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Objective To investigate the role of BMP-2/Smad signaling pathway in the osteogenic differentiation of human aortic smooth muscle cells (HASMCs) caused by hyperphosphatemia -induced calcium phosphate (CaP) crystals.Methods High-phosphate medium was incubated at 37℃ for 3 days.CaP crystals and supernatant were isolated by ultracentrifugation.Scanning electron microscope and energy dispersive X-ray spectroscopy were performed for analysis of physicochemical characteristics of CaP crystals.HASMCs were cultured in vitro,and divided into high-phosphate,control,crystals and supernatant groups.Calcification was visualized by Alizarin red staining.Calcium loads in cells were quantified by o-cresolphthalein complexone method.Protein expression of bone morphogenetic protein-2 (BMP-2),Runt-related transcription factor 2 (RUNX2),osteopontin (OPN),phospho-Smad1/5/9 (p-Smad1/5/9) were quantified by Western blotting.After knockdowns of BMP-2 and Smad1 with small hairpin RNA (shRNA) interfering respectively in HASMCs,protein expressions were measured by Western blotting.Results High-phosphate medium induced the formation of CaP crystals.Compared with the cells in control group,CaP crystals significantly induced HASMCs calcification,increased calcium loads and up-regulated the levels of BMP-2,RUNX2 and OPN proteins (all P ＜ 0.05).After the addition of CaP crystals into HASMCs,the level of p-Smad 1/5/9 protein peaked at 30 min (P ＜ 0.05).After BMP-2 was knocked down in HASMCs,the expression of p-Smad1 caused by CaP crystals was blocked completely,and the expressions of RUNX2 and OPN caused by CaP crystals were reduced significantly (all P ＜ 0.05).After Smad1 was knocked down in HASMCs,the expressions of RUNX2 and OPN caused by CaP crystals were decreased significantly (all P ＜ 0.05).Conclusions Hyperphosphatemia-induced CaP crystals promoted osteogenic differentiation of HASMCs through the BMP-2/Smad signaling pathway.
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Objective To investigate the factors affecting the efficacy of leflunomide combined with medium/low dose corticosteroids in the treatment of progressive IgA nephropathy (IgAN).Methods Clinical and pathological parameters were collected retrospectively in patients of primary IgAN with proteinuria＞ 1.0 g/24 h and chronic kidney disease (CKD) stage 1-3 treated with leflunomide combined with medium/low dose corticosteroids in Ren Ji Hospital,School of Medicine,Shanghai Jiao Tong University from Jan 2005 to Dec 2010.According to the treatment effects,patients were divided into complete remission group and non-complete remission group.The biochemical and pathological indexes of the two groups were compared.Results A total of 42 patients were included.The remission rates at 3,6,9 and 12 months were 62％,64％,67％ and 74％,respectively.Seventeen (40.5％) and fourteen (33.3％) patients achieved complete and partial remission after one-year treatment,and the remission rate remained stable within one year after withdrawal of drugs.The 24hour proteinuria was 1.50 (0.67,2.66) g,which was significantly reduced compared with the baseline 2.44 (1.36,3.74) g (P ＜ 0.01).The decrease rate was 31.3％.There was a slight decrease in proteinuriawithin one year after withdrawal of drugs.Estimated glomerular filtration rate (eGFR) remained stable during the treatment and a year of follow-up.No serious adverse event was observed during the followup period.Among 31 responder patients,6(19.4％) patients relapsed.Logistic multivariate regression analysis suggested that the degree of renal interstitial inflammatory infiltration was an independent predictor of complete remission with one-year treatment of leflunomide combined with medium / low dose corticosteroids (HR=0.067,95％ CI 0.008-0.535,P=0.011).Conclusions IgAN treated with leflunomide and medium/low dose corticosteroids can achieve remission in early stage,and the remission rate remains stable after withdrawal of drugs.It is a safe option for the treatment of IgAN.Renal interstitial inflammatory infiltration is an independent predictor of complete remission.
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Objective To compare the efficacy and safety of leflunomide (LEF) combined with medium/low dose corticosteroids and full dose of corticosteroids in the treatment of IgA nephropathy. Method Primary IgAN patients diagnosed by renal biopsy with 18?65 years old and eGFR≥30 ml·min?1·(1.73 m2)?1 and proteinuria>0.5 g/24 h were enrolled in a prospective controlled clinical study. They were randomly divided into leflunomide combined with medium/low dose corticosteroids (LEF group) and corticosteroids alone (steroid group). The primary outcomes were (1) end stage renal disease or dialysis (2) 50% increase in serum creatinine above the baseline. Secondary outcome was the remission of proteinuria. Results Ninety patients completed the follow?up. The 24?hour proteinuria at baseline were 2.00(1.10, 2.88) g and 1.87(1.13 ,3.08) g in LEF group and steroid group respectively. Compared with baseline, it was significantly decreased in both groups at 6 months [0.30(0.11, 0.93) g, 0.30(0.14, 1.33) g] and 12 months [0.30(0.09, 0.82) g, 0.32(0.14, 0.66) g], (P0.05]. At 6 and 12 months, there was no significant difference in terms of 24?hour proteinuria, serum creatinine and eGFR (CKD?EPI) between groups (P>0.05). There was no statistically significant difference in adverse events between groups during the treatment (9/40 cases in LEF group and 11/50 cases in steroid group, P>0.05). The average follow?up was 79 months, and there was no difference in the renal prognosis between the two groups. Multivariate Cox regression analysis revealed that serum creatinine at baseline and renal interstitial inflammatory cell infiltration predicted the risk of the progress of IgA nephropathy. Conclusion Leflunomide plus medium/low dose corticosteroids has a similar effect as full dose of corticosteroids in IgA nephropathy and does not increase the risk for adverse events during the treatment.
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ObjectiveTo investigate the outcome and risk factors for kidney involvement by analyzing 64 patients with anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis.MethodsData analyzed including the demographic information,survival status,renal survival status and laboratory parameters such asserum albumin level,serum creatinine level,urinary protein excretion level,hematuria,high sensitivity C-reactive protein(CRP),ANCA titer,and the Birmingham vasculitis activity score (BVAS).Logistic regression analysis,Cox regression analysis and ROC curve were used to evaluate the risk factors of patients with renal involvement and all-event survival.ResultsTotally 64 patients were enrolled [24 females with the average age of (59.9±2.0) years] and followed up for a median of (38±16) months.The morality rate was 14％,and the prevalence of end stage renal disease was 39％.Compared with those who had better outcomes,patients who died or with end stage renal disease had higher serum creatinine level [ (624±246),(245±127 ) μ mol/L,respectively,t=7.17,P＝0.005 ] and erythrocyte sediment rate [ (112±24),(76±48) mm/1 h,respectively,t=3.74,P＜0.01 ],but lower serum albumin level [(294±31 ),(316±42) g/L,respectively,t=-2.27,P=0.01 ] and hemoglobin level [ (79±13),(99±33) g/L,respectively,t=-3.23,P＜0.01 ] at baseline.Logistic regression analysis found that serum creatinine level and erythrocyte sediment rate at baseline were associated with poor outcome and Cox regression analysis further confirmed this result[Scrβ=1.004,95％CI1.002～1.006,P＜0.01; ESR β=l.018,95％CI 1.000～1.037,P=0.046].ROC curve analysis showed that serum creatinine and erythrocyte sediment rate were predictors for AAV patients' prognosis and their AUC were 0.95 and 0.80,the sensitivity of these parameters was both 94％,and the specificity was 93％ and 70％respectively.ConclusionThe intensity of initial treatment should be based on disease severity and activity in order to improve the prognosis of those with ANCA-associated vasculitis with renal involvement.Increased serum creatinine and erythrocyte sediment rate may serve as predictors for poor prognosis in this patient cohort.
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Objective To explore the effect of soluble tyrosine kinase 2 fusion protein (sTie-2-Fc) on peritoneal angiogenesis, solute transport and ultrafi]tration capacity in uremic rats undergoing peritoneal dialysis (PD). Methods Thirty-two male Wistar rats were randomly divided into sham-operation group, uremic group, uremic PD group, and sTie-2-Fc group (all n=8).Uremic PD group and sTie-2-Fc group received intraperitoneal infusion of 3 ml/100 g of peritoneal dialysis fluid (PDF) containing 4.25% glucose twice daily for 4 weeks. Rats in sTie-2-Fc group were infused with PDF supplemented with 1 μg sTie-2-Fc. Before the rats were sacrificed, a peritoneal equilibration test (PET) was performed to evaluate the peritoneal solute transport and ultrafiltration capacity, and omenta was obtained for anti-CD31 immunohistochemical staining to determine the vessel density. Results Compared to their counterparts in sham-operation group,rats in uremic group had higher 2 h-dialysate to plasma creatinine concentration ratio (D/Pcr, 0.78±0.05 vs 0.70±0.09, P=0.028), lower 2 h to initial dialysate glucose concentration ratio (D/D0, 0.69±0.05 vs 0.76±0.07, P=0.033), decreased peritoneal ultrafiltration [UF, (2.29±0.50) ml vs (4.58±1.64) ml, P=0.005], and increased omental vessel density [(5.8±3.0)/HP vs (1.6±0.5)/HP, P＜0.01]. When compared to uremic group, rats in uremic PD group showed higher D/Pcr (0.89±0.05 vs 0.78±0.05, P=0.001), lower D/D0 (0.47±0.09 vs 0.69±0.05, P＜0.01), decreased UF [(0.40±0.59) ml vs (2.29±0.50) mi, P=0.005] and more omental vessels [(16.7±1.2)/HP vs (5.8±3.0)/HP, P＜0.01]. Improved peritoneal UF [(1.56±0.48) ml vs (0.40±0.59) mi, P=0.014] and decreased omental vessels [(9.2± 1.2)/HP vs (16.7 ± 1.2)/HP, P＜0.01] were observed in rats treated with sTie-2-Fc compared with those in uremic PD group, however, the differences of D/Pcr (0.87±0.06 vs 0.89±0.05, P=0.122) and D/D0 (0.60±0.11 vs 0.47±0.09, P=0.06) between these two groups did not reach statistical significance. Conclusion sTie-2-Fc preserves peritoneal ultrafiltration capacity and ameliorates peritoneal angiogenesis caused by uremia and exposure to bioincompatibal PDF.
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Objective To differentiate proteinuria due to non-diabetic renal diseases(NDRD)from that of diabetic nephropathy(DN)in type 2 diabetic patients,and to evaluate the prevalence of NDRD.Methods A retrospective analysis was performed on diabetic patients who had undergone renal biopsy between Jan 1,2003 and Dec 3 1,2006.The data including history of diabetes,cardiac color ultrasound,color Doppler ultrasound of the carotid artery,retinal changes,examination of ocular fundus,giomerular filtration rate,hepatic and renal function,lipid profile,blood glucose,HbA1c,and urine protein were collected.Results Among 46 patients,22 cases (47.8%)were distinctly diagnosed as diabetic nephropathy(DN),while the other 24(52.2%)as NDRD.Focal segmental glomeruloselerosis Was the most common lesion found in patients with NDRD.In DN group,the fasting blood glucose was higher than that of NDRD group,as well as ejection fraction,carotid plaque,and intimamedia thickness(IMT)showed significant differences between 2 groups.Patients with NDRD were less frequently associated with diabetic retinopathy.Diabetic retinopathy showed hiigh sensitivity(72.7%)and specificity (91.7%)in diagnosing DN.Conclusions Blood glucose,ejection fraction,carotid plaques and IMT,and retinopathy may be helpful in differential diagnosis of diabetic patients with overt proteinuria.Renal biopsy is an important step lo establish the diagnosis.
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Objective To elucidate the prevalence and risk factors of cardiovascular disease (CVD) in end-stage renal disease (ESRD) patients on peritoneal dialysis (PD), and to investigate the associated problems in treatment. Methods A total of 254 PD patients in our division were enrolled in this study. CVD history, laboratory measurements, examinations of carotid atherosclerosis and left ventricular hypertrophy by ultrasonography were collected and associated factors were analyzed. The median follow-up time was 49 months. Results The overall prevalence of CVD was 37% (93/254). Diabetes, longer dialysis duration, hypertfiglyceridemia, hypoalbuminemia, hypoprealbuminemia were commonly found in the patients with new CVD event. The patients without pre-existing CVD had the higher Ccr, Kt/V, D/Pr, nPCR, serum albumin level. In those with pre-existing CVD, the hypertriglyceridemia and the duration of dialysis were independent predictors of progression of CVD. Differences of LAD, LVST, LVMI and IMT were significant between with and without pre-existing CVD groups. Kaplan-Meier curves showed that the presence of CVD was the independent risk factor of survival. Alb<330 g/L, LAD>39.6 mm and peritonitis were risk factors of CVD. Conclusion The prevalence of CVD in PD patients is quite high. CVD history should be realized, dialysis adequacy should be maintained, and peritonitis should be prevented.
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Objective To investigate the stroke occurrence of chronic kidney disease (CKD) and its related factors, especially the carotid atherosclerosis. Methods The data of stroke occurrence in 700 CKD patients hospitalized in Renji Hospital during 2007 were analyzed retrospectively. The incidences of stroke were compared among CKD [Ⅰ-Ⅱ, CKD Ⅲ-Ⅴ non-dialysis patients and dialysis patients. Carotid atherosclerosis of 409 CKD patients was examined by color Doppler ultrasound. The related factors were selected by Spearmnan correlation analysis and Logistic regression analysis. Results Of 700 CKD patients, 67 cases (9.57%) experienced at least one episode of stroke, which was much higher than that of general population. The related factors of stroke in CKD included GFR, age, SBP, CRP, Lpa, serum glucose, pre-albumin, HDL and carotid atherosclerosis. Logistic regression revealed that SBP (β=1.021, P=0.042), CRP (β=1.008, P=0.024) and carotid atherosclerosis (β =3.456, P=0.025) were risk factors of stroke in CKD. Incidence of carotid atherosclerosis was high (50.37%) in CKD patients, besides it was significantly higher in CKD patients with stroke history as compared to those without stroke history (80.0% vs 47.4%, P<0.01). Conclusions The incidence of stroke is quite high in CKD patients, which is closely associated with hypertension, inflammation and glyeolipid metabolism disorder. Carotid atherosclerosis is common in CKD patients with stroke, which may be helpful in screening cerebrovascular diseases in CKD patients.
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ObjectiveTo observe the influence of different dietary protein intake (DPI) on nitrogen balance and nutritional indices in peritoneal dialysis (PD) patients, and explore the minimal DPI to maintain nitrogen balance.MethodsThirty-four PD patients were randomly divided into group A, B and C with DPI as 1.2, 0.9 and 0.6 g·kg-1·d-1 respectively. All the patients admitted into our hospital and completed a 10-day assessment for nitrogen balance, as well as nutritional status including serum albumin (Alb), pre-albumin at baseline, the 7th and 10th day. ResultsThe DPI of group A, B and C was (1.18±0.05), (0.87±0.02), (0.66±0.03) g·kg-1·d-1, whose differences were significant (P<0.01). The dietary energy intake (DEI) was 129.29 (117.57-133.89), 111.71 (100.42-133.47), 146.86 (128.03-163.18) kJ·kg-1·d-1 respectively. Nitrogen balance was positive in group A, B, C [2.99 (2.15-4.72) g, 1.20(0.59-1.89) g, 0.24 (-0.87-1.27) g]. The BUN decreased at the 7th and 10th day (P<0.01) in group C. The BUN and phosphorus in group A increased, but without significant difference as compared to baseline. No significant differences of nutritional status were found among three groups throughout the trial. ConclusionMinimal DPI 0.65 g·kg-1·d-1 plus the supplement of protein loss in dialysate can maintain the nitrogen balance in peritoneal dialysis patients.
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ObjectiveTo evaluate the characteristics of patients on long-term peritoneal dialysis (PD). MethodsPatients who started PD since 1994 and received PD for at least one year were included in this study. According to dialysis duration, patients were divided into two groups. Group A (long-term) was defined as patients survived on PD for more than 5 years. Group B (short-term) was defined as patients who died or switched to bemodialysis within less than 5 years. Demography, biochemical indexes, dialysis prescription and adequacy were compared between two groups. ResultsThere were 68 patients in group A and 98 patients in group B. Mean followed-up period of group A and B was (84.80±19.42) months and (27.25±12.31) months, respectively. Younger, fewer episodes of diabetic comorbidity (group A 3/68 vs group B 18/98, P ＜0.05) and coronary heart disease (group A 6/68 vs group B 22/98, P＜0.05) were found in group A. Compared to group B, the level of serum albumin at the beginning of PD was much higher in group A [(35.56±4.74) g/L vs (33.69±5.45) g/L, P＜0.01). The levels of blood sugar, TC, TG, hemoglobin, calcium, phosphate and iPTH were not significantly different between two groups. Estimated GFR, renal Kt/V and renal Ccr at the beginning of dialysis were much higher in group A, however there was no significant difference in urinary volume between two groups. Both estimated GFR and urinary volume decreased more slowly in group A compared to group B. Peritonitis mobidity was lower in group A (1/81.22 months vs 1/29.03 months, P＜0.01). Conclusions In comparison to short-term survivors, long-term PD patients are characterized by being younger, less diabetic and coronary heart disease, fewer episodes of peritonitis, higher level of serum albumin, higher estimated GFR and less loss of residual renal function.
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OBJECTIVE: To assess the diagnostic value of CT peritoneography for peritoneal complications of continuous ambulatory peritoneal dialysis (CAPD). METHODS: CT peritoneography in 11 CAPD patients with clinically suspected dialysis-related complications was prospectively studied. The CAPD patients were all treated in Renji Hospital from 2005 to 2007. CT images were reviewed according to the evidence of peritoneal leaks, hernias, loculate pleural fluid collections, and adhesions. RESULTS: Abnormal findings were found in 9 of 11 CAPD cases including inguinal hernias (3 cases), umbilical hernia (1 case), hydrocele (1 case), leaks in catheter tunnel (2 cases), and peritoneal adhesions (2 cases). Parts of them were confirmed by surgical operation. CONCLUSION: CT peritoneography is useful for the evaluation of complications related to CAPD, and it offers excellent tissue contrast and multiplanar imaging for assessment of the complications.