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Kidney Week

Abstract: TH-PO466

Methylarginines in CKD

Session Information

Category: Chronic Kidney Disease (Non-Dialysis)

  • 303 CKD: Epidemiology, Outcomes - Cardiovascular

Authors

  • 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
Background

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.

Methods

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.

Results

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.

Conclusion

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.