Symmetric dimethylarginine as predictor of graft loss and all-cause mortality in renal transplant recipients

Transplantation. 2014 Dec 15;98(11):1219-25. doi: 10.1097/TP.0000000000000205.

Abstract

Background: Elevated symmetric dimethylarginine (SDMA) has been shown to predict cardiovascular events and all cause mortality in diverse populations. The potential role of SDMA as a risk marker in renal transplant recipients (RTR) has not been investigated.

Methods: We analyzed SDMA in the placebo arm of the Assessment of Lescol in Renal Transplantation study, a randomized controlled trial of fluvastatin in RTR. Mean follow-up was 5.1 years. Patients were grouped into quartiles based on SDMA levels at study inclusion. Relationships between SDMA and traditional risk factors for graft function and all-cause mortality were analyzed in 925 RTR using univariate and multivariate survival analyses.

Results: In univariate analysis, SDMA was significantly associated with renal graft loss, all-cause death, and major cardiovascular events. After adjustment for established risk factors including estimated glomerular filtration rate, an elevated SDMA-level (4th quartile, >1.38 μmol/L) was associated with renal graft loss; hazard ratio (HR), 5.51; 95% confidence interval (CI), 1.95-15.57; P=0.001, compared to the 1st quartile. Similarly, SDMA in the 4th quartile was independently associated with all-cause mortality (HR, 4.56; 95% CI, 2.15-9.71; P<0.001), and there was a strong borderline significant trend for an association with cardiovascular mortality (HR, 2.86; 95% CI, 0.99-8.21; P=0.051).

Conclusion: In stable RTR, an elevated SDMA level is independently associated with increased risk of all-cause mortality and renal graft loss.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Arginine / analogs & derivatives*
  • Arginine / blood
  • Biomarkers
  • Fatty Acids, Monounsaturated / therapeutic use
  • Female
  • Fluvastatin
  • Follow-Up Studies
  • Graft Rejection / etiology*
  • Humans
  • Indoles / therapeutic use
  • Kidney / immunology
  • Kidney Transplantation*
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Proportional Hazards Models
  • Renal Insufficiency / diagnosis
  • Renal Insufficiency / mortality
  • Renal Insufficiency / surgery*
  • Risk Factors
  • Time Factors
  • Transplant Recipients
  • Treatment Outcome

Substances

  • Biomarkers
  • Fatty Acids, Monounsaturated
  • Indoles
  • symmetric dimethylarginine
  • Fluvastatin
  • Arginine