1 Division of Nephrology, Department of Medicine, University Hospital Würzburg, Würzburg, Germany. 2 Comprehensive Heart Failure Centre, University Hospital of Würzburg, Würzburg, Germany. 3 Department of Organ Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway. 4 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria. 5 Department of Epidemiology and Biostatistics, EMGO Institute for Health and Care, Research, VU University Medical Centre, Amsterdam, the Netherlands. 6 Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical, University of Graz, Graz, Austria. 7 Department of Cardiology, Medical University of Graz, Graz, Austria. 8 Specialist Clinic for Rehabilitation Bad Aussee, Bad Aussee, Austria. 9 Division of Nephrology, Department of Medicine, Sykehuset i Vestfold, Tønsberg, Norway. 10 Division of Nephrology, Department of Internal Medicine, Uppsala University Hospital, Uppsala, Sweden. 11 Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK. 12 Department of Medicine V (Nephrology, Hypertensiology, Endocrinology, Rheumatologie) Mannheim Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. 13 Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria. 14 Synlab Academy, Synlab Services, Mannheim, Germany.
Transplantation. 2015 Jul;99(7):1470-6. doi: 10.1097/TP.0000000000000568.
Despite improvements in kidney transplantation, complications, including cardiovascular morbidity and graft loss, contribute to reduced graft and patient survival. The amino acid homoarginine exerts a variety of beneficial effects that may be relevant for cardiovascular and graft outcomes, which is investigated in the present study.
Homoarginine was measured in 829 renal transplant recipients participating in the placebo group of the Assessment of Lescol in Renal Transplantation study. Mean follow-up was 6.7 years. By Cox regression analyses, we determined hazard ratios (HRs) to reach prespecified, adjudicated endpoints according to baseline homoarginine levels: major adverse cardiovascular events (n = 103), cerebrovascular events (n = 53), graft failure or doubling of serum creatinine (n = 140), noncardiovascular mortality (n = 51), and all-cause mortality (n = 107).
Patients mean age was 50 ± 11 years, homoarginine concentration was 1.96 ± 0.76 μmol/L, and 65% were men. Patients in the lowest homoarginine quartile (<1.40 μmol/L) had an adjusted 2.6-fold higher risk of cerebrovascular events compared to those in the highest quartile (>2.34 μmol/L) (HR, 2.56; 95% confidence interval [95% CI], 1.13-5.82). Similarly, the renal endpoint occurred at a significantly increased rate in the lowest homoarginine quartile (HR, 2.34; 95% CI, 1.36-4.02). For noncardiovascular and all-cause mortality, there was also increased risk associated with the lowest levels of homoarginine, with HRs of 4.34 (95% CI, 1.63-10.69) and 2.50 (95% CI, 1.38-4.55), respectively.
Low homoarginine is strongly associated with cerebrovascular events, graft loss and progression of kidney failure and mortality in renal transplant recipients. Whether interventions with homoarginine supplementation improve clinical outcomes requires further evaluation.
尽管肾移植技术有所进步，但包括心血管发病率和移植物丢失在内的并发症仍导致移植物和患者存活率降低。精氨酸同型物具有多种有益作用，可能与心血管和移植物结局相关，本研究对此进行了评估。
在参与莱泽司他汀评估肾移植研究安慰剂组的 829 例肾移植受者中测量精氨酸同型物。平均随访 6.7 年。通过 Cox 回归分析，我们根据基线精氨酸同型物水平确定达到预定终点的风险比（HR）：主要不良心血管事件（n = 103）、脑血管事件（n = 53）、移植物衰竭或血清肌酐加倍（n = 140）、非心血管死亡率（n = 51）和全因死亡率（n = 107）。
患者平均年龄为 50 ± 11 岁，精氨酸同型物浓度为 1.96 ± 0.76 μmol/L，65%为男性。最低精氨酸四分位数（<1.40 μmol/L）的患者发生脑血管事件的调整风险比最高四分位数（>2.34 μmol/L）患者高 2.6 倍（HR，2.56；95%置信区间[95%CI]，1.13-5.82）。同样，最低精氨酸四分位数患者的肾脏终点发生率显著增加（HR，2.34；95%CI，1.36-4.02）。对于非心血管和全因死亡率，最低精氨酸水平也与更高的风险相关，HR 分别为 4.34（95%CI，1.63-10.69）和 2.50（95%CI，1.38-4.55）。
低精氨酸同型物与肾移植受者的脑血管事件、移植物丢失和肾功能衰竭进展以及死亡率密切相关。精氨酸同型物补充干预是否能改善临床结局尚需进一步评估。
