Transient insulin-dependent diabetes mellitus in children with steroid-dependent idiopathic nephrotic syndrome during tacrolimus treatment

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/m(2)) 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.

Clinical practice guideline for pediatric idiopathic nephrotic syndrome 2013: medical therapy

“…There are no randomized controlled trials that compare tacrolimus to cyclosporine or other immunosuppressive agents, and reports that are available are only smallnumber case series [17,83,[106][107][108]. Other reports describe that switching from cyclosporine to tacrolimus is only effectively reducing cosmetic side effects and such a switch merits caution for the potential onset of diabetes mellitus [105,108].…”

New therapies in steroid-sensitive and steroid-resistant idiopathic nephrotic syndrome

“…Initial series used tacrolimus in patients refractory to cyclosporine A (CSA) [26] and found no superiority (nor inferiority) to CSA [27]. In terms of side effects, the risk of diabetes may be increased in children with SSNS, possibly due to repeated steroid treatment [28]. Individual patients are treated with tacrolimus instead of cyclosporine to reduce cosmetic side effects; however, systematic data are lacking.…”

Rituximab treatment of collapsing C1q glomerulopathy: clinical and histopathological evolution

“…Glucocorticoids and tacrolimus can induce diabetes in patients with FSGS [35], with body mass as an independent risk factor [36]. It should be noted, however, that our patient had discontinued all prednisone more than 3 months before the initiation of rituximab treatment and that the tacrolimus dose remained unchanged before and after the administration of the antibody (Fig.…”