The Research Of Clinicopathological Changes And Mitochondrial Dysfunction Of Obesity-related Glomerulopathy

OBJECTIVE: Obesity is a disease associated with energy metabolism,and mitochondria play an important role in energy metabolism.Obesity-related glomerulopathy(ORG)is characterized by progressive increased in proteinuria and Scr.Pathological performance is glomerular hypertrophy with or without focal segmental glomerulosclerosis(FSGS).Mitochondrial dysfunction as the main feature of abnormal energy metabolism is the basic characteristics of obesity,but its relationship with the clinicopathological changes of ORG is not yet clear.This study collected clinical and pathological data of obesity-associated glomerulomegaly(O-GM)and obesityassociated focal and segmental glomerulosclerosis(O-FSGS)to observe their clinical and pathological characteristics and mitochondrial structure and function change,compared with early stage diabetic nephropathy(early-DN)and idiopathic focal segmental glomerulosclerosis(I-FSGS).To preliminarily explore the relationship between clinicopathological changes and mitochondrial dysfunction in ORG.METHODS: Forty-four patients with ORG were confirmed by renal biopsy from March 2007 to April 2017.Among them,29 were obesity-related glomerular hypertrophy(O-GM)and 15 were obesity-related focal segmental glomerulosclerosis(O-FSGS).Thirty-one patients with idiopathic focal segmental glomerulosclerosis(IFSGS),6 patients with early stage diabetic nephropathy(DN)and 6 patients with thin basement membrane nephropathy(control group)confirmed by renal biopsy pathology were enrolled in our hospital from February 2012 to March 2017.The clinical and pathological data of four groups of patients were collected,including sex,age,course of disease,body weight,height,blood pressure,albumin,serum creatinine,e GFR(CKD-EPI formula),urine erythrocyte count,24-hour urine protein etc.And the pathological changes of glomerular,renal tubules,renal interstitial and renal vascular in the light microscopic.The differences between the O-GM group and the O-FSGS group,the O-FSGS group and the I-FSGS group,the O-GM group and the early stage DN group were compared with the clinical and pathological.Six patients were selected from each group.Immunohistochemical method was used to detect the expression of WT1,mitochondrial marker(SDH),cytochrome oxidase(COX)and mitochondrialfusion protein-2(Mfn2).The glomerular podocytes and mitochondrial structure and function of renal tubular epithelial cells were compared.RESULT: 1.The age of ORG patients was 36.2±9.9 years,sex male: female = 31: 13,BMI 32.4±2.9kg / m2,Scr 75.7±26.4?mol / L,e GFR 104.9±24.4ml / min / 1.73m2,UA 412.2±115.0mmol / L,24 h urinary protein quantification 1.549±0.904 g / 24 h,ALB 41.4±5.0g / L.O-GM group and O-FSGS group: Clinically,there was a statistically significant difference between Scr and e GFR(P<0.05).Pathologically,the different of glomerular segment sclerosis ratio was statistically significant(P<0.05).2.O-FSGS group and I-FSGS group: Clinically,O-FSGS group had higher ALB,lower 24 h urinary protein count,and there was a statistically significant difference(P<0.05).In the I-FSGS group,12 patients had typical nephrotic syndrome(0% vs 38.7%,P<0.05).Pathologically,I-FSGS group segment sclerosis heavier,no statistical difference(P>0.05).3.O-GM group and early stage DN group: Clinically,patients in the early stage DN group were older(34.8±7.8 vs 38.0±9.9,P>0.05).Early stage DN group showed hypoproteinemia and a large number of proteinuria(0% vs 50.0%,P<0.05),and ALB lower,24 h urinary protein more,the difference was statistically significant(P<0.05).Pathologically,the performance of early stage DN group in mesangial proliferation,tubular atrophy and interstitial fibrosis is more heavy,and the difference was statistically significant(P<0.05).4.Immunohistochemical results showed that podocyte number in O-GM group,OFSGS group,I-FSGS group and early DN group was lower than that in control group.O-GM group was higher than early stage DN group(P<0.05).In the SDH expression,the ORG group and early stage DN group were higher than the control group(P<0.05),while the I-FSGS group decreased(P<0.05).O-GM group was higher than O-FSGS group(P>0.05).O-FSGS group was higher than I-FSGS group(P<0.05).O-GM group was higher than early stage DN group(P>0.05).In the COX expression,the OGM group and early stage DN group were higher than the control group(P<0.05),while the O-FSGS group and I-FSGS group were decreased(P>0.05).O-GM group was higher than O-FSGS group(P<0.05).O-FSGS group was higher than I-FSGS group(P>0.05).O-GM group was higher than early stage DN group(P>0.05).In theexpression of Mfn2,the expression of the latter four groups was lower than that of the control group.I-FSGS group was not statistically significant(P>0.05),the other groups were statistically significant(P<0.05).O-GM group was lower than O-FSGS group(P<0.05).O-FSGS group was higher than I-FSGS group(P<0.05).O-GM group was higher than early stage DN group(P>0.05).Electron microscopy showed that the number of mitochondria in the four groups of glomerular pods was significantly higher than that in the control group(P <0.05),but its morphology was irregular,and there were more vacuolar degeneration and mitochondrial autophagy.CONCLUSION:1.The detection rate of ORG is 0.8%.ORG is more common in young male patients,often expressed as moderate proteinuria.The glomerular filtration rate of ORG is in the normal range.2.ORG patients had sigenificant mitochondrial dysfunction in renal tubular epithelial cells,which may be an important pathogenesis of ORG.