Split catheters in children on chronic hemodialysis: a single-center experience.

Tunneled central venous catheters (CVCs) play an increasing role as vascular access for chronic hemodialysis (HD) in children, but limited data exist about the optimal CVC choice. We analyzed the outcome, efficacy, and complications of tunneled CVCs, placed in our unit in the last 3 years. Nineteen 10 F Split-Cath CVCs (two separate catheters fused along their length) were placed in 10 children, median age 9.19 years (range 2.15-13.31) and body weight (BW) between 10 and 40 kg. CVCs survival at 1, 3, 6, and 12 months was 94%, 77%, 51%, and 34%, respectively. Catheter survival was higher in children with BW > 20 kg than in smaller patients. Median survival was higher than that of 11 Quinton Permcath CVCs, placed in five children in the preceding 2 years (280 vs. 45 days, P < 0.05). Median blood flow rate and indices of HD adequacy were higher in children with lower BW (<20 kg vs. 20-30 kg vs. >30 kg) than in those with higher BW. Incidence of exit site and bloodstream infections was 2.32 and 0.66/1000 CVC days, respectively. One case of hemothorax due to subclavian artery puncture occurred during CVC placement. In conclusion, Split-Cath 10 F CVC allows for effective dialysis in children undergoing HD, particularly those between 10 and 30 kg BW. Catheter survival is acceptable, but could be improved in small children.

An open-label, randomized clinical trial assessing immunogenicity, safety and tolerability of pandemic influenza A/H1N1 MF59-adjuvanted vaccine administered sequentially or simultaneously with seasonal virosomal-adjuvanted influenza vaccine to paediatric kidney transplant recipients.

BACKGROUND: The aim of this study was to investigate the immunogenicity, safety and tolerability of the 2009 A/H1N1 MF59-adjuvanted influenza vaccine, administered sequentially or simultaneously with the seasonal 2009-10 virosomal-adjuvanted influenza vaccine, to paediatric kidney transplant recipients. METHODS: Thirty-two children and adolescents with transplanted kidneys and 32 age- and gender-matched healthy controls were randomized 1:1 to receive the pandemic vaccine upon enrolment and the seasonal vaccine 1 month later (16 transplant recipients and 16 healthy controls), or to receive the two vaccines simultaneously upon enrolment (16 transplant recipients and 16 healthy controls). RESULTS: When the pandemic vaccine was administered sequentially to the seasonal vaccine, it was significantly less immunogenic in the patients than in the controls (P < 0.05); when it was administered together with the seasonal vaccine, the immune response of both patients (P < 0.05) and controls (P < 0.05) was significantly greater than when it was administered sequentially. Seroconversion rates and the geometric mean titres of all of the seasonal antigens were significantly lower in the patients, regardless of the type of vaccine administration (P < 0.05). Simultaneous administration was associated with a better immune response against A/H1N1 and A/H3N2 antigens in both patients and controls, and did not increase the mild local and systemic reactions. No impact on renal function was observed. CONCLUSIONS: Paediatric kidney transplant recipients have a lower immune response to the pandemic influenza A/H1N1 MF59-adjuvanted and seasonal virosomal-adjuvanted influenza vaccines than healthy controls. The simultaneous administration of the two vaccines seems to increase immune response to both pandemic and seasonal A/H1N1 and A/H3N2 antigens, and has the same safety profile as that of the pandemic vaccine administered sequentially to the seasonal vaccine.

The effect of CYP3A5 polymorphisms on the pharmacokinetics of tacrolimus in adolescent kidney transplant recipients.

BACKGROUND: CYP3A5 gene polymorphism has been shown to influence tacrolimus (TAC) blood concentration and dose requirement in adult kidney transplant patients. The aim was to analyze retrospectively the modification induced by CYP3A5 gene polymorphism on TAC's pharmacokinetic parameters obtained from 26 adolescents receiving TAC as their main immunosuppressive drug. MATERIAL/METHODS: The adolescent kidney transplant patients were genotyped for CYP3A5*3 and grouped accordingly. TAC dose, blood levels, and dose-normalized TAC blood concentration and volume of distribution obtained at different post-transplant periods during the first post-transplant year were correlated with the corresponding genotype. RESULTS: During the first three months post-transplant, heterozygotes (CYP3A5*1/*3) displayed a lower TAC blood concentration than homozygotes (CYP3A5*3/*3) (at 1 month: 7.8+/-2.1 vs. 13.4+/-6 ng/ml, p=0.007) despite a therapeutic monitoring strategy. Between 3-12 months post-transplant, TAC blood concentration was comparable between the two groups, but a two-fold increase in the daily drug dose was necessary for the heterozygotes (at 6 months: 0.23+/-0.1 vs. 0.13+/-0.06 mg/kg, p=0.04). The dose-normalized TAC concentration [(ng/ml)/(mg/kg)] was significantly lower in patients displaying the CYP3A5*1/*3 polymorphism (at 2 weeks: 33+/-2.16 vs. 71.1+/-37.8, p=0.01; 6 months: 35.4+/-12.9 vs. 85.2+/-58.9, p=0.01). At the same time, the volume of distribution of the drug in the latter group was distinctly increased for the entire post-transplant year (at 6 months: 1.79+/-0.42 vs. 0.73+/-0.5 l/kg, p=0.001). CONCLUSIONS: The great influence of CYP3A5 on the pharmacokinetics and pharmacodynamics of TAC in young transplant recipients suggests the need for pre-transplant screening of this polymorphism to improve TAC therapy.

Reduced coronary flow reserve in young adults with renal transplant.

BACKGROUND: Some degree of cardiovascular disease should be suspected in young adults who have been paediatric renal transplant recipients also if no systematic data collection is routinely performed in clinical setting. The aim of our work was to evaluate the degree of cardiovascular damage in these young patients, using a minimally invasive technique. We then evaluated coronary flow reserve (CFR) and carotid intima-media thickness (IMT) in 25 patients (13 males, median age 23.7 years). METHODS: Coronary flow velocity on the left anterior descending coronary artery was assessed by transthoracic echocardiography, before and after dipyridamole, after standard echocardiography. CFR was compared with that of a small control group (n = 16; median age 25 yrs). RESULTS: In this relatively young sample, mean CFR was 2.8 +/- 0.6 (median 2.75), and half of the patients had reduced coronary reserve (P = 0.01). Mean IMT (0.48 +/- 0.08 mm) was only slightly, though significantly larger compared with the reference standard (P < 0.05) but was significantly thinner in normotensive than in hypertensive patients (0.42 +/- 0.06 vs 0.49 +/- 0.05 mm, P < 0.05). The time on dialysis prior to transplantation, hypertension and age at the time of CFR evaluation affect CFR. IMT did not correlate with CFR. CONCLUSIONS: CFR and IMT abnormalities are common in young transplant recipients, in spite of the fact that our paediatric population has much less of the atherosclerotic 'legacy' common to adult patients.

In vivo effects of maternal immunosuppression during pregnancy on the immune function of newborn infants.

When used in pregnancy, immunosuppressants can cross the placental barrier and enter foetal circulation, possibly affecting the immune system of the foetus. This study evaluated the immune function in eight children born by mothers with connective tissue diseases who received immunosuppressants (cyclosporine A or dexamethasone) during pregnancy and in six babies from mothers with similar diseases, but who did not receive any treatment. Judging by the cytokine production of interleukin-2 and interferon-gamma in peripheral blood mononuclear cells stimulated by phorbol-myristate-acetate (PMA) and ionomycin, immunosuppressive drugs given for rheumatic disorders during pregnancy do not induce significant immunosuppression in babies.