Clinical Study On The Treatment Of Idiopathic Membranous Nephropathy With Acute Kidney Injury By Reconciliation And Immunotherapy

ObjectiveTo explore the risk factors,common causes,and the effect of acute renal injury(AKI)on idiopathic membranous nephropathy(IMN).To evaluate the short-term clinical efficacy of the"Hejietongjiang Fa"combined immunomodulatory therapy in the treatment of IMN with AKI,and to provide a clinical basis for the effective treatment of IMN with AKI.MethodsThrough a retrospective study of the general situation,basic diseases,clinical manifestation,laboratory examination,treatment and follow-up datas of IMN patients which received kidney biopsy,data completed and regular follow-up for more:than 12 months in the Guang’anmen hospital from January 2012 to December 2017,analyze the clinical characteristics of patients IMN combined with AKI,and to evaluate the short-term clinical efficacy of the "Hejietongjiang Fa"combined immunomodulatory therapy in the treatment of IMN combined with AKI.Results1.Clinical Features94 cases of IMN patients were included which received kidney biopsy,data completed and regular follow-up for more than 12 months in the Guang’anmen hospital from January 2012 to December 2017.According to the 2012 KDIGO guidelines for AKI,45 patients were diagnosed with IMN combined with AKI,of which 8 cases were diagnosed when renal biopsy,and 37 cases occurred in the course of treatment.1.1 General SituationAge[62(54.5,71.5)vs 54(46.5,58),P=0.000]and body mass index(BMI)(25.7 ±4.1,23.9±2.6,P=0.010)were larger in Group AKI than N-AKI(NO-AKI),P<0.05,which had statistical difference.The ratio of male to female among the two groups was about 2:1,P>0.05,and there was no statistical difference.1.2 Basic DiseasesGroup AKI which combined with hypertension and coronary heart disease were more than group N-AKI,[39(96.3%)vs 27(55.1%),P=0.001],[14(31.1%)vs 3(6.1%),P=0.002],and P<0.05,with statistical difference.Group AKI and N-AKI combined with Type 2 diabetes mellitus(T2DM)were 19(42.2%)vs 14(28.6%),P=0.166,and there was no statistical difference.1.3 Pathological FeaturesCompared with group N-AKI,there were more tubulointerstitial damage in group AKI[35(77.8%)vs 14(28.6%),P=0.000],P<0.05,with statistical difference.There were 2 cases with other types of glomerulonephritis in group AKI,ANCA associated glomerulonephritis and capillaries proliferative glomerulonephritis with IgA deposited.1.4BaselineThere were statistical differences between group AKI and group N-AKI in the level of serum creatinine(Scr)[129.0186.3 vs 71.3±17.2,P=0.000]μmol/L,BUN[9.6(7.5,12.0)vs 4.9(4.2,6.1),P=0.032]mmol/L,hemoglobin(HBG)[109.2±24.6 vs 118.5±17.9,P=0.014]g/L and estimated glomerular filtration rate(eGFR)[58.4 + 23.9 vs 86.9 + 24.5,P=0.010]ml/min/1.73m2,P<0.05;while there was no significant difference in the level of triglyceride(TG)(3±1.9 vs 3.6±2.1,P=0.222)mmol/L,serum albumin(ALB)(22.5 + 6.2 vs 25 + 7,P=0.078)g/L,and serum uric acid(UA)(351.2±111.6 vs 372.6±71.3)between group AKI and group N-AKI.1.5TreatmentIn group AKI,the proportion of immunoregulation therapy was higher than that of in group N-AKI[35(77.8%)vs 18(36.7%),P=0.000],while N-AKI group accepted more basic therapy than AKI group[31(63.3%)vs 10(22.2%),P=0.000],both were with statistical difference.2.The Cause of AKIIn this study,the treatment related[15(33.3%),cyclosporine A(6,40%),RAAS blockers(5,33.3%),other diuretics(2,13.3%),diclofenac sodium(1,6.7%),vaccine(1,6.7%)]was the highest inducement,followed by infection[14(31.1%),lung infection most common(9,64.3%),idiopathic AKI[10(22.2%)].Others such as visible venous thrombosis,rhabdomyolysis,acute myocardial infarction,new onset atrial fibrillation,and upper gastrointestinal bleeding could also lead to AKI.3.Evaluation of the Recent Therapeutic Effect3.1 Symptoms of Traditional Chinese Medicine After the occurrence of AKI,the patients were characterized by nausea,shortness of breath,abdominal distention,loss of appetite,palpitation,cough,vomiting,constipation,oliguria and so on.The dialectical genus of qi deficiency and blood stasis water stopped,the function of Sanjiao decreased which caused humidity and damp turbidity.After the treatment with Hejiefenxiao Tang for 14 days,the above symptoms were obviously improved,with statistical difference.3.2 Renal FunctionThe changes of Scr[143.0(126.5,174.0)vs 101.0(80.0,145.0),P=0.000]μmol/L、BUN[12.1(9.3,15.2)vs 9.7(7.4,14.0),P=0.000]mmol/L,ALB(21.2±5.2 vs 22.31±5.0,P=0.015)g/L and eGFR(32.2±13.2 vs 50.71±24.0,P=0.000)ml/min/1.73m2 before and after treatment were noteworthy,P<0.05,.which meant the function of renal improved significantly.4.The Influence of AKI on IMN4.1 Adjustment of Immunomodulatory TherapyAfter AKI,32 cases(71.1%)adjusted the usage/dosage of hormone,of which 25 cases(71.1%)accepted methylprednisolone intravenous drip 40mg/d,4 cases increased the oral doses,and 4 cases discontinued hormones because of severe infection.After the renal function tends to be stable,immunosuppressive therapy was continued.There were 22 cases which accepted cyclosporin(CSA)before AKI,while 8 cases continued CSA,but the measurement was down,7 cases were adjusted to cyclophosphamide(CTX),and 7 cases were adjusted to malcophenol(MMF)after AKI.4.2The Remission of NS and PrognosisThe proportion of NS remission(complete remission and partial remission)in group AKI was lower than that of group N-AKI[21(46.7%)vs 38(77.6%),P=0.002],setting the decline of eGFR>50%as the renal terminal event,and the proportion of renal function in group AKI to renal endpoint was higher than group N-AKI group[15(33.3%)vs 7(14.3%),P=0.029],P<0.05,which had statistical difference.There were 3 cases died of all-cause and 2 cases accessed to maintenance dialysis in group AKI.5.Analysis Risk Factors of Renal Endpoint EventThe COX proportional risk regression model was used to study the risk factors of renal endpoint event,the cut-off time of the follow-up study was December 2017 and set the decline of eGFR>50%as the renal terminal event.Age,group,BMI,eGFR,baseline 24h-UTP,tubulointerstitial damagment,and the remission of NS in follow-up were brought into model,while the results showed that eGFR(P=0.033),and the remission of NS(P=0.033)were the independent risk factors for renal endpoint during the follow-up process(setting P<0.05 was significative of the end of the kidney risk factors).ConclusionOlder,higher BMI,poor basic renal function(lower eGFR,higher Scr,higher BUN),more proteinuria,higher TC,lower HBG,renal tubulointerstitial lesions,hypertension,T2DM,and coronary heart disease may be the risk factors for AKI in IMN patients.Treatment of drug related,infection are common inducement factors of AKI.The occurrence of AKI can seriously affect the natural course and prognosis of IMN.Tubulointerstitial disease,eGFR,and the remission of NS during follow-up were independent risk factors for the decline of eGFR>50%.The combination of "Hejietongjiaing Fa" and immunomodulatory therapy can effectively improve the short-term clinical efficacy of IMN combined with AKI(TCM symptoms and laboratory examination).