Clinical Significance Of Intrarenal Lymphoid Clusters In Patients With Idiopathic Membranous Nephropathy

Objective: To investigate the distribution of intrarenal lymphoid clusters,clinicopathological features and prognosis of patients with idiopathic membranous nephropathy.Methods: 78 patients with Idiopathic membranous nephropathy(IMN)diagnosed by renal biopsy from November 2019 to November 2020 were collected.74 patients with IMN were selected according to the inclusion and exclusion criteria.According to the distribution of intrarenal lymphoid clusters,they were divided into Grade 0,Grade 1,Grade 2,Grade 3 and Grade 4,further divided into low-grade group(including Grade 0and Grade 1,n=27),medium-grade group(including Grade 2,n=24)and high-grade group(including Grade 3 and Grade 4,n=23).The clinical manifestations,pathological features and the changes of clinical indicators after 3 months treatment of the three groups were retrospectively analyzed and compared.Results:1.74 patients with IMN were collected in this study,including 50 males(67.60%)and 24females(36.40%),with a male to female ratio of 2.08:1.The age ranged from 23 to 80 years,with an average age of 55.22 years.According to the distribution of intrarenal lymphoid clusters,they were divided into Grade 0,Grade 1,Grade 2,Grade 3 and Grade4.There are 0 in Grade 0(0.00%),27 in Grade 1(36.49%),24 in Grade 2(32.43%),13 in Grade 3(17.57%),10 in Grade 4(13.51%),which further divided into low-grade group(including Grade 0 and Grade 1,n=27,36.49%),medium-grade group(including Grade 2,n=24,32.43%)and high-grade group(including Grade 3 and Grade 4,n=23,31.08%).There were no significant differences in gender distribution,BMI,systolic blood pressure,diastolic blood pressure,mean arterial pressure,course of disease before renal biopsy,history of essential hypertension,history of diabetes,and with nephrotic syndrome among the three groups(P＞0.05).2.There were differences in baseline hemoglobin among the three groups by pair comparison,and baseline hemoglobin decreased with the increase of the classification of intrarenal lymphoid clusters(P<0.05).Compared with low-grade group and high-grade group,the baseline serum triglyceride of medium-grade group was higher(P<0.05).There was no significant difference in baseline serum triglyceride between the low-grade group and the high-grade group(P＞0.05).Baseline e GFR in the high-grade group was lower than that in the low-grade group and the medium-grade group(P<0.05).There was no significant difference in baseline e GFR between low-grade and medium-grade groups(P＞0.05).Compared with the low-grade group,the positive rate of serum anti-PLA2 R antibody in the medium-grade and high-grade groups was higher(P<0.05).There was no significant difference in the positive rate of anti-PLA2 R antibody between the middle grade group and the high grade group(P＞0.05).Three groups at baseline serum albumin,serum creatinine,serum uric acid,fasting blood glucose,serum total cholesterol,serum high density lipoprotein cholesterol,serum low density lipoprotein cholesterol,urine protein semi-quantitative analysis,microscopic examination of the urine red blood cell count,microscopic examination of the urine leucocyte number,microscopic examination of the urine tube type number,serum Ig G4,serum C3,serum C4 and serum Ig G,serum Ig A,serum Ig M,24 h urine protein on quantitative had no obvious difference(P＞0.05).3.Compared with the low-grade group,the incidence of glomerulosclerosis,renal small vessel disease,CI,TIL,positive rate of Ig G4 and positive rate of PLA2 R in the mediumgrade and high-grade groups were higher,and the degree of renal tubule atrophy was more serious,with statistical significance(P<0.05).However,there were no significant differences in the incidence of glomerulosclerosis,renal small vessel disease,CI,TIL,positive rate of Ig G4,positive rate of PLA2 R and the degree of renal tubule atrophy between the medium-grade and high-grade groups(P＞0.05).Compared with the low-grade group,renal interstitial fibrosis and interstitial inflammation in the high-grade group was more serious(P<0.05).There is no significant difference in crescentformation,Ig G positive rate of kidney,Ig M positive of kidney,Ig A positive rate of kidney,C3 positive rate of kidney among three groups(P＞0.05).4.Compared with the medium-grade group,the decrease rate of urinary protein in the high-grade group was lower after 3 months of treatment(P=0.043).However,there was no significant difference in urinary protein change rate between the low-grade group and the medium-grade group and the high-grade group after 3 months of treatment(P＞0.05).There were no significant differences in hormone and immunosuppressive therapy,the change rates of serum albumin,serum creatinine and e GFR among the three groups after 3 months of treatment(P＞0.05).Conclusions:1.The severity of renal injury was increased with the elevation of intrarenal lymphoid clusters of IMN patients,suggesting that the classification of the intrarenal lymphoid clusters may be related to the disease activity of IMN and can be used to assess the risk of disease progression in IMN patients.2.IMN patients with low and medium-grade intrarenal lymphoid clusters may have a better response in the early stage of hormone and immunosuppressive therapy,suggesting that the classification of the intrarenal lymphoid clusters in IMN patients may be related to the response and prognosis of hormone and immunosuppressive therapy.3.The classification of the intrarenal lymphoid clusters may be useful in assessing the potential and applicability of antigen-targeted therapy(e.g.anti-CD20 mc Ab)and in predicting the response and outcome of antigen-targeted therapy in IMN patients.