| Research backgroundIgA nephropathy(immunoglobulin A nephrology,IgAN)refers to the primary glomerular disease in the glomerular mesangial region that is centered on IgA and accompanied by the deposition of multiple immune complexes such as complements C3,which is the most common primary glomerular disease.The clinical manifestations of IgAN are diverse,heterogeneous,and progressive,and are one of the important causes of end stage renal disease(ESRD).The progress mechanism of etiology and course of IgAN has not been fully understood.At present,it is widely believed that the pathogenesis of IgA nephropathy is related to genetic factors and immune-mediated inflammation.Studies have discovered that IgM deposition is found in a variety of kidney diseases and has certain significance for prognosis of disease.However,there are few relevant researches and the conclusion is controversial.And TCM clinical studies on IgA nephropathy with IgM deposition have not been reported.Therefore,this study intends to use a retrospective cross-sectional research method to preliminarily discuss the clinical and pathological manifestations as well as TCM syndromes of IgA nephropathy with IgM deposition.In order to deepen the understanding of IgAN,the pathological research of modern medicine is combined with the treatment based on syndrome differentiation in traditional medicine.ObjectiveInitially explore the clinical traits,renal pathological features and the TCM syndromes differentiation in the patients of IgA nephropathy with IgM deposition methodsMethodologyThis study uses a retrospective cross-sectional study method.The case is based on the IgA nephropathy database of the Department of Nephrology,Guang’anmen Hospital,China Academy of Chinese Medical Sciences,and collected from January 1,2011 to November 31,2019.Patients with idiopathic IgA nephropathy are divided into IgM positive group and IgM negative group according to the immunofluorescence intensity of the glomerular mesangial area under immunofluorescence.The general information,clinical pathological data,and TCM syndrome data of the selected patients will be retrospectively studied.SPSS 24.0 software was used to analyze statistics and compare the clinical,pathological manifestations,and characteristics of TCM syndromes of IgA nephropathy with IgM deposition.Results1.General information1.1 IncorporationA total of 254 eligible IgAN patients were included,112 in the IgM negative group(44.09%),and 142 in the IgM positive group(55.91%).1.2 GenderIn the IgM negative group,there were 71 males(63.4%)and 41 females(36.6%).There were 72 males(50.7%)and 70 females(49.3%)in the IgM positive group.The comparison between the two groups was statistically significant(P=0.043,<0.05),and the proportion of females in the IgM positive group was higher.1.3 Age of renal biopsyThe mean age of IgM negative group was 39.95±12.22 years old,and that of IgM positive group was 38.34±12.51 years old.There was no significant difference between the two groups(P=0.305,>0.05).Age was divided into three age groups according to 16～40 years old,41～60 years old and 61～80 years old.There was no statistical significance in the comparison between the two groups of patients of different age groups(P=0.163,>0.05).1.4 Deasese course(course from onset to renal biopsy)The median duration of disease in the IgM negative group was 12.00(3.00,48.00)months,while the median duration of disease in the IgM positive group was 12.00(2.00,39.00)months,and the difference between the two groups was not statistically significant(P>,0.05).1.5 Body mass indexThe mean BMI of IgM negative group was 24.94±3.87 kg/m2,and that of IgM positive group was 25.20±3.92kg/m2.There was no statistically significant difference between the two groups(P>0.05).BMI<18.5,18.5≤BMI<28 and BMI≥28 were divided into three groups.There was no statistical significance in the comparison between the two groups with different obesity degrees(P>0.05).1.6 Predisposing factorsAmong the 254 patients,the inducing factors were:38 cases of respiratory tract infection(15%),11 cases of fatigue(4.3%),9 cases of urinary tract infection(3.5%),6 cases of pregnancy(2.4%),4 cases of gastrointestinal tract infection(1.6%),4 cases of alcohol consumption(1.6%),and others(1.2%).The inducing factors of the two groups were basically consistent with the overall distribution,and the comparison between the IgM negative group and the IgM positive group with different inducing factors had no statistical significance(P=0.874,>0.05).2.Clinical indicators2.1 hypertensionThe proportion of patients with hypertension during kidney biopsy in the IgM positive group was 95(66.9%),and the IgM negative group was slightly higher than the IgM positive group,but the comparison between the two groups with different blood pressure grades was not statistically significant(P=0.271,>0.05).2.2 24-hours urine total proteinThe median level of 24h-utp in IgM negative group was 1.52(0.76,3.19)g/24h,while that in IgM positive group was 1.84(0.92,2.96)g/24h.There was no significant difference between the two groups(P=0.891,>0.05).24h-utp was divided into three groups according to<1g/24h,1～3.5g/24h and>3.5g/24h,and there was no significant difference between the two groups and the levels of proteinuria(P=0.289,>0.05).2.3 Serum albuminThe average ALB of IgM negative group was 37.36±6.50g/L,and that of IgM positive group was 38.10±7.00g/L.There was no significant difference between the two groups(P=0.392,>0.05).2.4 Renal function and stages of chronic kidney diseaseDifferences in SCr,UA,BUN and eGFR between the two groups were not statistically significant(P>0.05).Stage 4 and stage 5 of IgAN in the IgM positive group were larger in the IgM negative group(12%vs 5.4%),but the difference between the two groups with different CKD stages was not statistically significant(P=0.426,>0.05).2.5 Serum IgA,IgM and complement levelThe median serum IgA level was 3.06(2.37,3.73)g/L in the IgM negative group and 3.08(2.39,4.15)g/L in the IgM positive group.The median serum IgM level was 0.84(0.60,1.16)g/L in the IgM negative group and 1.03(0.73,1.41)g/L in the IgM positive group.The median level of complement C3 was 0.98(0.85,1.12)g/L in the IgM negative group and 0.95(0.79,1.14)g/L in the IgM positive group.The median level of complement C4 was 0.23(0.21,0.30)g/L in the IgM negative group and 0.23(0.20,0.29)g/L in the IgM positive group.There was no significant difference in serum IgA,complement C3 and C4 between the two groups.The median serum IgM level in the IgM positive group was 1.03(0.73,1.41)g/L,which was significantly higher than that in the IgM negative group,which was 0.84(0.60,1.16)g/L.The difference between the two groups was statistically significant.2.6 Blood lipid spectrumThe mean CHO of IgM negative group was 5.34±1.97 mmol/L.The average CHO of IgM positive group was 5.23±1.42mmol/L.The median level of TG in the IgM negative group was 1.78(1.28,2.66)mmol/L.The median level of TG in the IgM positive group was 1.83(1.32,2.57)mmol/L.The mean ldl-c of IgM negative group was 3.31±1.33mmol/L.The mean ldl-c of IgM positive group was 3.18±1.08mmol/L.The mean hdl-c of IgM negative group was 1.22±0.44mmol/L.The mean hdl-c of IgM positive group was 1.24±0.49mmol/L.There was no significant difference in CHO,TG,ldl-c and hdl-c between the two groups(P>0.05).2.7 Urine red blood cell count at high magnificationThe median level of rbc-m in IgM negative group was 9.94(3.29,31.72)/HP.The median level of rbc-m in IgM positive group was 14.45(4.94,46.61)/HP.The difference between the two groups was not statistically significant(P=0.091,>0.05).2.8 Other indicatorsThe mean HCO3-was 24.61±3.06mmol/L in the IgM negative group and 24.11±3.28mmol/L in the IgM positive group.The average HGB of the IgM negative group was 139.37±20.19g/L,and the average HGB of the IgM positive group was 140.59±93.75g/L.There was no statistical significance in the comparison of HCO3-and HGB between the two groups(P>0.05).3.Renal Pathology3.1 Oxford pathological classificationThe incidence of each bovine pathological classification in IgM negative group and IgM positive group were:mesangial cell hyperplasia(M1)(87.5%vs85.9%,P=0.713),endothelial cell proliferation(E1)(16.1%vs28.2%,P=0.023),segmentative sclerosis(S1)(68.8%vs64.1%,P=0.435),renal tubular atrophy or interstitial fibrosis(t1-2)(72.3%vs66.2%,P=0.295),crescent(c1-2)(58.9%vs64.1%,P=0.401).There was no significant difference in the incidence of mesangial cell proliferation,glomerular segular sclerosis,renal tubular atrophy or interstitial fibrosis,or crescents between the two groups(all P>0.05).In terms of E lesions,the incidence of IgM positive group was higher than that of IgM negative group,and the comparison between the two groups was statistically significant(P<0.05).3.2 Immimofluorescence desipositionThe deposition rate of various immune indexes in IgM negative group and IgM positive group was compared:IgG deposition rate(2.7%vs15.5%,P=0.003).Complement C3 deposition rate(81.2%vs90.8%,P=0.125);Deposition rate of C1q(4.5%vs13.4%,P=0.027);FRA deposition rate(4.5%vs10.6%,P=0.073).There was no significant difference between the two groups(all P>0.05).The deposition rates of IgG and Clq in the IgM positive group were higher than those in the IgM negative group,and the differences between the two groups were statistically significant(all P<0.05).4 TCM symptomsThe stage distribution of IgA nephropathy patients in IgM negative group and IgM positive group was acute onset(12.5%vs25.4%)and chronic duration(87.5%vs74.6%).In IgM negative group and IgM positive group,the distribution of the main symptoms in the acute stage of IgA nephropathy patients was:exogenous wind heat syndrome(8.9%vs12.0%)and lower focal heat syndrome(3.6%vs11.3%).The distribution of chronic duration was:deficiency of lung and spleen(23.2%vs26.8%),deficiency of qi and Yin(29.5%vs21.1%),deficiency of liver and kidney Yin(29.5%vs19.7%),deficiency of spleen and kidney Yang(5.4%vs9.2%).The distribution of concurrent syndromes in IgM negative group and IgM positive group were:no concurrent syndromes(5.4%vs14.1%),water dampness(14.3%vs11.3%),phlegm dampness(10.7%vs15.5%),cold dampness(3.6%vs1.4%),damp heat(25.9%vs19.0%),blood stasis(29.5%vs26.1%),liver depression(7.1%vs7.0%),and turbidity toxicity(3.6%vs5.6%).There was no significant difference between the two groups(all P>0.05).Compared with the incidence of chronic duration,the proportion of acute episode in igm-positive group was higher(P=0.011<0.05).5.Linear analysis of IgM deposition and related indexesThere was no statistically significant correlation between IgM deposition intensity and eGFR,Scr,BUN,ALB,UA and 24-hour urinary protein quantification(P>,0.05),and IgM deposition intensity was positively correlated with serum IgM(rs=0.210,P=0.001).Conclusions(1)Clinical and pathological characteristics of IgAN with IgM deposition:IgM deposition is higher in female patients;the incidence of E lesions is higher in Oxford pathological classification.(2)TCM syndrome characteristics of IgAN with IgM deposition:The TCM dominant symptoms of IgAn patients with IgM deposition are mostly lung spleen deficiency syndromes and qi-yin deficiency syndromes,and accompanying symptoms are blood stasis and damp heat. |
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