Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea.
Am J Kidney Dis. 2013 Jun;61(6):899-909. doi: 10.1053/j.ajkd.2013.01.024. Epub 2013 Mar 27.
α-Klotho is reported to have protective effects against kidney injury, and its renal expression is decreased in many experimental models of kidney disease. However, circulating α-klotho levels in human chronic kidney disease (CKD) and the relationship to progression are unknown.
Post hoc analysis of a prospective cohort study.
SETTING & PARTICIPANTS: 243 of 301 participants from a CKD cohort at our institution between January 2006 and December 2011 were eligible for the study.
Baseline α-klotho levels.
Primary outcome was the composite of doubling of baseline serum creatinine concentration, end-stage renal disease, or death. End-stage renal disease was defined as onset of treatment by renal replacement therapy.
Serum α-klotho and fibroblast growth factor 23 (FGF-23) were measured using enzyme-linked immunosorbent assay.
Lower serum α-klotho levels were associated with more severe CKD stage in the cross-sectional analysis of the baseline data (P for trend < 0.001). In the adjusted multivariable linear regression model, log(α-klotho) was associated independently with estimated glomerular filtration rate (β = 0.154; P = 0.001). Cox regression analysis showed that baseline α-klotho level independently predicted the composite outcome after adjustment for age, diabetes, blood pressure, estimated glomerular filtration rate, proteinuria, parathyroid hormone level, and FGF-23 level (HR per 10-pg/mL increase, 0.96; 95% CI, 0.94-0.98; P < 0.001). When patients were categorized into 2 groups according to baseline median α-klotho value, 43 (35.2%) patients with α-klotho levels ≤396.3 pg/mL reached the primary composite outcome compared with 19 (15.7%) with α-klotho levels >396.3 pg/mL (HR, 2.03; 95% CI, 1.07-3.85; P = 0.03).
Uncontrolled dietary phosphorus intake and use of frozen samples.
This observational study showed that low circulating α-klotho levels were associated with adverse kidney disease outcome, suggesting that α-klotho is a novel biomarker for CKD progression. More data from larger prospective longitudinal studies are required to validate our findings.
α-klotho 据报道对肾损伤具有保护作用，其在许多肾脏疾病的实验模型中的肾表达降低。然而，在人类慢性肾脏病（CKD）中循环α-klotho 水平及其与进展的关系尚不清楚。
本研究为一项前瞻性队列研究的事后分析。
2006 年 1 月至 2011 年 12 月期间，我们机构的 CKD 队列中的 301 名参与者中有 243 名符合本研究的条件。
基线 α-klotho 水平。
主要结局是基线血清肌酐浓度翻倍、终末期肾脏疾病或死亡的复合结局。终末期肾脏疾病定义为开始进行肾脏替代治疗。
使用酶联免疫吸附试验测量血清 α-klotho 和成纤维细胞生长因子 23（FGF-23）。
在基线数据的横断面分析中，较低的血清α-klotho 水平与更严重的 CKD 分期相关（趋势 P<0.001）。在调整后的多变量线性回归模型中，log（α-klotho）与估算的肾小球滤过率独立相关（β=0.154；P=0.001）。Cox 回归分析表明，在调整年龄、糖尿病、血压、估算肾小球滤过率、蛋白尿、甲状旁腺激素水平和 FGF-23 水平后，基线 α-klotho 水平独立预测复合结局（每增加 10 pg/ml 的 HR，0.96；95%CI，0.94-0.98；P<0.001）。当根据基线中位数α-klotho 值将患者分为 2 组时，43 名（35.2%）α-klotho 水平≤396.3 pg/ml 的患者达到主要复合结局，而α-klotho 水平>396.3 pg/ml 的患者为 19 名（15.7%）（HR，2.03；95%CI，1.07-3.85；P=0.03）。
未控制的膳食磷摄入和使用冷冻样本。
本观察性研究表明，低循环α-klotho 水平与不良肾脏疾病结局相关，提示α-klotho 是 CKD 进展的新型生物标志物。需要更大规模的前瞻性纵向研究来验证我们的发现。
