Symmetric Dimethylarginine as Predictor of Graft Loss and All-Cause Mortality in Renal Transplant Recipients.

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, 91.38 Kmol/L) was associated with renal graft loss; hazard ratio (HR), 5.51; 95% confidence interval (CI), 1.95Y15.57; 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, 2.15Y9.71; PG0.001), and there was a strong borderline significant trend for an association with cardiovascular mortality (HR, 2.86; 95% CI, 0.99Y8.21; 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.

Symmetric dimethylarginine is a stronger predictor of mortality risk than asymmetric dimethylarginine among older people with kidney disease

“…A relationship between SDMA and mortality independent of GFR has also been reported in renal transplant recipients. 36 Recent evidence suggests potential direct pathophysiological links between SDMA and cardiovascular disease through indirect inhibition of nitric oxide synthesis. 15 The proposed mechanism is through competition with L-arginine for transport, thereby limiting the availability of L-arginine to nitric oxide synthase.…”

Asymmetric and symmetric dimethylarginine as risk markers for total mortality and cardiovascular outcomes: A systematic review and meta-analysis of prospective studies

“…[12] With respect to SDMA, initial studies did not find an association with adverse outcomes, [7,13,14] but some more recent studies reported positive associations with all-cause mortality or CVD. [11,15,16] Overall, prior studies on ADMA/SDMA and CVD or all-cause mortality were derived from many different study populations (general population, [15,17,18] patients with CVD, [9,11,19,20] renal diseases, [7,13,[21][22][23][24] diabetes, [25,26] or critically ill patients from intensive care unit,[27-29] respectively), differed in their methodological approaches (e.g. using types of samples (plasma vs. serum) or methods to determine the biomarker levels (HPLC vs. tandem mass spectroscopy vs. ELISA), or considered different confounders in their analysis.…”