Clinicopathological Study Of IgAN And Development And Validation Of A Non-invasive Diagnostic Model

ObjectivePart one:To analyze the clinical and pathological characteristics of patients with IgAN in our center from 2013 to 2020.To investigate the relationship between renal arteriolar lesions and progression of IgAN and the effects of different treatment regimens were summarized in order to provide scientific basis for the treatment and prognosis of IgAN.Part two:To explore the clinical parameters related to diagnosis of early IgAN and develop a Nomogram model for non-invasive diagnosis of IgAN.MethodsPart one:This study included 389 patients diagnosed with IgAN by renal biopsy in our center from Jan 1,2013 to Dec 31,2020.The clinical and pathological indicators of patients were described.Data analysis was performed using rank sum test and chi-square test.Patients with IgAN were divided into AL group and non-AL group according to the hyaline degeneration and/or thickening of renal arteriolar wall,and their clinical and pathological characteristics were compared.The patients were followed up from the date of renal biopsy to Oct 31,2021 for at least 6 months.End points were defined as serum creatinine doubled,e GFR reduction > 30%,ESRD,or death.Kaplan-Meier survival analysis compared the renal prognosis of the two groups of patients.Multivariable Cox regression model was used to analyze the correlation between renal arteriolar lesions and progression of IgAN.Patients were divided into ACEI/ARB therapy(SC)group,ACEI/ARB+corticosteroids therapy(CS)group,ACEI/ARB+ immunosuppressant or combined low-dose corticosteroids therapy(IS+CS)group according to treatment regimens.Chi-square test was used to compare the therapeutic effects of the three groups.Part two: A retrospective study was conducted on 712 patients with primary glomerular disease diagnosed with renal pathology and clinical features between Oct 1,2010 and Aug 31,2019.There were 241 cases of IgAN and 471 cases of non-IgA nephrology.They were divided into development cohort and validation cohort according to the time of inclusion.Univariate and multivariate Logistic regression analysis was applied in the development cohort to analyze the factors related to diagnosis of IgAN.Nomogram model for non-invasive diagnosis of IgAN was established according to akichi information criteria(AIC).The model was applied to the validation cohort for validation.Receiver operating characteristic curve(ROC),calibration curve and decision curve analysis(DCA)were used to validate and evaluate the discrimination,calibration and clinical usefulness of this model.ResultsPart one:1.Clinical data:(1)General data: A total of 389 patients with IgAN were included eventually with a male to female ratio of 1.04:1.The average age was 38.7±0.7 years old,and most patients were 20~40 years old(49.9%).(2)Clinical manifestations: 14.6%patients had a history of prodromal infection.The primary symptoms included edema(24.1%),gross hematuria(12.8%),and most of the cases were found by health examination(57.5%).There were 17.5% of patients had gross hematuria,and 78.7%presented with microscopic hematuria.The mean level of urinary protein was 2.36 ±0.12g/24 h and nephrotic syndrome was diagnosed in 11.6%.18.7% of patients had a history of hypertension,and 21.8% were diagnosed with new hypertension.11.8% of patients had anemia,and 40.6% had hyperuricemia.The mean baseline e GFR level was87.6±1.5 ml/min/1.73m2.The main stages of CKD were stage 1(49.9%)and stage 2(30.3%).2.Pathological features: The main pathological types of Oxford were M1E0S1T0-C0(25.7%)and M1E0S0T0-C0(23.9%).Crescent was presented in 12.9% of patients.Hyaline degeneration and/or arterial wall thickening were observed in 30.3% of patients.3.Grouping and follow-up study:(1)Comparison among groups: There were 118 cases in AL group and 271 cases in non-AL group,respectively.Compared with non-AL group,the age,BMI,MAP,urinary protein,serum creatinine,urea nitrogen,serum uric acid and triglyceride levels in AL group were significantly higher,the proportion of male,hypertension,smoking and drinking were significantly increased,and the incidence of gross hematuria,level of e GFR and Ig M deposition were significantly decreased(P <0.05).The AL group had higher CKD stage,Lee’s grade,and severer interstitial fibrosis/tubule atrophy(T1-2)(P < 0.05).(2)Cox regression: In a multivariable Cox regression model adjusting for clinical and pathologic variables available at the time of biopsy,the presence of arteriolar lesions was an independent risk factor for kidney failure(HR = 2.32,95 CI% 1.18~4.58,P = 0.015).(3)Prognosis analysis: The follow-up completion rate was 65% with a median follow-up time of 23(12,37)months.There were 24 patients in the AL group and 21 patients in the non-AL group had reached the composite end point(P < 0.05).Kaplan-Meier analysis illustrated that the cumulative renal survival rate in AL group was significantly reduced compared to that in non-AL group(P < 0.05).4.Treatment and effect evaluation:(1)There were 21.9%,14.3%,and 63.8% of patients in SC,CS,and IS+CS group,respectively,with no significant differences in basic clinical and pathological features among these three groups(P > 0.05).(2)The remission rate of IS+CS group(69.4%)and CS group(63.4%)was significantly higher than that of SC group(43.4%)(P = 0.016).(3)There was no significant difference in e GFR decrease rate among the three groups(P > 0.05).(4)The incidence of adverse reactions in CS group(30.0%)was significantly higher than IS + CS group(11.9%)and SC group(4.3%)(P < 0.05).Part two:Multivariate Logistic regression results showed that age,IgA/C3,serum albumin,total cholesterol,and gross hematuria were correlated with the diagnosis of IgAN.Based on these results,the diagnostic model was constructed.The area under the ROC curve was 0.880 and 0.887 in the development and validation cohort,respectively.The calibration curve shows that the predicted probabilities of the model was in good agreement with the actual probabilities.This model was safety and most patients would benefit from the model according to the decision curve analysis.ConclusionsPart one:(1)Patients with IgAN in our center had mild overall clinical and pathological lesions at initial diagnosis,suggesting that we can do a lot more.However,the completion rate of follow-up was low,so health education and follow-up should be strengthened.(2)Renal arteriolar lesions including hyaline degeneration and/or thickening of renal arteriolar wall were independent risk factors for progression of IgAN.(3)The complete remission and partial remission rates were significantly improved in IS + CS group and CS group,and the incidence of adverse reactions was lower in IS +CS group than CS group.Part two:This Nomogram model is highly accurate and clinically practical in diagnosis of IgAN.It can be used to assist the non-invasive and early diagnosis of IgAN,so that patients can get early treatment.