血清Klotho水平對慢性腎臟病患者腎功能進展的預測價值*

李莎莎，葉建明，董曉紅，郁麗霞，孫強，劉其鋒

(昆山市第一人民醫院，a.臨床實驗研究中心，b.腎臟內科，江蘇昆山 215300)

·臨床實驗研究·

血清Klotho水平對慢性腎臟病患者腎功能進展的預測價值*

李莎莎a，葉建明b，董曉紅b，郁麗霞b，孫強b，劉其鋒b

(昆山市第一人民醫院，a.臨床實驗研究中心，b.腎臟內科，江蘇昆山 215300)

目的觀察血清Klotho水平與慢性腎臟病(CKD)患者腎功能進展的關系，探討血清Klotho水平預測CKD患者腎功能進展的可行性。方法收集昆山市第一人民醫院非透析的CKD 3～5期患者81例，健康志愿者30例，隨訪12個月。用ELISA法檢測血清Klotho、成纖維細胞生長因子23(FGF23)水平，并檢測其他相關指標；隨訪前后用MDRD和GC公式分別計算CKD患者的GFR值；隨訪結束時根據GFR下降幅度分為腎功能穩定組及惡化組，分析血清Klotho水平與腎功能不全、腎功能進展的關系。結果隨訪時間(9.5±2.9)個月。CKD患者GFR由隨訪前(24.8±12.4)mL/min，降至隨訪后(18.7±12.1)mL/min，差異有統計學意義(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，差異有統計學意義(P<0.01)；其中，腎功能惡化組較腎功能穩定組降低明顯(P<0.01)。血清Klotho水平較高的患者中15例發生腎功能惡化，而血清Klotho較低的患者中26例發生腎功能惡化，差異有統計學意義(63.4% vs 36.5%，P=0.02)。Kaplan-Meier分析顯示，低Klotho水平患者發生不良腎臟預后的風險高于高Klotho水平患者(P=0.013)。結論CKD患者血清Klotho水平隨腎功能進展下降；血清Klotho水平降低的CKD患者發生腎功能惡化的風險增加，低Klotho水平有望成為CKD患者腎功能進展的預測指標。

Klotho；慢性腎臟??；腎功能損害；腎功能進展

Abstract:ObjectiveTo 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.MethodsEighty-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.ResultsThe 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<0.01), 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). Kaplan-Meier analysis revealed the high risk of adverse kidney outcomes arose in the CKD patients with lower Klotho level (P=0.013).ConclusionKlotho 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.

Keywords: Klotho; chronic kidney disease; renal dysfunction; renal function deterioration

Klotho基因是1997年發現的“抗衰老”基因，因腎臟是其主要表達器官，故腎臟疾病會影響Klotho表達水平[1]。有觀點認為，慢性腎臟病(chronic kidney disease，CKD)患者血清Klotho水平降低，不僅一定程度上反映CKD患者的腎功能損害程度，也有助于預測CKD患者的腎功能進展情況；但也有觀點認為，兩者之間并無相關性。本研究擬通過前瞻性觀察，連續監測81例非透析的CKD 3～5期患者血清Klotho水平，同時監測隨訪前后腎功能及其他指標的變化，了解血清Klotho水平變化與CKD患者腎功能進展的關系，為Klotho用于CKD患者的病情評估提供臨床依據。

1 對象與方法

1.1研究對象 收集2014年1月至2015年10月在我院腎臟內科隨訪的CKD患者130例， CKD分期診斷標準：CKD 1期，腎小球濾過率(GFR)≥90 mL/min；……