Department of Nephrology and Rheumatology, Iwate Prefectural Central Hospital, Morioka, Japan.
Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Hospital, Sendai, Japan.
Nephrology (Carlton). 2019 Sep;24(9):943-950. doi: 10.1111/nep.13526. Epub 2019 Apr 29.
Advanced glycation end products and their precursors cause vascular damage through oxidative stress. We investigated the hypothesis that methylglyoxal (MG), 3-deoxyglucosone (3-DG) and pentosidine influence outcomes of chronic kidney disease (CKD) patients.
We conducted a 3 years prospective observational study involving 150 outpatients at CKD stages 3-5. At enrolment, MG, 3-DG and pentosidine plasma concentrations were measured; patients were divided into tertiles according to the concentration of each substance. The primary endpoint was death, a cardiovascular event or end-stage renal disease. Survival analysis was performed using the Cox regression model.
The patients' mean age was 62 ± 12 years, 97 were men, and 20 had diabetic nephropathy. The mean estimated glomerular filtration rate was 25.0 ± 12.1 mL/min per 1.73 m , which negatively correlated with MG but not with 3-DG and pentosidine. Forty-eight patients reached the primary endpoint. Compared with the lowest MG tertile, the hazard ratio for the primary endpoint was 7.57 (95% confidence interval (CI): 1.71-33.54) in the middle tertile and 27.00 (CI: 6.46-112.82) in the highest tertile. When adjusted for characteristics at baseline, the corresponding hazard ratio decreased to 2.09 (CI: 0.37-11.96) and 6.13 (CI: 0.97-38.82), but MG tertile remained an independent risk factor for the primary endpoint. However, 3-DG and pentosidine were not related to the primary outcome.
Methylglyoxal has a close clinical association with CKD. Higher MG concentrations may contribute renal function deterioration in CKD. In CKD patients, MG concentration might be useful when determining the prognosis.
糖基化终产物及其前体通过氧化应激引起血管损伤。我们假设研究甲基乙二醛(MG)、3-脱氧葡萄糖(3-DG)和戊糖素是否会影响慢性肾脏病(CKD)患者的结局。
我们进行了一项为期 3 年的前瞻性观察性研究,共纳入 150 名 CKD 3-5 期的门诊患者。在入组时,测量了 MG、3-DG 和戊糖素的血浆浓度;根据每种物质的浓度将患者分为三分位。主要终点为死亡、心血管事件或终末期肾病。使用 Cox 回归模型进行生存分析。
患者的平均年龄为 62±12 岁,97 名男性,20 名患有糖尿病肾病。平均估计肾小球滤过率为 25.0±12.1mL/min/1.73m2,与 MG 呈负相关,与 3-DG 和戊糖素无关。48 名患者达到主要终点。与 MG 最低三分位相比,中间三分位的主要终点风险比为 7.57(95%置信区间(CI):1.71-33.54),最高三分位为 27.00(CI:6.46-112.82)。在调整基线特征后,相应的风险比分别降至 2.09(CI:0.37-11.96)和 6.13(CI:0.97-38.82),但 MG 三分位仍是主要终点的独立危险因素。然而,3-DG 和戊糖素与主要结局无关。
MG 与 CKD 具有密切的临床关联。较高的 MG 浓度可能导致 CKD 患者肾功能恶化。在 CKD 患者中,MG 浓度在判断预后时可能有用。