Clinicopathological And Prognostic Analysis Of 56 Children With Primary Focal Segmental Glomerulosclerosis In A Single Center

Background and ObjectivesFocal segmental glomerulosclerosis(FSGS)is a histological pattern of glomerular lesion that is characterized by sclerotic lesions in parts of some glomeruli and foot process effacement of podocytes.The main clinical manifestations are severe proteinuria and nephrotic syndrome,which is one of the most common causes of hormone-resistant nephrotic syndrome(SRNS)and end-stage nephrotic syndrome(ESRD)in children.In recent years,the lesion of FSGS has shown an increasing prevalence all over the world,but its pathogenesis is still unclear and there is no good means of prevention and treatment.According to the etiology,FSGS lesion has been classified into primary and secondary forms.Primary FSGS often presents with acute onset severe nephrotic syndrome and secondary FSGS often shows a chronic process.The clinical manifestations of those have a lot of overlap,and there may be a common pathophysiological mechanism in the occurrence and development of glomerulosclerosis.Primary FSGS is classified according to Columbia classification into 5 variants including COLL,CELL,PEL,TIP and NOS,which is proposed by D’agati in 2004.Some studies have reported the differences in clinical characteristics and prognosis of Columbia classification,some think that COLL is more likely to have severe proteinuria and hypoalbuminemia,and bad prognosis than that of TIP,the other part believes that there is no significant correlation between pathological classification and clinical manifestations.To find out the frequency,clinicopathological features and outcome among children with primary FSGS in a single center.MethodsFifty-six children with primary FSGS diagnosed as FSGS on January 1,2013 and December 1,2019 in our hospital were reviewed.Patient’s demographic along with clinical and laboratory data and pathological characteristics of renal biopsy were retrospectively noted.Analyze the follow-up data to detect the risk factors that may affect the prognosis of the group.Results1.A total of 56 children with primary FSGS were registered in this research,the median age was 7(3,10)years,and the median course of disease before renal biopsy was 3(1,12)months.Majority of the cases,35(62.5%)were male.2.As for the clinical manifestations,46(82.1%)were nephrotic syndrome,out of which,32(57.1%)were simple nephrotic syndrome and 14(25%)were nephritis nephrotic syndrome.There were 1 case with simple hematuria,6 cases were hematuria and 3 cases were proteinuria.There were 8(14.3%)cases with renal insufficiency,out of which,8 cases were acute renal insufficiency and 4 cases were chronic renal insufficiency.There were 8(14.3%)cases with hypertensive.3.Among the 56 children with primary FSGS,36(64.29%)cases were NOS variants,12(21.43%)cases were TIP variants,4(7.14%)cases were PH variants,and 4(7.14%)cases were COLL variants.No cellular FSGS cases were included in our research.All of the cases,everyone have segmental sclerosing glomeruli,out of which,40(71.43%)cases were segmental sclerosing glomeruli accounting for ≤25%of the total glomeruli,while 16(28.57%)cases were>25%of the total glomeruli.There were 12 cases have glomerulosclerosis.Most of the cases,32(57.1%)cases were mild tubulointerstitial lesions(TIL),15(26.8%)cases were moderate TIL,while 9(16.1%)cases were severe TIL.IF findings showed that 28(50%)cases were single IgM positive,9(16.07%)IgM combined with C3 positive,2(3.57%)were single C3 positive while 17(30.36%)had negative IF findings.4.There were statistical differences in the distribution of eGFR,TG,T-CHO,LDL,D-dimer,NAG enzyme among the four pathological variants in our research.Compared with the NOS variants,the TIP variants had the higher TG,T-CHO,LDL,NAG enzyme and D-dimer and the lower eGFR.The TIP variants had the higher NAG enzyme than the COLL variants.There was no significant differences in age,course of disease,distribution of HGB,BUN,FDP,UA,SCr,ALB,HDL,24hTP and urine P-2MG among different pathological variants.5.The distribution of deposition variant of immune complex and the severity of TIL lesions among the four pathological variants is no significant.The distribution of segmental glomerulosclerosis and positive glomerulosclerosis was significant different among different pathological variants,and the COLL variants had more segmental glomerulosclerosis than the TIP and CELL variants.6.The changes of eGFR,UA and SCr were statistically significant among different degrees of TIL lesions.With the aggravation of TIL lesions,the eGFR decreased and SCr and UA increased.There was no significant differences in age,HGB,BUN,T-CHO,ALB and 24-hour urinary protein among different TIL groups.The distribution of segmental sclerosing glomeruli and glomerular sclerosing glomeruli among different TIL groups was statistically significant.Out of which,severe TIL lesions had the most sclerotic glomeruli and the mild TIL lesions had the least glomerular sclerosing glomeruli.Spearman rank correlation analysis showed that acute TIL score was positively correlated with chronic TIL score,and the correlation coefficient was 0.722,which was statistically significant.7.The average follow-up time of primary FSGS was 29.96±26.50 months.Follow-up endpoints included progressing to ESRD or transplantation,dialysis,and death.During the follow-up period,10(17.86%)cases lost follow-up.And the other 46 follow-up children,including 19(33.93%)cases complete remission,9(16.07%)partial remission and 4(7.14%)cases were no response.While 14(25.0%)realize the follow-up end point,including 10(17.86%)death and 4(7.14%)progressed to ESKD.The multivariate logistic regression model was used to detect the risk factors,which including age,HGB,eGFR,C3 and TIL lesion scores that were statistically significant analyzed by t-test or non-parametric tests and chi-square test.The mode show that age and TIL lesion scores are the independent risk factors leading to the end point of follow-up.Further analysis showed that Age of onset(OR>1)and renal interstitial inflammatory cell infiltration(OR>1)were independent risk factors for the end point of follow-up.Conclusion1.Primary FSGS in children is mainly school-age male,with nephrotic syndrome as the main clinical manifestation,and hematuria,hypertension and renal insufficiency were present in our study.2.Among the four variants,the NOS variants was the most common variant,and the COLL,PH and TIP variant were present.The clinical manifestation of the TIP variant is more severer than that of the NOS variant,but there is no difference in long-term prognosis.The degree of TIL is mainly mild TIL.When renal function injury comes,we should pay attention to the existence of TIL.The IF findings was mainly IgM alone positive or in combination with other molecules.3.The onset age and renal interstitial inflammatory cell infiltration are the independent risk factors for the end point of follow-up.