The Association Between Human Epididymal Protein 4 And Heart Failure In Patients With Chronic Kidney Disease

Background: Cardiovascular disease(CVD)has become the main cause of death in chronic kidney disease(CKD).Human epididymal protein 4(HE4)is a tumor marker of female genital tract.Recently,studies have shown that HE4 is involved in the formation of renal fibrosis.Renal fibrosis is an important pathogenesis of CKD and eventually leads to renal insufficiency.objectives: 1.Evaluation of the correlation between serum HE4 and renal function in patients with CKD;2.Assessment of the association between HE4 and heart failure(HF)in patients with CKD.Methods: We collected 383 CKD patients who had been tested for serum HE4 in People’s Hospital of Wuhan University from January 2015 to December 2017.At the same time,we also collected 451 healthy population(control group)who underwent serum HE4 examination in these three years.In the CKD patients,49 have undergone renal biopsy and HF occurred in 48 patients.We evaluated the difference of serum HE4 between CKD patients and control patients,analyzed the correlation between serum HE4 and renal function in CKD patients and the relationship between serum HE4 and renal pathological changes in CKD patients and further analyzed the correlation between serum HE4 level and HF in CKD patients.Results: 1.Serum HE4 levels increased gradually from control group to CKD5 with the increase of renal function classification(P <0.01).2.In CKD patients,univariate correlation analysis showed that HE4 levels were positively correlated with serum creatinine(SCr),urea nitrogen(BUN),uric acid(UA),phosphorus(P)and systolic blood pressure(SBP)and were weakly negatively correlated with serum albumin(ALB),serum calcium(Ca),hemoglobin(Hb)and systolic blood pressure(DBP),But HE4 had no correlation with age and diastolic blood pressure(DBP).Multivariate linear regression analysis showed that serum HE4 level was positively correlated with eGFR after correction of other confounding factors.In this correction model,these factors could explain 87.5% of the difference in eGFR levels.3.In 49 patients with CKD who underwent renal biopsy,serum HE4 level was positively correlated with IF/TA score(P <0.01)and glomerular injury(GL)score(P<0.01).4.Spearman’s test analysis showed that HE4 was positively correlated withNYHA in 48 patients with HF(r=0.31,P =0.032)and serum HE4 level was positively correlated with NT-proBNP(r=0.651,P<0.001).Multivariate linear correlation analysis showed that HE4 was independently and positively correlated with NT-proBNP(r = 0.202,P <0.001).The results showed that serum HE4 level was closely related to the severity of heart failure.5.Univariate logistic regression analysis showed that serum HE4(OR = 2.453,95% CI 1.633-3.685,P <0.001)was a risk factor for heart failure in patients with CKD.Multivariate logistic regression showed that serum HE4(OR = 2.120,95% CI1.034-4.344,P <0.001)had a significant independent correlation with heart failure in patients with CKD.The results showed that serum HE4 may be an independent risk factor for heart failure during the progression of CKD.6.ROC curve analysis showed that the sensitivity,specificity and AUC value of serum HE4 were 74.2%,76.8% and 0.729(95% CI 0.640-0.819)for the diagnosis of heart failure in CKD patients when the optimal threshold value was 639.6 pmol/L.Conclusions: Serum HE4 level increases significantly with the decrease of renal function in CKD patients.Serum HE4 has a good value in identifying the occurrence of heart failure in CKD patients.