Calcineurin inhibition with tacrolimus has been used after renal transplantation (RTPL) as rescue therapy for insufficient immunological control or if cyclosporin A (CSA) toxicity occurred. Neurologic side-effects occur but are rare in children, usually presenting as tremor; however, serious complications, e.g. the posterior leukoencephalopathy syndrome are also documented. Twenty children (10 girls) were switched to tacrolimus: 11 (55%) for immunological reasons (n = 9: steroid-resistant rejection; n = 2: recurrent rejections) and nine for CSA side-effects. Tacrolimus was started at a median of 8 wk (range 10 d to 8.7 yr) after RTPL and was continued for a median of 2.5 yr (range 5 wk to 4.6 yr). Renal function significantly improved over a period of 12 months following conversion to tacrolimus (glomerular filtration rate 56 +/- 19 vs. 66 +/- 16 mL/min/1.73 m2; p < 0.03; n = 13). Fifteen of 20 (75%) patients tolerated tacrolimus well. The most frequent side-effects were neuropsychological and behavioral symptoms in three children, ranging from anorexia nervosa-like symptoms with weight loss, amenorrhea, depression and school problems to severe insomnia and to aggressive and anxious behavior in one child. Only the latter child was exposed to toxic tacrolimus blood levels. All side-effects were fully reversible after discontinuation of tacrolimus. In conclusion, tacrolimus had a beneficial effect on renal function and was well tolerated in the majority of pediatric patients. However, neuropsychologic and behavioral side-effects are important and maybe underrecognized in children.

Background. Withdrawal of steroids should be attempted after organ transplantation because of their adverse cardiovascular and metabolic effects. However, immunological, haemodynamic and symptomatic complications may occur due to the suppression of endogenous corticoid hormone synthesis under exogenous steroid intake. We have examined the effect of chronic steroid medication on adrenocortical function, and of steroid withdrawal, in immunologically stable renal transplant patients. Methods. Sixty-three patients under long-term prednisone therapy (mean±SD 36±47 months) were assessed regarding basal fasting cortisol concentration and adrenocortical stimulation by the low-dose Synacten test both prior to and after stepwise prednisone withdrawal. Renal graft function (determined as the calculated glomerular filtration rate according to the Cockroft-Gault formula), mean arterial blood pressure and clinical status were evaluated concomitantly. Results. Basal fasting cortisol concentration was clearly suppressed in 14% of patients under longterm steroid medication, and adrenocortical stimulation by the low-dose Synacten test was impaired in 31% after steroid withdrawal. About a third of all patients were symptomatic with fatigue (60%), arthralgias (60%), muscular weakness (20%), loss of appetite (20%), hypotension (15%) or headaches (5%). The incidence of symptoms was much higher in patients with low basal fasting cortisol concentration prior to steroid withdrawal, and after >2 years of steroid medication. Renal graft function, determined as glomerular filtration rate, decreased only slightly overall by $5%, and was more pronounced in symptomatic vs asymptomatic patients (À7 vs À2 ml/min, respectively), as was the fall in mean arterial pressure (À10 vs À4.2 mmHg, respectively).Conclusions. Adrenal function is impaired in renal transplant patients receiving long-term steroid medication as part of their immunosuppressive regimen. This may lead to mainly symptomatic complications when steroids are withdrawn. The slight decrease in glomerular filtration rate probably can be ascribed mostly to the effect of steroids on systemic renal haemodynamics. It is recommended to consider cessation of steroid medication within 48 months of therapy, and after determination of basal cortisol to identify patients with potential complications.

No abstract

No abstract