Skip to main content
Erschienen in: Pediatric Nephrology 9/2006

01.09.2006 | Original Article

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

verfasst von: Anna Wasilewska, Walentyna Zoch-Zwierz, Miroslawa Pietruczuk, Grzegorz Zalewski

Erschienen in: Pediatric Nephrology | Ausgabe 9/2006

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat 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 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
2.
Zurück zum Zitat 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 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
3.
Zurück zum Zitat 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 152:357–361PubMedCrossRef 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 152:357–361PubMedCrossRef
4.
Zurück zum Zitat Leung DJ, Bloom JW (2003) Update on glucocorticoid action and resistance. J Allergy Clin Immunol 111:3–22PubMedCrossRef Leung DJ, Bloom JW (2003) Update on glucocorticoid action and resistance. J Allergy Clin Immunol 111:3–22PubMedCrossRef
5.
Zurück zum Zitat 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 45:382–388PubMedCrossRef 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 45:382–388PubMedCrossRef
6.
Zurück zum Zitat Lane SJ, Lee TH (1996) Corticosteroid resistance in other disease states and tissues. Am J Respir Crit Care Med 154:S62–S65PubMed Lane SJ, Lee TH (1996) Corticosteroid resistance in other disease states and tissues. Am J Respir Crit Care Med 154:S62–S65PubMed
7.
Zurück zum Zitat Ling V (1997) Multidrug resistance: molecular mechanisms and clinical relevance. Cancer Chemother Pharmacol 40 [Suppl]:S3–S8PubMedCrossRef Ling V (1997) Multidrug resistance: molecular mechanisms and clinical relevance. Cancer Chemother Pharmacol 40 [Suppl]:S3–S8PubMedCrossRef
8.
Zurück zum Zitat Juliano RL, Ling V (1976) A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 455:152–162PubMedCrossRef Juliano RL, Ling V (1976) A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 455:152–162PubMedCrossRef
9.
Zurück zum Zitat Klimecki WT, Futscher BW, Grogan TM, Dalton WS (1994) P-glycoprotein expression and function in circulating blood cells from normal volunteers. Blood 83:2451–2458PubMed Klimecki WT, Futscher BW, Grogan TM, Dalton WS (1994) P-glycoprotein expression and function in circulating blood cells from normal volunteers. Blood 83:2451–2458PubMed
10.
Zurück zum Zitat Ford JM (1995) Modulators of multidrug resistance. Preclinical studies. Hematol Oncol Clin North Am 9:337–361PubMed Ford JM (1995) Modulators of multidrug resistance. Preclinical studies. Hematol Oncol Clin North Am 9:337–361PubMed
11.
Zurück zum Zitat 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 (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
12.
Zurück zum Zitat 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 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
13.
Zurück zum Zitat 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 100:1910–1912PubMed 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 100:1910–1912PubMed
14.
Zurück zum Zitat Siiteri PK, Murai JT, Hammond GL, Nisker JA, Raymoure WJ, Kuhn RW (1982) The serum transport of steroid hormones. Recent Prog Horm Res 38:457–510PubMed Siiteri PK, Murai JT, Hammond GL, Nisker JA, Raymoure WJ, Kuhn RW (1982) The serum transport of steroid hormones. Recent Prog Horm Res 38:457–510PubMed
15.
Zurück zum Zitat Beck WT, Grogan TM (1997) Methods to detect P-glycoprotein and implications for other drug resistance-associated proteins. Leukemia 11:1107–1109PubMedCrossRef Beck WT, Grogan TM (1997) Methods to detect P-glycoprotein and implications for other drug resistance-associated proteins. Leukemia 11:1107–1109PubMedCrossRef
16.
Zurück zum Zitat 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 9:1265–1273PubMedCrossRef 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 9:1265–1273PubMedCrossRef
17.
Zurück zum Zitat Tsuruo T (1983) Reversal of acquired resistance to vinca alkaloids and anthracycline antibiotics. Cancer Treat Rep 67:889–894PubMed Tsuruo T (1983) Reversal of acquired resistance to vinca alkaloids and anthracycline antibiotics. Cancer Treat Rep 67:889–894PubMed
18.
Zurück zum Zitat 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 7:840–851PubMedCrossRef 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 7:840–851PubMedCrossRef
19.
Zurück zum Zitat 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 139:1789–1793PubMedCrossRef 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 139:1789–1793PubMedCrossRef
20.
Zurück zum Zitat Inoue Y, Iijima K, Nakamura H, Yoshikawa N (1999) Two-year cyclosporin treatment in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol 13:33–38PubMedCrossRef Inoue Y, Iijima K, Nakamura H, Yoshikawa N (1999) Two-year cyclosporin treatment in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol 13:33–38PubMedCrossRef
21.
Zurück zum Zitat Farrell RJ, Kelleher D (2003) Glucocorticoid resistance in inflammatory bowel disease. J Endocrinol 178:339–346PubMedCrossRef Farrell RJ, Kelleher D (2003) Glucocorticoid resistance in inflammatory bowel disease. J Endocrinol 178:339–346PubMedCrossRef
22.
Zurück zum Zitat 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 6:14–21PubMed 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 6:14–21PubMed
23.
Zurück zum Zitat Szefler SJ (1991) Glucocorticoid therapy for asthma: clinical pharmacology. J Allergy Clin Immunol 88:147–165PubMedCrossRef Szefler SJ (1991) Glucocorticoid therapy for asthma: clinical pharmacology. J Allergy Clin Immunol 88:147–165PubMedCrossRef
24.
Zurück zum Zitat 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) 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)
25.
Zurück zum Zitat 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 31:483–487PubMedCrossRef 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 31:483–487PubMedCrossRef
26.
Zurück zum Zitat 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 67:40–48PubMed 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 67:40–48PubMed
27.
Zurück zum Zitat 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 52:1676–1683PubMedCrossRef 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 52:1676–1683PubMedCrossRef
28.
Zurück zum Zitat 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 35:430–435PubMedCrossRef 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 35:430–435PubMedCrossRef
Metadaten
Titel
Expression of P-glycoprotein in lymphocytes from children with nephrotic syndrome, depending on their steroid response
verfasst von
Anna Wasilewska
Walentyna Zoch-Zwierz
Miroslawa Pietruczuk
Grzegorz Zalewski
Publikationsdatum
01.09.2006
Verlag
Springer-Verlag
Erschienen in
Pediatric Nephrology / Ausgabe 9/2006
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-006-0187-2

Weitere Artikel der Ausgabe 9/2006

Pediatric Nephrology 9/2006 Zur Ausgabe

Update Pädiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.