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.
Similar content being viewed by others
References
Nasi M, Aedelmann CM, Berstein J, Barnett HL (1992) The nephrotic syndrome. In: Edelmann CM, Berstein J, Meadow SR, Spitzer A, Travis LB (eds) Pediatric kidney disease, vol 2. Little, Brown, Boston, pp 1247–1266
No authors listed (1981) The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. A report of the International Study of Kidney Disease in Children. J Pediatr 98:561–564
Ehrich JH, Brodehl J (1993) Long versus standard prednisone therapy for initial treatment of idiopathic nephrotic syndrome in children. Arbeitsgemeinschaft fur Padiatrische Nephrologie. Eur J Pediatr 152:357–361
Leung DJ, Bloom JW (2003) Update on glucocorticoid action and resistance. J Allergy Clin Immunol 111:3–22
Hearing SD, Norman M, Probert CS, Haslam N, Dayan CM (1999) Predicting therapeutic outcome in severe ulcerative colitis by measuring in vitro steroid sensitivity of proliferating peripheral blood lymphocytes. Gut 45:382–388
Lane SJ, Lee TH (1996) Corticosteroid resistance in other disease states and tissues. Am J Respir Crit Care Med 154:S62–S65
Ling V (1997) Multidrug resistance: molecular mechanisms and clinical relevance. Cancer Chemother Pharmacol 40 [Suppl]:S3–S8
Juliano RL, Ling V (1976) A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 455:152–162
Klimecki WT, Futscher BW, Grogan TM, Dalton WS (1994) P-glycoprotein expression and function in circulating blood cells from normal volunteers. Blood 83:2451–2458
Ford JM (1995) Modulators of multidrug resistance. Preclinical studies. Hematol Oncol Clin North Am 9:337–361
No authors listed (1982) Early identification of frequent relapsers among children with minimal change nephrotic syndrome. A report of the international study of kidney disease in children. J Pediatr 101:514–518
No authors listed (1987) Cyclophosphamide treatment of steroid dependent nephrotic syndrome: comparison of eight week with 12 week course. Report of Arbeitsgemeinschaft für Pädiatrische Nephrologie. Arch Dis Child 62:1102–1106
List AF, Kopecky KJ, Willman CL, Head DR, Slovak ML, Douer D, Dakhil SR, Appelbaum FR (2002) Cyclosporine inhibition of P-glycoprotein in chronic myeloid leukemia blast phase. Blood 100:1910–1912
Siiteri PK, Murai JT, Hammond GL, Nisker JA, Raymoure WJ, Kuhn RW (1982) The serum transport of steroid hormones. Recent Prog Horm Res 38:457–510
Beck WT, Grogan TM (1997) Methods to detect P-glycoprotein and implications for other drug resistance-associated proteins. Leukemia 11:1107–1109
Tsujimura S, Saito K, Nakayamada S, Nakano K, Tsukada J, Kohno K, Tanaka Y (2004) Transcriptional regulation of multidrug resistance-1 gene by interleukin-2 in lymphocytes. Genes Cells 9:1265–1273
Tsuruo T (1983) Reversal of acquired resistance to vinca alkaloids and anthracycline antibiotics. Cancer Treat Rep 67:889–894
Bourgeois S, Gruol DJ, Newby RF, Rajah FM (1993) Expression of an mdr gene is associated with a new form of resistance to dexamethasone-induced apoptosis. Mol Endocrinol 7:840–851
Meijer OC, de Lange EC, Breimer DD, de Boer AG, Workel JO, de Kloet ER (1998) Penetration of dexamethasone into brain glucocorticoid targets is enhanced in mdr1A P-glycoprotein knockout mice. Endocrinology 139:1789–1793
Inoue Y, Iijima K, Nakamura H, Yoshikawa N (1999) Two-year cyclosporin treatment in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol 13:33–38
Farrell RJ, Kelleher D (2003) Glucocorticoid resistance in inflammatory bowel disease. J Endocrinol 178:339–346
Montano E, Schmitz M, Blaser K, Simon HU (1996) P-glycoprotein expression in circulating blood leukocytes of patients with steroid-resistant asthma. J Investig Allergol Clin Immunol 6:14–21
Szefler SJ (1991) Glucocorticoid therapy for asthma: clinical pharmacology. J Allergy Clin Immunol 88:147–165
Wasilewska A, Zoch-Zwierz W, Pietruczuk M (2006) Expression of P-glycoprotein in lymphocytes of children with nephrotic syndrome treated with glucocorticoids. Eur J Pediatr (in press)
Ruiz-Soto R, Richaud-Patin Y, Lopez-Karpovitch X, Llorente L (2003) Multidrug resistance-1 (MDR-1) in autoimmune disorders III: increased P-glycoprotein activity in lymphocytes from immune thrombocytopenic purpura patients. Exp Hematol 31:483–487
Diaz-Borjon A, Richaud-Patin Y, Alvarado de la Barrera C, Jakez-Ocampo J, Ruiz-Arguelles A, Llorente L (2000) Multidrug resistance-1 (MDR-1) in rheumatic autoimmune disorders. Part II: increased P-glycoprotein activity in lymphocytes from systemic lupus erythematosus patients might affect steroid requirements for disease control. Joint Bone Spine 67:40–48
Tsujimura S, Saito K, Nakayamada S, Nakano K, Tanaka Y (2005) Clinical relevance of the expression of P-glycoprotein on peripheral blood lymphocytes to steroid resistance in patients with systemic lupus erythematosus. Arthritis Rheum 52:1676–1683
Maillefert JF, Maynadie M, Tebib JG, Aho S, Walker P, Chatard C, Dulieu V, Bouvier M, Carli PM, Tavernier C (1996) Expression of the multidrug resistance glycoprotein 170 in the peripheral blood lymphocytes of rheumatoid arthritis patients. The percentage of lymphocytes expressing glycoprotein 170 is increased in patients treated with prednisolone. Br J Rheumatol 35:430–435
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Wasilewska, A., Zoch-Zwierz, W., Pietruczuk, M. et al. Expression of P-glycoprotein in lymphocytes from children with nephrotic syndrome, depending on their steroid response. Pediatr Nephrol 21, 1274–1280 (2006). https://doi.org/10.1007/s00467-006-0187-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-006-0187-2