Maltese Giuseppe, Fountoulakis Nikolaos, Siow Richard C, Gnudi Luigi, Karalliedde Janaka
Unit for Metabolic Medicine, Cardiovascular Division, Faculty of Life Sciences and Medicine, King's College London, 150 Stamford Street, London, SE1 9NH, UK.
Diabetologia. 2017 May;60(5):911-914. doi: 10.1007/s00125-017-4219-1. Epub 2017 Feb 13.
AIMS/HYPOTHESIS: Patients with type 1 diabetes and microalbuminuria are at high risk of cardiovascular disease (CVD) and end-stage renal disease. Soluble Klotho is an anti-ageing circulating hormone involved in phosphate metabolism and vascular homeostasis through protective effects on the endothelium and antioxidant actions. The role of soluble Klotho in patients with type 1 diabetes and microalbuminuria is unknown.
In a cross-sectional single-centre study we evaluated the levels of circulating serum soluble Klotho in 33 participants with type 1 diabetes and a history of microalbuminuria (receiving renin-angiotensin system [RAS] inhibitors) and 45 participants with type 1 diabetes without a history of microalbuminuria (not receiving RAS or other antihypertensive drugs). All participants had an eGFR >45 ml/min, duration of diabetes >20 years and no history of CVD. Serum soluble Klotho levels were measured by a validated immunoassay.
Participants with microalbuminuria had significantly lower levels of serum Klotho compared with those without microalbuminuria (median [interquartile range], 659.3 [525.3, 827.6] vs 787.7 [629.5, 1007]; p = 0.023). This difference persisted after adjustment for variables including age and eGFR. In a subgroup of 30 individuals with and without microalbuminuria, other markers of phosphate balance were not significantly different.
CONCLUSIONS/INTERPRETATION: In individuals with type 1 diabetes, microalbuminuria is associated with soluble Klotho deficiency. Further studies are required to determine whether soluble Klotho is causally related to the development of cardio-renal disease in type 1 diabetes.
目的/假设：1型糖尿病合并微量白蛋白尿的患者患心血管疾病（CVD）和终末期肾病的风险很高。可溶性α-klotho是一种抗衰老循环激素，通过对内皮的保护作用和抗氧化作用参与磷代谢和血管稳态。可溶性α-klotho在1型糖尿病合并微量白蛋白尿患者中的作用尚不清楚。
在一项横断面单中心研究中，我们评估了33例有微量白蛋白尿病史（接受肾素-血管紧张素系统[RAS]抑制剂治疗）的1型糖尿病患者和45例无微量白蛋白尿病史（未接受RAS或其他抗高血压药物治疗）的1型糖尿病患者的循环血清可溶性α-klotho水平。所有参与者的估算肾小球滤过率（eGFR）>45 ml/min，糖尿病病程>20年，且无CVD病史。血清可溶性α-klotho水平通过经过验证的免疫测定法测量。
与无微量白蛋白尿的参与者相比，有微量白蛋白尿的参与者血清α-klotho水平显著降低（中位数[四分位间距]，659.3[525.3，827.6]对787.7[629.5，1007]；p = 0.023）。在对包括年龄和eGFR在内的变量进行调整后，这种差异仍然存在。在30例有和无微量白蛋白尿的个体亚组中，磷平衡的其他标志物无显著差异。
结论/解读：在1型糖尿病患者中，微量白蛋白尿与可溶性α-klotho缺乏有关。需要进一步研究以确定可溶性α-klotho是否与1型糖尿病中心肾疾病的发生存在因果关系。
