ABSTRACT
Objective· To explore the relationship of fibroblast growth factor-23 (FGF-23) and soluble klotho (sKL) with cardiac valve calcification in patients with continuous ambulatory peritoneal dialysis (CAPD).Methods· 147 CAPD patients from the dialysis center of the First Affiliated Hospital of Soochow University were enrolled.The concentrations of FGF-23 and sKL were measured by enzyme-linked immunosorbent assays (ELISA).Echocardiography was applied to evaluate cardiac valve calcification.The patients were divided into normal cardiac valve group (group A) and cardiac valve calcification group (group B).SPSS 23.0 software was used for data analysis.Results· The incidence of cardiac valve calcification in CAPD patients was 54.42％.The risk of cardiac valve calcification showed positive correlation with age,dialysis age,serum creatinine,corrected calcium,serum phosphorus,serum alkaline phosphatase,parathyroid hormone,and the level of FGF-23 (P=0.045,P=0.022,P=0.006,P=0.024,P=0.000,P=0.017,P=0.022,P=0.000),and negative correlation with urea clearance index,the level of sKL and residual renal function (P=0.045,P=0.000,P=0.011).Multivariate Logistic regression analysis showed that the increase of FGF-23 (OR=5.007,95％ CI 1.446-17.339,P=0.011) and serum phosphorus (OR=7.433,95％ CI 1.558-35.470,P=0.012) were two independent risk factors for cardiac valve calcification in CAPD patients,and the decrease of sKL (OR=0.310,95％ CI 0.108-0.891,P=0.030) was another independent risk factor as well.Receiver operator characteristic curves (ROC) indicated that to predict cardiac valve calcification in patients with CAPD,the optimal cut off points of FGF-23 and sKL were 2 172.64 pg/mL (sensitivity was 91.3％,specificity was 91％) and 231.88 pg/mL (sensitivity was 88.8％,specificity was 92.5％),respectively.Conclusion· The high level of FGF-23 and low level of sKL are two independent risk factors for cardiac valve calcification in CAPD patients.FGF-23 and sKL can be used to diagnose cardiac valve calcification in CAPD patients.
ABSTRACT
Objective·To screen NPHS2 mutations in adult focal segmental glomerulosclerosis(FSGS)patients based on a large Chinese FSGS cohort. Methods · All patients were biopsy determined FSGS by the Department of Nephrology at Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine. FSGS secondary to systemic disease and other hereditary kidney disease were excluded. After extraction of genomic DNA of peripheral blood,NPHS2 was screened by directly sequencing the exon/intron junction or high-throughput sequencing,including whole exon sequencing and Panel sequencing, and then verified by Sanger sequencing. One hundred healthy controls were enrolled to validate candidate mutations. Results · Two hundred and four FSGS patients were enrolled,including 52 familial(25.5%) and 152 sporadic patients(74.5%),of which steroid-resistant FSGS patients accounted for 30.3%(46/152).By sequencing NPHS2 in all patients of the cohort(Sanger sequencing in 61 patients and high-throughput sequencing in 143 patients), 2 novel conserved mutations were identified, one homozygous mutation in sporadic steroid-resistant FSGS, p.N199I and one heterozygous mutation in familial FSGS, p.L321fx346. Both of them were not detected in 100 healthy controls. These two variants were predicted to be damaging by Polyphen,SIFT and Mutation Taster.Totally,the mutation rate of NPHS2 in the FSGS cohort was 1%. Conclusion·Since the overall frequency of NPHS2 mutations is considerably low in Chinese adult-onset FSGS,NPHS2 is not the main disease-causing gene of this group of people.