TACROLIMUS DRUG LEVEL AND RESPONSE TO TREATMENT IN IDIOPATHIC CHILDHOOD STEROID RESISTANT NEPHROTIC SYNDROME
AbstractBackground: The management of Steroid Resistant Nephrotic Syndrome (SRNS) is an uphill task for paediatric nephrologists as immunosuppressive agents are the mainstay of treatment in these patients. Tacrolimus is used along with steroids. This study is conducted to see the relationship between the tacrolimus dose, drug level and response in the management of SRNS. Methods: This quasi experimental study was conducted at The Children’s Hospital Lahore over a period of one year. Patients with SRNS of either sex and 1–10years of age were included and those with secondary nephrotic syndrome were excluded. Tacrolimus was given at a dose of 0.05–0.1 mg/kg/day in 2 divided doses along with steroids. The follow-up was done for six months with proteinuria monitoring and tacrolimus drug levels done two weeks after initiation of treatment. Results: Out of 42 patients, 27 (64.3%) were males and 15 (35.7%) were females. The most common histological diagnosis observed was mesangio-proliferative glomerulonephritis in 30 (71.4%) patients. The tacrolimus trough level range was 0.5–15.20 ng/ml with a mean value of 4.68 ng/ml±2.85. Forty-one (97.6%) children showed complete response to treatment while one patient showed partial response. Conclusion: This study suggests that tacrolimus is an effective drug for treatment of SRNS in paediatric patients and there is no linear relationship between the drug dose, response and drug level.
Rachmadi D, Melani A, Monnens L.NPHS2 Gene Mutation and Polymorphisms in Indonesian Children with Steroid-Resistant Nephrotic Syndrome. Open J Pediatr 2015;5(1):27–33.
Kim JS, Bellew CA, Silverstein DM, Aviles DH, Boineau FG, Kim VM. High incidence of initial and late steroid resistance in childhood nephrotic syndrome. Kidney Int 2005;68:1275–81.
Habashy D, Hodson EM, Craig JC. Interventions for steroid-resistant nephrotic syndrome: a systematic review. Pediatr Nephrol 2003;18(9):906–12.
Barletta GM, SmoyerWE, Bunchman TE, Flynn JT, Kershaw DB. Use ofmycophenolate mofetil in steroid-dependent and resistant nephrotic syndrome. Pediatr Nephrol 2003;18(8):833–7.
Gulati S, Sengupta D, Sharma RK, Sharma A, Gupta RK, Singh U, et al. Steroid resistant nephroticsyndrome – role of histopathology. Indian Pediatr 2006;43:55–60.
Tryggvason K, Pettersson E. Causes and consequences of proteinuria: thekidney filtration barrier and progressive renal failure. J Intern Med 2003;254(3):216–24.
Choudhry S, Bagga A, Hari P, Sharma S, Kalaivani M, Dinda A. Efficacy and safety of tacrolimus versus cyclosporine in children with steroid-resistant nephrotic syndrome: a randomized controlled trial. Am J Kidney Dis 2009;53(5):760–9.
Butani L, Ramsamooj R. Experience with tacrolimus in children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 2009;24(8):1517–23.
Bhimma R, Adhikari M, Asharam K, Connolly C. Management of steroid-resistant focal segmental glomerulosclerosis in children using tacrolimus. Am J Nephrol 2006;26(6):544–51.
Roberti I, Vyas S. Long-term outcome of children with steroid-resistant nephrotic syndrome treated with tacrolimus. Pediatr Nephrol 2010;25(6):1117–24.
Westhoff T, Schmidt S, Zidek W, Beige J, van der Giet M. Tacrolimus in steroid-resistant and steroid-dependent nephrotic syndrome. Clin Nephrol 2006;65(6):393–400.
Denton MD, Magee CC, Sayegh MH. Immunosuppressive strategies in transplantation. Lancet 1999;353(9158):1081–91.
Kaneko K, Tsuji S, Kimata T, Kitao T, Yamanouchi S, Kato S. Pathogenesis of childhood idiopathic nephrotic syndrome: a paradigm shift from T-cells to podocytes. World J Pediatr 2015;11(1):21–8.
Faul C, Donnelly M, Merscher-Gomez S, Chang YH, Franz S, Delfgaauw J, et al. The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med 2008;14:931–8.
Wu B, Mao J, Shen H, Fu H, Wang J, Liu A, et al. Triple immunosuppressive therapy in steroid-resistant nephrotic syndrome children with tacrolimus resistance or tacrolimus sensitivity but frequently relapsing. Nephrology 2015;20(1):18–24.
Samuel S, Bitzan M, Zappitelli M, Dart A, Mammen C, Pinsk M, et al. Canadian Society of Nephrology Commentary on the 2012KDIGO Clinical Practice Guideline for Glomerulonephritis: Management of Nephrotic Syndrome in Children. Am J Kidney Dis 2014;63(3):354–62.
Gulati S, Prasad N, Sharm RK, Kumar A, Gupta A, Baburaj VP. Tacrolimus: a new therapy for steroid resistant nephrotic syndrome in children. Nephrol Dial Transplant 2008;23(3):910–13.
Tran TH. Bentley LE. Pediatric Idiopathic Nephrotic Syndrome. US Pharm 2014;5:16.
Loeffler K, Gowrishankar M, Yiu V. Tacrolimus therapy in pediatric patientswith treatment-resistant nephrotic syndrome. Pediatr Nephrol 2004;19(3):281–7.
Sinha A, Bagga A. Nephrotic Syndrome. Indian J Pediatr 2012;79(8):1045–55.
Gulati A, Sinha A, Gupta A, Kanitkar M, Sreenivas V, Sharma J, et al. Treatment with tacrolimus and prednisolone ispreferable to intravenous cyclophosphamide asthe initial therapy for children with steroid-resistantnephrotic syndrome. Kidney Int 2012;82(10):1130–5.
Peyser K, Steinberg Y, Frank R, Vento S, Infante L, Sethna C, et al. The Value Of Tacrolimus Drug Levels In The Management Of Nephrotic Syndrome In Children. Internet J Nephrol 2012;6(2).