Protocol for thiamine and folic acid in the treatment of cognitive impairment in maintenance haemodialysis patients: a prospective, randomised, placebo-controlled, double-blind, multicentre study.

INTRODUCTION: Cognitive impairment (CI) is the common complications in maintenance haemodialysis (MHD) patients. Recently, the pathogenesis of CI has been discussed and oxidative stress is one of the main mechanisms in these patients. Thiamine and folic acid, which play an important role in relieving the production of reactive oxygen species, reducing homocysteine levels, improving oxidative stress in the nervous system. In pilot study, cognitive function was significantly improved in the group with thiamine and folic supplementation. Based on this result, we hypothesise that thiamine combined with folic acid supplementation may improve cognitive function in patients with MHD. METHODS AND ANALYSIS: In this prospective, randomised, placebo-controlled, double-blind, multicentre study, we will enrol patients undergoing haemodialysis who has the Montreal Cognitive Assessment score lower than 26 to treatment group (thiamine 90 mg/day combined with folic acid 30 mg/day) or control group (thiamine placebo 90 mg/day combined with folic acid placebo 30 mg/day). All subjects will be followed up for 96 weeks. The primary endpoint is the comparison of Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) score between treatment group and control group at 96 weeks of follow-up. The secondary endpoints include serum thiamine, folate, homocysteine levels, cranial functional MRI and survival. The central randomisation method will be adopted and the principles of placebo-controlled, double-blind randomised control will be followed. The comparisons among ADAS-Cog scores and other secondary endpoints over time within subjects is conducted by using repeated measure analysis of variance (ANOVA) or generalised estimating equations (GEE). Pairwise t-test with Bonferroni adjustment is performed for multiple comparisons. On the other hand, for comparisons between treatment and control group, simple one-way ANOVA, GEE or Wilcoxon rank sum test is used. The χ2 method is used for statistical analysis of the categorical data. Kaplan-Meier survival curve is used for survival analysis. A p<0.05 is considered statistically significant difference. ETHICS AND DISSEMINATION: This trial has been approved by Shanghai Jiao Tong University School of Medicine, Renji Hospital Ethics Committee (KY2019-199). After publication of study results, trial report will be published in peer-reviewed journals and/or in national or international conferences. TRIAL REGISTRATION NUMBER: ChiCTR2000029297.

Adiponectin is related to carotid artery plaque and a predictor of cardiovascular outcome in a cohort of non-diabetic peritoneal dialysis patients.

AIMS: Adiponectin is an adipocytokine with antiatherogenic and anti-inflammatory properties. We investigated associations between circulating adiponectin, inflammation and cardiovascular disease in peritoneal dialysis patients. METHODS: A prospective study was performed in 59 non-diabetic patients. The concentrations of serum adiponectin, biochemical data and ultrasound of carotid artery were measured at enrollment. The patients were followed up to 39 months mainly for cardiovascular events. RESULTS: The serum adiponectin concentration was elevated and inversely related to C-reactive protein and interleukin-6 in the patients. The adiponectin level of patients with carotid plaques was significantly lower than in those without plaques (p < 0.01). Kaplan-Meier analysis showed that the cumulative survival without new cardiovascular events was better in patients with higher adiponectin levels than in those with lower adiponectin levels. CONCLUSION: Serum adiponectin levels are inversely related with markers of systemic inflammation and signs of atherosclerosis which may explain why hyperadiponectinemia in this study was associated with better cardiovascular outcome.

[Effects of Astragalus on expression of renal angiopoietin receptor Tie-2 in diabetic rats].

OBJECTIVE: To study the expression of angiopoietin receptor Tie-2 in the renal tissue of diabetic rats and the effects of Astragalus. METHODS: SD rats were randomly divided into normal control group, diabetes group and Astragalus-treated group. The expression of receptor Tie-2 in the renal tissue was assessed by using real-time quantitative polymerase chain reaction and immunohistochemical method. RESULTS: Glomerule Tie-2 protein expression was significantly elevated in the diabetes group as compared with the normal control group (P<0.01). Glomerule Tie-2 protein expression in the Astragalus-treated group was decreased as compared with the diabetes group (P<0.01). CONCLUSION: Tie-2 may play an important role in the pathogenesis of the early stage diabetic renal injury. The reno-protection effect of Astragalus may be mediated by down-regulating the expression of Tie-2 in the kidney tissue of diabetic rats.

[Relationship of brain natriuretic peptide to renal function and left ventricular hypertrophy in patients with chronic kidney disease].

OBJECTIVE: To clarify the association of brain natriuretic peptide * BNP) with renal function and cardiac dysfunction in non-dialysis-dependent patients with chronic kidney disease (CKD). METHODS: Fluorescence immuno-assay was used to detect the whole blood concentration of BNP in a cohort of 203 CKD patients and 16 hypertensive controls. Color ultrasonography was conducted to determine the left ventricular mass index (LVMI). Estimated glomerular filtration rate (eGFR) was examined. The relationship of BNP to eGFR and LVMI in these patients. RESULTS: There was a trend that the BNP level increased with the decrease of the level of eGFR [9.35 (7.35-15.00) vs 54.40 (15.10-173.00) ng/L, P < 0.01]. Spearman correlation showed that BNP level was correlated negatively with eGFR (r = -0.417, P < 0.01). Multiple regression analysis showed that eGFR was the independent determinant of BNP (beta = -0. 293, P < 0.01), and lgBNP concentration increased by 0.293 ng/L per 1 ml x min(-1) x (1.73 m2)(-1) reduction in lgGFR. The incidence of LV hypertrophy was much higher in the CKD patients than in the controls (53.2% vs 10.0%, P < 0.05). BNP level was greater in the patients with LV hypertrophy [93.05 (37.70-272.00) vs 17.30 (7.20-63.70) ng/L, P < 0.01], and LVMI had an independent effect on BNP concentration ( beta = 0.266, P < 0.01). lgBNP level increased by 0.266 ng/L per 1 g/m2 increase in lgLVMI. CONCLUSION: The declining eGFR level independently elevates the BNP level in non-dialysis-dependent CKD patients. Although renal dysfunction itself may affects the BNP concentration, LV hypertrophy is a powerful independent determinant of BNP.