Expression of P-glycoprotein in lymphocytes from children with nephrotic syndrome, depending on their steroid response

Abstract

The aim of this study was to examine the expression of P-glycoprotein (P-gp) in CD3 lymphocytes of children with nephrotic syndrome (NS) in relation to their clinical response to glucocorticoid (GC) treatment. The examinations were performed on two groups. The study group (I) consisted of 88 children aged 2.0-20.0 years with NS, divided according to their clinical response to GC: NFR-non-frequent relapse NS; FR-frequent relapse NS; SD-steroid-dependent NS. The control group (II) consisted of 18 healthy children never treated with GC. We measured P-gp expression on CD3 lymphocytes of patients with NS using a flow cytometry assay. The CD3/P-gp was significantly higher than in controls. The difference was higher in SD (P=0.0001) and FR - (P=0.0002) group. The difference in NFR was smaller. Mean CD3/P-gp (in percent) was twice as high in SD children than in NFR, and the difference, as between FR and NFR, was statistically significant (P<0.01). Worse response to GC or dependency may be due to overexpression of P-gp. Further examinations are necessary to establish whether increased P-gp activity is a result of MDR-1 polymorphism and to determine GC response, or to ascertain if such activity is only a result of GC therapy.

A PRISMA-compliant meta-analysis of MDR1 polymorphisms and idiopathic nephrotic syndrome

“…[9] In addition, expression of MDR1 and P-gp activity are negatively correlated with steroid sensitivity in children with NS. [10–12] Furthermore, there is evidence that polymorphisms in MDR1 may influence disease occurrence and response to drug treatment through changes in gene expression and P-gp activity. [13] …”

Polymorphisms of the MDR1 and MIF genes in children with nephrotic syndrome

“…Several studies have been conducted to evaluate the association of P-gp expression with the responsiveness to steroids in patients with idiopathic NS [36][37][38]. Wasilewska et al [38] measured P-gp expression on CD3-positive lymphocytes and found that CD3/P-gp expression was significantly higher in patients with NS than in the controls and that the difference was higher in steroid-dependent and frequent relapsing groups than in the non-frequent relapsing group. Funaki et al [36] reported that the MDR1 mRNA expression level in nucleated cells of peripheral blood was variable in patients with idiopathic NS prior to remission, but apparently decreased after complete remission.…”

“…Various types of structurally unrelated drugs, including steroids, are known to be substrates for P-gp [34,35]. Several studies have been conducted to evaluate the association of P-gp expression with the responsiveness to steroids in patients with idiopathic NS [36][37][38]. Wasilewska et al [38] measured P-gp expression on CD3-positive lymphocytes and found that CD3/P-gp expression was significantly higher in patients with NS than in the controls and that the difference was higher in steroid-dependent and frequent relapsing groups than in the non-frequent relapsing group.…”

Pharmacology and pharmacogenetics of prednisone and prednisolone in patients with nephrotic syndrome

“…Increased expression of P-glycoprotein results in decreased intracellular drug concentrations and may consequently decrease treatment response. Previous research has shown higher expression of MDR1 and increased P-glycoprotein activity in children with steroid-resistant nephrotic syndrome [116,117]. To date, approximately 50 genetic polymorphisms have been reported in the MDR1 gene.…”