Immunosuppressive therapy in children with steroid-resistant, frequently-relapsing, and steroid-dependent idiopathic nephrotic syndrome
A single center experience
Keywords:
childhood nephrotic syndrome, steroid resistance, steroid dependence, relapse, immunosuppressantAbstract
Introduction: Immunosuppressive agents are recommended for the management of children with steroid-resistant (SRNS), frequently-relapsing (FRNS), and steroid-dependent idiopathic nephrotic syndrome (SDNS). This study evaluated the efficacy of immunosuppressive agents in these cases.
Methods: This is a retrospective analysis of the records of 130 pediatric cases recruited from a tertiary-care center over a period of two years. They were divided into two groups: 51 patients with SRNS (Group I) and 79 cases with SDNS and FRNS (Group II). They were treated with immunosuppressive agents in addition to steroids, either as double- or triple-combination therapy. Complete or partial remission was considered a good response.
Results: In group I, the proportions of good response to cyclophosphamide, cyclosporine A, and mycophenolate mofetil were 48.6, 60, and 80%, respectively (p = 0.162). In group II, the resistance rate was significantly higher with levamisole than with cyclophosphamide and azathioprine (p = 0.046). Leukopenia was reported infrequently after the administration of cyclophosphamide or azathioprine. The most serious adverse reaction was to cyclosporine A, which induced nephrotoxicity (6.4%), while no adverse effects related to levamisole were reported. Histopathological diagnoses were available in only 39 patients.
Conclusion: The high potency of cyclosporine with steroids recommends its use in patients with idiopathic SRNS with a normal glomerular filtration rate. Its efficacy is augmented when combined with mycophenolate mofetil. Cyclophosphamide, orally or as intravenous boluses, together with alternate-day steroids, could be a good option outside the peripubertal age. The outcomes of FRNS and SDNS could be improved by encouraging compliance with the use of levamisole.
References
Niaudet P, Boyer O. Idiopathic Nephrotic Syndrome in Children: Clinical Aspects. In: Avner ED, Harmon
WE, Niaudet P, Yoshikawa N, editors. Pediatric Nephrology. 6th ed. Berlin Heidelberg: Springer-Verlag;
p. 667-702. doi: 10.1007/978-3-540-76341-3_28.
Indian Society of Pediatric Nephrology, Gulati A, Bagga A, Gulati S, Mehta KP, Vijayakumar M.
Management of Steroid resistant Nephrotic Syndrome. Indian Pediatr. 2009; 46(1): 35-47. PMID:
Moustafa B. Mapping Pediatric Nephrology in Africa. First Congress of African Pediatric Nephrology
Association (AFPNA), Cairo-Egypt, February 2000.
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. 1981; 98(4): 561-4. doi: 10.1016/S0022-3476(81)80760-3. PMID: 7205481.
Teeninga N, Kist-van Holthe JE, van Rijswijk N, de Mos NI, Hop WC, Wetzels JF, et al. Extending
prednisolone treatment does not reduce relapses in childhood nephrotic syndrome. J Am Soc Nephrol.
; 24(1): 149-59. doi: 10.1681/ASN.2012070646. PMID: 23274956, PMCID: PMC3537218.
AlSalloum AA, Muthanna A, Bassrawi R, Al Shehab AA, Al Ibrahim A, Islam MZ, et al. Long-term
outcome of the difficult nephrotic syndrome in children. Saudi J Kidney Dis Transpl. 2012; 23(5): 965-72.
doi: 10.4103/1319-2442.100877, PMID: 22982908.
Kari JA, Halawani M, Mokhtar G, Jalalah SM, Anshasi W. Pattern of steroid resistant nephrotic syndrome
in children living in the kingdom of Saudi Arabia. Saudi J Kidney Dis Transpl. 2009; 20(5): 854-57. PMID:
Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at
time of diagnosis. A report of the International Study of Kidney Disease in Children. Kidney Int. 1978:
(2): 159-65. doi: 10.1038/ki.1978.23, PMID: 713276.
Gipson DS, Massengill SF, Yao L, Nagaraj S, Smoyer WE, Mahan JD, et al. Management of childhood
onset nephrotic syndrome. Pediatrics. 2009; 124(2): 747-57. doi: 10.1542/peds.2008-1559, PMID:
Chesney R. The changing face of childhood nephrotic syndrome. Kidney Int. 2004; 66(3): 1294-302. doi:
1111/j.1523/1755.2004.00885.x, PMID: 15327442.
Mekahli D, Liutkus A, Ranchin B, Yu A, Bessenay L, Girardin E, et al. Long-term outcome of idiopathic
steroid-resistant nephrotic syndrome: a multicenter study. Pediatr Nephrol. 2009; 24(8): 1525-32. doi:
1007/s00467-009-1138-5, PMID: 19280229.
Anochie I, Eke F, Okpere A. Childhood nephrotic syndrome change in pattern and response to steroids. J
Natl Med Assoc. 2006; 98(12): 1977-81. PMID: 17225845, PMCID: PMC2569667.
Coppo R. Non-steroidal and non-cytotoxic therapies for nephrotic syndrome. Nephrol Dial Transplant.
; 23(6): 1793-6. doi: 10.1093/ndt/gfn211, PMID: 18441003.
Peña A, Bravo J, Melgosa M, Fernandez C, Meseguer C, Espinosa L, et al. Steroid-resistant nephrotic
syndrome: long-term evolutionafter sequential therapy. Pediatr Nephrol. 2007; 22(11): 1875-80. doi:
1007/s00467-007-0567-2, PMID: 17876609.
Banaszak B, Banaszak P. The increasing incidence of initial steroid resistance in childhood nephrotic
syndrome. Pediatr Nephrol. 2012; 27(6): 927-32. doi: 10.1007/s00467-011-2083-7, PMID: 22231438,
PMCID: PMC3337414.
Bagga A. Revised guidelines for management of steroid-sensitive nephrotic syndrome. Indian J Nephrol.
; 18(1): 31-9. doi: 10.4103/0971-4065.41289, PMCID: PMC2847730.
Zagury A, Oliveira AL, Montalvão JA, Novaes RH, Sá VM, Moraes CA, et al. Steroid-resistant idiopathic
nephrotic syndrome in children: long-term follow-up and risk factors for end-stage renal disease. J Bras
Nefrol. 2013; 35(3): 191-9. doi: 10.5935/0101-2800.20130031, PMID: 24100738.
Iyengar A, Karthik S, Kumar A, Biswas S, Phadke K. Cyclosporine in steroid dependent and resistant
childhood nephrotic syndrome. Indian Pediatr. 2006; 43(1): 14-9. PMID: 16465001.
Ekambaram S, Mahalingam V, Nageswaran P, Udani A, Geminiganesan S, Priyadarshini S. Efficacy of
levamisole in children with frequently relapsing and steroid-dependent nephrotic syndrome. Indian Pediatr.
; 51(5): 371-3. doi: 10.1007/s13312-014-0419-7. PMID: 24953577.
Gipson DS, Chin H, Presler TP, Jennette C, Ferris ME, Massengill S, et al. Differential risk of remission
and ESRD in childhood FSGS. Pediatr Nephrol. 2006: 21(3): 344-9. doi: 10.1007/s00467/005/2097/0.
PMID: 16395603.
Cattran DC, Wang MM, Appel G, Matalon A, Briggs W. Mycophenolatemofetil in the treatment of focal
segmental glomerulosclerosis. Clin Nephrol. 2004; 62(6): 405-11. doi: 10.5414/CNP62405. PMID:
Brandis M, Burghard R, Leititis J, Zimmerhackl B, Hildebrandt F, Helmchen U. Cyclosporine A for
treatment of nephrotic syndrome. Transplant Proc. 1988; 20(3 Suppl 4): 275- 9. PMID: 3381283.
Niaudet P. Treatment of childhood steroid-resistant idiopathic nephrosis with a combination of
cyclosporine and prednisone. French Society of Pediatric Nephrology. J Pediatr. 1994; 125(6 Pt 1): 981-6.
doi: 10.1016/S0022-3476(05)82020-7. PMID: 7996374.
Echeverri CV, Valencia GA, Higuita LM, GayuboAK, Ochoa CL, Rosas LF, et al. Immunosupressive
therapy in children with steroid-resistant nephrotic syndrome: single center experience. J Bras Nefrol.
; 35(3): 200-5. doi: 10.5935/0101-2800.20130032, PMID: 24100739.
Ulinski T, Dubourg L, Saïd MH, Parchoux B, Ranchin B, Cochat P. Switch from cyclosporine A to
mycophenolatemofetil in nephrotic children. Pediatr Nephrol. 2005; 20: 482-5. doi:
1007/s00467/004/1778/4, PMID: 15719253.
Nikibakhsh AA, Mahmoodzadeh H, Karamyyar M, Hejazi S, Noroozi M, Macooie AA. Treatment of
steroid and cyclosporine-resistant idiopathic nephrotic syndrome in children. Int J Nephrol. 2011; 2011:
doi: 10.4061/2011/930965, PMID: 21949905.
Kari JA, Halawani M. Treatment of steroid resistant nephrotic syndrome in children. Saudi J kidney Dis
Transpl. 2010; 21(3): 484-7. PMID: 20427873.
Siegel NI, Gur A, Krassner LS, Kashgarian M. Minimal-lesion nephrotic syndrome with early resistance to
steroid therapy. J Pediatr. 1975; 87(3): 377-80. PMID: 1165516.
Cameron JS, Turner DR, Ogg CS, Sharpstone P, Brown CB. The nephrotic syndrome in adults with
‘minimal change’ glomerular lesions. Q J Med. 1974; 43(171): 461-88. PMID: 4422336.
Tejani A, Phadke K, Nicastri A, Adamson O, Chen CK, Trachtman H, et al. Efficacy of cyclophosphamide
in steroid-sensitive childhood nephrotic syndrome with different morphological lesions. Nephron. 1985;
(2): 170-3. PMID: 4047274.
Bajpai A, Bagga A, Hari P, Dinda A, Srivastava RN. Intravenous cyclophosphamide in steroid-resistant
nephrotic syndrome. Pediatr Nephrol. 2003; 18(4): 351-6. PMID: 12700961.
Madani A, Isfahani ST, Rahimzadeh N, Fereshtehnejad SM, Hoseini R, Moghtaderi M, et al. Effect of
levamisole in steroid-dependent nephrotic syndrome. Iran J Kidney Dis. 2010; 4(4): 292-6. PMID:
Levamisole for corticosteroid-dependent nephrotic syndrome in childhood. British Association for
Paediatric Nephrology. Lancet. 1991; 337(8757): 1555-7. PMID: 1675705.
Barratt TM, Soothill JF. Controlled trial of cyclophosphamide in steroid-sensitive relapsing nephrotic
syndrome of childhood. Lancet. 1970; 2(7671): 479-82. doi: 10.1016/S0140/6736(70)90108-8. PMID:
Chen SY, Wu CY, Tsai IJ, Tsau YK. Treatment course of steroid-dependent nephrotic syndrome:
emphasized on treatment effect. Nephrology. 2010; 15(3): 336-9. doi: 10.1111/j.1440-1797.2009.01190.x.
PMID: 20470303.
Ueda N, Kuno K, Ito S. Eight and 12 week courses of cyclophosphamide in nephrotic syndrome. Arch Dis
Child. 1990; 65(10): 1147-50. PMID: 2248508, PMCID: PMC1792340.
Kyrieleis HA, Levtchenko EN, Wetzels JF. Long-term outcome after cyclophosphamide treatment in
children with steroid dependent and frequently relapsing minimal change nephrotic syndrome. Am J
Kidney Dis. 2007; 49(5): 592-7. PMID: 17472840.
Durkan AM, HodsonEM, Willis NS, Craig JC. Immunosuppressive agents in childhood nephrotic
syndrome: a meta-analysis of randomized controlled trials. Kidney Int. 2001; 59(5): 1919-27. doi:
1046/j.1523/1755.2001. 0590051919.x, PMID: 11318964.
Published
Issue
Section
License
Copyright (c) 2020 KNOWLEDGE KINGDOM PUBLISHING
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
