Study On Prognostic Factors Of IgA Nephropathy Based On Clinicopathological Features And TCM Syndromes And Evaluation Of The Curative Effect Of Traditional Chinese Medicine

BackgroundIgA nephropathy has now become the most common primary glomerular disease worldwide,accounting for about half of the primary glomerular disease in our country.10% to 30% of IgAN patients progressed to ESRD within 10 years.The prognosis of IgA nephropathy is difficult to predict because of its diverse clinical manifestations and complicated pathological mechanism.With the development of China's economy and the popularization of national medical care,more and more asymptomatic IgA nephropathy has been diagnosed,which has caused the burden of health finance in China to increase year by year.At present,there is no specific treatment for the pathogenesis of IgA nephropathy.Hormone and immunosuppressive therapy are not suitable for all patients because of their side effects.Chinese medicine treatment of IgA nephropathy is widely applied in China,and its curative effect is exact.However,most of previous studies are single center,small sample size and low quality research,and its efficacy needs to be verified by more large-scale and high-quality clinical studies.AimTo explore the risk factors of Chinese and Western medicine related to the prognosis of IgA nephropathy,and to provide a scientific basis for individualized assessment of the risk of disease progression.To evaluate the clinical efficacy of traditional Chinese medicine in the treatment of IgA nephropathy,and to provide scientific decision-making for the prevention and treatment of IgA nephropathy.Methods(1)A historical cohort study was used in this study.All patients who had been diagnosed as primary IgAN by renal biopsy were from Guangdong Province Traditional Chinese Medical Hospital,Shaanxi Provincial Hospital of traditional Chinese medicine,the First Affiliated Hospital of Guangzhou University of Chinese Medicine and Jiangmen Wuyi Hospital of Traditional Chinese Medicine(September 1,2005 to December 31,2016).A total of 536 patients were enrolled in the study.The related baseline indicators such as demography,clinicopathology and TCM syndrome were collected,and the follow-up data were collected.Doubled Serum creatinine,eGFR decreased more than 50%,ESRD and death were defined as the composite endpoint.The Cox proportional risk regression model was used to screen the factors associated with the composite endpoint of IgA nephropathy.The Kaplan-meier survival curve was used to calculate the renal cumulative survival rate of the patients,and the logarithmic rank test(Log-rank)was used to compare the groups.(2)Cases and data collection were included in the first part.The patients were divided into Chinese medicine group(413 cases)and non Chinese medicine group(123 cases)according to whether the patients were exposed to Chinese medicine.The propensity score was used to control the confounding factors between the two groups.The Cox proportional risk regression model was used to calculate the risk ratio and the 95% confidence interval.Analysis of the results and explore whether traditional Chinese medicine treatment can reduce the risk of progression of IgA nephropathy.ResultsA total of 536 patients were included in this study.The median age was 33(26-41 years.277 cases were female,accounting for 51.7%.The median of the course of disease was 6(1-24)months.The median follow-up time was 2.3(1.4-3.4)years.A total of 57 patients(10.6%)had composite endpoint.(1)Cox regression univariate analysis found that pregnancy as the cause of disease,onset symptoms for other,asymptomatic at onset,hypertension,urinary protein,serum creatinine,urea nitrogen,eGFR,blood uric acid,blood total carbon dioxide,chlorine,potassium,phosphorus,serum total protein,serum albumin,T score,C score,fatigue,edema,frequent urination at night,poor appetite,intolerance of cold and cold limbs,nausea,heavy limbs,pale tongue,pale red tongue,greasy tongue fur,yang deficiency of spleen and kidney,blood stasis,water dampness,number of subordinate syndromes,Bailing capsule,Huangkui capsule and Uremic Clearance Granule are closely related with the composite endpoint of IgA nephropathy.The average arterial pressure was added to the baseline,and 35 variables were eventually entered into multivariable analysis.Cox regression multivariable analysis showed that pregnancy as the cause of disease,onset symptoms for other,urinary protein,serum creatinine,Oxford T score,Oxford C score,edema,intolerance of cold and cold limbs are independent risk factors of composite endpoint of IgA nephropathy.(2)Screening in the Cox regression univariate analysis and multivariate Cox regression analysis results,a total of 14 variables were selected into the propensity score matching:gender,age at renal biopsy,mean arterial pressure,urinary protein,serum creatinine,urea nitrogen,serum albumin,eGFR,Oxford T score,Oxford C score,yang deficiency of spleen and kidney,ACEI,ARB and Glucocorticoid/cyclophosphamide.Before propensity score matching,there was a significant difference between two groups of patients in yang deficiency of spleen and kidney,eGFR,serum creatinine,Oxford T score and ARB(P<0.05).Cox regression analysis showed that the risk of non Chinese medicine group entering the composite endpoint was significantly higher than that of the Chinese medicine group(HR,5.49;95% CI,3.22~9.38;P=0.000).After propensity score matching,the statistical difference between all variables had been balanced(P>0.05).Cox regression analysis showed that the risk of entering the composite endpoint in the non Chinese medicine group was significantly higher than that of the Chinese medicine group(HR,2.56,95% CI,1.02~6.45,P=0.046).For other propensity score methods,in addition to regression adjustment method(P=0.108),stratification method(5 layers)(HR,2.8;95% CI,1.6~4.92;P=0.000),stratification method(10 layers)(HR,2.44;95% CI,1.37~4.36;P=0.003),inverse probability of treatment weighting method(HR,10.51;95% CI,5.69~19.4;P=0.000)and standardized mortality ratio weighting method(HR,11.9;95% CI,5.27~26.76;P=0.000)all showed that the risk of entering the composite endpoint in the non Chinese medicine group was higher than that of the Chinese medicine group.For Single endpoint:1)Doubled Serum creatinine:before propensity score matching,the risk of doubling blood creatinine in non Chinese medicine group was higher than that of the Chinese medicine group(HR,3.52;95% CI,1.59~7.8;P=0.002).After matching,the risk of doubling blood creatinine between the two groups was equal(HR,1.54;95% CI,0.46~5.1;P=0.482).The results of the propensity score regression adjustment method and stratification method(5 layer,10 layer)all suggested that the risk of doubling blood creatinine in two groups was equal(P>0.05).The inverse probability of treatment weighting method(HR,5.88,95% CI,2.06~16.77,P=0.001)and standardized mortality ratio weighting method(HR,5.64,95% CI,1.28~24.76;P=0.022)both indicated that the risk of doubling of serum creatinine in the non Chinese medicine group was higher than that of the Chinese medicine group.2)eGFR decreased more than 50%:before propensity score matching,the risk of eGFR decreased more than 50% in the non Chinese medicine group was higher than that of the Chinese medicine group(HR,4.08;95% CI,2.19~7.61;P=0.000).After matching,the risk of eGFR decreased more than 50% between the two groups was equal(HR,1.92;95% CI,0.71~5.18;P=0.201).The results of the propensity score regression adjustment method and stratification method(10 layer)both suggested that the risk of eGFR decreased more than 50% in two groups was equal(P>0.05).The stratification method(5 layer)(HR,2.0;95% CI,1.04~3.85;P=0.039),inverse probability of treatment weighting method(HR,6.4;95% CI,2.92~14.21;P=0.000)and standardized mortality ratio weighting method(HR,6.9;95% CI,2.33~20.73;P=0.001)indicated that the risk of eGFR decreased more than 50% in the non Chinese medicine group was higher than that of the Chinese medicine group.3)ESRD:before propensity score matching,the risk of ESRD in the non Chinese medicine group was higher than that of the Chinese medicine group(HR,6.38;95% CI,3.42~11.93;P=0.000).After matching,the risk of ESRD between the two groups was equal(HR,2.01;95% CI,0.72~5.59;P=0.182).For other propensity score methods,in addition to regression adjustment method(P=0.208),stratification method(5 layers)(HR,3;95% CI,1.57~5.72;P=0.001),stratification method(10 layers)(HR,2.53;95% CI,1.3~4.93;P=0.006),inverse probability of treatment weighting method(HR,13.96;95% CI,7.1~27.44;P=0.000)and standardized mortality ratio weighting method(HR,15.95;95% CI,6.6~38.44;P=0.000)all showed that the risk of ESRD in the non Chinese medicine group was higher than that of the Chinese medicine group.4)Death:in addition to inverse probability of treatment weighting method(HR,27.6;95% CI,1.16~657.17;P=0.04),the results of other propensity score methods showed no difference in death risk between the Chinese medicine group and non Chinese medicine group.ConclusionCox regression multivariable analysis showed that pregnancy as the cause of disease,onset symptoms for other,urinary protein,serum creatinine,Oxford T score,Oxford C score,edema,intolerance of cold and cold limbs were independent risk factors of composite endpoint of IgA nephropathy.Traditional Chinese medicine treatment could reduce the risk of progression of IgA nephropathy.