment for confounders including eGFR & traditional cardiovascular risk factors, only high plasma SDMA remained significantly associated with incident cardiovascular events.
In the future, we need further investigations to analyze the underlying acetylation’s mechanism & we have to clarify the role of SDMA in cardiorenal pathophysiology.