ABSTRACT
Objective To analyze the predictive value of apolipoprotein B (ApoB) in the risk of progression to renal replacement therapy (RRT) in diabetic kidney disease (DKD) patients with chronic kidney disease (CKD) stage 3-5. Methods The data of DKD patients with CKD stage 3-5 who were hospitalized and followed up with detailed clinical data from January 2011 to November 2014 in the Third Affiliated Hospital of Sun Yat-sen University were retrospectively collected. Estimated glomerular filtration rate (eGFR) was calculated according to the CKD-EPI formula. After 2 years of follow-up, the patients were divided into RRT group and non-RRT group according to whether they had entered renal replacement therapy. Cox regression analysis was used to analyze the influencing factors of DKD progression to RRT. The predicted value of ApoB in the risk of progression to renal replacement therapy (RRT) of DKD patients within 2 years of follow-up was analyzed by plotting the receiver operating characteristic curve (ROC). By establishing multiple Cox models, the effect of ApoB elevation on the progression of DKD patients to RRT was analyzed after adjusting for the influencing factors gradually. Results A total of 258 cases were included in this study, including 156 males and 102 females. They were (66.13±11.88) years old (27-91 years old). CKD 3-5 patients were 181 cases, 50 cases and 27 cases respectively. There were 165 cases in the non-RRT group and 93 cases in the RRT group. There were statistically significant difference in hemoglobin, hematocrit, blood phosphorus, ApoB, serum creatinine, urea nitrogen, serum cystatin C, eGFR and in the proportion of using angiotensin converting enzyme inhibitor, diuretic, β blockers between the two groups (all P＜0.05). Multivariate Cox regression analysis showed that ApoB was an independent predictor of progression to RRT in patients with DKD within 2 years (HR=2.203, 95% CI 1.352-3.589, P=0.002). The area under the ROC curve of ApoB for DKD progression to RRT within 2 years of follow-up was 0.641 (C-index=0.749, P＜0.01). After adjusting for confounding factors, Cox regression analysis showed that for every 1 mmol/L increase in ApoB, the risk of RRT increased by 1.038 times in DKD patients with CKD stage 3-5 (HR=2.038, 95% CI 1.312-3.168, P=0.002). Conclusions ApoB is an independent predictor of progression to RRT with CKD stage 3-5 diabetic kidney disease (DKD). For every 1 mmol/L increase in ApoB, the risk of progression to RRT in patients with CKD 3-5 DKD increases by 1.038 times.
ABSTRACT
Objective To investigate the effect of advanced glycation end products (AGEs) on the disruption of tight junctions in rat glomerular endothelial cells (rGEnCs) and the role of renin-angiotensin system (RAS) in this pathological procedure.Methods Primary cultured rGEnCs were incubated with AGEs at concentrations of 20 mg/L,40 mg/L and 80 mg/L,for 6 h,12 h and 24 h respectively.The cells were treated with captopril (1 mmol/L) or valsartan (10 μ mol/L)to block RAS.The endothelial permeability was investigated by transendothelial electrical resistance and the flux of fluorescein isothiocyanate-conjugated bovine serum albumin.The expression of AGEs receptor (RAGE),tight junction proteins [occludin,claudin-5,junctional adhesion molecules A (JAM-A) and zona occludens-1 (ZO-1)]and RAS components [angiotensinogen,renin and angiotensin Ⅱ type 1 receptor (AT1)]were detected by Western blotting.Immunofluorescence was used to demonstrate the disruptions of the tight junction proteins.The activity of angiotensin converting enzyme (ACE) was evaluated by UV spectrophotometry.Angiotensin Ⅱ (Ang Ⅱ ) was measured by enzyme immunoassay.Results The monolayer permeability,the expression of RAGE,the activity of ACE,the concentration of Ang Ⅱ and the expression of AT1 of rGEnCs were increased after induced by AGEs.Meanwhile,AGEs decreased the expression of occludin,claudin5 and JAM-A and induced disruption of tight junction proteins.Pretreatment with anti-RAGE antibody (100 mg/L),captopril or valsartan could attenuate the detrimental effect of AGEs.Conclusion The changes of permeability induced by AGEs in glomerular endothelial cells are partly mediated by RAS through RAGE.