Skip to main content
Erschienen in: Pediatric Nephrology 11/2012

01.11.2012 | Original Article

Treatment of tacrolimus or cyclosporine A in children with idiopathic nephrotic syndrome

verfasst von: Wenjing Wang, Yonghui Xia, Jianhua Mao, Yifang Chen, Dayan Wang, Huijun Shen, Haidong Fu, Lizhong Du, Ai’min Liu

Erschienen in: Pediatric Nephrology | Ausgabe 11/2012

Einloggen, um Zugang zu erhalten

Abstract

Background

Cyclosporine A (CsA) and tacrolimus (TAC) are often alternative treatment choices for patients with nephrotic syndrome.

Methods

In this prospective study, the efficacy and safety of CsA and TAC in inducing and maintaining remission in 74 children with idiopathic nephrotic syndrome (INS) were evaluated.

Results

In terms of short-term efficacy, TAC was more effective than CsA in children with steroid-resistant nephrotic syndrome (χ2 = 13.75, P = 0.001), although no significant difference in number of episodes of relapse were found in patients with complete remission between the two treatment groups (first year: χ2 = 0.261, P = 0.88; second year: χ2 = 2.685, P = 0.26). In patients with frequently relapsing or steroid-dependent nephrotic syndrome, no significant difference in short-term remission (χ2 = 1.908, P = 0.39) or in relapse frequency during follow-up (within first year: χ2 = 1.046, P = 0.59; within second year: χ2 = 0.587, P = 0.75) were found between the two groups. There was a difference in the rate of adverse effects between the two treatment groups [nephrotoxicity: 4/24 (CsA) vs .0/50 (TAC), P = 0.002; hirsutism: 8/24 (CsA) vs. 0/50 (TAC), P < 0.001].

Conclusions

In our pediatric patient cohort, the treatment of steroid-resistant nephrotic syndrome with tacrolimus was associated with higher efficacy and lower renal toxicity in comparison to CsA, although no favorable outcome in relapse rate during long-term follow-up was seen. On the other hand, tacrolimus was not always the better choice to replace CsA in the treatment of severe frequently relapsing or steroid-dependent nephrotic syndrome.
Literatur
1.
Zurück zum Zitat Zagury A, de Oliveira AL, de Moraes CA, de Araujo Montalvao JA, Novaes RH, de Sa VM, Monteiro de Carvalho DD, Matuck T (2011) Long-term follow-up after cyclophosphamide therapy in steroid-dependent nephrotic syndrome. Pediatr Nephrol 26:915–920PubMedCrossRef Zagury A, de Oliveira AL, de Moraes CA, de Araujo Montalvao JA, Novaes RH, de Sa VM, Monteiro de Carvalho DD, Matuck T (2011) Long-term follow-up after cyclophosphamide therapy in steroid-dependent nephrotic syndrome. Pediatr Nephrol 26:915–920PubMedCrossRef
2.
Zurück zum Zitat Chin J Pediatr 39:746-747 (2001) Clinical classification, diagnosis, and treatment of childhood glomerular diseases. Chin J Pediatr 39:746–747 Chin J Pediatr 39:746-747 (2001) Clinical classification, diagnosis, and treatment of childhood glomerular diseases. Chin J Pediatr 39:746–747
3.
Zurück zum Zitat Cammas B, Harambat J, Bertholet-Thomas A, Bouissou F, Morin D, Guigonis V, Bendeddouche S, Afroukh-Hacini N, Cochat P, Llanas B, Decramer S, Ranchin B (2011) Long-term effects of cyclophosphamide therapy in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. Nephrol Dial Transplant 26:178–184PubMedCrossRef Cammas B, Harambat J, Bertholet-Thomas A, Bouissou F, Morin D, Guigonis V, Bendeddouche S, Afroukh-Hacini N, Cochat P, Llanas B, Decramer S, Ranchin B (2011) Long-term effects of cyclophosphamide therapy in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. Nephrol Dial Transplant 26:178–184PubMedCrossRef
4.
Zurück zum Zitat Boyer O, Moulder JK, Grandin L, Somers MJ (2008) Short- and long-term efficacy of levamisole as adjunctive therapy in childhood nephrotic syndrome. Pediatr Nephrol 23:575–580PubMedCrossRef Boyer O, Moulder JK, Grandin L, Somers MJ (2008) Short- and long-term efficacy of levamisole as adjunctive therapy in childhood nephrotic syndrome. Pediatr Nephrol 23:575–580PubMedCrossRef
5.
Zurück zum Zitat de Mello VR, Rodrigues MT, Mastrocinque TH, Martins SP, de Andrade OV, Guidoni EB, Scheffer DK, Martini Filho D, Toporovski J, Benini V (2010) Mycophenolate mofetil in children with steroid/cyclophosphamide-resistant nephrotic syndrome. Pediatr Nephrol 25:453–460PubMedCrossRef de Mello VR, Rodrigues MT, Mastrocinque TH, Martins SP, de Andrade OV, Guidoni EB, Scheffer DK, Martini Filho D, Toporovski J, Benini V (2010) Mycophenolate mofetil in children with steroid/cyclophosphamide-resistant nephrotic syndrome. Pediatr Nephrol 25:453–460PubMedCrossRef
6.
Zurück zum Zitat Okada T, Matsumoto H, Nagaoka Y, Tomaru R, Iwasawa H, Wada T, Nakao T (2011) Clinical evaluation of chronic nephrotoxicity of long-term cyclosporine A treatment in adult patients with steroid-dependent nephrotic syndrome. Nephrology (Carlton) 16:319–325CrossRef Okada T, Matsumoto H, Nagaoka Y, Tomaru R, Iwasawa H, Wada T, Nakao T (2011) Clinical evaluation of chronic nephrotoxicity of long-term cyclosporine A treatment in adult patients with steroid-dependent nephrotic syndrome. Nephrology (Carlton) 16:319–325CrossRef
7.
Zurück zum Zitat Kelly D (2011) Safety and efficacy of tacrolimus in pediatric liver recipients. Pediatr Transplant 15:19–24PubMedCrossRef Kelly D (2011) Safety and efficacy of tacrolimus in pediatric liver recipients. Pediatr Transplant 15:19–24PubMedCrossRef
8.
Zurück zum Zitat Li H, Rao A, Hogan PG (2011) Interaction of calcineurin with substrates and targeting proteins. Trends Cell Biol 21:91–103PubMedCrossRef Li H, Rao A, Hogan PG (2011) Interaction of calcineurin with substrates and targeting proteins. Trends Cell Biol 21:91–103PubMedCrossRef
9.
Zurück zum Zitat El-Dahshan KF, Bakr MA, Donia AF, Badr Ael S, Sobh MA (2006) Ketoconazole-tacrolimus coadministration in kidney transplant recipients: two-year results of a prospective randomized study. Am J Nephrol 26:293–298PubMedCrossRef El-Dahshan KF, Bakr MA, Donia AF, Badr Ael S, Sobh MA (2006) Ketoconazole-tacrolimus coadministration in kidney transplant recipients: two-year results of a prospective randomized study. Am J Nephrol 26:293–298PubMedCrossRef
10.
Zurück zum Zitat Xue W, Ding X, Tian P, Pan X, Yan H, Hou J, Feng X, Xiang H, Tian X (2010) Long-term follow-up of co-administration of diltiazem and cyclosporine in Chinese kidney transplant recipients. Ren Fail 32:314–319PubMedCrossRef Xue W, Ding X, Tian P, Pan X, Yan H, Hou J, Feng X, Xiang H, Tian X (2010) Long-term follow-up of co-administration of diltiazem and cyclosporine in Chinese kidney transplant recipients. Ren Fail 32:314–319PubMedCrossRef
11.
Zurück zum Zitat Schwartz GJ, Brion LP, Spitzer A (1987) The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am 34:571–590PubMed Schwartz GJ, Brion LP, Spitzer A (1987) The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin North Am 34:571–590PubMed
12.
Zurück zum Zitat Mao J, Zhang Y, Du L, Dai Y, Gu W, Liu A, Shang S, Liang L (2007) NPHS1 and NPHS2 gene mutations in Chinese children with sporadic nephrotic syndrome. Pediatr Res 61:117–122PubMedCrossRef Mao J, Zhang Y, Du L, Dai Y, Gu W, Liu A, Shang S, Liang L (2007) NPHS1 and NPHS2 gene mutations in Chinese children with sporadic nephrotic syndrome. Pediatr Res 61:117–122PubMedCrossRef
13.
Zurück zum Zitat Mao J, Zhang Y, Du L, Dai Y, Yang C, Liang L (2006) Expression profile of nephrin, podocin, and CD2AP in Chinese children with MCNS and IgA nephropathy. Pediatr Nephrol 21:1666–1675PubMedCrossRef Mao J, Zhang Y, Du L, Dai Y, Yang C, Liang L (2006) Expression profile of nephrin, podocin, and CD2AP in Chinese children with MCNS and IgA nephropathy. Pediatr Nephrol 21:1666–1675PubMedCrossRef
14.
Zurück zum Zitat Mao J, Du L, Gu W, Dai Y, Liu A, Xia Y, Zhang Y (2007) Lack of association between NPHS2 gene polymorphisms and sporadic IgA nephropathy. Nephrology (Carlton) 12:371–375CrossRef Mao J, Du L, Gu W, Dai Y, Liu A, Xia Y, Zhang Y (2007) Lack of association between NPHS2 gene polymorphisms and sporadic IgA nephropathy. Nephrology (Carlton) 12:371–375CrossRef
15.
Zurück zum Zitat Roberti I, Vyas S (2010) Long-term outcome of children with steroid-resistant nephrotic syndrome treated with tacrolimus. Pediatr Nephrol 25:1117–1124PubMedCrossRef Roberti I, Vyas S (2010) Long-term outcome of children with steroid-resistant nephrotic syndrome treated with tacrolimus. Pediatr Nephrol 25:1117–1124PubMedCrossRef
16.
Zurück zum Zitat Butani L, Ramsamooj R (2009) Experience with tacrolimus in children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 24:1517–1523PubMedCrossRef Butani L, Ramsamooj R (2009) Experience with tacrolimus in children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 24:1517–1523PubMedCrossRef
17.
Zurück zum Zitat Gulati S, Prasad N, Sharma RK, Kumar A, Gupta A, Baburaj VP (2008) Tacrolimus: a new therapy for steroid-resistant nephrotic syndrome in children. Nephrol Dial Transplant 23:910–913PubMedCrossRef Gulati S, Prasad N, Sharma RK, Kumar A, Gupta A, Baburaj VP (2008) Tacrolimus: a new therapy for steroid-resistant nephrotic syndrome in children. Nephrol Dial Transplant 23:910–913PubMedCrossRef
18.
Zurück zum Zitat Ehrich JH, Geerlings C, Zivicnjak M, Franke D, Geerlings H, Gellermann J (2007) Steroid-resistant idiopathic childhood nephrosis: overdiagnosed and undertreated. Nephrol Dial Transplant 22:2183–2193PubMedCrossRef Ehrich JH, Geerlings C, Zivicnjak M, Franke D, Geerlings H, Gellermann J (2007) Steroid-resistant idiopathic childhood nephrosis: overdiagnosed and undertreated. Nephrol Dial Transplant 22:2183–2193PubMedCrossRef
19.
Zurück zum Zitat El-Husseini A, El-Basuony F, Mahmoud I, Sheashaa H, Sabry A, Hassan R, Taha N, Hassan N, Sayed-Ahmad N, Sobh M (2005) Long-term effects of cyclosporine in children with idiopathic nephrotic syndrome: a single-centre experience. Nephrol Dial Transplant 20:2433–2438PubMedCrossRef El-Husseini A, El-Basuony F, Mahmoud I, Sheashaa H, Sabry A, Hassan R, Taha N, Hassan N, Sayed-Ahmad N, Sobh M (2005) Long-term effects of cyclosporine in children with idiopathic nephrotic syndrome: a single-centre experience. Nephrol Dial Transplant 20:2433–2438PubMedCrossRef
20.
Zurück zum Zitat Choudhry S, Bagga A, Hari P, Sharma S, Kalaivani M, Dinda A (2009) Efficacy and safety of tacrolimus versus cyclosporine in children with steroid-resistant nephrotic syndrome: a randomized controlled trial. Am J Kidney Dis 53:760–769PubMedCrossRef Choudhry S, Bagga A, Hari P, Sharma S, Kalaivani M, Dinda A (2009) Efficacy and safety of tacrolimus versus cyclosporine in children with steroid-resistant nephrotic syndrome: a randomized controlled trial. Am J Kidney Dis 53:760–769PubMedCrossRef
21.
Zurück zum Zitat Sinha MD, MacLeod R, Rigby E, Clark AG (2006) Treatment of severe steroid-dependent nephrotic syndrome (SDNS) in children with tacrolimus. Nephrol Dial Transplant 21:1848–1854PubMedCrossRef Sinha MD, MacLeod R, Rigby E, Clark AG (2006) Treatment of severe steroid-dependent nephrotic syndrome (SDNS) in children with tacrolimus. Nephrol Dial Transplant 21:1848–1854PubMedCrossRef
22.
Zurück zum Zitat Morgan C, Sis B, Pinsk M, Yiu V (2011) Renal interstitial fibrosis in children treated with FK506 for nephrotic syndrome. Nephrol Dial Transplant 26:2860–2865PubMedCrossRef Morgan C, Sis B, Pinsk M, Yiu V (2011) Renal interstitial fibrosis in children treated with FK506 for nephrotic syndrome. Nephrol Dial Transplant 26:2860–2865PubMedCrossRef
23.
Zurück zum Zitat Carlos CP, Mendes GE, Miquelin AR, Luz MA, da Silva CG, van Rooijen N, Coimbra TM, Burdmann EA (2010) Macrophage depletion attenuates chronic cyclosporine A nephrotoxicity. Transplantation 89:1362–1370PubMedCrossRef Carlos CP, Mendes GE, Miquelin AR, Luz MA, da Silva CG, van Rooijen N, Coimbra TM, Burdmann EA (2010) Macrophage depletion attenuates chronic cyclosporine A nephrotoxicity. Transplantation 89:1362–1370PubMedCrossRef
24.
Zurück zum Zitat Fujinaga S, Kaneko K, Muto T, Ohtomo Y, Murakami H, Yamashiro Y (2006) Independent risk factors for chronic cyclosporine induced nephropathy in children with nephrotic syndrome. Arch Dis Child 91:666–670PubMedCrossRef Fujinaga S, Kaneko K, Muto T, Ohtomo Y, Murakami H, Yamashiro Y (2006) Independent risk factors for chronic cyclosporine induced nephropathy in children with nephrotic syndrome. Arch Dis Child 91:666–670PubMedCrossRef
25.
Zurück zum Zitat Duncan N, Dhaygude A, Owen J, Cairns TD, Griffith M, McLean AG, Palmer A, Taube D (2004) Treatment of focal and segmental glomerulosclerosis in adults with tacrolimus monotherapy. Nephrol Dial Transplant 19:3062–3067PubMedCrossRef Duncan N, Dhaygude A, Owen J, Cairns TD, Griffith M, McLean AG, Palmer A, Taube D (2004) Treatment of focal and segmental glomerulosclerosis in adults with tacrolimus monotherapy. Nephrol Dial Transplant 19:3062–3067PubMedCrossRef
26.
Zurück zum Zitat Segarra A, Vila J, Pou L, Majo J, Arbos A, Quiles T, Piera LL (2002) Combined therapy of tacrolimus and corticosteroids in cyclosporin-resistant or -dependent idiopathic focal glomerulosclerosis: a preliminary uncontrolled study with prospective follow-up. Nephrol Dial Transplant 17:655–662PubMedCrossRef Segarra A, Vila J, Pou L, Majo J, Arbos A, Quiles T, Piera LL (2002) Combined therapy of tacrolimus and corticosteroids in cyclosporin-resistant or -dependent idiopathic focal glomerulosclerosis: a preliminary uncontrolled study with prospective follow-up. Nephrol Dial Transplant 17:655–662PubMedCrossRef
27.
Zurück zum Zitat Ruf RG, Lichtenberger A, Karle SM, Haas JP, Anacleto FE, Schultheiss M, Zalewski I, Imm A, Ruf EM, Mucha B, Bagga A, Neuhaus T, Fuchshuber A, Bakkaloglu A, Hildebrandt F (2004) Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome. J Am Soc Nephrol 15:722–732PubMedCrossRef Ruf RG, Lichtenberger A, Karle SM, Haas JP, Anacleto FE, Schultheiss M, Zalewski I, Imm A, Ruf EM, Mucha B, Bagga A, Neuhaus T, Fuchshuber A, Bakkaloglu A, Hildebrandt F (2004) Patients with mutations in NPHS2 (podocin) do not respond to standard steroid treatment of nephrotic syndrome. J Am Soc Nephrol 15:722–732PubMedCrossRef
Metadaten
Titel
Treatment of tacrolimus or cyclosporine A in children with idiopathic nephrotic syndrome
verfasst von
Wenjing Wang
Yonghui Xia
Jianhua Mao
Yifang Chen
Dayan Wang
Huijun Shen
Haidong Fu
Lizhong Du
Ai’min Liu
Publikationsdatum
01.11.2012
Verlag
Springer-Verlag
Erschienen in
Pediatric Nephrology / Ausgabe 11/2012
Print ISSN: 0931-041X
Elektronische ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-012-2228-3

Weitere Artikel der Ausgabe 11/2012

Pediatric Nephrology 11/2012 Zur Ausgabe

Update Pädiatrie

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