Pihlstrøm Hege, Mjøen Geir, Dahle Dag Olav, Pilz Stefan, Midtvedt Karsten, März Winfried, Abedini Sadollah, Holme Ingar, Fellström Bengt, Jardine Alan, Holdaas Hallvard
1 Division of Nephrology, Department of Organ Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway. 2 Division of Nephrology, Department of Medicine, Oslo University Hospital Ullevål, Oslo, Norway. 3 Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Graz, Austria. 4 Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Centre, Amsterdam, the Netherlands. 5 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria. 6 Synlab Center of Laboratory Diagnostics, Heidelberg, Germany. 7 Medical Faculty Mannheim, Mannheim Institute of Public Health, Social and Preventive Medicine, University of Heidelberg, Mannheim, Germany. 8 Department of Medicine, Division of Nephrology, Vestfold Hospital, Tønsberg, Norway. 9 Department of Preventive Medicine and Unit of Biostatistics and Epidemiology, Oslo University Hospital Ullevål, Oslo, Norway. 10 Division of Nephrology, Department of Internal Medicine, Uppsala University Hospital, Uppsala, Sweden. 11 British Heart Foundation, Glasgow Cardiovascular Research Centre, Glasgow, Scotland, United Kingdom. 12 Address correspondence to: Hege Pihlstrøm, M.D., Department of Organ Transplantation, Division of Nephrology, Oslo University Hospital, Rikshospitalet, P.B. 4950 Nydalen, 0424 Oslo, Norway.
Transplantation. 2014 Dec 15;98(11):1219-25. doi: 10.1097/TP.0000000000000205.
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.
对称二甲基精氨酸（SDMA）水平升高已被证明可预测不同人群的心血管事件和全因死亡率。尚未研究SDMA作为肾移植受者（RTR）风险标志物的潜在作用。
我们在肾移植中瑞舒伐他汀评估研究的安慰剂组中分析了SDMA，这是一项在RTR中进行的氟伐他汀随机对照试验。平均随访时间为5.1年。根据研究纳入时的SDMA水平将患者分为四分位数组。使用单变量和多变量生存分析，在925名RTR中分析了SDMA与移植肾功能和全因死亡率的传统风险因素之间的关系。
在单变量分析中，SDMA与肾移植丢失、全因死亡和主要心血管事件显著相关。在对包括估计肾小球滤过率在内的既定风险因素进行调整后，SDMA水平升高（第四四分位数，>1.38μmol/L）与肾移植丢失相关；风险比（HR）为5.51；95%置信区间（CI）为1.95 - 15.57；P = 0.001，与第一四分位数相比。同样，第四四分位数的SDMA与全因死亡率独立相关（HR，4.56；95%CI，2.15 - 9.71；P < 0.001），并且与心血管死亡率的关联有很强的临界显著趋势（HR，2.86；95%CI，0.99 - 8.21；P = 0.051）。
在稳定的RTR中，SDMA水平升高与全因死亡率和肾移植丢失风险增加独立相关。
