Expression of multidrug resistance P-glycoprotein on lymphocytes from nephrotic children treated with cyclosporine A and ACE-inhibitor.
The aim of this work was to determine the expression of P-glycoprotein (P-gp) on peripheral lymphocytes (CD3) in children with steroid-dependent nephrotic syndrome (SDNS) during cyclosporine A (CyA) and ACE-inhibitor (ACE-I) treatment. The study group (I) consisted of 20 children with SDNS aged 5-18 years, with a subsequent proteinuria relapse at the time of prednisone dose reduction. All nephrotic syndrome (NS) children were examined three times: A--at proteinuria relapse, before CyA treatment; B--after 3 months; C--after 12 months of CyA administration. The control group (II) consisted of 20 healthy children. CD3/P-gp was measured using a flow cytometry assay. The serum CyA level was assessed by means of the immunofluorescence method. The expression of CD3/P-gp in NS relapse, prior to CyA+ACE-I administration, was much higher (median 9.15%, range 1.50-13.50%) when compared to healthy controls (median 1.20%, range 0.30-5.70%). The absolute number of CD3/P-gp in this examination was almost five times higher when compared to healthy controls (p<0.01). After 3 months of CyA+ACE-I therapy, the expression of CD3/P-gp decreased dramatically and was similar to the controls. Similar results were obtained after 12 months of treatment. A strong negative correlation was found between CD3/P-gp and serum CyA concentration in both examinations (r=-0.624, p<0.01; r=-0.464, p<0.01). We conclude that the results of our studies indicate that CyA+ACE-I in SDNS inhibits the expression of P-gp. CyA is an alternative therapy that may lead to the optimization of glucocorticoid (GC) doses, thus, reducing the risk that is associated with the treatment.
Wasilewska
Anna
A
1st Department of Pediatrics, Medical University of Białystok, ul. Waszyngtona 17, 15-274, Białystok, Poland. annwasil@interia.pl
Zoch-Zwierz
Walentyna
W
Pietruczuk
Mirosława
M
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000293:Adolescent; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017252:CD3 Complex; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D018432:Drug Resistance, Multiple; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018655:Lymphocyte Count; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000378:metabolism; D012008:Recurrence; D012074:Remission Induction; D018709:Statistics, Nonparametric; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000806:Angiotensin-Converting Enzyme Inhibitors; D017252:CD3 Complex; D016572:Cyclosporine