| Background:Epidemiological data shows that the incidence of chronic kidney disease(CKD)in the world is as high as 11%,and the hospitalization and mortality are also increasing year by year,which has caused great health and economic burden to patients and countries.Therefore,CKD has become the focus of global public health.Once CKD occurs,it shows irreversible deterioration of renal function and eventually into chronic renal failure and end-stage renal disease(ESRD).Currently,there lacks effective treatment for the progression of CKD.Once patients reached the stage of ESRD,the only way is to receive renal replacement therapy,such as hemodialysis,peritoneal dialysis and kidney transplantation.The incidence and mortality of Cardiovascular disease(CVD)in patients with CKD are significantly higher than the general population,it is demonstrated that the CVD is the main complication and cause of death in patients with CKD.As the renal function further declines,mineral homeostasis becomes disrupted,which also can further aggravate the severity and rate of renal progression.Meanwhile,the deterioration of calcium and phosphorus homeostasis is closely related to the complications of CVD,which in turn leads to vascular calcification and left ventricular hypertrophy,thus increasing the morbidity and mortality of CVD.Moreover,atherosclerosis is common in patients with advanced CKD,which is believed to be associated with poor prognosis of CVD.Traditional risk factors for renal progression,CVD complications and death include hypertension,diabetes,anemia,and malnutrition.However,recent studies have suggested that abnormal mineral bone metabolism,protein energy wasting,FGF23/Klotho axis,etc.are emerging risk factors for renal adverse outcomes.So,finding and controlling these risk factors can help to delay the progression of CKD and prevent the occurrence of long-term complications and death.Klotho was first identified in 1997 as a protein closely related to anti-aging in humans and is mainly expressed in the kidney,heart,brain and parathyroid glands.In physiological conditions,the kidney is the primary organ for maintaining soluble Klotho levels,but Klotho expression is significantly reduced in patients with CKD and ESRD.Numerous studies have found that soluble Klotho may play a role in renal protection against ischemia,hypoxia,inflammation,obstruction and other factors of renal injury,and has become a research hotspot in the fields of kidney,heart and related complications in recent years.Previous researches have confirmed that Klotho has a pleiotropic effect on anti-inflammatory,anti-aging,anti-apoptotic and organ protection.Klotho plays a role in renal protection and ameliorate renal fibrosis by inhibiting the FGF2,the Wnt,TGF-β1 signaling pathway and antagonizing the renin-angiotensin-aldosterone system,as well.Meanwhile,Klotho is also involved in the regulation of calcium and phosphate homeostasis,playing a protective role by inhibiting phosphate-driven vascular calcification,maintaining vascular endothelial function and arterial wall integrity.Showing that Klotho plays a key protective role in the pathogenesis and progression of CKD complicated with CVD.Current studies have also shown that in maintenance hemodialysis patients,low serum Klotho levels are not only associated with CVD and all-cause mortality,but also with adverse renal outcomes and atherosclerosis in patients with CKD and all-cause mortality in elderly community.At present,several large CKD cohort studies have also explored the predictive role of soluble Klotho levels in the progression of CKD and the outcome of CV D events.However,their conclusions on the predictive value of Klotho in the progression of CKD and the occurrence of CVD events remains a controversy.Therefore,we selected advanced non-diabetic CKD patients to determine whether serum Klotho level can b e used as a predictor of renal progression,CVD events and all-cause death in CKD patients.Contents and methods:Firstly,to understand the relationship between serum Klotho level and the progression of CKD,and then,to explore the relationship between s erum Klotho level and CVD events and overall mortality in patients with CKD.We enrolled participants with CKD from stages 2 to 5 which diagnosed in the department of nephrology of XX Hospital from January 2012 to December 2015 who did not receive dialysis treatment and were not caused by diabetes.Serum Klotho protein levels were detected by ELISA Kit,and CKD patients were divided into four groups according to their quartiles.Kaplan-Meier survival analysis was used to compare the CKD progression-free survival,CVD events progression-free survival,and overall survival of the four groups of patients.Cox regression analysis was used to analyze the risk factors related to the outcome events,and multiple models were used for adjusted analysis.The main finding:A total of 336 patients were included in this study,with a mean age of 48.10 years,49.4% of whom were male,and a median follow-up time of 3.52 years(a quartile interval of 3.34-3.76 years).There were 187(55.65%)patients who reached renal endpoint events,76(22.62%)developed cardiovascular disease events,and 32 patients(9.52%)died during the follow-up.Results showed that serum Klotho level was positively correlated with eGFR level.patients were divided into four groups according to the level of serum Klotho(Quartile 1,2,3 and 4).Kaplan-Meier survival analysis showed that compared with the patients with the highest quartile(Q4,as the reference group),the patients in Q1 took less time to reach the renal endpoint.Using Cox regression analysis,after adjusting for the multivariate model,the risk of renal endpoint in the Q2 remained 1.98 times higher than in the Q4.Then,Kaplan-Meier survival analysis was used to explore the relation between serum Klotho and the CVD event and all-cause mortality,results showed that the lower serum Klotho level is associated with a greater risk of CVD events and all-cause mortality.In addition,In the multivariate-adjusted model,Cox proportional analysis indicated that the low serum Klotho level was still an independent predictor of death in CKD patients.Conclusion:In summary,in non-diabetic patients with predialysis CKD,serum Klotho level was significant associated with renal progression,cardiovascular events and all-cause mortality.Low serum Klotho levels are independent risk factors for renal progression,cardiovascular disease and all-cause mortality. |
