Abstract
Despite the availability of immunosuppressive drugs such as prednisone, cyclophosphamide, cyclosporine A (CyA) and mycophenolate mofetil for the treatment of steroid-dependent idiopathic nephrotic syndrome (SDNS), medication-free remission is not achieved in a number of patients. To avoid excessive steroid toxicity, the use of tacrolimus (Tac) has been discussed. We report on five children diagnosed with SDNS on the histological basis of minimal change glomerulopathy or focal segmental glomerulosclerosis. Following the failure of other medications to achieve sustained remission, Tac was administered to these patients who varied in age from 10.5 to 13.5 years. Only one patient showed a substantial reduction in the number of relapses with the Tac treatment. Two boys, after 9 and 44 months on therapy, respectively, developed insulin-dependent diabetes mellitus (IDDM), necessitating the withdrawal of Tac and the daily use of insulin for 3 and 6 months. In both patients hyperglycemia had occurred during prednisone-based relapse therapy of SDNS. The patients had low serum protein concentrations, presumably increasing the free active Tac fraction, while trough levels of the drug remained unchanged. Both of the affected patients had additional risk factors for impaired glucose tolerance, such as morbid obesity (patient 1; BMI: 41.6 kg/m2) and African American origin (patient 2). Our case reports demonstrate that the use of Tac in patients with SDNS may be associated with an increased risk for IDDM, especially during relapse of NS, and particularly if additional risk factors are present. Moreover, Tac does not appear to substantially increase the success of treatment.
Similar content being viewed by others
References
Loeffler K, Gowrishankar M, Yiu V (2004) Tacrolimus therapy in pediatric patients with treatment resistant nephrotic syndrome. Pediatr Nephrol 19:281–287
Duncan N, Dhaygude A, Owen J, Cairns TD, Griffith M, McLean AG, Palmer A, Taube D (2004) Treatment of focal segmental glomerulosclerosis in adults with tacrolimus monotherapy. Nephrol Dial Transplant 3062–3067
Lechner BL, Bockenhauer D, Iragorri S, Kennedy TL, Siegel NJ (2004) The risk of cardiovascular disease in adults who have had childhood nephrotic syndrome. Pediatr Nephrol 19:744–748
Filler G, Neuschutz I, Vollmer I, Amendt P, Hocher B (2000) Tacrolimus reversibly reduces insulin secretion in pediatric renal transplant recipients. Nephrol Dial Tranplant 15:867–871
Mayer AD, Dmitrewski J, Squifflet J-P, Besse T, Grabensee B, Klein B, Eigler FW, Heemann U, Pichlmayr R, Behrend M, Vanrenterghem Y, Donck J, van Hooff J, Christiaans M, Morales JM, Andres A, Johnson RWG, Short C, Buchholz B, Rehmert N, Land W, Schleibner S, Forsythe JLR, Talbot D, Neumayer H-H, Hauser I, Ericzon B-G, Brattström C, Claesson K, Mühlbacher F, Pohanka E (1997) Multicenter randomized trial comparing tacrolimus (FK506) and Cyclosporine in the prevention of renal allograft rejection: a report of the European Tacrolimus Multicenter Renal Study Group. Transplantation 64:436–443
Trompeter R, Filler G, Webb NJ (2002) Randomized trial of tacrolimus versus cyclosporin microemulsion in renal transplantation. Pediatr Nephrol 17:141–149
Al-Uzri A, Stablein DM, Cohn R (2001) Posttransplant diabetes mellitus in pediatric renal transplant recipients: a report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). Transplantation 72:1020–1024
Benz K, Dötsch J, Rascher W, Stachel D (2004) Change of the course of steroid-dependent nephrotic syndrome after rituximab therapy. Pediatr Nephrol 19:794–797
Calne R, Collier DS, Thiru S (1987) Observations about FK-506 in primates. Transplant Proc 19:63
Venkataramanan R, Jain A, Warty VS (1991) Pharmacokinetics of FK506 in transplant patients. Transplant Proc 23:2736–2740
Beysens AJ, Wijnen RNH, Beuman GH, van der Heyden J, Kootstra G, van As H (1991) FK 506: monitoring in plasma or whole blood? Transplant Proc 23:2745–2747
Kasiske BL, Snyder JJ, Gilbertson D, Matas AJ (2003) Diabetes mellitus after kidney transplantation in the United States. Am J Tranplant 3:178–185
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Dittrich, K., Knerr, I., Rascher, W. et al. Transient insulin-dependent diabetes mellitus in children with steroid-dependent idiopathic nephrotic syndrome during tacrolimus treatment. Pediatr Nephrol 21, 958–961 (2006). https://doi.org/10.1007/s00467-006-0102-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00467-006-0102-x