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Published in: Pediatric Nephrology 4/2005

01-04-2005 | Original Article

Switch from cyclosporine A to mycophenolate mofetil in nephrotic children

Authors: Tim Ulinski, Laurence Dubourg, Marie Hélène Saïd, Bernadette Parchoux, Bruno Ranchin, Pierre Cochat

Published in: Pediatric Nephrology | Issue 4/2005

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Abstract

Nephrotoxicity is a well-known adverse effect of cyclosporine A (CyA) treatment in children with steroid-dependent (SD) and steroid-resistant (SR) nephrotic syndrome (NS). We analyzed nine children (age: 3.3–15.7 years, two girls) with SD or SR NS who experienced a significant decrease in their GFR under CyA treatment as measured by inulin clearance (CIN). Mycophenolate mofetil (MMF) was introduced progressively until doses of 1 g/1.73 m2 twice daily were reached. CyA treatment was stopped after introduction of MMF and oral steroids were reduced if possible. After a median follow up of 261 days, no adverse effects of MMF such as diarrhea or hematological anomalies occurred in our patients. After switching from CyA to MMF, those children with SD NS remained in remission without proteinuria and those with SR NS did not show any significant changes in their residual proteinuria. The serum protein level did not change significantly in any of the children analyzed. GFR increased from a mean of 76.9±4.8 to 119.9±5.9 mL/1.73 m2 per min (P<0.001). Oral steroid treatment could be reduced from a median [range] prednisone dose of 0.85 [0.26–2.94] mg/kg/d pre-MMF to 0.29 [0–1.1] mg/kg per day (P=0.026), and blood pressure decreased moderately after CyA withdrawal, but the difference did not reach statistical significance. We conclude that a switch from CyA to MMF seems to be safe for children with SDNS and SRNS in terms of side effects as well as disease control, at least in the short term. Interruption of CyA treatment lead to rapid amelioration of kidney function in these children, often associated with steroid sparing, which may lead to additional benefit for growth velocity, blood pressure and physical appearance.
Literature
1.
go back to reference Day CJ, Cockwell P, Lipkin GW, Savage CO, Howie AJ, Adu D (2002) Mycophenolate mofetil in the treatment of resistant idiopathic nephrotic syndrome. Nephrol Dial Transplant 17:2011–2013 Day CJ, Cockwell P, Lipkin GW, Savage CO, Howie AJ, Adu D (2002) Mycophenolate mofetil in the treatment of resistant idiopathic nephrotic syndrome. Nephrol Dial Transplant 17:2011–2013
2.
go back to reference Seikaly MG, Prashner H, Nolde-Hurlbert B, Browne R (2000) Long-term clinical and pathological effects of cyclosporin in children with nephrosis. Pediatr Nephrol 14:214–217 Seikaly MG, Prashner H, Nolde-Hurlbert B, Browne R (2000) Long-term clinical and pathological effects of cyclosporin in children with nephrosis. Pediatr Nephrol 14:214–217
3.
go back to reference Allison AC, Eugui EM (1993) Immunosuppressive and other anti-rheumatic activities of mycophenolate mofetil. Agents Actions Suppl 44:165–188 Allison AC, Eugui EM (1993) Immunosuppressive and other anti-rheumatic activities of mycophenolate mofetil. Agents Actions Suppl 44:165–188
4.
go back to reference Barletta GM, Smoyer WE, Bunchman TE, Flynn JT, Kershaw DB (2003) Use of mycophenolate mofetil in steroid-dependent and -resistant nephrotic syndrome. Pediatr Nephrol 18:833–837 Barletta GM, Smoyer WE, Bunchman TE, Flynn JT, Kershaw DB (2003) Use of mycophenolate mofetil in steroid-dependent and -resistant nephrotic syndrome. Pediatr Nephrol 18:833–837
5.
go back to reference Montane B, Abitbol C, Chandar J, Strauss J, Zilleruelo G (2003) Novel therapy of focal glomerulosclerosis with mycophenolate and angiotensin blockade. Pediatr Nephrol 18:772–777 Montane B, Abitbol C, Chandar J, Strauss J, Zilleruelo G (2003) Novel therapy of focal glomerulosclerosis with mycophenolate and angiotensin blockade. Pediatr Nephrol 18:772–777
6.
go back to reference Eugui EM, Mirkovich A, Allison AC (1991) Lymphocyte-selective antiproliferative and immunosuppressive activity of mycophenolic acid and its morpholinoethyl ester (RS-61443) in rodents. Transplant Proc 23:15–18 Eugui EM, Mirkovich A, Allison AC (1991) Lymphocyte-selective antiproliferative and immunosuppressive activity of mycophenolic acid and its morpholinoethyl ester (RS-61443) in rodents. Transplant Proc 23:15–18
7.
go back to reference Allison AC, Kowalski WJ, Muller CJ, Waters RV, Eugui EM (1993) Mycophenolic acid and brequinar, inhibitors of purine and pyrimidine synthesis, block the glycosylation of adhesion molecules. Transplant Proc 25:67–70 Allison AC, Kowalski WJ, Muller CJ, Waters RV, Eugui EM (1993) Mycophenolic acid and brequinar, inhibitors of purine and pyrimidine synthesis, block the glycosylation of adhesion molecules. Transplant Proc 25:67–70
8.
go back to reference Allison AC, Eugui EM (1993) The design and development of an immunosuppressive drug, mycophenolate mofetil. Springer Semin Immunopathol 14:353–380 Allison AC, Eugui EM (1993) The design and development of an immunosuppressive drug, mycophenolate mofetil. Springer Semin Immunopathol 14:353–380
9.
go back to reference Chang CC, Naiki M, Halpern GM, Gershwin ME (1993) Pharmacological regulation of the immune system. J Investig Allergol Clin Immunol 3:8–18 Chang CC, Naiki M, Halpern GM, Gershwin ME (1993) Pharmacological regulation of the immune system. J Investig Allergol Clin Immunol 3:8–18
10.
go back to reference Chang CC, Aversa G, Punnonen J, Yssel H, de Vries JE (1993) Brequinar sodium, mycophenolic acid, and cyclosporin A inhibit different stages of IL-4- or IL-13-induced human IgG4 and IgE production in vitro. Ann NY Acad Sci 696:108–122 Chang CC, Aversa G, Punnonen J, Yssel H, de Vries JE (1993) Brequinar sodium, mycophenolic acid, and cyclosporin A inhibit different stages of IL-4- or IL-13-induced human IgG4 and IgE production in vitro. Ann NY Acad Sci 696:108–122
11.
go back to reference Hauser IA, Renders L, Radeke HH, Sterzel RB, Goppelt-Struebe M (1999) Mycophenolate mofetil inhibits rat and human mesangial cell proliferation by guanosine depletion. Nephrol Dial Transplant 14:58–63 Hauser IA, Renders L, Radeke HH, Sterzel RB, Goppelt-Struebe M (1999) Mycophenolate mofetil inhibits rat and human mesangial cell proliferation by guanosine depletion. Nephrol Dial Transplant 14:58–63
12.
go back to reference Senda M, DeLustro B, Eugui E, Natsumeda Y (1995) Mycophenolic acid, an inhibitor of IMP dehydrogenase that is also an immunosuppressive agent, suppresses the cytokine-induced nitric oxide production in mouse and rat vascular endothelial cells. Transplantation 60:1143–1148 Senda M, DeLustro B, Eugui E, Natsumeda Y (1995) Mycophenolic acid, an inhibitor of IMP dehydrogenase that is also an immunosuppressive agent, suppresses the cytokine-induced nitric oxide production in mouse and rat vascular endothelial cells. Transplantation 60:1143–1148
13.
go back to reference Cohn RG, Mirkovich A, Dunlap B, Burton P, Chiu SH, Eugui E, Caulfield JP (1999) Mycophenolic acid increases apoptosis, lysosomes and lipid droplets in human lymphoid and monocytic cell lines. Transplantation 68:411–418 Cohn RG, Mirkovich A, Dunlap B, Burton P, Chiu SH, Eugui E, Caulfield JP (1999) Mycophenolic acid increases apoptosis, lysosomes and lipid droplets in human lymphoid and monocytic cell lines. Transplantation 68:411–418
14.
go back to reference Penny MJ, Boyd RA, Hall BM (1998) Mycophenolate mofetil prevents the induction of active Heymann nephritis: association with Th2 cytokine inhibition. J Am Soc Nephrol 9:2272–2282 Penny MJ, Boyd RA, Hall BM (1998) Mycophenolate mofetil prevents the induction of active Heymann nephritis: association with Th2 cytokine inhibition. J Am Soc Nephrol 9:2272–2282
15.
go back to reference Fujihara CK, De Lourdes Noronha I, Malheiros, Antunes GR, de Oliveira IB, Zatz R (2000) Combined mycophenolate mofetil and losartan therapy arrests established injury in the remnant kidney. J Am Soc Nephrol 11:283–290PubMed Fujihara CK, De Lourdes Noronha I, Malheiros, Antunes GR, de Oliveira IB, Zatz R (2000) Combined mycophenolate mofetil and losartan therapy arrests established injury in the remnant kidney. J Am Soc Nephrol 11:283–290PubMed
16.
go back to reference Corna D, Morigi M, Facchinetti D, Bertani T, Zoja C, Remuzzi G (1997) Mycophenolate mofetil limits renal damage and prolongs life in murine lupus autoimmune disease. Kidney Int 51:1583–1589 Corna D, Morigi M, Facchinetti D, Bertani T, Zoja C, Remuzzi G (1997) Mycophenolate mofetil limits renal damage and prolongs life in murine lupus autoimmune disease. Kidney Int 51:1583–1589
17.
go back to reference Gellermann J, Querfeld U (2004) Frequently relapsing nephrotic syndrome: treatment with mycophenolate mofetil. Pediatr Nephrol 19:101–104 Gellermann J, Querfeld U (2004) Frequently relapsing nephrotic syndrome: treatment with mycophenolate mofetil. Pediatr Nephrol 19:101–104
Metadata
Title
Switch from cyclosporine A to mycophenolate mofetil in nephrotic children
Authors
Tim Ulinski
Laurence Dubourg
Marie Hélène Saïd
Bernadette Parchoux
Bruno Ranchin
Pierre Cochat
Publication date
01-04-2005
Publisher
Springer-Verlag
Published in
Pediatric Nephrology / Issue 4/2005
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-004-1778-4

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