The Clinical Significance Of Renal Calpain-1 And Calcineurin In Patients With Idiopathic Membranous Nephropathy

Objective:To detect the levels of renal calpain-1 and calcineurin(CaN)of patients with idiopathic membranous nephropathy(IMN),and to explore the relationship between the different calpain-1 or CaN expression and post-CNIs treatment outcome.Provide a basis for whether to choose CNIs as immunosuppressive drugs for IMN patients.Methods:63 IMN patients of the Third Hospital of Hebei Medical University were selected from January 2018 to June 2020.They were diagnosed by renal biopsy and treated with CNIs(59 cases with tacrolimus and 4 cases with cyclosporine)for at least 6 months.According to the treatment effects,these patients were divided into the complete remission(CR)group,the partial remission(PR)group,and the no-remission(NR)group.The groups contain 18 patients,33 patients and 12 patients respectively.There was a control group,consisted of 5 para-cancerous normal renal tissues.Collect clinical and pathological data:24-hour urine protein,serum albumin,serum creatinine,serum anti-PLA2R antibody,glomerular sclerosis ratio,and PLA2R expression in kidney tissue,etc.The immunohistochemical staining method was used to detect the expression of calpain-1 and CaN in the renal tissues of the IMN group and the control group,and to analyze the relationship between relevant clinical and pathological indicators.Results:(1)There was no significant difference in the blood concentration of tacrolimus(4-10ng/ml,P=0.384)of the CR,PR or NR patients.Only 4 patients were treated with cyclosporine(1 case in CR group,2cases in PR group,1 case in NR group),whose drug blood concentration fluctuated at 100-150ng/ml.The baseline 24-hour urine proteins of the three groups of patients were all>4g/d,and the glomerular filtration rates were>30m L/min/1.73 m~2.There were no significant differences in serum albumin levels and serum anti-PLA2R antibody levels among the three groups.The serum creatinine levels of CR group were significantly lower than those of the NR group(P=0.008).The proportion of glomerular sclerosis in CR group was significantly lower than that in PR group(P=0.003)and NR group(P=0.003).(2)Compared with the control group,the expression of calpain-1and CaN in the kidney of IMN patients increased significantly(P<0.05).There was no significant difference in renal CaN expression among CR,PR or NR groups.The levels of glomeruli calpain-1 was gradually increased in the CR,PR and NR groups(P<0.05).There was no correlation between the expression levels of calpain-1 and CaN in kidney tissue(r=0.151,P=0.237;r=0.206,P=0.106),and there were no significant correlation between the two proteins and 24-hour urine protein,serum albumin,serum creatinine,serum anti-PLA2R antibodies,and glomerular sclerosis ratio.Conclusions:1.Compared with the normal group,the levels of renal calpain-1 and CaN of IMN patients were higher,suggesting that both calpain-1 and CaN were involved in the development of IMN.2.The glomeruli calpain-1 level gradually increased among CR,PR and NR groups.The glomeruli calpain-1 could be a useful marker in IMN to negatively predict the response to CNIs treatment.