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

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

Transplantation (2014-07-08)
Hege Pihlstrøm, Geir Mjøen, Dag Olav Dahle, Stefan Pilz, Karsten Midtvedt, Winfried März, Sadollah Abedini, Ingar Holme, Bengt Fellström, Alan Jardine, Hallvard Holdaas
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.

MATERIALS
Product Number
Brand
Product Description

USP
Fluvastatin sodium, United States Pharmacopeia (USP) Reference Standard
Fluvastatin sodium, European Pharmacopoeia (EP) Reference Standard
Supelco
L-Arginine, Pharmaceutical Secondary Standard; Certified Reference Material
Arginine, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Fluvastatin sodium hydrate, ≥98% (HPLC)
Sigma-Aldrich
L-Arginine, 99%, FCC, FG
Sigma-Aldrich
L-Arginine, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
NG,NG′-Dimethyl-L-arginine di(p-hydroxyazobenzene-p′-sulfonate) salt, ≥99% (TLC)
SAFC
L-Arginine
Sigma-Aldrich
L-Arginine, reagent grade, ≥98%
Sigma-Aldrich
L-Arginine, from non-animal source, meets EP, USP testing specifications, suitable for cell culture, 98.5-101.0%
Fluvastatin for system suitability, European Pharmacopoeia (EP) Reference Standard