Immunoprophylaxis with Simulect (basiliximab) in pediatric kidney transplant recipients: results from routine clinical practice at 5 kidney transplant units.

BACKGROUND: Simulect (basiliximab) was introduced in Spain in February 1999, being the first anti-interleukin-2 receptor monoclonal antibody used in our country for the prevention of acute rejection in kidney transplantation. The objective of this study was to assess the efficacy and safety of Simulect (basiliximab) in routine clinical practice in pediatric Spanish kidney transplantation units. METHODS: In this prospective, observational study, we collected data related to demographics, parameters of efficacy, immunosuppressive therapy, and safety on kidney transplant patients treated with Simulect (basiliximab) using an on-line collection system. RESULTS: Fifty pediatric patients at 5 kidney transplant units with 12 months follow-up included recipient mean age of 10.00 years (DS 5.40). Twenty-nine (58.00%) were boys and 21 (42.00%) were girls. Cold ischemia time was 15 hours and 50 minutes (DS 9.70 h). No patient presented with a PRA >50%. For prophylactic immunosuppression, 85.70% of patients received triple therapy with CNI (cyclosporine 48.97% or tacrolimus 36.73%), MMF (87.76%) or AZA (12.24%), and steroids. Acute rejection incidence at 12 months was 22%, including 3 steroid-resistant episodes (6%). One patient lost the graft (2%), 7 adverse events (AE) were reported (1 mild, 4 moderate, and 1 severe AE), of which none were attributed to the study drug. CONCLUSIONS: Simulect (basiliximab) treatment of pediatric patients who underwent kidney transplantations performed in routine clinical practice showed good prophylaxis against acute rejection with excellent safety.

Mutations in the mineralocorticoid receptor gene cause autosomal dominant pseudohypoaldosteronism type I.

Pseudohypoaldosteronism type I (PHA1) is characterized by neonatal renal salt wasting with dehydration, hypotension, hyperkalaemia and metabolic acidosis, despite elevated aldosterone levels. Two forms of PHA1 exist. An autosomal recessive form features severe disease with manifestations persisting into adulthood. This form is caused by loss-of-function mutations in genes encoding subunits of the amiloride-sensitive epithelial sodium channel (ENaC; refs 2,3). Autosomal dominant or sporadic PHA1 is a milder disease that remits with age. Among six dominant and seven sporadic PHA1 kindreds, we have found no ENaC gene mutations, implicating mutations in other genes. As ENaC activity in the kidney is regulated by the steroid hormone aldosterone acting through the mineralocorticoid receptor, we have screened the mineralocorticoid receptor gene (MLR) for variants and have identified heterozygous mutations in one sporadic and four dominant kindreds. These include two frameshift mutations (one a de novo mutation), two premature termination codons and one splice donor mutation. These mutations segregate with PHA1 and are not found in unaffected subjects. These findings demonstrate that heterozygous MLR mutations cause PHA1, underscore the important role of mineralocorticoid receptor function in regulation of salt and blood pressure homeostasis in humans and motivate further study of this gene for a potential role in blood pressure variation.

[Treatment of idiopathic nephrotic syndrome with cyclosporin A]. / Tratamiento del síndrome nefrótico idiopático con ciclosporina A.

OBJECTIVE: Cyclosporin A (CyA) has been used in steroid-dependent and steroid-resistant nephrotic syndrome (NS) with the aim to prolong or to induce remission, respectively. PATIENTS AND METHODS: The efficacy and side-effects of CyA therapy were evaluated in 25 children with idiopathic NS. Twelve patients had steroid-dependent NS and 13 patients had steroid-resistant NS. In all cases, CyA was given as a third alternative drug, once therapies with prednisone and alkylating agents had failed. In steroid-resistant patients CyA administration was always associated with low-dose prednisone. RESULTS: All 12 patients with steroid-dependent NS entered into remission during CyA administration, but 7 patients relapsed when the drug was withdrawn or tapered and 7 of 8 patients requiring long-term therapy continued to present new relapses. Prednisone requirement was lower and growth velocity higher during the year on CyA therapy than during the year preceding CyA therapy. Only 5 of the 13 patients with steroid-resistant NS had a complete remission. Three of these patients relapsed upon cessation of therapy, but these relapses became steroid-sensitive. Clinical side-effects (hirsutism, gum hyperplasia, arterial hypertension) were only observed in a few patients. Biochemical side-effects (hyperuricemia, hypomagnesemia) were more frequently observed, but always reverted upon cessation of therapy. The development of osteosarcoma in one patient may represent a coincidental finding. CONCLUSIONS: The results suggest that CyA therapy is capable of inducing remission in all patients with steroid-dependent NS and in about one third of patients with steroid-resistant NS. However, most patients relapse when the CyA is stopped and require long-term therapy, often associated with administration of predisone.

[Ornithine-transcarbamylase deficiency: prognostic difficulties]. / El déficit en ornitin-transcarbamilasa: dificultades pronósticas.

We report six cases of Ornithine-transcarbamylase deficiency. Unlike some classical descriptions but in accordance with recent reports, sex had no determinant influence on the outcome.