Long-term prognostic analysis of IgA nephropathy with focal segmental glomerulosclerosis in children / 中华肾脏病杂志

Objective:To analyze the long-term prognosis of IgA nephropathy (IgAN) with focal segmental glomerulosclerosis (FSGS) and the risk factors related to renal prognosis in children with IgAN-FSGS.Methods:A retrospective study was concluded in IgAN-FSGS children who were followed up for more than 5 years and diagnosed by renal biopsy for the first time in the Eastern Theater General Hospital from January, 2004 to December, 2018. The end-point events of the study were entering end-stage kidney disease (ESKD) or estimated glomerular filtration rate (eGFR) decreased by ≥50% from baseline, which were defined as poor renal prognosis. Baseline clinicopathologic data of IgAN-FSGS children were compared between the end-point event group and the non-end-point event group. The cumulative renal survival rate of IgAN-FSGS children was calculated by Kaplan-Meier survival analysis. The influencing factors of poor renal prognosis in IgAN-FSGS children were analyzed by Cox proportional hazards model, and the diagnostic value was evaluated by the receiver operating characteristic curve (ROC curve) and area under the curve (AUC). The diagnostic value was verified by time dependent-ROC and time dependent-AUC.Results:A total of 204 IgAN-FSGS children were enrolled in this study, of whom 132 cases were males (64.7%). The median age of renal biopsy was 16 (14, 17) years old. During a median follow-up time of 90.7 (71.7, 114.8) months, 57 cases (27.9%) reached the end-point events. Compared with the non-end-point event group ( n=147), the end-point event group ( n=57) had higher proportions of males and hypertension, higher levels of 24-hour urinary protein, serum creatinine, serum uric acid, urinary N-acetyl-β- D-glucosaminidase, urinary retinol binding protein, higher proportions of glomerular segmental sclerosis (S1) ≥25% and tubular atrophy/interstitial fibrosis (T1/T2), and lower levels of serum albumin, serum IgA, and serum IgG (all P<0.05). There was no statistical difference between the two groups in treatment (all P>0.05). Kaplan-Meier survival analysis showed that with entry of ESKD or eGFR decreased by ≥50% from baseline as the end-point events, the 5-year, 10-year, and 15-year cumulative renal survival rates in IgAN-FSGS children were 88.7%, 67.6%, and 50.7%, respectively. Multivariate Cox regression analysis showed that proteinuria >1 g/24 h ( HR=3.702, 95% CI 1.657-8.272, P=0.001), hyperuricemia ( HR=3.066, 95% CI 1.793-5.245, P<0.001), S1≥25% ( HR=2.017, 95% CI 1.050-3.874, P=0.035), T1/T2 ( HR=1.863, 95% CI 1.021-3.158, P=0.016) were the independent related factors for poor renal prognosis. ROC curve analysis showed that S1≥25% ( AUC=0.605, P=0.021, sensitivity 26.3%, specificity 94.6%), T1/T2 ( AUC=0.624, P=0.006, sensitivity 43.9%, specificity 81.0%), hyperuricemia ( AUC=0.658, P<0.001, sensitivity 52.6%, specificity 78.9%), proteinuria>1 g/24 h ( AUC=0.670, P<0.001, sensitivity 87.7%, specificity 46.3%) could accurately predict the renal outcome of IgAN-FSGS. Time dependent-ROC curve validation showed that the combined diagnosis of S1≥25%, T1/T2, hyperuricemia and proteinuria>1 g/24 h had a good predictive value for renal prognosis (3-year AUC=0.846 and 5-year AUC=0.777, respectively). Conclusions:During a median follow-up of 90.7 months, 27.9% of IgAN-FSGS children have poor renal prognosis, and the 5-year, 10-year, and 15-year cumulative renal survival rates are 88.7%, 67.6%, and 50.7%, respectively. Urinary protein >1 g/24 h, hyperuricemia, T1/T2, and S1 ≥25% are the risk factors for renal prognosis in IgAN-FSGS children.

A five-year follow-up study on the clinicopathology of 130 children with Henoch-Sch?nlein purpura nephritis / 中华肾脏病杂志

Objective:To analyze the clinicopathologic features and prognosis of children with Henoch-Sch?nlein purpura nephritis (HSPN).Methods:The clinicopathological data of children with HSPN who were followed up for more than 5 years and underwent renal biopsy in Jinling Hospital affiliated to Medical School of Nanjing University from January 2001 to June 2015 were retrospectively analyzed. The follow-up endpoint event was defined as estimated glomerular filtration rate (eGFR)<90 ml·min -1·(1.73 m 2) -1. Participants were divided into two groups according to whether the children had reached the primary endpoint event or not. Cox proportional hazards model was used to analyze the influencing factors of renal poor prognosis in children with HSPN. Kaplan-Meier survival curve method was used for survival analysis, and log-rank test was used to compare the difference of renal cumulative survival rate between segmental sclerosis/adhesion (S1) group and non-segmental sclerosis/adhesion (S0) group. Receiver operating characteristic curve (ROC curve) and area under the curve ( AUC) were used to evaluate the diagnostic value. Results:A total of 130 children with HSPN were enrolled in the study. The median onset age was 11.7(8.6, 13.3) years old, of whom 71 cases were males (54.6%). At a median follow-up time of 100.0(75.8, 119.0) months, 12 cases (9.23%) with HSPN reached the primary endpoint event. Compared with the non-endpoint event group, the endpoint event group had higher proportion of hypertension, higher levels of 24-hour urinary protein, serum cholesterol, serum uric acid, and serum creatinine, and lower levels of serum albumin (all P<0.05). There was no statistical difference in treatment between the two groups (all P>0.05). In terms of pathological features, compared with the non-endpoint event group, the endpoint event group had higher proportion of mesangial hyperplasia (M1), S1, tubular atrophy/interstitial fibrosis (T1/T2) and Glomerulus-Bowman's capsule adhesion (all P<0.05). Multivariate Cox regression model showed that S1 was significantly correlated with renal poor prognosis ( HR=7.739, 95% CI 1.422-42.114, P=0.018). As was revealed in a Kaplan-Meier plot, renal cumulative survival rate in the S1 group was significantly lower than that in the S0 group (log-rank χ2=17.069, P<0.001). The ROC curve showed S1 accurately predicted the outcome ( AUC=0.710, 95% CI 0.549-0.872) with specificity of 0.667(95% CI 0.349-0.901) and specificity of 0.754(95% CI 0.667-0.829). Conclusions:S1 is an independent risk factor affecting renal poor prognosis and has a diagnostic value.

Value of Oxford classification and ISKDC classification in the prognosis of children with Henoch-Sch(o)nlein purpura nephritis / 中华肾脏病杂志

Objective To analyze the Oxford classification (MESTC) and the International Study of Kidney Disease in Children (ISKDC) classification for evaluating the clinical manifestations,histological lesion and short-term prognosis of children with Henoch-Sch(o)nlein purpura nephritis (HSPN).Methods According to the Oxford classification and ISKDC classification,the histological lesions of children with HSPN diagnosed by renal biopsy from Beijing Children's Hospital affiliated to Capital Medical University from January 2018 to December 2018 were re-evaluated.The renal biopsy specimens of the selected subjects were scored according to the Oxford classification and the ISKDC classification.According to whether the first symptom was combined with renal performance,MESTC score and ISKDC classification,children were grouped.The differences in clinicopathological manifestations between the groups were compared.Correlation between MESTC and ISKDC grades was analyzed by nonparametric test rank correlation.Kaplan-Meier survival curve and Log-rank test were used to compare the difference of proteinuria remission rate between the two groups.Univariate and multivariate Cox regression equations were used to analyze the influencing factors of the proteinuria remission rate.Results A total of 78 children with HSPN were enrolled.There were 37 male patients (47.4％) with age of (10.4+2.9) years.When the patients were divided according to MESTC scores and ISKDC classification,the results showed that the proportion of children with nephrotic-range proteinuria in the group of endocapillary hypercellularity (E1,P=0.008),segmental glomerulosclerosis (S1,P=0.015) and ISKDC Ⅲ (P=0.041) was higher than that of E0,S0 and ISKDC Ⅱ groups.The proportion of children with E1 (P=0.015),crescents (C1&C2,P=0.025) or ISKDC Ⅲ (P=0.017) that had been treated with high-dose methylprednisolone was higher.The result of Kaplan-Meier survival curve showed more difficult for proteinuria remission in children with C2 are than C0&C1 group (P=0.026),while no difference were found when children were grouped by M,E,S,T and ISKDC.Multivariate Cox regression analysis showed that the C2 (HR=0.143,95％C1 0.020-1.046,P=0.055) might be a risk factor for proteinuria remission,while the P value was close to 0.05.Conclusions Children with HSPN scored as ISKDC Ⅲ,E1 and S1 are more likely to show nephrotic-range proteinuria.C2 may indicate that patients are more difficult to achieve proteinuria remission.

Value of Oxford classification and ISKDC classification in the prognosis of children with Henoch-Schönlein purpura nephritis / 中华肾脏病杂志

Objective@#To analyze the Oxford classification (MESTC) and the International Study of Kidney Disease in Children (ISKDC) classification for evaluating the clinical manifestations, histological lesion and short-term prognosis of children with Henoch-Schönlein purpura nephritis (HSPN).@*Methods@#According to the Oxford classification and ISKDC classification, the histological lesions of children with HSPN diagnosed by renal biopsy from Beijing Children's Hospital affiliated to Capital Medical University from January 2018 to December 2018 were re-evaluated. The renal biopsy specimens of the selected subjects were scored according to the Oxford classification and the ISKDC classification. According to whether the first symptom was combined with renal performance, MESTC score and ISKDC classification, children were grouped. The differences in clinicopathological manifestations between the groups were compared. Correlation between MESTC and ISKDC grades was analyzed by nonparametric test rank correlation. Kaplan-Meier survival curve and Log-rank test were used to compare the difference of proteinuria remission rate between the two groups. Univariate and multivariate Cox regression equations were used to analyze the influencing factors of the proteinuria remission rate.@*Results@#A total of 78 children with HSPN were enrolled. There were 37 male patients (47.4%) with age of (10.4±2.9) years. When the patients were divided according to MESTC scores and ISKDC classification, the results showed that the proportion of children with nephrotic-range proteinuria in the group of endocapillary hypercellularity (E1, P=0.008), segmental glomerulosclerosis (S1, P=0.015) and ISKDCⅢ(P=0.041) was higher than that of E0, S0 and ISKDCⅡ groups. The proportion of children with E1 (P=0.015), crescents (C1&C2, P=0.025) or ISKDCⅢ(P=0.017) that had been treated with high-dose methylprednisolone was higher. The result of Kaplan-Meier survival curve showed more difficult for proteinuria remission in children with C2 are than C0&C1 group (P=0.026), while no difference were found when children were grouped by M, E, S, T and ISKDC. Multivariate Cox regression analysis showed that the C2 (HR=0.143, 95%CI 0.020-1.046, P=0.055) might be a risk factor for proteinuria remission, while the P value was close to 0.05.@*Conclusions@#Children with HSPN scored as ISKDCⅢ, E1 and S1 are more likely to show nephrotic-range proteinuria. C2 may indicate that patients are more difficult to achieve proteinuria remission.

The Oxford Classification predictors of chronic kidney disease in pediatric patients with IgA nephropathy / Preditores da doença renal crônica segundo a Classificação de Oxford em pacientes pediátricos com nefropatia por IgA

Abstract Objective: The Oxford Classification for Immunoglobulin A nephropathy (IgAN) identifies pathological variables that may predict the decline of renal function. This study aimed to evaluate the Oxford Classification variables as predictors of renal dysfunction in a cohort of Brazilian children and adolescents with IgAN. Methods: A total of 54 patients with IgAN biopsied from 1982 to 2010 were assessed. Biopsies were re-evaluated and classified according to the Oxford Classification. Multivariate analysis of laboratory and pathological data was performed. The primary outcomes were decline of baseline estimated glomerular filtration rate (eGFR) greater than or equal to 50%. Results: Mean follow-up was 7.6 ± 5.0 years. Mean renal survival was 13.5 ± 0.8 years and probability of decline ≥50% in baseline eGFR was 8% at five years of follow-up and 15% at ten years. Ten children (18.5%) had a decline of baseline eGFR ≥ 50% and five (9.3%) evolved to end-stage renal disease. Kaplan-Meier analysis showed that baseline proteinuria, proteinuria during follow-up, endocapillary proliferation, and tubular atrophy/interstitial fibrosis were associated with the primary outcome. Multivariate Cox analysis showed that only baseline proteinuria (HR, 1.73; 95% CI, 1.20-2.50, p = 0.003) and endocapillary hypercellularity (HR, 37.18; 95% CI, 3.85-358.94, p = 0.002) were independent predictors of renal dysfunction. No other pathological variable was associated with eGFR decline in the multivariate analysis. Conclusion: This is the first cohort study that evaluated the predictive role of the Oxford Classification in pediatric patients with IgAN from South America. Endocapillary proliferation was the unique pathological feature that independently predicted renal outcome.

Resumo Objetivo: A Classificação Oxford para a Nefropatia por Imunoglobulina A (IgAN) identificou variáveis patológicas de risco para disfunção renal. O presente estudo teve como objetivo avaliar as variáveis da Classificação de Oxford como preditores de disfunção renal em crianças brasileiras com IgAN. Métodos: Foram analisados 54 pacientes com diagnóstico de IgAN entre 1982-2010. As biópsias renais foram reavaliadas pela Classificação de Oxford. Foram feitas análises uni e multivariada das variáveis clínicas e patológicas. O desfecho primário foi queda da taxa de filtração glomerular (TFG) ≥ 50% da filtração basal. Resultados: O acompanhamento médio foi de 7,6 ± 5,0 anos. A sobrevida renal média foi de 13,5 ± 0,8 anos e a probabilidade de atingir o desfecho primário foi de 8% em cinco anos e 15% em 10 anos de seguimento. Dez crianças (18,5%) apresentaram queda na TFG basal ≥ 50% e cinco (9,3%) evoluíram para doença renal crônica terminal. A análise de Kaplan-Meier mostrou que a proteinúria basal e de seguimento, a proliferação endocapilar e a atrofia tubular/fibrose intersticial foram associadas com o desfecho primário. A análise multivariada de Cox mostrou que a proteinúria basal (HR = 1,73; IC95% 1,20-2,50, p = 0,003) e a proliferação endocapilar (HR = 37,18; IC95% 3,85-358,94, p = 0,002) foram preditores independentes de disfunção renal. Nenhuma outra variável patológica foi associada com declínio da TFG na análise multivariada. Conclusão: Este é o primeiro estudo brasileiro que avaliou a Classificação Oxford em crianças com IgAN. A proliferação endocapilar foi a única característica patológica capaz de predizer independentemente o declínio da função renal.

Risk Factors and Correlation Analysis between the Oxford Classification and Clinical Indicators of IgA Nephropathy / 中国医科大学学报

Objective To analyze the risk factors and correlation between clinical indicators and the four main pathological lesions of IgA ne?phropathy in the Oxford classification:mesangial hypercellularity(M0/1),endocapillary proliferation(E0/1),segmental sclerosis or adhesion(S0/1), and tubular atrophy/interstitial fibrosis(T0/1/2). Methods Clinical and pathological data were collected from 514 patients with biopsy?proven IgA nephropathy admitted in our hospital from February 17,2006 to October 11,2011. These patients were all above 18 years old. Cases with sec?ondary causes of mesangial IgA deposition were excluded,such as Henoch?chonlein purpura,ankylosing spondylitis and psoriasis et al. The inde?pendent risk factors affecting the pathological classification were analyzed by Spearman rank correlation analysis and two?category and multi?classi?fication logistic regression using SPSS 17.0 statistical software. Results In 514 IgAN patients,the ratio of males to females was 1.06:1. The aver?age age was 35.70±11.99 years,and the average disease duration was 18.31±30.42 months. M0E0S0T0 was the major pathologic classification of isolated hematuria. Chronic kidney disease(CKD)stage,24 hours proteinuria,albuminuria,urine transferrin and IgG levels were positively corre? lated with M lesion;serum albumin,C3 and PLT showed a negative correlation with M lesion. Twenty four hours proteinuria and blood platelet count were the independent risk factors for M lesion. As shown by stratified analysis ,the proportion of M1 in cases with 24 hours proteinuria≥3.5 g/d is much higher than that in cases with non?nephrotic range proteinuria. Age,systolic blood pressure,uRBC,24 hours proteinuria,albuminuria urine transferrin and IgG levels were positively correlated with E lesion,Duration,serum albumin showed a negative correlation with E lesion. Age and duration of nephritis were independent risk factors for E lesion. 73.3%of patients that above 60 years old showed endothelial proliferation. CKD stage,24 hours proteinuria were positively correlated with S lesion. Age,CKD stage,systolic blood pressure,diastolic blood pressure,C4,TC, LDL?C,CRP,Fib,UA,Cys?C and 24 hours proteinuria,urineβ2?microglobulin,albumin,transferrin and IgG levels were positively associated with T lesion;hemoglobin,serum albumin,serum IgG showed a negative correlation with T lesion. Infection history,high CRP levels,DBP more than 90 mmHg,hypoalbuminemia,high low density lipoproteinemia,and anemia were independent risk factors for T lesion. Conclusion Twenty four hours proteinuria,blood platelet count,age,duration of nephritis,hypoalbuminemia,anemia,hyperlipidemia,DBP≥90 mmHg and high CRP lev?els were risk factors for the Oxford classification of IgA nephropathy. Renal biopsy should be carried out in time to make clear the pathological clas?sification and individual treatment,so as to improve the prognosis.

Pathology and Renal Outcome of IgA Nephropathy / 대한내과학회지

BACKGROUND/AIMS: The Oxford classification of immunoglobulin A nephropathy (IgAN) is a pathology-based prognostic classification system. However, further study is needed to determine its validity. We studied the relationships between the Oxford classification and established prognostic factors and renal survival. We also examined associations between electron microscopy findings and these parameters. METHODS: We reviewed and reclassified 213 patients who were diagnosed with IgAN from 1997 to 2007 using the Oxford and World Health Organization (WHO) classification systems. The patients were also categorized by a pathologist using electron microscopy findings, including foot process fusion, glomerular basement membrane thickness, and electron-dense deposits. We examined the correlations between light and electron microscopy data and known prognostic factors (e.g., age, sex, proteinuria, serum creatinine, estimated glomerular filtration rate [eGFR], and blood pressure). The same procedure was applied to renal survival. RESULTS: Patient age increased with the grades of segmental sclerosis (S) and tubular atrophy/interstitial fibrosis (T) (P < 0.05). eGFR decreased significantly with increasing mesangial hypercellularity (M) (p = 0.0034), S (p = 0.0003), endocapillary hypercellularity (E) (p = 0.0411), and T (P < 0.0001). MSET differed significantly by sex (P < 0.0001). The 24-h urine protein/creatinine ratio increased significantly with the degrees of S (p = 0.036), E (p = 0.0155), and T (p = 0.015). The serum creatinine level was significantly higher in patients with T2 than T1 or T0 (P < 0.0001). At the time of biopsy, the degree of tubular atrophy/interstitial fibrosis affected the doubling of serum creatinine or end-stage renal disease. However, the electron microscopy findings did not predict the renal outcome. CONCLUSIONS: Our study suggests that tubular atrophy/interstitial fibrosis is significantly associated with proteinuria and renal progression in IgAN.

Application of Oxford classification in 123 cases of child IgA nephropathy / 重庆医学

Objective To verify the application value of the Oxford classification in child IgA nephropathy (IgAN) .Methods The clinical and pathological data by renal biospy in 123 children patients with IgAN from January 2010 to September 2013 were collected and retrospectively analyzed .84 cases were followed up .The results were divided into 4 grades(A ,B ,C ,D) based on the manifestations at the end of follow‐up .Finally the pathological analysis was performed .Results Among 123 cases ,the clinical man‐ifestations were dominated by nephrotic syndrome (42 .28% ) ,followed by hematuria complicating proteinuria (24 .39% ) .The scores of 4 pathological indexes were dominated by M 1 (82 .11% ) ,E1 (53 .66% ) ,S0 (59 .35% ) and T0 (82 .11% ) respectively ;the mesangial cells proliferation and endocapillary proliferation were related with the hematuria severity (P<0 .01);mesangial cells pro‐liferation ,endocapillary proliferation and renal tubule atrophy/interstitial fibrosis were related with the edema occurrence ( P<0 .05);the mesangial cells proliferation ,segmental glomerulosclerosis and renal tubule atrophy/interstitial fibrosis were related with the average arterial pressure increase(P<0 .05) .4 pathological indexes were related with 24 h urinary protein amount(P<0 .01);the segmental glomerulosclerosis and renal tubule atrophy/interstitial fibrosis were related with the decrease of the estimated glo‐merular filtration rate(P<0 .01) .84 cases were successfully followed up ,the clinical outcome was grade A in 43 cases(51 .19% ) , grade B in 30 cases(31 .71% ) ,grade C in 8 cases(9 .52% ) and grade D in 3 cases(3 .57% ) .Only the renal tubule atrophy/intersti‐tial fibrosis was related with prognosis(P<0 .05) .Conclusion The Oxford classification has certain relation with clinical indexes of children with IgAN .Only the renal tubule atrophy/interstitial fibrosis are the risk factors of prognosis .

Clinical characteristics and Oxford classification of IgA nephropathy patients with hyperuri-cemia / 临床与实验病理学杂志

Purpose To investigate the clinical characteristics and Oxford classification of IgA nephropathy patients with hyperurice-mia. Methods 151 IgA nephropathy patients confirmed by renal biopsy in 2013 were analyzed retrospectively. The patients were di-vided into the two groups:IgA nephropathy patients with or without hyperuricemia. Morphological changes were evaluated with Oxford classification scoring system and Lee’s grades. A comparative analysis of clinical manifestations and pathological injuries was performed between the two groups. Results Incidence of hyperuricemia in IgA nephropathy patients was 48. 3% and was more common in young men. Hypertension was associated with hyperuricemia. Oxford classification of IgA nephropathy patients with hyperuricemia was pre-dominant M1E0S1T0 and Lee’s grades presented with grade Ⅲ. The outstanding histopathologic features with higher plasma uric acid levels indicated higher tubulointerstitial chronicity, higher glomerular sclerosis ratio, accompanied by a decline in glomerular filtration rate. There was no significant difference of vascular lesions. Conclusions The prevalence of hyperuricemia in IgA nephropathy pa-tients is high. Oxford classification shows IgA nephropathy with hyperuricemia are associated with more severe tubulointerstitial lesions and lower GFR.

Validation of the Oxford classification for pediatric IgA nephropathy / 国际儿科学杂志

Objective To assess the validity of the Oxford classification for pediatric patients with primary IgA nephropathy (IgAN) and to analyze the correlations between clinical characteristics at time of biopsy and the Oxford classification,which identified four definitive histological features:mesangial hypereellularity,endocapillary proliferation,segmental sclerosis and tubular atrophy/interstitial fibrosis.Methods Clinical and pathological characteristics of 35 children with primary IgAN were analyzed.The scoring sheet was based on the Oxford classification of IgAN,and four pathological variables,namely mesangial hypercellularity (M),endocapillary proliferation (E),segmental sclerosis (S),and tubular atrophy/interstitial fibrosis (T) were assessed.A total of 35 children with IgAN were grouped according to the scores(M,E,S,T):the M0 and M1 group,E0 and E1 group,S0 and S1 group,T0 and T1/T2 group.These groups were compared in terms of estimated glomeralar filtration rate (eGFR),mean artery pressure (MAP) and proteinuria at time of biopsy.Results We found that the Oxford classification was significantly negatively correlated with eGFR (Pearson's correlation coefficient r =-0.48).However,the Oxford classification was shown to be positively associated with initial proteinuria per day(Pearson's correlation coefficient r =0.35).The M,E,S,T scores were strongly associated with proteinuria at biopsy (P ＜ 0.05),and the lesion S was not correlated with eGFR (P ＞ 0.05).The lesion T was significantly associated with eGFR (P =0.001) and MAP (P =0.03) at biopsy.Conclusion We confirmed that the Oxford classification of IgA nephropathy was valid for children.In addition,our study indicated that the four histological lesions M,E,S and T were significantly associated with clinical features.