Detection of calcineurin expression in podocyte in patients with membranous nephropathy

Objective:The increased expression of calcineurin(CaN)in podocyte can directly damage the cytoskeleton structure,leading to podocyte injury and proteinuria.It is interesting to know the expression of CaN in podocyte of patients with membranous nephropathy(MN)and its change after treatment with calcineurin inhibitor(CNI).Methodology:In the present study,the α isform of calcineurin A subunit(CnAα)expression in podocyte was detected by immunohistochemistry in 49 biopsy proven idiopathic MN,and the cytoskeleton protein,synaptopodin expression was observed at the same time in these patients.In addition,the alteration of podocyte CnAα expression after tacrolimus treatment in 2 cases of idiopathic MN were observed.Furthermore,28 cases of type V lupus nephritis and 15 cases of hepatitis B virus associated MN were used as disease controls to clarify the specifity of the podocyte CnAα expression in idiopathic MN.Results:It was found that in 49 cases of idiopathic MN patients,20 patients showed increased expression of CnAα in podocyte(40.8%),accompanied by the decreased expression and discontinuous distribution of synaptopodin in the podocyte.Repeat renal biopsy revealed that after complete remission treated with tacrolimus,the CnAα expression significantly reduced,meanwhile the intensity of synaptopodin expression increased with normalized distribution in the podocyte.None of the hepatitis B virus associated MN patients had increased expression of CnAα in podocyte,however,11 out of 28 cases of type V lupus nephritis had increased expression of CnAα in podocyte(37.9%),the frequency is similar with idiopathic MN.Conclusion:Increased expression of CnAα in podocyte was present in part of patients with idiopathic MN,this change was accompanied by the podocyte cytoskeleton destruction.After complete remission treated with CNI,the podocyte CnAα expression decreased significantly,with normalized synaptopodin expression and distribution.The tpye V lupus nephritis patients showed the similar frequency of increased expression of CnAα in podocyte with idiopathic MN,while none of the hepatitis B virus associated MN patients had increased CnAα expression.This result shed light on the individual therapy not only for idiopathic MN,but also for other podocyte disease.