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The effects of the calcimimetic drug Cinacalcet were assessed in six children with uncontrolled hyperparathyroidism secondary to stage 5 chronic kidney disease (CKD). Data were collected retrospectively regarding bone biochemistry and medications. Patients were between the ages of 11 months and 14 years on commencing Cinacalcet at initial doses of 0.4-1.4 mg/kg. Treatment, which was well tolerated in the majority and still on going in five patients, was for periods ranging between 3 months and 3 years. All six cases saw at least an 86% reduction in serum parathyroid hormone (PTH). Hypophosphataemia and/or hypocalcaemia were observed in three cases. Overall, achievement of UK Renal Association targets for corrected calcium (Ca), phosphate (P) and the calcium x phosphate product (Ca x P) were unaffected. We conclude that Cinacalcet is an effective treatment for correcting and sustaining correction of uncontrollable PTH levels seen in a difficult group of patients. Importantly, it has allowed the avoidance of parathyroidectomy for a significant time period in all cases. There remain questions about the effect of Cinacalcet on linear growth amongst paediatric dialysis patients, and future studies should aim to address this.

This study was undertaken to compare the efficacy and safety of tacrolimus (Tac) with the microemulsion formulation of cyclosporin (CyA) in children undergoing renal transplantation. A 6-month, randomized, prospective, open, parallel group study with an open extension phase was conducted in 18 centers from nine European countries. In total, 196 pediatric patients (<18 years) were randomly assigned (1:1) to receive either Tac ( n=103) or CyA microemulsion ( n=93) administered concomitantly with azathioprine and corticosteroids. The primary endpoint was incidence and time to first acute rejection. Baseline characteristics were comparable between treatment groups. Tac therapy resulted in a significantly lower incidence of acute rejection (36.9%) compared with CyA therapy (59.1%) ( P=0.003). The incidence of corticosteroid-resistant rejection was also significantly lower in the Tac group compared with the CyA group (7.8% vs. 25.8%, P=0.001). The differences were also significant for biopsy-confirmed acute rejection (16.5% vs. 39.8%, P<0.001). At 1 year, patient survival was similar (96.1% vs. 96.6%), while 10 grafts were lost in the Tac group compared with 17 graft losses in the CyA group ( P=0.06). At 1 year, mean glomerular filtration rate (Schwartz estimate) was significantly higher in the Tac group (62+/-20 ml/min per 1.73 m(2), n=84) than in the CyA group (56+/-21 ml/min per 1.73 m(2), n=74, P=0.03). The most frequent adverse events during the first 6 months were hypertension (68.9% vs. 61.3%), hypomagnesemia (34.0% vs. 12.9%, P=0.001), and urinary tract infection (29.1% vs. 33.3%). Statistically significant differences ( P<0.05) were observed for diarrhea (13.6% vs. 3.2%), hypertrichosis (0.0% vs. 7.5%), flu syndrome (0.0% vs. 5.4%), and gum hyperplasia (0.0% vs. 5.4%). In previously non-diabetic children, the incidence of long-term (>30 days) insulin use was 3.0% (Tac) and 2.2% (CyA). Post-transplant lymphoproliferative disease was observed in 1 patient in the Tac group and 2 patients in the CyA group. In conclusion, Tac was significantly more effective than CyA microemulsion in preventing acute rejection after renal transplantation in a pediatric population. The overall safety profiles of the two regimens were comparable.

Individuals with IgA nephropathy (IgAN) who are homozygous for the deletion (D) polymorphism of the gene for angiotensin converting enzyme (ACE) are reported to be at increased risk of progressive renal damage. Since IgAN and Henoch-Schönlein purpura with associated nephritis (HSPN) share a common aetiology, we have investigated this influence in 31 children with HSPN. The distribution of genotypes was as follows: II: 4, ID: 17 and DD: 10 patients. Median length of follow-up was 4.5 years (range 0.5-15.75 years). Severe onset with nephrotic oedema and crescent formation on renal biopsy was seen in 10 of 17 patients with ID genotype and 5 of 10 patients with DD genotype. In the ID group, 2 patients have undergone renal transplantation and 4 have persistent proteinuria 4, 7, 9 and 10 years after presentation. One patient in the DD group has been transplanted and 1 patient has proteinuria and a reduced glomerular filtration rate 5 years after initial presentation. All other patients have either made a complete recovery or have microscopic haematuria alone. These results do not support an association between disease severity and DD genotype in children with HSPN; however larger studies are required to confirm this.

Thrombotic microangiopathy is an uncommon complication of cyclosporin immunosuppression following renal transplantation. We present a 15-year-old girl who developed clinical features of acute rejection, but in whom an early biopsy revealed thrombotic microangiopathy, allowing a change to FK506 immunosuppression resulting in excellent graft recovery.

Two male infants born to consanguineous parents were investigated for feeding difficulties in the 1st month of life. Both were found to have distal renal tubular acidosis (dRTA) with hypercalciuria. Nephrocalcinosis was present in the first child but not in the second. Urinary organic acid profile demonstrated an excess of methylmalonic acid (MMA) in both children in the absence of any other organic acid. MMA mutase activity and propionate incorporation were normal. There have been no neurological symptoms in either child. The first child has normal growth and psychomotor development at 4 years. His brother, who also has significant gastrooesophageal reflux, has failed to thrive and currently requires nasogastric feeding and caloric supplements to maintain weight along the 3rd percentile. Urinary and plasma MMA continue to be raised in both cases. The association of increased urinary and plasma MMA and dRTA presenting in the 1st month of life has not previously been reported and may represent a new syndrome of autosomal recessive inheritance.

Two children who developed acute renal failure in the immediate post-renal transplantation period are presented. Each was immunosuppressed with cyclosporin and was also receiving oral acyclovir for prophylaxis against cytomegalovirus infection. Renal biopsy findings suggested drug toxicity. Discontinuation of acyclovir coincided with reversal of renal impairment. As cyclosporin levels were at the lower end of the therapeutic range, we believe acyclovir to be the likely causative agent.

In three children with haemolytic uraemic syndrome (HUS), evidence of red cell polyagglutinability due to Thomsen Friedenreich antigen (T-antigen) exposure was demonstrated. This was suspected after difficulties in ABO typing and was confirmed using specific antisera. Further supportive evidence included elevation of plasma sialic acid, alteration in red cell surface charge and evidence of T-antigen exposure in the renal biopsy specimen of one patient. Although involvement of this antigen in the pathogenesis of HUS has been associated with a high mortality, all three children have made a complete recovery. With early recognition and subsequent avoidance of plasma products, prognosis of this condition may be improved.