Benefits of conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in pediatric renal transplant patients with stable graft function

Abstract:  Conversion from MMF to EC-MPS may reduce GI complications and permit increased MPA dosing with a concomitant reduction in CNI dose. In a prospective trial, paediatric renal transplant patients with stable graft function were converted from MMF to EC-MPS and followed-up for 12 months. Data from 28 patients (mean age 13.9 ± 3.1 yr) were available for analysis. Mean EC-MPS dose increased significantly from conversion to month 12 (668 ± 81 mg/m²/day vs. 747 ± 98 mg/m²/day, p < 0.001). CsA-ME dose (n = 23) decreased from 5.3 ± 1.7 mg/kg/day at conversion to 4.6 ± 1.4 mg/kg/day at month 12 (p = 0.010). cGFR increased from 69.5 ± 23.3 mL/min/1.73 m² at the time of conversion to 80.7 ± 30.7 mL/min/1.73 m² at month 12 (p = 0.007). The number of patients reporting at least one GI event during six months prior to conversion was 15/28 (53.6%), declining to 8/28 (28.6%) at month 6 post-conversion and 5/28 (17.8%) at month 12. This single-arm study suggests that conversion of paediatric renal transplant patients from MMF to EC-MPS does not compromise efficacy and leads to improved GI tolerability. MPA dose increased and CsA-ME dose decreased significantly, with an associated improvement in calculated GFR. A large-scale controlled trial is required to confirm these promising findings.     

Improved long-term graft function in pediatric transplant renal recipients with chronic allograft nephropathy

Abstract:  CAN is the leading cause of graft loss in pediatric renal transplant recipients. A retrospective single centre analysis of pediatric transplant patients with CAN treated with MMF in conjunction with CNI minimisation/withdrawal is reported. 35 children were successfully started on MMF. The mean age at transplant was 7.9 ± 0.1 years. MMF was introduced 3.5 ± 0.1 years after transplantation and patients were followed up for a mean of 32.2 ± 0.5 months. CAN was confirmed on biopsy in 31 patients. CNI was stopped in 23 patients at a mean time of 16.5 ± 0.6 months after MMF introduction and minimised in the remaining patients. Prior to MMF introduction, GFR was deteriorating by 21.6 ± 0.07 ml/min/1.73 m²/yr. After MMF, there was an overall improvement in GFR of 4.0 ± 0.03 ml/min/1.73 m²/yr. This was most marked in the first six months when the GFR improved by 20.8 ± 0.06 ml/min/1.73 m²/day. Mean acute rejection episode rate prior to MMF was significantly reduced after MMF introduction. MMF was discontinued in a total of 4 patients due to adverse effects. CNI minimisation/withdrawal with MMF introduction is safe and leads to significant initial improvement with subsequent stabilisation of GFR and improved long term graft survival in pediatric renal transplant recipients with CAN.     

Association of mast cells and liver allograft rejection

Abstract:  MCs are important effector cells in a broad range of immune responses. Their role in liver allograft rejection is not clear. Twenty-one liver transplant recipients (mean age ± s.d.; 10.2 ± 4.1 yr) who experienced a rejection episode are included in this study. Biopsy specimens from normal livers (allograft biopsy with normal histopathology n = 5 and naïve livers n = 6), transplanted livers with CR (n = 5), and transplanted livers with ACR (n = 26) were studied. The total number of PT in each biopsy specimen was documented, and the number of PT that contained MCs was expressed as a percentage of the total number of PT. MCs, percentage of PT containing MCs and the average number of MCs/PT was significantly higher in rejection specimens than in control biopsy samples. All parameters were significantly higher in CR group than AR groups. Increasing grades of rejection was also associated with progressively more MCs and MC/PT ( r  = 0.68 p = 0.000; r  = 0.58 p = 0.002). Only serum bilirubin level was related to the MCs in AR group. Only MC/PT was detected as an independent predictor of graft survival (p = 0.011, RR 2.87 95% CI 1.3–6.5). Despite the fact that the role of MCs in liver allograft rejection is still unknown; they exist in inflammatory infiltrates during pediatric liver allograft rejection. MC-rich portal infiltrates may distinguish chronic liver rejection from other inflammatory states such as AR, hepatitis and biliary obstruction.     

Potential influence of tacrolimus and steroid avoidance on early graft function in pediatric renal transplantation

Abstract:  With the increasing adoption of steroid-sparing immunosuppression protocols in renal transplantation, it is important to evaluate any adverse effects of steroid avoidance on graft function. Early graft function, measured by CrCl was retrospectively studied in 158 consecutive pediatric renal transplant recipients from 1996 to 2005, receiving either steroid-free or steroid-based immunosuppression. Patients receiving steroid-free immunosuppression vs. steroid-based immunosuppression had no difference change in CrCl (ΔCrCl) in the first week post-transplantation (p = 0.12). When stratified by corticosteroid usage, patients with higher tacrolimus trough levels (≥14 ng/mL) had slower graft function recovery in the first week post-transplantation than those with lower tacrolimus trough levels (p = 0.008) in the steroid-free group only. Despite initial slower graft function recovery in this subgroup, there was no negative impact on graft function in the steroid-free group; in fact steroid-free patients trended towards better CrCl at six months (p = 0.047) and 12 months (p < 0.001) post-transplant than the steroid-based group. With the improved immunological outcomes with steroid avoidance, close surveillance should be performed of tacrolimus levels to avoid levels >14 ng/mL. In patients with slow recovery of early graft function, short-term perioperative steroids may be considered.     

Standardizing resistive indices in healthy pediatric transplant recipients of adult-sized kidneys

Gholami S, Sarwal MM, Naesens M, Ringertz HG, Barth RA, Balise RR, Salvatierra O. Standardizing resistive indices in healthy pediatric transplant recipients of adult-sized kidneys.
Pediatr Transplantation 2010: 14: 126–131. © 2009 John Wiley & Sons A/S.
Abstract:  Small pediatric recipients of an adult-sized kidney have insufficient renal blood flow early after transplantation, with secondary chronic hypoperfusion and irreversible histological damage of the tubulo-interstitial compartment. It is unknown whether this is reflected by renal resistive indices. We measured renal graft resistive indices and volumes of 47 healthy pediatric kidney transplant recipients of an adult-sized kidney in a prospective study for six months post-transplant. A total of 205 measurements were performed. The smallest recipients (BSA ≤0.75 m²) had higher resistive indices compared to recipients with a BSA between 0.75 and 1.5 m² (p < 0.0001) and to recipients with a BSA ≥ 1.5 m² (p < 0.0001). Resistive indices increased during the first six months in the smallest recipients (p = 0.02), but not in the two larger recipient groups (BSA 0.75–1.5 m² and ≥1.5 m²). All three BSA groups showed a reduction in renal volume after transplantation, with the greatest reduction occurring in the smallest recipients. In conclusion, renal transplant resistive indices reflect pediatric recipient BSA dependency. The higher resistance to intra-renal vascular flow and significant decrease in renal volume in the smallest group likely reflect accommodation of the size discrepant transplanted adult-sized kidney to the smaller pediatric recipient vasculature with associated lower renal artery flow.     

SRL-based immunosuppression vs. CNI minimization in pediatric renal transplant recipients with chronic CNI nephrotoxicity

Because calcineurin inhibitor (CNI)-induced nephrotoxicity contributes significantly to late renal allograft loss, sirolimus (SRL)-based, CNI-free maintenance immunosuppression has been advocated, but data in the pediatric population are scarce. We therefore analyzed the efficacy and safety of an SRL-based immunosuppressive regimen plus mycophenolate mofetil (MMF) and corticosteroids vs. CNI minimization (mean dose reduction by 39%) plus MMF and corticosteroids in 19 pediatric recipients with biopsy-proven CNI-induced nephrotoxicity in a single-center case-control study. In the SRL group, we observed, one yr after study entry, an improvement of glomerular filtration rate (GFR) by 10.3 +/- 3.0 mL/min/1.73 m2 (p < 0.05 vs. baseline) in seven of 10 patients and a stabilization in the remaining three, while in the CNI minimization group GFR improved by 17.7 +/- 7.1 mL/min/1.73 m2 (p < 0.05) in six of nine recipients and stabilized in the remaining three. No patient in either group experienced an acute rejection episode. The main adverse event under SRL therapy was a transient hyperlipidemia in 70% of patients. In pediatric renal transplant recipients with declining graft function because of CNI-induced nephrotoxicity, CNI withdrawal and switch to SRL-based therapy or CNI minimization are associated with a comparable improvement of GFR after 12 months of observation.     

Standard dosing of tacrolimus leads to overexposure in pediatric renal transplantation recipients

Abstract:  Tacrolimus dosage in pediatric RTRs is empirically based on weight. There is evidence that adolescents are at greater risk of toxicity than young children on this dosing regimen. We investigated the rate of tacrolimus overexposure within the first three wk post-transplantation in pediatric RTRs receiving tacrolimus 0.15 mg/kg twice daily. Of 63 RTRs studied, 41 (65.1%) experienced a tacrolimus level above the therapeutic range (supratherapeutic), the majority (48.8%) on days two to four post-transplant. Patients with supratherapeutic levels were older (14.2 vs. 9.9 yr, p = 0.016), taller (146.7 vs. 126.5 cm, p = 0.029), larger (1.36 vs. 1.01 m², p = 0.039) and heavier (44.1 vs. 29.3 kg, p = 0.043) and by day 12 were receiving much lower tacrolimus doses than those without supratherapeutic levels (0.425 vs. 0.198 mg/kg/day, p = 0.0002). Supratherapeutic levels were more common among white (British) children than other ethnic groups (74 vs. 45%, p = 0.02). There were no observed differences in rates of patient or graft survival, or acute rejection during the three-yr study period. Adolescent patients appear to be at greater risk of excessive tacrolimus dosing on a standard regimen. We therefore outline a regimen restricting tacrolimus dosage given to larger/older patients, but emphasize the need for a prospective randomized trial to define optimal dosing.     

Multicenter trial of everolimus in pediatric renal transplant recipients: results at three year

Abstract:  There are few prospective clinical trials of mTOR inhibitors (or proliferation signal inhibitors) combined with CNI inhibitors in de novo pediatric renal transplantation. Results reported here are from a multicenter, open-label study in de novo pediatric renal transplant patients (≤16 yr), in which patients received everolimus with cyclosporine and corticosteroids for one yr, then entered an extension study for a further two yr. Nineteen patients completed the one-yr study, of whom three discontinued study medication. Fifteen of the remaining 16 patients entered the extension study, eight of whom were aged <10 yr (Group 1) and seven were aged 10–16 yr (Group 2). Mean daily dose of everolimus during the first 36 months was 1.53 mg/m² BSA. Biopsy-proven acute rejection occurred in three patients in Group 2 and in one patient in Group 1. Biopsy-proven chronic allograft rejection was reported in four patients (two in each age group). Graft survival at one yr was 100%; one patient in Group 2 lost their graft subsequently during the extension. For patients entering the extension, patient survival at three yr was 100%. There were three cases of viral infection, including one case of cytomegalovirus infection. At three yr, mean total cholesterol was 5.5 ± 0.8 m m /L (213 ± 31 mg/dL) and four patients received statin therapy. Mean serum creatinine at 36 months was 96 ± 36 μ m /L (1.1 ± 0.4 mg/dL). This is the first long-term prospective study to demonstrate that a regimen of everolimus, cyclosporine, and corticosteroids provides good efficacy, tolerability, and safety in de novo pediatric renal transplant patients.     

Renal function evaluated by measured GFR during follow-up in pediatric liver transplant recipients

Abstract:  Calcineurin inhibitors form the mainstay of immunosuppression in pediatric liver transplantation, but may cause significant nephrotoxicity. We evaluated renal function in liver transplant recipients treated with a tacrolimus-based immunosuppressive regimen. GFR was measured using 99 mTc-DTPA in patients pretransplant and annually thereafter. GFR calculated by Schwartz formula was compared with the measured values. Sixty patients who underwent 69 transplants were followed for at least one yr post-transplant (median three yr). In children over two yr of age at transplant GFR fell significantly from pretransplant (140 mL/min/1.73 m²) to one yr post-transplant (112 mL/min/1.73 m²) (p = 0.01) but thereafter there was no significant decline. In younger children the picture was confounded by maturation of renal function, but again there was no significant fall to five yr post-transplant. Although 13 (22%) patients developed renal dysfunction post-transplant, none required renal replacement therapy. cGFR correlated poorly with measured values (r = 0.21). Use of a tacrolimus-based immunosuppressive regimen is associated with an initial decline in GFR, though this picture is confounded in younger children by normal maturation of renal function. There is no further significant fall in GFR in the medium-term. The Schwartz formula is inaccurate in determining GFR in this patient group.     

Rapid discontinuation of corticosteroids in pediatric renal transplantation

Abstract:  Corticosteroid immunosuppression has permitted the development of successful allotransplantation; however, corticosteroids are associated significant post-transplant complications. To circumvent these problems, we implemented a protocol of rapid discontinuation of corticosteroids in 19 consecutive pediatric primary kidney transplant recipients. Mean age at time of transplant was 13.4 (±4.5) yr, 52.6% were male, 63.2% underwent living donor transplantation. All patients were administered Thymoglobulin^® [anti-thymocyte globulin (rabbit)] as induction immunosuppression with a rapid tapering dose of corticosteroids (total of five daily doses), and maintained on mycophenolate mofetil and tacrolimus. Two patients had immediate recurrence of primary disease (FSGS), requiring further corticosteroid therapy. Otherwise, remaining 17 patients were maintained off corticosteroids, with excellent graft function; mean baseline eGFR of 112 mL/min/1.73 m² (±19) at 28 months (±14) post-transplantation. There was 100% patient and rejection-free graft survival at 27 months (range 5–58 months) post-transplantation; 47% underwent renal transplant biopsy secondary to acute rise in serum creatinine with or without worsening hypertension. All biopsies had no evidence of acute rejection; 62.5% had findings consistent with tacrolimus toxicity. Renal transplantation utilizing a rapid discontinuation of corticosteroid protocol in pediatric patients appears to be safe and effective, without increasing the risk of acute rejection or graft loss.     

Umbilical cord-blood transplantations from unrelated donors in patients with inherited metabolic diseases: Single-institute experience

Abstract:  We evaluated the feasibility of UCBT from unrelated donors and a myeloablative preparative regimen that did not involve anti-thymocyte globulin in five children with lysosomal and peroxisomal diseases. Patients with MPS II (n = 1), adrenoleukodystrophy (n = 1), metachromatic leukodystrophy (n = 2), and Krabbe disease (n = 1) received UCBT between December 2001 and September 2005. All patients received oral Bu (600 mg/m²), CY (200 mg/kg IV), and fludarabine (180 mg/m² IV). Prophylaxis for GVHD consisted of a combination of tacrolimus and a short methotrexate course. Neutrophil engraftment occurred a median of 24 days (range, 21–25) after transplantation. None had graft rejection. One patient developed grade III acute GVHD and the other four patients had grade I acute GVHD; none had extensive chronic GVHD. One patient developed hemorrhagic cystitis. There were no treatment-related deaths. Although one child with MPS II died of PTLD 10 months after the UCBT, four of the five children are alive 14, 20, 31, and 55 months after transplantation with complete donor chimerism. These results suggest the feasibility of the UCBT with Bu, fludarabine, and CY-preparative regimen for patients with inherited metabolic diseases.     

Complications of chronic kidney disease in children post-renal transplantation – A single center experience

Abstract:  Similar to adults, CKD may persist after pediatric RTx. Clinical and laboratory parameters were analyzed retrospectively in 23 RTx recipients (13 males, age 11.9 ± 5.2 yr), initially treated with prednisone, calcineurin inhibitor (TAC = 18, cyclosporine neoral = 5), and MMF at four months post-RTx (T1) and at 3.4 ± 2.8 yr post-RTx (T2). Mean (±s.d.) cystatin C GFR (mL/min/1.73 m²) was 72 ± 19 at T1 and 70 ± 22 at T2 (NS). At T2, CKD stage I was present in five patients (22%), stage II in eight patients (35%), and stage III in 10 patients (43%). At T2, calcineurin inhibitors were utilized in 19, MMF in 13, and SIR in 13 patients. The prevalence of hypertension was 69% at T1 and 87% at T2 (p = NS). Anemia was diagnosed in 61% at T1 and 69% at T2 with average therapeutic MMF (2.78 ± 1.3 mg/mL) and SIR (7.62 ± 2.3 mg/mL) trough levels. Hypercholesterolemia was detected in 44.0% at T1 and 47% at T2. Bone disease was diagnosed in 26.0% at T1 and 21.7% at T2. Mean height Z-scores were −1.0 ± 1.2 (T1) and −1.0 ± 1.59 (T2, NS), with 21% at T1 and 30% at T2 below two SDS. We observed suboptimal growth, hypertension, hypercholesterolemia, bone disease, and anemia in a significant proportion of transplanted children.     

The profile of renal function over time in a cohort of pediatric heart transplant recipients

Abstract:  To assess the burden over time of renal dysfunction in pediatric heart transplant patients using an objective measure on an annual basis for serial comparison. GFR was measured at regular interval by nuclear medicine scintigraphy. Results were analyzed in relation to age, time post-transplantation, gender, and average calcineurin-inhibitor dose for the first two months post-transplantation. Results were compared with cGFR using the Schwartz equation. A total of 91 patients (56 males) transplanted between 1990 and 2004 underwent 373 GFR measurements. Median age at transplantation was 3.3 yr (birth – 17.8). Median first GFR at 0.7 yr (0.1–4.1) post-transplant was normal (94 mL/kg/1.73 m²). Freedom from at least mild renal insufficiency was 84% and 33% at one and five years post-transplant. Females had better renal function early post-transplant (GFR 105 mL/min/1.73 m²) but an increased probability of an abnormal GFR over time. Higher calcineurin inhibitor dose in the first two months post-transplantation was associated with an increasing probability of an abnormal GFR over time. The cGFR overestimated the measured GFR by 33 ± 26 mL/kg/1.73 m². Renal insufficiency is an important morbidity after pediatric transplantation with the majority of patients experiencing at least mild renal dysfunction. Calculated GFR significantly underestimates the burden of renal insufficiency in this patient population.     

Kidney transplantation from pediatric donors: size-match-based allocation

Abstract:  Use of kidneys from pediatric donors has been associated with worse outcome. We review our 20-yr experience using pediatric kidneys as single grafts in children and adult recipients. Charts review of 29 recipients, transplanted between 1986 and 2005, who received a graft from a donor ≤6 yr was performed. One recipient received "en bloc" graft and the remaining patients received a single kidney. Nine recipients were adults and 21 were children. Creatinine at discharge and at follow-up was recorded and actuarial graft and patient survivals were calculated using life table analysis. All 29 recipients are alive at mean follow-up of 92 months. Five grafts were lost for: primary non-function (1), recurrent FSGS at 14 month (1) and chronic rejection (3). All five recipients who lost their graft received a graft from donors ≤3 yr. Mean calculated GFR (Schwartz formula) at one and five yr were 84.2 mL/m²/1.73 and 98.3 mL/m²/1.73, respectively. Actuarial graft survival was 93.2%, 89.6%, and 81.9% at one, five and at 10 yr after transplant. The use of a single kidney graft from pediatric donors yields good long-term results. Kidneys from small pediatric donors should be allocated first to matched-weight recipients but otherwise can be transplanted in older children or in adults.     

Double apheresis of peripheral blood stem cells in a single day in children mobilized by granulocyte colony-stimulating factor for transplantation

Abstract:  Due to the movement of hematopoietic stem cells through the bone marrow environment, it may be possible to effectively harvest peripheral blood stem cells in a second apheresis within a few hours after a first apheresis. In a retrospective analysis, 107 aphereses were performed in consecutive 33 pediatric and six healthy pediatric donors who received granulocyte-colony stimulating factor at 10 μg/kg/day or 400 μg/m²/day for five days. The median age and weight of cases were seven yr (range 1–19) and 20 kg (range 8–87). The toxicities related to apheresis procedure were minimal in both aphereses. In 22 double aphereses, the average number of CD34-positive cells per body weight (kg) collected was 5.3 ± 4.2 (range 0.6–16.6) and 4.7 ± 3.1 (range 0.2–10.9) × 10⁶ in the first and second aphereses, respectively (p = 0.569). Multivariate analysis showed that number of CD34-positive cells collected in the first apheresis (p = 0.008) was an independent factor of increased CD34-positive cells in the second apheresis. Double apheresis in a single day was feasible and this procedure may be able to lessen the burden of apheresis compared to two consecutive-day apheresis.     

Urinary tract infections in pediatric renal transplant recipients – a two center risk factors study

Abstract:  UTI are common in renal Tx recipients and may significantly impact on the graft function. The aim of our study was to evaluate the prevalence, risk factors, and significance of UTI in Tx children. We performed a retrospective cross-sectional study of 76 Tx patients, median age at Tx was 13.4 yr. Twenty-one of 76 (28%) patients developed at least one UTI during the mean follow-up time of 3.3 ± 2.0 yr post-Tx. The first UTI occurred at a median of 160 days post-Tx. The RR of having UTI was significantly higher in patients with the primary diagnosis of obstructive uropathy (RR = 2.6, 95th CI = 1.1–6.0, p = 0.032), history of PN pre Tx (RR = 2.7, 95th CI = 1.3–5.4, p = 0.009) and pre Tx VUR (RR = 2.2, 95th CI = 1.1–4.5, p = 0.045). These three factors also significantly decreased the infection-free survival time to the first UTI. Most UTI caused reversible acute allograft dysfunction, but the long-term graft function could not be reliably assessed with SCr. In conclusion, UTI occurred in 28% of pediatric Tx recipients, mostly during the first year post-Tx despite antibiotic prophylaxis. The diagnosis of obstructive uropathy, history of UTI and VUR prior to Tx were significant risk factors.     

Survival among children with portal vein thrombosis and end-stage liver disease

Al-Holou S, Mathur AK, Ranney D, Kubus J, Englesbe MJ. Survival among children with portal vein thrombosis and end-stage liver disease.
Pediatr Transplantation 2010: 14: 132–137. © 2009 John Wiley & Sons A/S.
Abstract:  Occlusive PVT concurrent with chronic liver disease is a common clinical entity among pediatric patients referred for transplantation. The natural history of PVT is unknown. Our aim was to determine, using a retrospective cohort design, if children under 13 yr with chronic liver disease and concomitant PVT have an increased mortality risk prior to and after transplantation. A total of 203 patients were included in the study. Nearly 10% of the population had PVT (n = 19); 63.2% of PVT patients (5.9% of total cohort) underwent liver transplantation (n = 12). PVT patients tended to be younger than non-PVT patients at evaluation (1.94 ± 3.51 vs. 3.79 ± 4.11, p = 0.059). Clinical and demographic factors were similar between the two groups. Regarding survival, four PVT patients died, of which two had undergone transplantation. Kaplan–Meier analyses indicated that PVT and non-PVT patients had similar survival from the time of evaluation, on the waiting list, and after transplant. Although limited by sample size, our study suggests that a diagnosis of PVT does not increase the mortality risk for children waiting for a liver transplant. Further study is needed to discern variations in mortality risk that may occur in the pediatric chronic liver disease population with PVT.     

Post-transplant lymphoproliferative disorders in children: The role of chemotherapy in the era of rituximab

Gallego S, Llort A, Gros L, Sanchez de Toledo Jr J, Bueno J, Moreno A, Nieto J, Sanchez de Toledo J. Post-transplant lymphoproliferative disorders in children: The role of chemotherapy in the era of rituximab.
Pediatr Transplantation 2010: 14: 61–66. © 2009 John Wiley & Sons A/S.
Abstract:  PTLD are the most frequent neoplasms in children postorgan transplantation. We describe our experience in the treatment of 14 children (three with early and 11 with late-onset disease) treated with a step-wise protocol developed at our institution. Treatment consisted of reducing immunosuppressants, followed by rituximab and chemotherapy if required. Rituximab, incorporated into the protocol in 2001, has been determinant for the total chemotherapy burden patients need to achieve remission. In seven patients who did not receive rituximab, anthracycline total dose ranged from 160 to 240 mg/m², while only one of the patients receiving rituximab required DOXO (range: 0–120 mg/m²) (p = 0.003). The use of alkylating agents was also notably lower in patients receiving rituximab (median dose = 1200 mg/m²) compared with those who did not receive rituximab (median dose = 5800 mg/m²) (p = 0.006). Twelve patients are in remission and two died, one from refractory disease and the other from septic shock. Two-year OS and EFS were 85.7% and 57%, respectively. In conclusion, our experience with the use of rituximab in children with PTLD after solid organ transplantation appeared to be associated with a lesser requirement for alkylating agents and anthracyclines compared with historical subjects, suggesting a reduction in the side effects of these agents.     

Lower levels of plasmacytoid dendritic cells in peripheral blood are associated with a diagnosis of asthma 6 yr after severe respiratory syncytial virus bronchiolitis

Plasmacytoid dendritic cells (pDC) play a crucial role in antiviral immunity and promoting Th1 polarization, possibly protecting against development of allergic disease. Examination of the relationship between peripheral blood plasmacytoid DC levels and manifestations of asthma and atopy early in life. We have isolated peripheral blood mononuclear cells (PBMC) from 73 children (mean age ± SD: 6.6 ± 0.5 yr old) participating in the RSV Bronchiolitis in Early Life (RBEL) study. Flow cytometry was performed on PBMC detecting DC surface-markers: Blood Dendritic Cell Antigens (BDCA) 1, 3, and 2 which identify myeloid type 1, type 2, and plasmacytoid cells, respectively. Total serum IgE, peripheral eosinophil count, and allergy skin tests were documented. About 45% (n = 33) of study participants had physician-diagnosed asthma by 6 yr of age. These children had significantly lower quantities (mean ± SD) of plasmacytoid DC than their non-asthmatic counterparts (1020 ± 921 vs. 1952 ± 1170 cells per 10⁶ PBMC, p = 0.003). We found significantly lower numbers of myeloid dendritic cells in children with asthma (3836 ± 2472 cells per 10⁶ PBMC) compared with those without asthma (4768 ± 2224 cells per 10⁶ PBMC, p = 0.02); however, this divergence was not significant after adjusting for covariates of age, gender, race, skin test reactivity, smoke exposure, and daycare attendance. We did not identify any direct association between DC levels and markers of atopy: skin test reactivity, peripheral eosinophilia, and IgE level. Children who are diagnosed with asthma after severe RSV bronchiolitis appear to have a relative deficiency of plasmacytoid DC in peripheral blood.     

Chronic kidney disease in children following lung and heart–lung transplantation

Abstract:  CKD is a major co-morbidity in pediatric lung transplant recipients. We report the prevalence of renal impairment post-lung transplant at a single center, using a modified, age-adjusted eGFR for the best approximation of true GFR, and investigated associations and possible predictors of decline in renal function post-transplant. Renal function was assessed by eGFR pre-transplant, three and 12 months post-transplant, and at last follow-up. Decline in renal function was analyzed as percentage fall in eGFR in two phases (0–3 and 3–12). Furthermore, we investigated impact of gender, age, pre-transplant diagnosis and renal function, transplant type, early post-transplant dialysis, and tacrolimus trough levels on decline in eGFR using multivariate analysis. Over a five-yr period, 30 transplants were performed. Mean eGFR pretransplant was 117 mL/min/1.73 m² (s.d. 35) with mean decline in eGFR during the first three months post-transplant of 33% (s.d. 31, p < 0.001). Thereafter, mean decline in eGFR was 8% (s.d. 18, p = 0.02). None of the factors assessed were significantly associated with decline in eGFR post-transplant. In conclusion, many children have decline in renal function following lung transplantation, particularly early post-transplant. Unlike in adults, we were unable to detect any predictors of renal impairment in pediatric lung transplant recipients.