BackgroundPrevious clinical studies found inconsistent relationship between circulating sclerostin levels and treatment outcome in patients undergoing maintenance hemodialysis (MHD). Therefore, this study aimed to assess the associations of sclerostin with carotid artery atherosclerosis and all-cause mortality in Chinese patients undergoing MHD.MethodsThis retrospective study assessed 84 patients undergoing MHD at the Nephrology Department of Beijing Hospital from January to April 2012, with a median follow-up of 61.2 months (range: 11.5 to 63 months). Carotid artery intima-media thicknesses (CIMTs) and atherosclerotic plaques were measured by B-mode Doppler ultrasound at baseline. Blood samples were collected for measuring serum sclerostin and soluble klotho (s-klotho) levels. The associations of sclerostin levels with carotid artery atherosclerosis was evaluated by correlation methods. Predictive factors of mortality were assessed by multivariate COX regression.ResultsBaseline serum sclerostin averaged 162.01 pmol/L, with an interquartile range of 121.69 to 225.22 pmol/L, while CIMT values were 1.35 ± 0.39 mm. Carotid artery atherosclerotic plaques were detected in 68 subjects (81%). Subjects with sclerostin levels above the median value had higher CIMT (p = 0.038) and higher prevalence of atherosclerotic plaque (p = 0.025). During follow-up, 27 patients died; Kaplan-Meier curves indicated that subjects with high sclerostin levels (above the median value at baseline) had shorter survival (log rank p = 0.011). In multivariate COX regression analysis, serum sclerostin (HR, 1.095; 95% confidence interval [CI] 1.022–1.174, p = 0.010) and albumin (HR, 0.742; 95%CI 0.612–0.900, p = 0.002) levels were independent predictors of all-cause mortality.ConclusionsSclerostin is positively associated with CIMT. In addition, patients with low baseline serum sclerostin undergoing MHD show better survival.Electronic supplementary materialThe online version of this article (10.1186/s12882-018-1046-7) contains supplementary material, which is available to authorized users.
Background. Diabetic nephropathy (DN) is a major cause of chronic kidney disease (CKD). There are no effective treatments to prevent or reverse the progression of DN. A preliminary study showed that Tripterygium glycosides from Tripterygium wilfordii Hook F (TwHF) with valsartan decrease proteinuria in patients with DN. Objectives. The objective of the present study is to investigate the efficacy and safety of Tripterygium glycosides from TwHF, a traditional Chinese medicine, for the treatment of DN. Methods and Analysis. This is a prospective, single-center randomized controlled trial. Seventy participants diagnosed with DN were recruited and randomized 1 : 1 to two groups: (1) angiotensin receptor blocker (ARB) combined with TwHF and (2) ARB-only. The treatment period is 48 weeks. The primary endpoint is 24 h proteinuria decreased level (reduction of 30% vs. baseline) after 48 weeks of treatment. The secondary endpoints are (1) all-cause and cardiovascular-related mortality, (2) development of ESRD (serum creatinine>530.4 μmol/L or estimated glomerular filtration rate eGFR<15 mL/min/1.73 m2), (3) the need for renal replacement therapy, and (4) increased serum creatinine (2-fold higher than the baseline value or ≥442 μmol/L, with confirmation of the initial results after 4 weeks). A health economics analysis will be carried out. Discussion. A meta-analysis of RCTs carried out in patients with stage 4 (Mogensen classification) diabetic CKD showed that TwHF combined with an ARB was more effective than an ARB alone when considering 24 h proteinuria and serum albumin, but with an increase in adverse event (AE) frequency of 8%. This is a prospective clinical trial that may provide information on a safe and effective novel method for the treatment of DN, especially for patients with macroproteinuria. Ethics and Dissemination. The protocol is approved by the ethics committee of Beijing Hospital (2016BJYYEC-059-02). The results will be disseminated through peer-reviewed publications and international conferences. This trial is registered with ChiCTR-IOR-17010623.
Purpose Sclerostin is an antagonist of the Wnt/β-catenin pathway. We previously reported that sclerostin is closely related to carotid artery atherosclerosis and long-term outcome in hemodialysis patients. The present study investigated the association between sclerostin, renal function, and carotid artery atherosclerosis in non-dialysis patients with stage 3-5 chronic kidney disease (CKD 3-5ND). Methods A total of 140 patients with CKD 3-5ND were enrolled in this cross-sectional study. The Chronic Kidney Disease Epidemiology Collaboration equation was used to calculate estimated glomerular filtration rate (eGFR). Atherosclerotic plaques in the carotid artery were detected by B-mode Doppler ultrasound. Blood samples were collected to assess serum sclerostin levels. Unconditional logistic regression analysis was used to identify risk factors for carotid atherosclerotic plaques. Results The median eGFR was 24.9 ml/min/1.73 m 2 (interquartile range [IQR] 10.0-40.3 ml/min/1.73 m 2) and median serum sclerostin level was 46.76 pmol/l (IQR 30.18-67.56 pmol/l). Carotid atherosclerotic plaques were detected in 104 subjects (74.3%). There was a negative association between sclerostin level and eGFR (r = − 0.214, p = 0.011). Unconditional logistic regression analysis revealed that sclerostin level was an independent risk factor for the occurrence of carotid plaques, with an odds ratio (95% confidence interval) of 1.026 (1.003, 1.051). Conclusion Serum sclerostin increases with declining renal function in patients with CKD 3-5ND. Sclerostin is an independent risk factor for carotid atherosclerosis.
We investigated how age affected renal function in healthy subjects in Beijing and compared different estimated glomerular filtration rate (eGFR) equations. Kidney function was evaluated by five equations: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI); Modification of Diet in Renal Disease Study (MDRD); the Chinese version of the MDRD (MDRDc); Full Age Spectrum (FAS); and Berlin Initiative Study (BIS). A total of 46,708 subjects were enrolled and followed-up for 3 years. All showed an increase in sCr and a reduction in eGFR with increasing age. Over the 3 years, the eGFR and serum creatinine (sCr) remained unchanged in most subjects. Different equations showed good consistency; the intraclass correlation coefficients (ICC) was 0.849 for males, and 0.817 for females. The CKD-EPI equation yielded higher GFR values than the other equations (according to sCr levels). For subjects aged over 70 years, the BIS equation produced the lowest eGFR values. In summary, we observed that the renal function of individuals was relatively stable with increasing age, although different eGFR equations yielded data that varied across different populations of subjects and sCr levels.
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