ABPM vs office blood pressure to define blood pressure control in treated hypertensive paediatric renal transplant recipients

While 24-h ambulatory blood pressure monitoring (ABPM) is an established tool for monitoring antihypertensive therapy in adults, data in children are scarce. We retrospectively analysed whether office blood pressure (BP) is reliable for the diagnosis of BP control in 26 treated hypertensive paediatric renal transplants. Controlled office BP was defined as the mean of three replicate systolic and diastolic BP recordings less than or equal to the 95th age-, sex- and height-matched percentile on the three-outpatient visits closest to ABPM. Controlled ABPM was defined as systolic and diastolic daytime BP < or =95th distribution adjusted height- and sex-related percentile of the adapted ABPM reference. Eight recipients (30%) with controlled office BP were in fact categorized as having non-controlled BP by ABPM criteria. Overall, when office BP and ABPM were compared using the Bland and Altman method, the 95% limits of agreement between office and daytime values ranged from -12.6 to 34.1 mmHg for systolic and -23.9 to 31.7 mmHg for diastolic BP, and the mean difference was 10.7 and 3.9 mmHg respectively. Office readings miss a substantial number of recipients who are hypertensive by ABPM criteria. Undertreatment of hypertension could be avoided if ABPM is applied as an adjunct to office readings.     

Ambulatory blood pressure monitoring in pediatric renal transplantation

Over last two decades ABPM has evolved from a research device to an established and valuable clinical tool for BP evaluation. More than 10 yrs ago ABPM was introduced to pediatrics and since that time, its importance has been increasing in the management of hypertension in children and adolescents. This review summarizes the information gathered from the studies of ABPM in adult and pediatric patients with renal transplants. We will review the importance of hypertension in this patient subset, discuss the advantage of ABPM over CBP and focus on specific abnormalities and clinical significance of ABPM in renal transplant recipients.     

Hypogammaglobulinemia in pediatric liver transplant recipients

Hypogammaglobulinemia has been reported after solid organ transplantation in adults, however immunoglobulin replacement [intravenous immunoglobulins (IVIG)] is only necessary in a minority of affected patients. We here present three pediatric patients with severe post-transplant hypogammaglobulinemia following liver transplantation (LTx) receiving a cyclosporine-based standard immunosuppression. Patient 1 was transplanted at the age of 10 months for biliary atresia. Eight weeks post-Ltx the serum IgG was 1.7 g/L. Patient 2 was transplanted at the age of 12 yr for acute liver failure. Four weeks post-Ltx the IgG dropped to 2.6 g/L. Patient 3 was transplanted at the age of 4 months for biliary atresia. Ten weeks post-Ltx severe hypogammaglobulinemia (IgG < 1.48 g/L) was diagnosed during a severe infectious complication. Patients 1 and 3 received a steroid bolus therapy for acute graft rejection. All patients had normal IgG concentrations prior to Ltx and lymphocyte subsets were post-operatively in the normal range. There was no extensive loss of protein by ascites. IGIV were replaced in the three patients monthly without further complications. In two of the patients (1 and 3) IVIG therapy was discontinued 8 and 10 months after Ltx when the immunosuppression has been reduced and serum IgG concentrations were found in the normal range without further immunoglobulin replacement. Severe hypogammaglobulinemia is a rare phenomenon following pediatric LTx and seems to be mainly caused by immunosuppressive drugs, however, the exact underlying mechanisms are unclear. A screening for hypogammaglobulinemia is useful after pediatric LTx, especially in patients with an intensified immunosuppression. Moreover, further immunologic research in affected patients is necessary.     

Nocturnal hypertension and left ventricular hypertrophy in pediatric renal transplant recipients in South India

HTN after renal transplantation is associated with cardiovascular morbidity. ABPM allows diagnosis of masked HTN and isolated nocturnal HTN. Longitudinal ABPM data in children post‐transplant are limited. ABPM was performed in children post‐transplant and repeated in 6‐12 months. BP indices were used to determine the prevalence of masked HTN, masked uncontrolled HTN (masked HTN in patients on antihypertensive medications), and isolated nocturnal HTN. Linear regression determined the association between LVMI and ABPM indices. Thirty children underwent a baseline ABPM. Ambulatory HTN was present in 25 (83%). Masked HTN was present in 18 (60%) and isolated nocturnal HTN in 13 (43%). Nocturnal ambulatory BP was higher than corresponding daytime BPs (P < .001 for systolic and diastolic) and 25 (83%) had a blunted nocturnal dip. Prednisone dose predicted nocturnal DBP index and DBP load (r² = .40, P = .024 and r² = .178, P = .02). ABPM was repeated in 18 patients within 11 (±3) months. BP indices decreased with time, but nocturnal BPs remained higher than daytime (P < .001 for SBP and DBP). Blunted nocturnal dip did not improve. LVH was present in 12 (57%). LVMI was directly related to the nocturnal SBP index (r² = .377, P = .003) and nocturnal DBP index (r² = .493, P < .001). We found no association between LVMI and daytime BP indices. The prevalence of masked HTN, isolated nocturnal HTN, and blunted nocturnal dip was high in children with kidney transplants. Nocturnal BP predicted LVMI. Ambulatory BP improved on longitudinal follow‐up, but the pattern of isolated nocturnal HTN persisted.     

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??Objective To discuss the changes of ambulatory blood pressure monitoring??ABPM?? in children with vasovagal syncope ??VVS??.Methods A total of 72 children ??VVS group??32 males??40 females??mean age ??10.98±1.86??years?? were enrolled in this study??who came from Children Syncope Outpatient Department or Inpatient Department of the Second Xiangya Hospital of Central South University from Sep 2008 to Feb 2010.After confirmed diagnosis of VVS by positive head-up tilt test ??HUTT????each patient was given ABPM.Forty healthy children ??19 males??21 females??mean age 10.24 ± 2.01 years?? were as controls ??control group??.Parameters of ABPM in children were analyzed.SPSS 17.0 software was used for the statistical analysis of these data.Results ??1??Mean pressure??24-hour mean systolic pressure ??24hSBP????24-hour mean diastolic pressure ??24hDBP????daytime mean systolic pressure ??DSBP?? and nighttime mean systolic pressure ??NSBP?? in VVS group were higher than those of the control group ??P??0.05??.??2??Blood pressure pattern??the ratio of non-spoon pressure pattern was higher than that of spoon pressure pattern with VVS ??67%vs.18%??P ??0.05??.NDBP ??P??0.05?? and NSBP ??P ??0.05?? were decreased and the systolic pressure differences and diastolic pressure differences in the daytime and at nighttime were higher in spoon pressure pattern than those of non-spoon pressure pattern with VVS ??P??0.05??.??3??Diagnostic experimental evaluation??the specificity??sensitivity??diagnostic coincidence??positive predict value and negative predict value of non-spoon pattern of ambulatory blood pressure pattern to VVS was 82.5%??66.67%??72.32%??87.27% and 57.89%??respectively.The Youden index was 45.28%.Conclusion There is autonomic nerve adjustment imbalance in children with VVS during asymptomatic time periods??especially the sympathetic nerve.The non-spoon pattern rate of fluctuation curve of ambulatory blood pressure in VVS children is higher??which is of diagnosis value to VVS children.     

Abnormal circadian blood pressure regulation in liver transplanted children

HT is a frequent cardiovascular risk factor in liver transplant recipients. However, there are only few studies in the literature regarding the risk of HT in liver transplanted children. The aim of this study was to assess the 24 h BP profiles of liver transplanted patients and to compare the results with healthy children. ABPM was performed on 20 liver transplanted patients and 27 healthy children aged 7.1 ± 4.8 and 8.5 ± 2.9 yr, respectively. HT was defined as SDS > 1.64 (i.e., >95th percentile) adjusted for gender and height. The mean duration of post-transplant follow-up was 32 ± 19 months. Six (30%) patients were found to be hypertensive. The physiological nocturnal BP fall was attenuated significantly in the study group for diastolic BP (11.5 ± 6.1 mmHg vs. 17.7 ± 7.1 mmHg, p = 0.006). Specifically, the number of patients with high nighttime systolic and diastolic BP SDS (p = 0.02 and p = 0.004, respectively) as well as elevated nighttime systolic (p = 0.03) and diastolic (p = 0.003) BPLs was found to be significantly higher than those in the controls. Alteration of the "normal" circadian rhythm is very frequent in liver transplant recipients. Thus, it is recommended to perform ABPM on all liver transplanted children not to underdiagnose HT.     

Simultaneous or sequential gastrectomy in pediatric liver transplant recipients

The association between LT and gastrectomy is not common. Only two studies reported the gastrectomy/LT association in children. Here, we report three children who underwent LT who required a concomitant or sequential gastrectomy for different reasons. Patient 1, a 16‐yr‐old boy, during the LT, underwent a partial gastrectomy due to extensive injury to the duodenum. He had a previous and unusual portoenterostomy performed in the duodenum. Bowel reconstruction was performed using an intestinal loop that was first used for the bilio‐enteric anastomosis and then connected to the gastric stump. Patient 2, a 22‐month‐old female child, underwent a partial gastrectomy with a Roux‐en‐Y reconstruction during a retransplantation. She had a large perforated gastric ulcer blocked by the allograft liver. Patient 3, a 26‐month‐old male child, five yr after living donor LT, was submitted to a partial gastrectomy because of gastric outlet obstruction. The histopathology was compatible with eosinophilic gastritis. The association between LT and gastrectomy in the pediatric population is extremely rare. Appropriate knowledge of the previous transplantation technique is very important. Further studies are required to assess the outcomes of the different types of gastric reconstruction in pediatric recipients.     

Renal function outcome in pediatric liver transplant recipients

The orthotopic liver transplantation (OLT) allows survival of children followed for severe hepatic injury, provided that the immunosuppressive treatment is prolonged. The nephrotoxicity of cyclosporine predicts the long-term outcome of the adult patients receiving a liver transplant. The aim of this study was to determine the long-term outcome of renal function in children receiving OLT. This study included 12 children, with a median for age of 7.1 yr (2-15 yr) at the time of OLT. The duration of follow-up was at least 4 yr, being 7 yr in 10 patients and more than 10 yr in seven. Renal function was evaluated with the serum level of creatinine, calculated glomerular filtration rate (cGFR), and measurement of glomerular filtration rate using chrome 51 ethylenediaminetetraacetate ((51)Cr EDTA) clearance performed at least once during follow-up. The doses and the serum concentrations (C(0)) of cyclosporine were reported at each study time. The cGFR decreased significantly 2 yr after the OLT [median (range): 106 mL/min/1.73 m(2) (71-150) at the time of OLT vs. 85 mL/min/1.73 m(2) (57-128) 2 yr after the OLT, p = 0.03], and decreased again between 7 and 10 yr after OLT [median (range): 99 mL/min/1.73 m(2) (76-125) 7 yr after OLT vs. 81 mL/min/1.73 m(2) (66-140) 10 yr after OLT, p = 0.04]. Six patients developed chronic renal failure (cGFR from 57 to 80 mL/min/1.73 m(2)) 2 yr after OLT associated with high doses of cyclosporine [median (range): 8.8 mg/kg/day (3.5-13)]. The cGFR overestimated renal function by 16% compared with the isotopic measurement of GFR (p = 0.03). Using the (51)Cr EDTA measurement, six of seven patients followed up more than 10 yr after OLT presented mild (n = 3) or moderate (n = 3) chronic renal failure. In our study, the majority of OLT recipients developed a chronic renal failure 10 yr after transplantation. Cyclosporine seems to be the most important factor responsible for the impairment of renal function. The use of the mycophenolate mofetil, a new immunosuppressive agent, allowing a reduction in the dose of cyclosporine, could minimize renal dysfunction. While awaiting the results of a prospective long-term study, close drug monitoring is advised.     

Prospective analysis of carotid arterial wall structure in pediatric renal transplants with ambulatory normotension and in treated hypertensive recipients

Increased carotid IMT was found to be associated with cardiovascular risk factors. As pediatric renal transplants are at high risk for cardiovascular disease, we examined whether there is a relationship between BP and IMT in normotensive and in treated hypertensive recipients after transplantation. Thirty-one recipients aged 10 +/- 3.5 yr (16 M, 15 F) underwent repeated carotid ultrasound examinations 5.4 +/- 3.2 yr after transplantation with a 4.1 +/- 1 yr interval and were followed with annual ambulatory BP monitoring. Baseline IMT was significantly higher in transplants compared with controls. When recipients were again investigated, follow-up IMT measurements were similar compared with measurements obtained at baseline. The analysis of variance showed that baseline IMT both in recipients with strict normotension, i.e., ambulatory normotension without antihypertensive therapy at baseline and throughout the study period (n = 9), and in recipients with treated hypertension or newly diagnosed hypertension (n = 22) was significantly higher than in healthy controls (n = 21). Baseline IMT did not differ between these subgroups of recipients. Similarly, pairwise comparisons showed that baseline and follow-up IMT within each subgroup of recipients were not significantly different. Overall and regardless of time-point, no significant associations were found between systolic and diastolic 24-h BP, daytime BP, night-time BP, ambulatory BP standard deviation scores, BP loads and IMT. Our results suggest that increased IMT in pediatric renal transplants does not seem to be related to BP but more likely to other factor(s) not investigated in this study.     

Liver allograft pathology in healthy pediatric liver transplant recipients

Liver transplantation offers excellent results for children with end‐stage liver disease, and efforts should be directed toward maintaining long‐term graft health. We evaluate graft pathology in healthy pediatric transplant recipients with low‐maintenance immunosuppressive medications to assess whether protocol biopsies are helpful for adapting immunosuppression and protecting long‐term graft function. Liver biopsies were performed on 60 healthy pediatric liver transplant recipients, and histological findings were correlated with laboratory, serological, and radiological results. Fourteen patients (23%) were diagnosed with acute or early chronic rejection, and immunosuppressive medications were increased in these children. Liver function tests did not correlate with histological findings. The incidence of fibrosis was 36% in transplant recipients five or more years after liver transplantation. We observed an unexpectedly high prevalence of rejection and fibrosis in children with no laboratory abnormalities, which led to changes in their immunosuppressive medications. Scheduled biopsies appear to be useful in pediatric transplant recipients with low immunosuppressive medications for early detection of morphological changes in liver transplants. Further studies are needed to evaluate whether adaption of immunosuppression helps to reduce tissue damage and the incidence of allograft dysfunction in the long term.     

Efficacy and pharmacokinetics of tacrolimus oral suspension in pediatric liver transplant recipients

The use of tacrolimus in small pediatric graft recipients may require the availability of a suspension formulation for appropriate dose titration and easier administration. The pharmacokinetics (Pk) of an extemporaneously prepared oral suspension of tacrolimus (OST) was investigated in 15 pediatric liver transplant recipients, and was compared with the corresponding data with tacrolimus capsules (TC). Graft and patient survival rates were 100%. Acute rejection and steroid-resistant rejection were encountered in 9/15 and 3/15 patients, respectively. Comparison of Pk data showed a lower oral absorption of OST when compared with TC. No significant correlation could be made between the Pk parameters and rejection. Despite the lower bioavailability of OST when compared with TC, the rejection incidence was similar with both formulations (60% vs. 55%, respectively). Accordingly, the use of OST may constitute an alternative option for tacrolimus administration in low body weight organ recipients, to allow dosage titration in the early post-transplant weeks.     

Long-term results of basiliximab induction immunosuppression in pediatric liver transplant recipients

It has been shown that an induction therapy with the monoclonal anti-interleukin-2 receptor antibody basiliximab (Simulect) is capable to reduce the incidence of acute graft rejection in adult and pediatric liver transplantation (Ltx). However, data on long-term results using basiliximab in children post-Ltx are still pending. Therefore, the objective of our study was to report on the long-term results of basiliximab induction therapy in pediatric liver transplant recipients. A total of 54 children received two single doses of basiliximab in addition to cyclosporine and prednisolone following Ltx. We analyzed the incidence of acute and chronic graft rejection that of post-transplant lymphoproliferative disease (PTLD), and patient and graft survival. The follow-up was 22-46 months. The historical control group (matched controls) consisted of 54 patients treated with a cyclosporine and prednisolone dual therapy. Patient survival was 53 of 54 in the treatment group and 51 of 54 in the controls. One patient was retransplanted in the treatment group vs. three patients in the control group. The incidence of acute graft rejection was 16.6% compared with 53.7% in the control group (p < 0.001), that of chronic rejection was comparable in both groups (one of 54 vs. one of 54). The incidence of steroid resistant rejection was four of 54 vs. six of 54 that of PTLD were one of 54 vs. zero of 54. There were no adverse effects observed, which could be related to the antibody treatment. We conclude that basiliximab provides safe and effective induction immunosuppression in pediatric liver graft recipients. Short- and even long-term results are excellent.     

Home blood pressure in children and adolescents: a comparison with office and ambulatory blood pressure measurements

Aim: To compare BP measurements of children and adolescents using different methods office BP (OBP), ambulatory BP monitoring (ABPM) and home BP measurement (HBPM) and to study their correlations. Method: Individuals were evaluated between 5 and 15 years of age who had been referred because of a previous high BP. OBP was measured with the OMRON‐705CP. Three measurements were carried out at 5‐min intervals. HBPM were taken using the same device, two measurements at 5‐min intervals in the morning and in the evening during 7 days. ABPM was performed using the SpaceLabs 90207 monitors. Results: A total of 109 children and adolescents were evaluated (9.82 ± 2.63 years), 52.3% boys, 56.9% non‐white. The office systolic BP (SBP) was lower than in daytime ABPM (p < 0.001) but similar HBPM (p = 0.294), and the office diastolic BP (DBP) was lower than daytime ABPM (p < 0.001) and in HBPM (p = 0.035). The SBP and DBP at HBPM was lower than daytime ABPM (p < 0.001). Daytime ambulatory BP was more closely associated with home readings (SBP r = 0.731 and DBP r = 0.616) than with office’s readings (SBP r = 0.653 and DBP r = 0.394). Conclusion: The BP of children and adolescents varies depending on the place and manner of measurement. ABPM presents better correlation with HBPM than with the office measurements.     

Risk factors for fungal infection in paediatric liver transplant recipients

Fungal infection (FI) is a major and potentially fatal complication in liver transplantation (LT). Published experience of FI in paediatric LT is limited. We therefore reviewed case records of 79 children, aged between 0.16 and 16 yr, who underwent LT between 1997 and 1998 to document the incidence of, and identify risk factors for, FI. Sixty-eight pre-, peri- and post-LT variables were assessed in relation to FI by univariate and multivariate analyses. The major indications for LT were biliary atresia in 26 (33%) patients, fulminant hepatic failure in 16 (20%) and intrahepatic cholestasis in 11 (14%); eight patients required re-LT. Thirty-two (40.5%) children developed a FI within 1 yr of LT. The median time to FI was 42 days (range 1-342 days). Candida spp. caused 29 (90.7%) FIs; 21 (66%) of these were Candida albicans. Although FI was associated with increased mortality, most patients responded well to antifungal treatment. The variables independently associated with FI were pre-LT fungal colonization and pyrexia and, post-LT, bacterial infection, Epstein-Barr virus (EBV) infection and tacrolimus administration. Identifying risk factors for FI should contribute to the development of strategies for prophylaxis or preemptive therapy.     

Sirolimus as renal and immunological rescue agent in pediatric liver transplant recipients

CNI have improved the outcome of LT. However, their inherent potential to nephrotoxic and sometimes-inadequate immunosuppressive effect has lead to the usage of newer drugs like SRL. Aim of this study was to review children who received SRL. Thirty-seven (20 women) children post-LT, median age 10.4 yr (0.8-17.4) with a minimum follow-up of six months comprised the study group. Indications for SRL were biopsy-proven resistant acute allograft rejection (n = 12), early CR (n = 12), and CNI-induced nephropathy with MMF intolerance (n = 11). In two patients, the indication was the recurrence of BSEP disease in the allograft. In patients with acute rejection, AST normalized in 10/12 patients. In patients with CR, AST normalized in 6/12 patients. Those with renal impairment showed improvement in their creatinine levels from a mean baseline of 99-56.7 μm (p = 0.03) and their mean cystatin C was 1.02 after SRL. Side effects leading to discontinuation of SRL were seen in three patients. SRL was effective in rescuing patients with acute and chronic allograft rejection and improving renal function in CNI-induced nephropathy group.     

Pharmacodynamic monitoring by residual NFAT-regulated gene expression in stable pediatric liver transplant recipients

Pharmacokinetic monitoring of CNI is unsatisfactory, because at comparable CNI blood concentrations frequency and severity of adverse effects vary considerably among individual patients. Determining the RGE of NFAT-regulated genes in leukocytes is a new pharmacodynamic approach to measure directly the functional consequences of calcineurin inhibition in T-lymphocytes. We compared clinical outcome parameters and RGE of activated T-cells after pLtx. We measured prospectively RGE of NFAT regulated genes in 33 pLTX recipients in the maintenance period after pLTX. CsA-treated patients with recurrent infections had significantly lower RGE rates (27%) than children without recurrent infections (50%; p = 0.04), whereas pharmacokinetic parameters of CsA and the concomitant immunosuppressive therapy were comparable between both groups. In patients on tacrolimus-based IS therapy NFAT RGE was only slightly reduced (90%). Pharmacodynamic monitoring of CsA by measurement of RGE in T-lymphocytes has the potential to identify over-immunosuppressed pediatric liver transplant recipients on a CsA-based IS therapy, while in children on low-dose tacrolimus therapy, RGE measurement does not provide additional clinically useful information.