Our data suggest that prophylactic theophylline, given early after birth, has beneficial effects on reducing the renal dysfunction in asphyxiated full-term infants. (ABSTRACT TRUNCATED)

Twenty-four-hour ambulatory blood pressure monitoring (ABPM) has proven to have better reproducibility than office blood pressure (BP) and is increasingly used for the study of hypertension in children and adolescents. The aim of our study was to assess 24-h BP profiles and to compare the results of office BP measurements with ABPM in stable liver transplant recipients transplanted before the age of 18 yr. ABPM was performed in 29 patients (nine males, 20 females), aged 3.9-24.8 yr (median 10.8 yr). The investigation was conducted 1.1-11.5 yr (median 5.1 yr) following transplantation. ABPM confirmed hypertension in one out of three office hypertensive patients. Seven patients (24%), whose office BP recordings were within the normotensive range, were reclassified as hypertensive. Non-dippers (n = 17), arbitrarily defined as patients with less than 10% nocturnal fall in BP, were similarly distributed among patients with ambulatory normotension and ambulatory hypertension (chi(2), p = 0.79). In addition, non-dippers showed a negative correlation between 24-h total urinary albumin excretion and both systolic and diastolic nocturnal decline in BP (Rho = -0.48, p < 0.05 and Rho = -0.86, p < 0.01, respectively). Our study found office BP readings to be poorly representative of 24-h BP profile. Larger studies are needed to confirm our observations as well as to determine whether routine BP measurements in the follow-up of paediatric liver transplant recipients should be based solely on office BP.

TAC, MMF and MP are used in pediatric kidney tx. The cytochrome P450 (CYP)3A5 enzyme appears to play a role in TAC metabolism. The aims of this study were to investigate CYP3A5 polymorphism's effect on TAC dosing and the age dependency of TAC dosing by testing blood concentrations, and the interaction between steroids and TAC during the first year after tx. Genomic DNA was extracted and amplified with specific primers. CYP3A5 alleles were confirmed by direct sequencing of PCR products on an automated AB13100 capillary sequencer. We studied 48 renal transplant patients (age at tx 12±0.5yr, 22 boys) receiving TAC, MMF, MP. Of these, 79% were CYP3A5*3/*3 (non-expressers homozygotes) and 21% were CYP3A5*1/*3 (expressers). TAC trough levels were 7.1±0.4ng/mL in CYP3A5*3/*3 patients and 6.5±0.7ng/mL in CYP3A5*1/*3 group (p=0.03). CYP3A5*1/*3 patients had lower levels of dose-adjusted TAC (36.7±5.8ng/mL/mg/kg/day) to achieve target blood concentration and required higher daily dose per weight (0.21±0.03mg/kg/day) than CYP3A5*3/*3 patients, 72.4±8.0ng/mL/mg/kg/day and 0.13±0.01mg/kg/day (p<0.001). Prepubertal patients with different CYP3A5 polymorphisms required significant higher TAC doses and achieved lower dose-normalized concentration compared with pubertal patients. Both TAC dose and adjusted-dose correlated with daily MP dose in CYP3A5*1*3 (r: 0.4, p<0.03 and r: 0.4, p<0.03) and in CYP3A5*3*3 (r: 0.6, p<0.01 and r: 0.47, p<0.001) patients. CYP3A5 polymorphism performed before tx could contribute to a better individualization of TAC therapy. The higher TAC dose in prepubertal patients and the pharmacological interactions between MP and TAC may not be fully explained by different CYP3A5 polymorphisms.

The aim of this study was to study the incidence of chronic renal dysfunction in patients with more than 5 yr of follow-up following liver transplantation and to evaluate the benefit of decreasing cyclosporine A (CsA) dose combined with mycophenolate mofetil (MMF) on renal function and immune response in these patients. Between 1988 and 1994, 60 children were transplanted, and 86% survived >5 yr post-liver transplantation. Fourteen patients developed chronic renal dysfunction secondary to CsA toxicity as evaluated by renal biopsy. In 11 patients CsA dose was decreased to 40-90 mg/ml target levels and MMF 600 mg/m(2) twice daily was added to the immunosuppressive regimen. Plasma creatinine decreased (from 1.0 +/- 0.03 to 0.8 +/- 0.03 ng/dl, p < 0.007), creatinine clearance increased (from 66.8 +/- 3.0 to 99.2 +/- 6.3 ml/min/1.73 m(2), p < 0.002) and microalbuminuria decreased (from 21.0 +/- 8.6 to 3.6 +/- 1.1 mg/24 h, p < 0.05) after 12 months of CsA combined with MMF therapy. During combined therapy the proliferative, cytolytic response and cytotoxic antibodies showed no significant changes, whereas CD4/CD8 ratio increased (from 1.2 +/- 0.2 to 1.4 +/- 0.1, p < 0.05). Tumor necrosis factor-alpha secretion increased (p < 0.005) during MMF therapy. The release of interleukin-10 was strikingly augmented under both immunosuppressive regimens, but the release of transforming growth factor-beta and interferon-gamma did not change. Our findings indicate that initiation of MMF combined with reduced doses of CsA allowed the recovery of renal function with minor changes in the immune response.