血清Klotho水平对慢性肾脏病患者肾功能进展的预测价值

摘要

目的 观察血清Klotho水平与慢性肾脏病(CKD)患者肾功能进展的关系,探讨血清Klotho水平预测CKD患者肾功能进展的可行性.方法 收集昆山市第一人民医院非透析的CKD3～5期患者81例,健康志愿者30例,随访12个月.用ELISA法检测血清Klotho、成纤维细胞生长因子23(FGF23)水平,并检测其他相关指标;随访前后用MDRD和GC公式分别计算CKD患者的GFR值;随访结束时根据GFR下降幅度分为肾功能稳定组及恶化组,分析血清Klotho水平与肾功能不全、肾功能进展的关系.结果 随访时间(9.5±2.9)个月.CKD患者GFR由随访前(24.8±12.4) mL/min,降至随访后(18.7±12.1)mL/min,差异有统计学意义(P＜0.01).血清Klotho水平由2.53(1.41,3.67) ng/mL降至1.63(1.07,3.19) ng/mL,差异有统计学意义(P＜0.01);其中,肾功能恶化组较肾功能稳定组降低明显(P＜0.01).血清Klotho水平较高的患者中15例发生肾功能恶化,而血清Klotho较低的患者中26例发生肾功能恶化,差异有统计学意义(63.4％vs 36.5％,P=0.02).Kaplan-Meier分析显示,低Klotho水平患者发生不良肾脏预后的风险高于高Klotho水平患者(P =0.013).结论 CKD患者血清Klotho水平随肾功能进展下降;血清Klotho水平降低的CKD患者发生肾功能恶化的风险增加,低Klotho水平有望成为CKD患者肾功能进展的预测指标.%Objective To observe the relationship between serum Klotho levels and the progression of renal function in patients with chronic kidney disease (CKD)and investigate further the feasibility of serum Klotho levels for predicting the progression of renal function in CKD patients.Methods Eighty-one non-dialysis patients with CKD 3 to 5 stages and 30 healthy volunteers in the First People's Hospital of Kunshan were enrolled for a 12 months of follow-up.The levels of Klotho and fibroblast growth factor 23 (FGF23) in serum were detected by ELISA at the beginning and the end of the follow-up.The other related indicators were also tested simultaneously.GFR values were calculated by MDRD and GC formulas.According to the decreasing range of GFR,the CKD patients were subdivided into two groups:deterioration group and stability group for renal function,and the relationships between Klotho levels and progression of kidney function were evaluated.Results The patients were followed up for an average of (9.5 + 2.9) months.GFR in CKD patients decreased from (24.8 ± 12.4) mL/min to (18.7 ± 12.1) mL/min (P ＜ 0.0 1),and serum Klotho level decreased from 2.53 (1.41,3.67)ng/mL to 1.63 (1.07,3.19)ng/mL (P ＜0.01)with more pronounced trend in the patients with renal function deterioration than the patients in stability group (P ＜0.01).Fifteen patients with high Klotho level suffered from adverse kidney outcomes while 26 ones with lower Klotho level suffered from deterioration of renal function (63.4％ vs 36.5％,P =0.02).KaplanMeier analysis revealed the high risk of adverse kidney outcomes arose in the CKD patients with lower Klotho level (P =0.013).Conclusion Klotho level in CKD patients may significantly decrease and should be more apparent with renal function progresses.Lower Klotho level in serum may be associated with high risk of adverse kidney outcomes and become a promising marker to predict CKD progression.