Changes Of P-gp170Expression In Children With Steroid-resistant Nephrotic Syndrome During Cyclophosphamide Treatment And Its Clinical Significance

Objective To study the expression of Permeability-glycoprotein170(P-gp170) onperipheral blood lymphocytes of patients with Idiopathic Nephrotic Syndrome (INS)andthe changes and clinical significance of P-gp170expression in children with Steroidresistant nephrotic syndrome during cyclophosphamide treatment.Method24children with INS without any glucocorticoid(GC) treatment beforeadmission were divided into two groups,12children with steroid-sensitive nephroticsyndrome (SSNS) and12children with steroid-resistant nephrotic syndrome (SRNS)according to their response to glucocorticoid,12healthy children serving as normal controlgroup (Control). Flowcytometry (FCM) were applied to detect the expression of P-gp170on peripheral blood lymphocytes at different time point:(1) before prednisone treatment;（2）after four weeks’ prednisone treatment;（3）after4courses of treatment withcyclophosphamide on children with SRNS;（4） after8courses of treatment withcyclophosphamide on children with SRNS.Renal biopsy was adopted to get samples fromchildren with SRNS after four weeks’prednisone treatment.Results (1)The expression of P-gp170on peripheral blood lymphocytes was foundin children with SSNS、SRNS and Control.(2) There were significant differences of theexpression of P-gp170between SSNS、SRNS and Control before treatment(P<0.01).Afterfour weeks’prednisone treatment,the expression of P-gp170on peripheral bloodlymphocytes was rised(SSNS： P<0.05；SRNS： P<0.01).(3) The expresstion of P-gp170on peripheral blood lymphocytes in SRNS was higher than SSNS before prednisonetreatment,but no statistically significant(P＞0.05),and also higher than Control beforeprednisone treatment(P<0.01), after four weeks’prednisone treatment,the expression ofP-gp170was higher than before and also higher than both SSNS and Control (P<0.01).(4) After4courses of treatment with cyclophosphamide, the expresstion of P-gp170onperipheral blood lymphocytes in SRNS was declined than that before treatment withcyclophosphamide(P<0.01),but also higher than that without prednisonetreatment(P<0.05).(5)Closely correlation was found between the expresstion of P-gp170on peripheral blood lymphocytes and renal pathological integral in twelve SRNS afterprednisone treatment(r=0.714，P<0.01).Conclusion：(1) Glucocorticoid itself may induce the high increase of P-gp170expression on peripheral blood lymphocytes of patients with INS;(2)The high expression of P-gp170on peripheral blood lymphocytes may take part inthe occurrence and development of glucocorticoid resistance in SRNS patients;(3) After prednisone treatment,the level of P-gp170on peripheral blood lymphocytes ofthe SRNS patients could reflect the severity of the disease;(4)CTX pulse therapy can down regulate the expression of P-gp170in SRNS children.