Abstract
We report the outcome of our single-center, long-term follow-up study of tacrolimus therapy in children with steroid-resistant nephrotic syndrome (SRNS). All cases of nephrotic syndrome (NS) with kidney biopsies treated at our center between January 2000 and July 2008 were reviewed. Children with systemic lupus erythematosus and steroid-dependent NS were excluded. Nineteen children with SRNS received tacrolimus. Histopathological analysis of the biopsy revealed the underlying conditions of these 19 patients to be focal segmental glomerulosclerosis (ten patients), C1q nephropathy (four), membranous nephropathy (two), minimal change disease (one), membranoproliferative glomerulonephritis (one), and immunoglobulin A nephropathy (one). The mean follow-up was 55 months, and the median age of the patient cohort was 10 years. We observed complete remission in 11 (58%) patients, partial remission in six (32%), and failure to respond in two (9%). The median time to response was 8 weeks. Side effects were mild and transient (one case of acute kidney injury and three cases of hyperglycemia). The initial rate for combined partial and complete remission of the NS in children with SRNS was 81%, which was sustained in 58% of the patients on follow-up. Among children with FSGS, the sustained remission rate was 50%, while 40% progressed to end-stage renal disease (ESRD) (mean time 52 months). Based on the results of this study, we conclude that tacrolimus is an effective and well-tolerated therapeutic option for the treatment of SRNS in children. However, the occurrence of relapses of the NS with progression to ESRD during the long-term follow-up indicates the need for careful monitoring of such patients.
Similar content being viewed by others
References
Cameron JS (1990) Proteinuria and progression in human glomerular diseases. Am J Nephrol 10[Suppl 1]:81–87
Tryggvason K, Pettersson E (2003) Causes and consequences of proteinuria: the kidney filtration barrier and progressive renal failure. J Intern Med 254:216–224
Ho S, Clipston N, Timmermann L, Northrop J, Graef I, Fiorentino D, Nourse J, Crabtree GR (1996) The mechanism of action of cyclosporine A and FK506. Clin Immunol Immunopathol 80:S40–S45
McCauley J, Shapiro R, Ellis D, Igdall H, Tzakis A, Starzl TE (1993) Pilot trial of FK506 in the management of steroid-resistant nephrotic syndrome. Nephrol Dial Transplant 8:1286–1290
Li X, Li H, Ye H, Li Q, He H, Zhang X, Chen Y, Han F, He Q, Wang H, Chen J (2009) Tacrolimus therapy in Adults with Steroid- and cyclophosphamide- resistant nephritic syndrome and normal or mildly reduced GFR. Am J Kidney Dis 54:51–58
Loeffler K, Gowrishankar M, Yiu V (2004) Tacrolimus therapy in pediatric patients with treatment-resistant nephrotic syndrome. Pediatr Nephrol 19:281–287
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 23:910–913
Butani L, Ramsamooj R (2009) Experience with tacrolimus in children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 24:1517–1523
National High Blood Pressure Education Program (1996) Update on the 1987 task force report on high-blood pressure in children and adolescents: a working group report from the National High Blood Pressure Education Program. Pediatrics 98:649–658
Schwartz GJ, Haycock GB, Edelman CM, Spitzer A (1967) A simple estimation of glomerular filtration rate in children derived from body weight and plasma creatinine. Pediatrics 58:259–263
Ruggenenti P, Perna A, Mosconi L, Pisoni R, Remuzzi G (1998) Urinary protein excretion rate is the best independent predictor of ESRF in non-diabetic proteinuric chronic nephropathies. ‘Gruppo Italiano di Studi Epidemiologici in Nefrologia’ (GISEN). Kidney Int 53:1209–1216
Faul C, Donnelly M, Merscher-Gomez S, Chang YH, Franz S, Delgaauw J, Chang JM, Choi HY, Campbell KN, Kim K, Reiser J, Mundel P (2008) The actin cytoskeleton of kidney podocytes is a direct target of the antiproteinuric effect of cyclosporine A. Nat Med 14:931–938
Colquitt JL, Kirby J, Green C, Cooper T, Trompeter RS (2007) The clinical effectiveness and cost effectiveness of treatments for children with idiopathic steroid-resistant nephrotic syndrome: a systematic review. Health Technol Assess 11:iii–iv, ix–xi, 1–93
Segarra A, Vila J, Pou L, Majo J, Arbos A, Quiles T, Piera LL (2002) Combined therapy of tacrolimus and corticosteroids in cyclosporine-resistant or dependent idiopathic focal glomerulosclerosis: a preliminary uncontrolled study with prospective follow-up. Nephrol Dial Transplant 17:655–662
Westhoff TH, Schmidt S, Zidek W, Beige J, van der Geit M (2006) Tacrolimus in steroid-resistant and steroid-dependant nephrotic syndrome. Clin Nephrol 65:393–400
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 nephritic syndrome: a randomized controlled trial. Am J Kidney Dis 53:760–769
Bhimma R, Adhikari M, Asharam K, Connolly C (2006) Management of steroid-resistant focal segmental glomerulosclerosis in children using tacrolimus. Am J Nephrol 26:544–551
Suzuki K, Tsugawa K, Tanaka H (2006) Tacrolimus for treatment of focal segemental glomerulosclerosis resistant to cyclosporine A. Pediatr Nephrol 21:1913–1914
Hamasaki Y, Yoshikawa N, Hattori S, Sasaki S, Iijima K, Nakanishi K, Matsuyama T, Ishikura K, Yata N, Kaneko T, Honda M, Japanese Study Group of Renal Disease (2009) Cyclosporine and steroid therapy in children with steroid resistant nephrotic syndrome. Pediatr Nephrol 24:2177–2185
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Roberti, I., Vyas, S. Long-term outcome of children with steroid-resistant nephrotic syndrome treated with tacrolimus. Pediatr Nephrol 25, 1117–1124 (2010). https://doi.org/10.1007/s00467-010-1471-8
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-010-1471-8