| Objective：The purpose of this study was to test whether serum Klotho andfibroblast growth factor23(FGF-23) levels, detected by Enzyme-linked ImmunosorbentAssay(ELISA), might be associated with the mineral metabolic disorders and cardiacstructure changes in chronic kidney disease(CKD) patients.Methods: A total of75CKD patients who were admitted in the NephrologyDepartment of the Second Affiliated Hospital of Dalian Medical University from2013July to2014January were enrolled. Exclusion criteria: serious infection, hepatobiliarydiseases, chronic consumptions diseases (such as malignant neoplasm or tuberculosis);acute myocardial infarction, heart failure, acute cerebrovascular disease; primaryparathyroid diseases, parathyroidectomy patients, kidney transplant recipients. Thecontrol group consisted of13cases. With reference to estimated glomerular filtrationrate (eGRF), CKD patients were divided into four groups,12patients with CKD stage2,14patients with CKD stage3,12patients with CKD stage4,37patients with CKDstage5(including21patients with non-dialysis,10patients with hemodialysis and6patients with peritoneal dialysis). With reference to the international recommendationstandards of left ventricular hypertrophy (LVH)(left ventricular mass index (LVMI),Man>135g/m2, Woman>110g/m2), the non-dialysis patients with CKD stages2-5weresubdivided into2groups:14cases with LVH and45cases with non-LVH. Basic clinicalinformation of all the research objects, including gender, age, body mass index andprimary disease and so on, were collected. Hemoglobin, albumin, triglyceride, cholesterol, low density lipoprotein-cholesterol, high density lipoprotein-cholesterol,serum creatinine, serum calcium, serum phosphorus, were assessed by autobiochemistrymachine. Intact parathyroid hormone (iPTH) was detected by immunoradiometric assay.Furthermore, the glomerular filtration rate (eGRF) was calculated, based on MDRDformula, and corrected serum calcium levels and calcium-phosphorus product wereestimated. Serum Klotho and FGF-23levels were tested by ELISA. Left ventricularposterior wall thickness, interventricular septal thickness and left ventricular enddiastolic dimension were all measured with echocardiography, following which theLVMI was calculated. All statistical analyses were performed using SPSS13.0, Pvalues<0.05were considered as statistically significant. Besides, locally weightedscatter plot smoothing (LOESS), functions of Klotho and FGF-23were plotted versuseGFR to illustrate the pattern of the relationship.Result:1. Klotho levels in non-dialysis patients with CKD stages2-5were found to besignificantly lower compared with normal control group(P<0.05); Klotho levels ofpatients with CKD stages4and5were lower than in patients with CKD stages2and3(P <0.01). FGF-23levels in patients with CKD stages3-5were found to be significantlyhigher than in the control ones (P <0.05); FGF-23levels were higher among CKD stage4patients compared with CKD stages2and3patients (P <0.05); CKD stage5patientshad higher Klotho levels than CKD stages2-4patients (P <0.05).The ionized calciumlevels remained unchanged across CKD stages2-5patients (P>0.05).By contrast Serumphosphate show a modest reduction during CKD2-3stages (P>0.05) compared to thecontrol group. Only patients at CKD stage5had serum phosphate, calcium-phosphorusproduct and iPTH levels different from those observed in control group. Klotho levelswere negatively correlated with FGF-23(r=-0.524, P<0.01), serum phosphorus(r=-0.486, P<0.01), calcium phosphorus product (r=-0.494, P<0.01) and iPTH(r=-0.0.466, P<0.01). After adjustment for age, gender and eGFR, Klotho remainedindependently associated with age and eGFR. FGF-23was positively correlated with serum phosphorus(r=0.658, P<0.01), calcium phosphorus product (r=0.638, P<0.01)and iPTH(r=0.603, P<0.01).2. In HD, PD and non-dialysis patients with CKD stages5: compared with the HDgroup and PD group, Klotho levels were significantly increased in non-dialysispatients (P<0.05), while FGF-23levels showed no significant difference (P>0.05). PTHlevel of non-dialysis group was higher than HD (P<0.05), but lower than PD (P>0.05).The level of Klotho in HD group was lower than PD (P>0.05). iPTH level of HD groupwas increased (P<0.05) compared with PD group.3. To illustrate the relationship of Klotho, FGF23, iPTH, phosphorus, calciumversus eGFR with LOESS in non-dialysis patients with CKD stages2-5, a graph wasplotted. Klotho linearly decreased with eGFR. Klotho levels declined by4.79pg/ml(95%CI3.73–5.86pg/ml, P<0.01) as eGFR declined by1ml/min/1.73m2. Afteradjustment for age, we estimated that the mean Klotho change was4.75pg/mL (95%CI3.83–5.66pg/ml, P<0.01) for each1ml/min/1.73m2GFR change. FGF23, iPTH andserum phosphorus showed a baseline at CKD stages2for FGF23, stages2–3for iPTHand phosphorus, and then a dramatic increase at higher respective CKD stages. FGF23started to rise at an eGFR of50mL/min/1.73m2, whereas iPTH rose from the baseline atan eGFR of27mL/min/1.73m2and serum phosphorus rose at an eGFR of26ml/min/1.73m2respectively.4. In non-dialysis patients with CKD, BMI, HGB, LDL-C and FGF-23wereincreased in LVH group (P <0.05) compared with the N-LVH group; FGF-23levelsdeclined (P <0.05). LVMI was negatively correlated with Klotho (P <0.05), andpositively correlated with FGF-23(P <0.05). By means of multivariate analysis withbinary logistic regression, we found Klotho (OR=0.995, P<0.01), FGF-23(OR=1.002,P<0.05) were independent factors for the occurrence of LVH.Conclusions:1. In non-dialysis patients with chronic kidney disease, an increase in FGF-23precedes an increase in serum phosphorus or parathyroid hormone, whereas a decline inKlotho levels precedes an increase in FGF-23. Klotho may be a sensitive marker for the early detection of the mineral metabolic disorder in chronic kidney disease.2. In non-dialysis patients with chronic kidney disease, Klotho and FGF-23may bethe influential factors for the occurrence of LVH, Klotho is a protective factor, whileFGF-23is an independent risk factor. |
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