Clinical And Renal Pathological Characteristics Of C3 Glomerulopathy In Children And The Significance Of C3 Deposition In IgAN And HSPN

Background and Objective:The third complement component(C3)is the core component of all components of the complement system and plays a central role in three complement activation pathways.The kidney is the most vulnerable organ with abnormal complement activation,which also plays a pathogenic role in a variety of glomerular diseases.As the most important and the highest complement component contents in the complement system,C3 has been widely concerned in recent years.In children,the primary glomerular disease characterized by glomerular C3 deposition which is the deposition intensity of C3 is greater than other deposition intensity of 1+of immunofluorescence staining mainly are C3 glomerulopathy(C3G)and post-infectious glomerulonephritis with isolated C3 deposition(C3-PIGN).C3G and C3-PIGN have the same renal immunopathology,,but their treatment and prognosis are different.The purpose of this study was to:(1)investigate the incidence of C3 glomerulopathy in primary glomerular diseases with glomerular C3 deposition.(2)analyze clinical manifestations,laboratory examination and renal pathological changes of C3G,C3-PIGN or isolated C3 deposition in renal tubules in primary glomerular disease.Methods:(1)In the retrospective study,we enrolled children with primary glomerular disease diagnosed by renal biopsy were admitted to Children's Hospital of Soochow University from January 2002 to October 2017.(2)Children with C3G,children with C3-PIGN,and children with isolated C3 deposition in renal tubules were selected for further study.The age,weight,gender,course of disease prior to the renal biopsy and length of stay of the children at the time of admission were recorded;clinical manifestations before renal biopsy,including edema,hydrothorax,ascites,blood pressure,gross and microscopic hematuria and proteinuria;blood biochemical findings,results from humoral immunity examination,urine routine,urine protein quantification,urine protein spectrum at the first admission as well as light microscopy,electron microscopy and immunofluorescence staining examination for renal biopsy.Result:(1)A total of 894 children were counted in the first part of the study,of which 456(51.0%)were primary glomerular diseases and 438(49.0%)were secondary glomerular diseases.Among the 35 cases(7.7%)with glomerular C3 deposition in primary glomerular disease,15 cases(3.3%)were C3G,8 cases were C3-PIGN,and the other 12 cases included 6 cases of primary nephrotic syndrome,2 cases of rapidly progressive glomerulonephritis,1 case of chronic glomerulonephritis,2 cases of isolated proteinuria,and 1 case of isolated hematuria.17 cases were isolated C3 deposition in renal tubules.(2)There was not any difference in clinical manifestations between children with C3G and C3-PIGN.The serum C4 of children with C3G was higher than that of children with C3-PIGN,but the triglyceride of C3G was lower than that of children with C3-PIGN(P=0.049,P=0.012).The number of children with RBC tubular types in C3G was higher than that of C3-PIGN(P=0.039).(3)Among the 17 cases with isolated C3 deposition in renal tubules,there were 1 case of acute glomerulonephritis,5 cases of nephrotic syndrome,and 11 cases of isolated hematuria.Compared with children with isolated C3 deposition in renal tubules,children with C3G had the shorter course of disease and longer length of stay prior to renal biopsy,and the number of the children with edema,hypertension,macroscopic hematuria,proteinuria and AKI in C3G were higher than that of children with C3G(P<0.05).The children of C3G had higher serum creatinine,blood urea nitrogen,serum IgA,serum IgG and the ratios of serum IgA/C3,ulgG/uCr,uTRF/uCr,uAlb/uCr,ual-MG/uCr and uNAG/uCr,lower serum C3 and the ratios of serum C3/C4 than those with isolated C3 deposition in renal tubules(P<0.05).In terms of renal pathological changes,the number of the children with acute lesions,capillary loop collapse or occlusion,RBC casts in tubular,interstitial inflammatory cells infiltration and severe renal tubular injury in the children with C3G were higher than those of children with isolated C3 deposition in renal tubules(P<0.05).Conclusion:1.Among 894 children with renal biopsy included in the study,there were 456(51.0%)patients with primary glomerular diseases.Among them,the glomerular diseases with mainly glomerular C3 deposition accounted for 7.7%in primary glomerular disease,and the incidence of C3G was 3.3%.2.There was no difference in clinical manifestations and renal pathological changes between children with C3G and C3-PIGN,but the prognosis of C3G and C3-PIGN is quite different.Therefore,children with glomerular C3 deposition should be followed up regularly and closely to avoid end-stage renal disease,so as to increase the survival rate of children with C3G.3.Different from disease types in which glomerular C3 deposition,isolated hematuria(64.7%)and nephrotic syndrome(29.4%)were the main disease types of isolated C3 deposition in renal tubules.4.Compared with isolated C3 deposition in renal tubules,the number of the children with edema,hypertension,macroscopic hematuria,proteinuria,AKI,capillary loop collapse or occlusion,RBC casts in tubular,interstitial inflammatory cells infiltration and severe renal tubular injury in the children with C3G were higher,suggesting that the clinical manifestations and pathological injury of glomerular C3 deposition were more serious than that of C3 deposition in renal tubules.However,the significance of C3 deposition in renal tubules and its effect on prognosis have yet to be studied.Background and Objective:IgA nephropathy(IgAN)is the most common primary glomerulonephritis in the world.Although IgA deposition in the mesangial region is a hallmark of IgAN,C3 deposition is also common in the mesangium.There are studies have shown that C3 deposition in the mesangium is an independent risk factor for IgAN progression in adults.Henoch-Schonlein purpura nephritis(HSPN)is one of the most common secondary glomerular diseases in children,and it is also one of the important causes of end-stage renal disease(ESRD).Similar to the deposition in IgAN,IgA deposition was also observed in glomerular mesangial region of HSPN,but the two had different histological characteristics and clinical processes.The influences of glomerular C3 deposition on the clinical manifestations and renal pathology of IgAN and HSPN in children remains unclear.The purpose of this study was to investigate the significance of glomerular C3 deposition in children with IgAN and HSPN.Methods:(1)In the retrospective study,we enrolled children who were admitted to Children's Hospital of Soochow University from January 2002 to October 2017 with renal biopsy.(2)Children diagnosed with IgAN and HSPN were selected for further study.Record and arrange the general information of the children at the time of admission,the same as "abstract(1)".(3)According to whether there was glomerular C3 deposition in the kidney,children of IgAN and HSPN were divided into children with and without C3 deposition.Result:(1)In primary glomerular disease,104 children with glomerular IgA deposition were diagnosed with IgAN.Among them,children with C3 deposition were 65 cases(62.5%).The proportion of glomerular IgG deposition in children with C3 deposition was higher than that children without C3 deposition(P=0.001).However,there were no significant differences between the two in clinical manifestations,laboratory results and renal pathological changes.(2)Among 274 cases of HSPN included in this study,children with C3 deposition were 84 cases(30.7%).The length of stay of children with C3 deposition were longer than that without C3 deposition(P=0.007).Compared with children without C3 deposition,children with C3 deposition had higher serum creatinine,blood urea nitrogen,serum IgA and the ratios of serum IgA/C3,uIgG/uCr,uTRP/uCr and uAlb/uCr(P<0.05).The number of children with renal tubular epithelial cells swelling and degeneration and renal tubular epithelial cells necrosis in children with C3 deposition was higher than children without C3 deposition(P=0.001,P=0.028).The proportion of glomerular IgA deposition,IgM deposition,IgG deposition and C1q deposition in children with children with C3 deposition were all higher than those of children without C3 deposition in HSPN(P<0.05).(3)Of the 104 IgAN cases included in the study,children with C3 deposition were 65(62.5%).Among the 274 children with HSPN,children with C3 deposition were 84(30.7%)(P<0.001).There were differences between IgAN and HSPN in clinical manifestations,laboratory examination and renal pathological changes.Compared with them,the results of children with C3 deposition in HSPN and IgAN and children without C3 deposition in HSPN and IgAN were different:1.The proportion of capsular synechia,peribulbar fibrosis and chronic lesions of children with C3 deposition in HSPN was higher than that children with C3 deposition in IgAN(P=0.010,P=0.035).However,there were no difference in the length of stay;clinical manifestations:hydrothorax,ascites,microscopic hematuria,massive proteinuria and AKI;the laboratory examination:serum C4,serum IgG,urine protein quantification,uIgG/uCr,ual-MG/uCr;pathological changes of kidney:severe mesangial cell proliferation,interstitial inflammatory cells infiltration,interstitial fibrosis,acute lesions,acute renal tubulointerstitial injury and IF/IA;glomerular IgA deposition and IgG deposition in immunofluorescence in children with C3 deposition in IgAN and HSPN.2.Compared with children without C3 deposition in HSPN,children without C3 deposition in IgAN had the shorter course of disease prior to renal biopsy,the higher proteinuria and the ratios of uTRF/uCr(P=0.027,P=0.038,P=0.011).However,there were no difference in clinical manifestations:hydrothorax,ascites and AKI;the laboratory examination:serum creatinine,serum IgG,urine protein quantification,uIgG/uCr,u?1-MG/uCr and uNAG/uCr;pathological changes of kidney:glomerular fibrosis and GS;glomerular IgA deposition and Fib deposition in immunofluorescence in IgAN and HSPN children without C3 deposition.Conclusion:1.In IgAN,there was no significant difference in the clinical manifestations,laboratory examination and renal pathological changes between children with and without C3 deposition.2.In HSPN,children with C3 deposition had higher the ratios of uIgG/Cr,uTRF/uCr and uAlb/uCr and the proportion of renal tubular epithelial cells swelling and degeneration and renal tubular epithelial cells necrosis than that of children without C3 deposition.It is suggested that children with C3 deposition in HSPN have more severe glomerular and tubular injury.3.The proportion of glomerular C3 deposition in IgAN was higher than that of HSPN;however glomerular C3 deposition in HSPN has a great influence on the clinical and pathological changes.