Disparities in policies, practices and rates of pediatric kidney transplantation in Europe.

We aimed to provide an overview of kidney allocation policies related to children and pediatric kidney transplantation (KTx) practices and rates in Europe, and to study factors associated with KTx rates. A survey was distributed among renal registry representatives in 38 European countries. Additional data were obtained from the ESPN/ERA-EDTA and ERA-EDTA registries. Thirty-two countries (84%) responded. The median incidence rate of pediatric KTx was 5.7 (range 0-13.5) per million children (pmc). A median proportion of 17% (interquartile range 2-29) of KTx was performed preemptively, while the median proportion of living donor KTx was 43% (interquartile range 10-52). The median percentage of children on renal replacement therapy (RRT) with a functioning graft was 62%. The level of pediatric prioritization was associated with a decreased waiting time for deceased donor KTx, an increased pediatric KTx rate, and a lower proportion of living donor KTx. The rates of pediatric KTx, distribution of donor source and time on waiting list vary considerably between European countries. The lack of harmonization in kidney allocation to children raises medical and ethical issues. Harmonization of pediatric allocation policies should be prioritized.

Cytogenetic analysis of peripheral blood lymphocytes of children treated with nitrofurantoin for recurrent urinary tract infection.

The objective of this study was to determine whether nitrofurantoin, used for long-term antimicrobial prophylaxis of urinary tract infection, may induce chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) in lymphocytes of treated children. Ninety-nine blood samples were taken from 69 children aged from 0.2 to 13 years and suffering from urinary tract infection. The treatment consisted of oral administration of nitrofurantoin at doses of 5-8 mg/kg/day for the first 7 days and at doses of 1-2 mg/kg/day for the rest of the treatment period. Blood was sampled before the start of the nitrofurantoin therapy and after 1, 3, 6 and 12 months of the therapy. Analysis of variance showed no statistically significant increase in CA and SCE frequencies in lymphocytes of children treated with nitrofurantoin for 1-12 months. However, a significant increase in SCE rates was determined in lymphocytes of those patients whose blood samples were available both before and after treatment with nitrofurantoin (6.21 +/- 0.28 and 7.30 +/- 0.39 SCE/cell, respectively, P = 0.0315, Student's paired t-test). Moreover, there was a statistically significant correlation (r = 0.6603, P = 0.0270) between cumulative dose of nitrofurantoin and SCE frequency in lymphocytes of children after 1 month of the therapy. Also, in vitro experiments indicated that nitrofurantoin was able to induce both CAs and SCEs in human lymphocytes. Positive findings with chromosome aberrations and SCEs in vitro and suggestive results with SCEs in vivo indicate that further, much larger follow-up studies are needed to elucidate the genetic safety of the therapeutic use of nitrofurantoin.

Cytogenetic analysis of children under long-term antibacterial therapy with nitroheterocyclic compound furagin.

Cytogenetic analysis of chromosome aberrations (CAs) and sister chromatid exchanges (SCEs) was performed in 109 blood samples from 95 pediatric patients with urinary tract infections (UTIs). Children were exposed to diagnostic levels of X-rays during voiding cystourethrography and subsequently treated for one to 12 months with low doses of furagin - N-(5-nitro-2-furyl)-allylidene-1-aminohydantoin. Furagin is 2-substituted 5-nitrofuran, chemically and structurally similar to well-known antibacterial compound nitrofurantoin. Increased frequencies of CAs were found in children undergoing voiding cystourethrography as compared with the unexposed, acentric fragments being the most frequent alteration (2.03 versus 0.88 per 100 cells, P=0.006). However, a significant decrease in the frequency of acentric fragments was determined with the time elapsed since X-ray examination was performed. A time-independent increase in SCE frequency was found in lymphocytes of children treated with furagin. Total CA frequency did not differ significantly between groups of children with various duration of furagin treatment. However, frequency of chromatid exchanges (triradials and quadriradials) increased significantly with duration of treatment.

Cyclosporine nephrotoxicity: associated allograft dysfunction at low trough concentration.

A case report on the nephrotoxic effect of cyclosporine in a 9-year-old boy with a kidney transplant is presented. Nephrotoxicity was present even at low trough cyclosporine concentration. The literature on the range of cyclosporine nephrotoxicity is reviewed. Cyclosporine (CsA), a fungal decapeptide first introduced in 1983, has significantly improved the outcome of renal transplantation, and remains the first line immunosupressant for pediatric recipients. CsA has a narrow therapeutic range because of the fine line between adequate immunosuppression and the risk of drug-induced side effects. Furthermore, considerable inter- and intrapatient variability does exist [Filler et al. 1999]. The pre-dose trough concentration is routinely used for therapeutic drug monitoring [Bunchman et al. 1998]. The most significant side effect is nephrotoxicity, which may present differently at different times after transplantation. Renal vasoconstriction, especially involving the afferent renal arterioles, has been strongly implicated as a primary factor in acute reversible CsA nephrotoxicity. Alpha-adrenergic and calcium channel blockade with either verapamil or nifedipine ameliorates vasospasm and impairment of renal function that accompany CsA toxicity. Because of this vasoconstrictive effect, CsA may increase ischemic graft damage in the early posttransplant period. CsA side effects can be eliminated by reducing the dosage of the drug. We present an unusual case of nephrotoxicity and impaired renal function with a very low CsA blood trough concentration (50 ng/ml) on posttransplant treatment. The side effects subsided only after the discontinuation of CsA.

Multicystic dysplastic kidney associated with Waardenburg syndrome type 1.

A 16-day-old girl with Waardenburg syndrome type 1 presented with a right multicystic dysplastic kidney (MDK) and hydronephrosis in the left kidney. To our knowledge, such an association has not yet been reported and should be added to the list of MDK-associated genetic syndromes.