This is a retrospective analysis of 16 children started on tacrolimus with various types of treatment-resistant nephrotic syndrome. There are 13 patients with focal glomerulosclerosis, 1 minimal change disease, and 2 IgA nephropathy with nephrosis. The mean age of the children was 11.4 years (range 3.5-18.1 years) with a mean age at diagnosis of 5.6 years (range 1.6-13.3 years). All patients initially received prednisone 2 mg/kg per day. Other therapies for 15 of 16 included cyclosporine (n=15), chlorambucil (n=5), mycophenolate mofetil (n=5), levamisole (n=3), i.v. methylprednisolone (n=3), and cyclophosphamide (n=2). The major indication for the initiation of tacrolimus included treatment resistance/dependence (n=15) and intolerable side effects from other therapies (n=1). The average time from the diagnosis to initiation of tacrolimus was 5.3 years (range 0.3-13.3 years, median 6 years). The initial dosage of tacrolimus utilized was 0.1 mg/kg per day divided into two doses. The mean follow-up period was 6.5 months (range 2.5-18 months). Thirteen patients (81%) went into a complete remission within an average of 2 months (range 0.5-5.5 months), with 3 patients relapsing while on treatment. Three patients did not respond. Of these, 2 had partial remissions (13%) and 1 failed to respond. Adverse events included anemia (n=1), seizure (n=1), worsening or new-onset hypertension (n=5), and sepsis (n=1). All patients remain on tacrolimus. Tacrolimus is an effective, well-tolerated medication for treatment-resistant forms of nephrotic syndrome in children, with a complete remission rate of 81% and a partial remission rate of 13% (totaling 94%).

The diagnosis of UTI in NICU is hampered by use of urine collection methods that are subject to contamination. Outcome is generally excellent, but there is a great need for guidelines on management of positive urine cultures in the NICU.

dRTA (distal renal tubular acidosis) and HS (hereditary spherocytosis) are two diseases that can be caused by mutations in the gene encoding the AE1 (anion exchanger 1; Band 3). dRTA is characterized by defective urinary acidification, leading to metabolic acidosis, renal stones and failure to thrive. HS results in anaemia, which may require regular blood transfusions and splenectomy. Mutations in the gene encoding AE1 rarely cause both HS and dRTA. In the present paper, we describe a novel AE1 mutation, Band 3 Edmonton I, which causes dominant HS and recessive dRTA. The patient is a compound heterozygote with the new mutation C479W and the previously described mutation G701D. Red blood cells from the patient presented a reduced amount of AE1. Expression in a kidney cell line showed that kAE1 (kidney AE1) C479W is retained intracellularly. As kAE1 is a dimer, we performed co-expression studies and found that, in kidney cells, kAE1 C479W and G701D proteins traffic independently from each other despite their ability to form heterodimers. Therefore the patient carries one kAE1 mutant that is retained in the Golgi (G701D) and another kAE1 mutant (C479W) located in the endoplasmic reticulum of kidney cells, and is thus probably unable to reabsorb bicarbonate into the blood. We conclude that the C479W mutant is a novel trafficking mutant of AE1, which causes HS due to a decreased cell-surface AE1 protein and results in dRTA due to its intracellular retention in kidney.