Expression of P-glycoprotein in lymphocytes of children with nephrotic syndrome treated with glucocorticoids

Glucocorticoids are still the mainstay of therapy for nephrotic syndrome (NS) in children. Poor response to glucocorticoids may relate, in part, to the overexpression of P-glycoprotein (P-gp). The aim of the present study was to determine the expression of P-gp in lymphocytes (CD3) in the peripheral blood of children with steroid-sensitive nephrotic syndrome in the dynamics of the disease. The study group (I) consisted of 18 children, median age 5.75 years, with steroid-sensitive nephrotic syndrome, in whom the examinations were carried out three times: (A) before treatment, during relapse; (B) after 3–4 weeks of prednisone treatment; (C) 2 months after finishing prednisone treatment. The control group (II) consisted of 18 healthy children of the same age. P-gp expression in CD3 lymphocytes of peripheral blood was measured using flow cytometry. During NS relapse and prior to glucocorticoid administration, the CD3/P-gp level was higher (median 3.20%, range 0.80–7.80%) when compared to healthy controls (1.10%, range 0.30– 2.20%) (p<0.01). During glucocorticoid treatment, CD3/P-gp increased significantly and was much higher than in the control group (p<0.01) and in the NS children before treatment (p<0.01). In remission, the P-gp expression decreased, but did not achieve the values of the controls (p<0.05). Fourteen out of eighteen (14/18) children still showed P-gp values above the cut-off level. We also found a positive correlation between the P-gp expression and total prednisone dose in the NS children in all examinations: A: (r=0.540, p<0.05); B: (r=0.630, p<0.01); C: (r=0.653, p<0.01).

In conclusion, the overexpression of P-gp in remission, after finishing glucocorticoid treatment, may indicate that P-gp plays a role in the response to corticosteroids in nephrotic children.