| Backgroundprofessor Berger was the first one who proposed the IgA nephropathy(IgAN),one of the commonest primary glomerulopathy which is characterized by mesangial mostly deposited by IgA,under the immunofluorescence,Its onset is concealed,mainly involving young adults,as well as children and the elderly.About 30%-40% patients,who had a 20-30 years IgAN history,would develop into the end stage of the kidney disease,and they survived by hemodialysis treatment and peritoneal dialysis treatment.It's a large amount of financial and spirit pressure for both patients and their family.The diagnosis of IgA nephropathy is based on renal biopsy.The pathological features are variable,such as mesangial cell proliferation?increased mesangial matrix\interstitial fibrosis as well as tubular atrophy,and all of these are caused by immune complex deposition in the glomerular mesangial area,whose component is still unclear up to now.According to the previous study,the mainstream doctrine of IgAN mechanism research is “four-hit theory”,IgA-contained immune complex is the key step leading to the latter damage,besides,many researchers proved soluble CD89,fibronectin,as well as transglutaminase could combined with IgA and participated in the pathogenesis of IgAN,however,the component of macromolecular complexes were remained obscure.Previous studies have also shown that the immune complexes deposited in the Mesangial region of the kidney originate from the peripheral circulation,suggesting that there are important pathogenic factors in the macromolecular complexes of the peripheral circulation.Recently,the incidence of diabetes mellitus is increasing year by year.Diabetes mellitus is the most important factor that patients end in the end-stage kidney disease.Previous studies have reported that primary IgA nephropathy is most common in non-diabetic renal lesions in patients with diabetes mellitus,however,whether there was difference between patients only with IgAN and patients both with IgAN and diabetes mellitus,remained unclear,and there are limited reports about this.And taking into account the high incidence of diabetes mellitus,diabetic patients can be associated with non-diabetic renal injury.Previous studies have reported that primary IgA nephropathy is common in diabetic patients with non-diabetic renal damage.In China,it is common for patients with IgAN complicated with diabetes mellitus,However,there are limited reports on whether there are differences in mechanism between patients with IgAN complicated with diabetes mellitus and patients with simple IgAN.Most of the studies are about the comparison between diabetic nephropathy and IgAN.Therefore,the purpose of this study was to analyze the clinical manifestations of IgAN patients with diabetes mellitus and simple IgAN patients.The similarities and differences of pathological changes and prognosis and further analysis of immune complex in plasma of patients with IgAN complicated with diabetes mellitus and simple IgAN at molecular level for promoting proliferation and proinflammatory factors of human glomerular Mesangial cells The similarities and differences of secretory ability.ObjectiveThe purpose of this study was to analyze the clinical manifestations,pathological changes and prognosis of patients with IgAN complicated with diabetes mellitus and patients with simple IgAN By collecting the clinical,pathological and prognostic data of patients with IgA nephropathy complicated with diabetes mellitus and patients with simple IgAN.And by observing the immune complex in the plasma of patients with IgA nephropathy complicated with diabetes mellitus and simple IgAN to stimulate human Mesangial cells,The differences of immune complexes in plasma between IgAN patients with diabetes mellitus and simple IgAN patients in promoting proliferation and proinflammatory factor secretion of human glomerular Mesangial cells were further analyzed at the molecular level.Methods1?Object1.1 From January 2015 to January 2017,the clinical,pathological and prognostic data of 500 patients with primary IgAN diagnosed by renal biopsy and hospitalized in the Department of Nephrology,the first affiliated Hospital of Zhengzhou University,were collected.1.2 Human Mesangial cell2?Group2.1 Clinical and pathological data of 500 patients with primary IgAN diagnosed by renal biopsy from January 2015 to January 2017 in the Department of Nephrology,first affiliated Hospital of Zhengzhou University,and divided into groups according to diabetes mellitus or not,There were 25 patients with IgAN combined with diabetes mellitus and 475 patients with simple IgAN.2.2 From January 2015 to January 2017,28 patients with primary IgAN(8 with diabetes mellitus,20 with simple IgAN)were diagnosed by renal biopsy in the Department of Nephrology,first affiliated Hospital of Zhengzhou University.From February 2017 to February 2018,7 healthy volunteers were recruited for age and sex matching.3?Method3.1 The following 500 patients with IgA nephropathy were selected as study subjects.1?The clinical data,pathological data and prognosis data of 500 patients were collected.2?Comparison of clinical manifestations,renal histology and prognosis between patients with simple IgA nephropathy and patients with IgA nephropathy complicated with diabetes mellitus.3.2 Human Mesangial cells as the object of study1 ? According to the grouping situation in 2.2,plasma collection and determination of circulating immune complex concentration were extracted.2?Human Mesangial cell stimulation experiment: human Mesangial cells were stimulated by the extracted plasma circulating immune complex.They were divided into three groups according to simple IgA nephropathy group,IgA nephropathy with diabetes mellitus group and normal control group.To observe the expression of IL-6,CXCL-1 in the supernatant of human Mesangial cells stimulated by plasma circulating immune complex for 24 hours,and to detect the expression level of IL-6,CXCL-1 by elisa kit.To observe the proliferation of human Mesangial cells stimulated by circulating immune complex in three groups for 24 hours.The proliferation of Mesangial cells was determined by CCK.The proliferation ability of Mesangial cells in three groups was detected by 8 kit.Results1?The difference between IgA Nephropathy patients and IgA Nephropathy patients with Diabetes Mellitus.Compared with simple IgAN group,the patients in IgAN with diabetes mellitus group were older [(46.36 ±13.49)vs(34.00 ±13.80)years,P < 0.001] and higher in serum triacylglycerol [2.06(1.52,3.11)vs 1.51(1.01,P < 0.01)].2.25)mmol/L,P=0.012].2?The difference of pathological manifestations between IgA Nephropathy patients and IgA Nephropathy patients with Diabetes Mellitus.The thickness of glomerular basement membrane in IgAN with diabetes mellitus group was significantly higher than that in IgAN group [(384.33 ±61.20)vs(346.72 ±52.65),P < 0.044].3?The difference of prognosis between IgA Nephropathy patients and IgA Nephropathy patients with Diabetes Mellitus.Compared with simple IgAN group,the incidence of end-point events in IgAN with diabetes mellitus group was higher [25(9.33%)vs 4(57.14%)mmol/L,P < 0.001],and the prognosis was worse than that in,(Log Rank test(P < 0.004).4? Effect of plasma circulating immune complex on the expression of IL-6,CXCL-1 in the supernatant of human Mesangial cells.4.1 Compared with the normal control group,the immune complex in IgA nephropathy group promoted the secretion of IL-6 by Mesangial cells(IL-6: 85.25 ±22.70 pg/ml vs 70.58 ±8.74 pg/ml,p = 0.023).4.2 Compared with the normal control group,the immune complex in IgA nephropathy group promoted the secretion of CXCL-1 by Mesangial cells(CXCL-1:493.03 ±188.71 pg/ml vs 339.17 ±143.95 pg/ml,p = 0.043).4.3 There was no significant difference between the IgA nephropathy group and the diabetic group(P > 0 05).4.4 The level of IL-6 in IgA nephropathy complicated with diabetes mellitus group was significantly higher than that in normal control group(IL-6: 84.322 pg / ml vs 70.58 ±8.74 pg / ml,p=0.047).4.5 Compared with the normal control group,the level of CXCL-1 in the IgA nephropathy complicated with diabetes mellitus group showed an increasing trend,but it did not reach the statistical significance(CXCL-1:460.91 ±188.69 pg/ml vs 339.17 ±143.95 pg/ml,p=0.181).5?Effect of plasma circulating immune complex on proliferation of human Mesangial cells.5.1 Compared with the normal control group,the cell proliferation ability was enhanced after the plasma circulating immune complex in the IgA nephropathy group stimulated the human mesangial cells(1.08% 0.18vs0.77 and 0.13,p <0.001);5.2 Compared with IgA nephropathy with diabetes mellitus group,the proliferation of human Mesangial cells stimulated by circulating immune complex in IgA nephropathy group was enhanced(1.08 ±0.18vs0.85 ±0.14,p = 0.002).5.3 Compared with the normal control group,the proliferation of human glomerular Mesangial cells stimulated by circulating immune complex in patients with IgA nephropathy combined with diabetes mellitus showed no significant difference(0.85 ±0.14vs0.77 ±0.13,0.85 ±0.13,0.85 ±0.13,0.85 ±0.13,0.85 ±0.13,P < 0.01).(P = 0.285).Conclusion1?Compared with simple IgAN patients,IgAN patients with diabetes mellitus have different clinical,pathological features and prognosis,and this kind of patients need close monitoring and active treatment.2?The effect of circulating immune complex in patients with IgA nephropathy complicated with diabetes mellitus was similar to that in patients with simple IgA nephropathy,but its function was lower.However,the ability to promote the proliferation of Mesangial cells is weak,suggesting that there may be differences in the composition of circulating immune complex in diabetic patients. |
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