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

Hege Pihlstrøm, Geir Mjøen, Dag Olav Dahle, Stefan Pilz, Karsten Midtvedt, Winfried März, Sadollah Abedini, Ingar Holme, Bengt Fellström, Alan Jardine, Hallvard Holdaas

Index: Transplantation 98(11) , 1219-25, (2014)

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Abstract

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