Clinical Study On Relationship Between FGF23, Klotho And Cardiovascular System Of CKD-MBD Patients

Objective:Cardiovascular disease is the leading cause of death and complications in patients with uremia. CKD-MBD is a major contributor to cardiovascular disease. Cardiovascular calcification in end stage renal disease with high incidence occurs early and progresses rapidly. Fibroblast growth factor23(FGF23), Klotho and parathyroid hormone (PTH) are the main regulation factors of calcium and phosphorus metabolism. In this study we investigated the serum calcium and phosphorus levels, cardiovascular injury and drug’s effect of patients who had undergone hemodialysis in Xiangya Hospital. We also explored the risk factors of cardiovascular events in patients with CKD, investigated the therapeutic effect of hemodialysis and parathyroidectomy (PTx) on calcium and phosphorus metabolism and cardiovascular complications in patients with CKD. This study provided a basis for the early diagnosis and treatment for CKD-MBD and cardiovascular complications.Methods:We investigated serum calcium, phosphorus and iPTH levels, echocardiography, abdominal plain X rays and medication regimens of200patients who had undergone hemodialysis in the blood purification center of Xiangya hospital during2102to2013. This study was carried out on a cohort of randomly selected30health controls and76patients of whom30patients were undergoing regular hemodialysis,30patients were CKD3-5stage without any renal replacement therapy and16patients were diagnosed as second hyperparathyroidism (age, race, and gender-matched). We collected serum samples and recorded demographical, clinical and biochemical data, including echocardiography and plain abdominal X rays. Blood samples were centrifuged at2000r/min for20minutes, and the supernatant were stored at-80℃. FGF23and Klotho levels in those serum samples were analyzed by ELISA.Results:1. The mean serum calcium level of our blood purification center was2.10±0.29mmol/L.60%of the patients reached the calcium regulating goal. The mean serum phosphorus level of our blood purification center was2.07±0.71mmol/L.38%of the patient reaching the calcium regulating goal. The treatments of hyperphosphatemia included calcium containing phosphate binders, lanthanun carbonate, sevelamer and parathyroidectomy. Oral calcium containing phosphate remained the mainstay of therapy for patients with hyperphosphatemia (76.47%). Risk factors for cardiovascular events in patients with CKD included interdialytic diastolic blood pressure, serum PTH, Hb, Alb and phosphorus.2. Compared with normal control group, serum FGF23level was markedly elevated in patients with CKD, whereas serum Klotho level was modestly decreased. Heterotopic calcification, left ventricular hypertrophy and left ventricular dilation were much more serious in those patients. Serum FGF23and Klotho were risk factors of cardiac valve calcification in patients with chronic kidney disease (p<0.05). Other risk factors included serum phosphorus, triglyceride, total protein, smoking (p<0.05). Receiver operator characteristic curve(ROC) analysis showed that the area under the curve(AUC) of FGF23was0.699(95%CI:0.578-0.821, p<0.05) and the AUC of Klotho was0.458(95%CI:0.293-0.622, p=0.581). Higher serum FGF23had strong predictive value of development of cardiac valve calcification with an odds ratio(OR) of2.756. In patient underwent hemodialysis OR raise to4.667. Higher serum Klotho had strong predictive value of development of left ventricular hypertrophy with an odds ratio(OR) of0.286, OR=0.286,95%CI(0.084,0.972).Conclusions:1. CKD-MBD was the main complication for maintenance hemodialysis patients。Our datas showed that incidence of CKD-MBD was59.5%2. Cardiovascular functions was inpacted seriously in CKD-MBD patients, especially myocardial hypertrophy and cardiac valve calcification. The incidence of left ventricular hypertrophy was65.33%, and the incidence of cardiac calcification was8%. The cardiovascular system injury incidence was significantly higher in patients receiving hemodialysis than those who were not.3. As serum Klotho level reduced, the risk of cardiovascular calcification in patients with CKD increased1times, while the risk of left ventricular hypertrophy in patients increased2.5times. Klotho was a protective factor of cardiovascular system in patients with CKD-MBD.4. With serum FGF23levels increased, the risk of cardiovascular calcification in patients increased2.8times. Serum FGF23was one risk factor of CKD-MBD patients with cardiovascular injury and also was an excellent predictor of cardiovascular disease caused by CKD-MBD. FGF23might serve as a novel universal biomarker for cardiovascular system injury in patients with CKD-MBD.