Three‐yr safety and efficacy of everolimus and low‐dose cyclosporine in de novo pediatric kidney transplant patients

The three yr results of a multicenter trial in de novo pediatric KT treated with a proliferative signal inhibitor and low dose CNI are presented. Thirty‐seven children (9.1 ± 5 yr old) received basiliximab, cyclosporine A (CyA C2:1400 ng/mL), (MMF C0:1.5–3 μg/mL), and prednisone. Three wk later everolimus was started (C0:5–10 ng/mL), CyA was reduced (C2:600 ng/mL after 90 days 300 ng/mL), and MMF discontinued. During the three‐yr period patient and graft survivals were 96%. One patient died for causes unrelated to the immunosuppression. Cumulative acute rejection rate including protocol and indication biopsies was 21.9%. None of the patients had signs of chronic humoral rejection. Incidence of dnDSA was 5%, 11%, and 22% at one, two, and three yr post‐transplant, respectively. Mean glomerular filtration rate measured at one yr and three yr post‐transplant was 105.5 ± 31 and 110.7 ± 27 mL/min/1.73 m², respectively. A growth velocity of 7.7 ± 6.7 cm/yr was achieved with positive catch‐up growth. No malignancy or post‐transplant lymphoproliferative diseases were diagnosed. In conclusion, the treatment based on basiliximab induction, everolimus, low‐dose cyclosporine, and low‐dose prednisone leads to good long‐term efficacy in de novo pediatric KT recipients.     

What is the intrapatient variability of mycophenolic acid trough levels?

TDM of MPA, the active compound of MMF, is rarely used despite its substantial intra‐ and interpatient variability. Little is known about the utility of long‐term MPA TDM. Data are expressed as mean (one standard deviation). All available data from 27 renal transplant recipients (mean age at transplantation: 7.7 [5.0] yr) with an average follow‐up of 9.3 (4.6) yr were analyzed. MPA levels were measured using the EMIT. GFR was measured using cystatin C and eGFR was calculated using the Filler formula. Intrapatient CV of the trough level was calculated as the ratio of the mean divided by one standard deviation. Mean cystatin C eGFR was 56.9 (24.4) mL/min/1.73 m². There was a weak but significant correlation between the MPA trough level and the AUC (Spearman r = 0.6592, p < 0.0001). A total of 1964 MPA trough levels (73 [45]/patient) were measured, as compared to 3462 Tac trough levels (144 [71]/patient). The average MPA trough level was 3.01 (1.26) mg/L and the average trough Tac level was 7.3 (1.8) ng/mL. Intrapatient CV was statistically higher (p = 0.00093) for MPA at 0.68 (0.29) when compared to Tac with a CV of 0.46 (0.12). CV did not correlate with eGFR. Intrapatient MPA trough level CV is significantly higher than for Tac, while CV for both MPA and Tac was high. MPA trough level monitoring may be a feasible monitoring option to improve patient exposure and possibly outcomes.     

Empiric switch from calcineurin inhibitor to sirolimus‐based immunosuppression in pediatric heart transplantation recipients

Sirolimus is used in heart transplant patients with CAV and CNI‐induced nephropathy. However, little is known regarding the tolerability, rejection rate, and effect on renal function when used empirically in children. We describe our experience with the empiric use of a sirolimus‐based immunosuppressive regimen in pediatric heart transplantation recipients. We reviewed records of patients in whom conversion was attempted to a CNI‐free sirolimus‐based regimen. Rejection episodes and measures of renal function were recorded. We attempted to convert 20 patients, of which 16 were successful. In total, six of 20 patients (30%) experienced adverse effects. Of the 16 converted, four patients converted to sirolimus due to CNI‐induced disease (three nephropathy, one CAV), while 12 patients (mean age 5.5 yr, range 0.1–21 yr; 33% female; 33% with a history of congenital heart disease) were empirically switched to sirolimus at a mean of 2.3 yr after transplant. Follow‐up was available for a mean of 2.5 yr after conversion (range 0.5–8.3 yr). The rate of rejection while taking CNIs was 0.18 rejection episodes per patient‐year (total of five episodes), compared with 0.03 rejection episodes per patient‐year (total of one episode) while on sirolimus. Renal function, in terms of GFR, significantly improved after sirolimus conversion at latest follow‐up (from 86 ± 37 mL/min to 130 ± 49 mL/min, p = 0.02). Here, we demonstrate the potential benefit of empiric use of sirolimus in pediatric heart transplant patients in a CNI‐free regimen. Larger and longer studies are needed to further clarify risks of rejection and adverse effect profiles.     

Using individual DSA titers to assess for accommodation after late humoral rejection

Management of late humoral rejection remains challenging, and DSA may persist. A case report illustrates how individual DSA titers using solid‐phase‐based assays may help to assess for accommodation. A male cystinosis patient received a cadaveric renal transplant at the age of 12 yr with a daclizumab, tacrolimus, MMF, and steroids‐based immunosuppression. After three acute rejection episodes over the first eight months, interstitial fibrosis/tubular atrophy (IF/TA) was diagnosed on biopsy, while the immunosuppression was left unchanged with a high target exposure for both tacrolimus and MPA. One yr later, AMR type III (C4d and DSA positive) was treated with daily plasmapheresis, IVIG 100 mg/kg and pulse steroids 5 mg/kg. DSA (DR 53, DQ4, and DQ 2) were not responding until the plasma volume was increased to 2.5 plasma volumes. A second rise of creatinine confirmed worse humoral rejection; daily plasma exchange was resumed, and two doses of rituximab (375 mg/m²) were given. Subsequently, all DSA dropped, but only DR53 DSA remained unchanged, whereas the DQ antibodies rebounded to very strong titers. With a follow‐up of over 120 days after recovery of the CD19 count, off all additional treatment and on identical immunosuppression with tacrolimus and MMF and prednisone, the patient's creatinine remained stable between 45 and 50 um while DQ DSA remain strong to very strong. We conclude that the patient is in a state of accommodation. DSA titers should be monitored when managing late humoral rejection.     

De novo therapy with everolimus and reduced‐exposure cyclosporine following pediatric kidney transplantation: A prospective,multicenter, 12‐month study

Prospective data regarding the de novo use of everolimus following kidney transplantation in children are sparse. In a prospective, 12‐month, single‐arm, open‐label study, pediatric kidney transplant patients received everolimus (target trough concentration ≥3 ng/mL) with reduced‐exposure CsA and corticosteroids, with or without basiliximab induction. Sixteen of the 18 patients completed the study on‐treatment. Age range was 2–16 yr (mean 10.9 yr); eight patients received a living donor graft. Mean (s.d.) everolimus level was 7.4 (3.1) ng/mL during the first 12 months post‐transplant. There were no cases of BPAR, graft loss, or death during the study. Protocol biopsies were performed at month 12 in seven patients, with subclinical (untreated) acute rejection diagnosed in one case. Mean (s.d.) estimated GFR (Schwartz formula) was 98 (34) mL/min/1.73 m² at month 12. Three patients experienced one or more serious adverse events with a suspected relation to study medication. One patient discontinued study medication due to post‐transplant lymphoproliferative disease (5.6%). Everolimus with reduced‐dose CsA and corticosteroids achieved good efficacy and renal function and was well tolerated in this small cohort of pediatric kidney transplant patients. Controlled trials are required to answer remaining questions about the optimal use of everolimus in this setting.     

Outcomes in pediatric hepatitis C transplant recipients: Analysis of the UNOS database

HCV may lead to the development of ESLD in late childhood and, consequently, contributes to the need for liver transplantation. The aim of this study was to examine post‐transplant outcomes in HCV‐positive pediatric patients with ESLD from any cause and to determine the impact of the PELD scoring system, introduced in February 2002, on post‐transplant patient and graft survival. A retrospective analysis of the UNOS database from 1994 to 2010 was performed to assess graft and patient survival in pediatric HCV‐seropositive liver transplant recipients. Graft survival and patient survival comparing subjects in the pre‐PELD era and post‐PELD era were analyzed using Kaplan–Meier statistics. Factors associated with survival were identified using Cox regression analysis. Of 120 pediatric HCV transplant recipients, 80 were transplanted in the pre‐PELD era and 40 were transplanted post‐PELD. Median serum total bilirubin, INR, and creatinine were 4.8 mg/dL, 1.6, and 0.7 mg/dL in the pre‐PELD era vs. 5.5 mg/dL, 1.7, and 0.6 mg/mL, respectively, in the post‐PELD era (p NS). One‐yr graft survival in the pre‐PELD vs. post‐PELD era was 65.0% and 89.7%, respectively (p < 0.01); corresponding three‐yr graft survival was 57.3% vs. 76.2% (p = 0.04). One‐yr patient survival in the pre‐PELD vs. post‐PELD era was 79.0% and 97.5%, respectively (p < 0.01); corresponding three‐yr survival was 79.0% vs. 89.4% (p = 0.17). Twenty‐eight patients (23.3%) were retransplanted: 24 (30%) in the pre‐PELD era (median time to retransplant 272 days) and four (10%) in the post‐PELD era (median time to retransplant 586 days). Early follow‐up demonstrates a trend toward improved pediatric HCV liver transplant graft and patient survival in the post‐PELD era. Superior outcomes may be attributed to pretransplant factors, improved surgical technique and better treatment options for HCV infection.     

Mycophenolate mofetil in pediatric heart transplant recipients: a single-center experience

Mycophenolate mofetil (MMF) is emerging as an effective agent for the treatment of both established rejection and primary rejection prophylaxis in solid-organ transplantation (Tx). However, little data is available on the use of MMF in the pediatric population. We therefore report on our experience with MMF in 21 pediatric heart transplant recipients. Data were obtained by retrospective chart review. Median age at time of review was 12.3 yr (range 11 months to 16.9 yr). Median age at Tx was 10.7 yr (range 55 days to 16.7 yr). MMF was started at a median of 4.3 months after Tx (range 1 day to 4.5 yr). At the time of MMF institution, all patients were concurrently on prednisone and azathioprine; 20 of these patients were also undergoing treatment with tacrolimus (median dose 0.18 mg/kg, range 0.03-0.64 mg/kg) and one with cyclo-sporin A (10 mg/kg). Azathioprine was discontinued at the time of commencing MMF. The average MMF dose was 40 +/- 14 mg/kg. The rationale for switching to MMF included rejection (International Society for Heart and Lung Transplantation [ISHLT] 3A/B), 66%; inability to wean steroids, 14%; ABO blood group donor-recipient mismatch, 10%; coronary artery disease (CAD), 5%; and side-effects of immuno-suppression, 5%. Of the patients switched for rejection, 93% demonstrated resolved or improving rejection. Both ABO donor-recipient mismatch patients were started on tacrolimus/MMF as primary therapy and had no significant episodes of rejection. Two patients had rejection classified as unchanged (one with CAD, one treated with addition of sirolimus prior to improvement). Corticosteroids were successfully discontinued in 28% of patients, and 20% are currently on a reduced dose. Fourteen per cent developed significant rejection while attempting to reduce the steroid dose. Steroid reduction has not yet been attempted in 38% of patients. The following side-effects were reported in 38% of the patients: diarrhea, 10%; gastrointestinal discomfort, 20%; and leukopenia, 20%. Dose reduction or temporary discontinuation was required in 63% of the patients who experienced side-effects (24% of the total number of patients). Opportunistic infections developed in 10% (cryptococcus, cytomegalovirus). Hence, MMF appears to be effective for treatment of rejection in the pediatric heart transplant population and has an acceptable side-effect profile. In addition, it may have a role in primary rejection prophylaxis and may facilitate a reduced steroid dosage or a steroid-free immunosuppression regimen.     

Alemtuzumab with corticosteroid minimization for pediatric deceased donor renal transplantation: A seven‐yr experience

Alemtuzumab is a monoclonal antibody targeting CD52 receptors on B and T lymphocytes and is an effective induction agent in pediatric renal transplantation. We report a seven‐yr experience using alemtuzumab induction and steroid‐free protocol in the pediatric population as safe and effective. Twenty‐one pediatric deceased donor renal transplants were performed at a single academic institution. All received induction with single‐dose alemtuzumab and were maintained on a steroid‐free protocol using TAC and MMF immunosuppression. There were 15 males and six females in the study whose ages ranged from one to 19 yr. The average follow‐up was 32 months (range from 12 to 78.2 months and median 33.7 ± 23.7 months). All patients had immediate graft function. Graft survival was 95%, and patient survival was 100%. Mean 12 and 36 months eGFR were 63.33 ± 21.01 and 59.90 ± 15.27 mL/min/1.73m², respectively. Three patients developed acute T‐cell‐mediated rejection due to non‐adherence while no recipients developed cytomegalovirus infection, PTLD, or polyoma BK viral nephropathy. Steroid avoidance with single‐dose alemtuzumab induction provides adequate and safe immunosuppression in pediatric deceased donor renal transplant recipients receiving TAC and low‐dose MMF maintenance therapy.     

Single-center experience with mycophenolate mofetil in pediatric renal transplant recipients

Mycophenolate mofetil (MMF), a potent and specific inhibitor of guanosine nucleotide synthesis, is a new immunosuppressive drug used to prevent rejection in transplant patients. Extensive data on its utility and efficacy exists in adult patients but there is limited experience in pediatrics. Twenty-four children (14 male, 10 female; 2-19 yr of age), eight of whom had received living-related donor (LRD) transplants and 16 of whom had received cadaveric donor (CD) transplants, have been treated with MMF in our institution since September 1996. MMF was administered for a duration ranging from 13 weeks to 38 months, at an average dose of 600 mg/m2 (range: 200-1,000 mg/dose) every 12 h, for a total experience of 304 patient months. MMF capsules were used in 16 patients and/or pediatric suspension in eight. Five patients were switched to MMF from azathioprine as a result of rejection episodes or inability to taper prednisone, between 5 weeks and 3.5 yr post-transplant. All patients received prednisone, cyclosporin A (CsA), and induction therapy with anti-lymphocyte globulin (19 patients), anti-thymocyte globulin (one patient) or daclizumab (four patients). In 12 patients started on MMF at the time of CD transplant, five (42%) had an acute rejection episode. In seven who received a LRD transplant, one (14%) had an acute rejection episode. No patients who were converted to MMF were treated for acute rejection following conversion to MMF. One LRD graft was lost at 19 days following injury to the donor artery at the time of retrieval. At the last follow-up, the average creatinine level was 93 micromol/L and average urea level was 8.6 mmol/L. One patient developed epigastric distress. Three patients developed diarrhea/abdominal pain requiring dose adjustment. Five episodes of leukopenia and one episode of thrombocytopenia required dose adjustment. Two patients developed symptomatic cytomegalovirus (CMV) infection, one while on acyclovir prophylaxis. No malignancy has been encountered to date. Hence, MMF can be administered safely to children with good effect and with an acceptable side-effect profile.     

Minimum mycophenolic acid levels are associated with donor‐specific antibody formation

Although de novo DSA are associated with inferior graft survival, there are no effective strategies to prevent their formation. Underexposure to MPA (prodrug: MMF) also contributes to rejection rates early after transplantation, but the effect of this phenomenon on the formation of DSA long‐term post‐transplantation is unknown. Data are expressed as mean (standard deviation). All available data from 32 renal transplant recipients (age at transplantation 7.5 [4.5] yr) on tacrolimus and MPA immunosuppression with an average follow‐up of 9.4 (s.d. 4.6) yr were analyzed. DSA were measured using the Luminex assay (>500 MFI was considered DSA‐positive). Tacrolimus and MPA levels were measured with the Abbot Tacro II and EMIT assay, respectively. Among 1964 MPA and 3462 tacrolimus trough levels, the average MPA trough level was 3.2 (1.5) mg/L and the average tacrolimus level was 6.7 (2.8) ng/mL. At last follow‐up, only 5/32 patients had undetectable DSA, with 5/32 having no class I antibodies and 6/32 having no class II antibodies. DSA formation was associated with a lower minimum MPA trough level (0.27 [0.23] vs. 0.47 [0.18] mg) and cystatin C eGFR (48 [21] vs. 70 [23] mL/min/1.73 m²) for class I DSA formers. The average eGFR of patients without class I DSA was 70 (23) mL/min/1.73 m², whereas the average eGFR of patients with class I DSA was 48 (21) mL/min/1.73 m² (p = 0.0071). MPA trough levels <1.3 mg/L long‐term post‐transplantation are associated with the formation of DSA. The association between the formation of DSA and minimum MPA exposure may support a strategy for preventing the formation of DSA.     

Pediatric renal transplantation with mycophenolate mofetil immunosuppression in a single center from Mexico

An MMF-based immunosuppression has reduced the acute rejection rate in adults and in children in the early post-transplantation period. In the present study, pediatric renal transplantation patients on a CyA, MMF, and steroids regimen were prospectively evaluated. Patients with CyA, MMF, and steroid therapy without antibody induction were evaluated for surgical aspects, renal function, rejection, and survival, growth after transplantation, adverse events and medication discontinuation. Between February 2003 and May 2005, 21 kidney transplantation patients under 18 yr old were followed for at least 12 months. Within one year after transplantation, three patients developed four episodes of acute rejection (19%). Graft loss because of rejection occurred in one patient. One-year mean serum creatinine was 1.19 +/- 0.3 mg/dL. Mean calculated CrCl by Schwartz formula was 82.3 +/- 19.7 mL/min*1.73 m(2). Major adverse events included infections of the urinary tract and diarrhea, abdominal pain, and GI symptoms. No patients have discontinued the use of MMF. Good results in pediatric kidney transplantation can be achieved by using CyA/MMF/steroids. MMF is effective and relatively safe in reducing the incidence of acute rejection even without induction therapy 12 months after transplantation.     

Basiliximab with delayed introduction of calcineurin inhibitors as a renal‐sparing protocol following liver transplantation in children with renal impairment

Renal impairment is frequently compromised in patients with end‐stage liver disease and is associated with increased long‐term mortality post‐LT. In contrast to CNI, basiliximab is an immunosuppressive agent with minimal nephrotoxic potential. This study reviews the experience of a single pediatric liver transplant center's renal‐sparing approach with the use of basiliximab and MMF to compensate for delayed entry of CNI in children with renal impairment at the time of organ availability. There were no differences in renal function between pediatric patients with and without pre‐LT renal impairment within the first year (cGFR: 135 mL/min/1.73 m² vs. 144 mL/min/1.73 m²; p = 0.56) or at 5–8 yr following LT, (129 mL/min/1.73 m² vs. 130 mL/min/1.73 m²; p = 0.97). In addition, there was no difference in ACR rates (50% vs. 43%, p = 0.62) between patients in the basiliximab group and those patients receiving standard CNI and steroid strategies. The utilization of a renal‐sparing approach with basiliximab alongside delayed entry and lower early target trough levels of CNI in children with renal impairment at the time of LT is safe and maintains excellent long‐term kidney function.     

Eosinophilic esophagitis in children following cardiac transplantation: Association with post‐transplant lymphoproliferative disorder and other transplant outcomes

Although cardiac transplantation is life‐saving, morbidities from immunosuppression are significant. EoE is a complication of calcineurin inhibitors following liver transplant causing feeding intolerance, weight loss, vomiting, and dysphagia. There are limited reports of EoE following heart transplantation. We performed a retrospective single‐center review of pediatric cardiac transplant patients from 2000 to 2010. A case–control analysis of patients with and without EoE was performed evaluating heart transplantation outcomes such as rates of rejection, CAV, PTLD, and graft loss. Eighty‐six transplants were performed in 84 patients; 34 (40%) underwent diagnostic endoscopy, and 10 (12%) had EoE. Median time to diagnosis of EoE was 3.7 yr (IQR: 2.0–5.2). There were no differences in demographics or use of induction medications between patients with or without EoE. Patients with EoE had fewer episodes of treated rejection (1.0 vs. 2.5; p = 0.04). Four of 10 (40%) EoE patients had PTLD compared with only 2/24 (8%) of those without EoE (p = 0.048; OR 7.33 [95% CI: 1.1–50.2]). There were no differences in CAV or graft loss between groups. EoE should be considered as a cause of GI symptoms in children after cardiac transplantation and may be associated with fewer rejection episodes and increased rates of PTLD, thus representing a marker of over‐immunosuppression.     

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.     

Angiotensin II type 1 receptor antibodies in childhood kidney transplantation

Angiotensin II type 1 receptor antibodies (AT₁RAb) have emerged as non‐HLA Ab present in patients with acute AMR and risk of graft loss. Furthermore, AT₁RAb have been shown to increase angiotensin II sensitivity which may play a role in the development of CVD and hypertension. Data on AT₁RAb in stable transplant recipients are lacking. The aim of this study was to analyze the levels of AT₁RAb in a cohort of stable patients after kidney transplantation (tx) in childhood. A cross‐sectional study of 30 children (median age 14, range 3–19 yr, median time since tx five yr) and 28 adults who were transplanted in childhood (median age 26, range 20–40 yr, median time since tx 18 yr) transplanted between 1993–2006 and 1983–2002, respectively, was performed. Healthy controls were 51 healthy children (5–8 yr) and 199 healthy donors (median age 56.5 yr, range 42–83 yr). Plasma AT₁RAb were analyzed by immunoassay. Median total AT₁RAb IgG concentration was significantly higher in the pediatric‐tx group as compared to the adult‐tx group (40.0 and 10.95 U/mL, p < 0.0001). For both groups, the tx group showed higher levels: the pediatric‐tx group vs. control group (40.0 vs. 13.3 U/mL, p = 0.0006) and the adult‐tx group vs. adult control group (10.95 vs. 6.5 U/mL, p < 0.0001). Age was the strongest indicator of high levels of AT₁RAb IgG (p = 0.0003). AT₁RAb total IgG levels are significantly higher in a stable pediatric‐tx cohort as compared to adult‐tx patients and healthy controls of comparable age groups. The relevance of our findings in relation to age, time since tx, previous or future rejection, and CVD risk merits future studies.     

Immune cell function assay in pediatric heart transplant recipients

The ImmuKnow^® ICFA reports ex vivo CD4 lymphocyte activation to quantify immunosuppression. Limited organ and age‐specific data exist for pediatric heart transplant recipients. We sought to examine their normative values and ICFA's association with rejection/infection. A total of 380 ICFAs from 58 heart transplant recipients (6.5/recipient) were studied retrospectively. The median age at the time of their first ICFA was 5.3 yr (IQR 2.4–12.1 yr). ICFA levels during immunologic stability (n = 311) were a median of 305 (IQR: 172–483) and mean of 353 (s.d. ± 224) ng ATP/mL. ICFA levels trended lower with advancing age. ICFA levels during immunologic stability increased over time from transplant after the first six months but were not correlated with calcineurin inhibitor levels or the type used. There is no association between ICFA values during stability and rejection (median 368 ATP ng/mL; IQR 153–527) or infection (median 293 ATP ng/mL; IQR 198–432). In contrast to the manufacturer's suggested ranges, the immunologic stable ranges in pediatric cardiac recipients were very different. ICFA values during immunologic stability are related to time from transplant in pediatric heart recipients. ICFA's ability to discriminate rejection or infection from immunologic stability was not demonstrated.     

Neutropenia in pediatric heart transplant recipients

Neutropenia has been reported in pediatric heart transplant recipients, but its association with infectious morbidity and mortality is unknown. We sought to determine neutropenia's prevalence and impact on infection, rejection, and survival. A retrospective analysis of pediatric heart transplant recipients from March 2005 to August 2015 was performed. Demographics, medications, infection, and rejection data were collected. Of 142 pediatric heart transplant recipients, 77 (54.2%) developed neutropenia within 4.7 months [3.3‐12.1 months] of transplant. In all patients, the adjusted 5‐year cumulative incidence of neutropenia was 30.2%. Fifty‐one patients (66.2%) had recurrent neutropenia. Six of 14 tested had positive antineutrophil antibodies. Medications associated with neutropenia were decreased in 15 (19.5%) and discontinued in 42 (54.4%) patients with no change in 1‐year rejection rates compared to published data. Fifteen patients developed infection within 30 days of neutropenia and two from 30 days to 1 year, with an infection rate similar to the non‐neutropenic group. There was no significant difference in survival, ANC, rate of rejection or PTLD in neutropenic patients with and without infection at median follow‐up (5.5 years). Neutropenia is common in pediatric heart transplant recipients. Neutropenia had <20% risk of associated infection, similar to non‐neutropenic patients. Infection in neutropenic patients did not increase mortality.     

Favorable four‐yr outcome after renal transplantation in a patient with complement factor H antibody and CFHR1/CFHR3 gene mutation‐associated HUS

aHUS is a clinical challenge for successful renal transplantation. Case report: A 14‐yr‐old girl lost her kidneys at the age of 7, due to CFH antibodies and CFH‐related protein (CFHR1/CFHR3) homozygous deletion‐associated aHUS. CFH, CFI, and MCP gene mutations were excluded. The patient was a candidate for renal transplantation despite persistent presence of CFH antibodies (up to 539 AU/mL). Treatment with MMF, IVIG, and repeated PF (n = 8) was introduced while being placed on urgent waiting list. Three years after aHUS onset, the patient underwent the deceased donor renal transplantation “under cover” of PF, as PF was performed directly prior to surgery and, then, PFs were repeated up to overall 14 sessions. Quadruple immunosuppression (basiliximab + tacrolimus + MMF + prednisolone) was used. Moderate symptoms of aHUS (hemolysis, low platelets, and low C3) were present within first seven days post‐transplant and then normalized with PF therapy. The patient remained stable during four yr of further follow‐up after transplantation. Conclusion: Specific pre‐ and post‐transplant management allowed successful renal transplantation in a CFH antibody‐positive patient.     

Tolerability of up to 200 days of prophylaxis with valganciclovir oral solution and/or film‐coated tablets in pediatric kidney transplant recipients at risk of cytomegalovirus disease

This multicenter, open‐label study evaluated the tolerability of extended prophylaxis with valganciclovir in pediatric kidney transplant recipients at risk of CMV disease. Fifty‐six patients aged 4 months to 16 years received once‐daily valganciclovir oral solution and/or tablets, dosed by BSA and renal function, for up to 200 days. The most common AEs on treatment were upper respiratory tract infection (33.9%), urinary tract infection (33.9%), diarrhea (32.1%), leukopenia (25.0%), neutropenia (23.2%), and headache (21.4%). There were fewer AEs during days 101‐228 vs days 1‐100. Twenty‐seven patients (48.2%) had treatment‐related AEs during valganciclovir treatment, most commonly leukopenia (21.4%), neutropenia (19.6%), anemia (7.1%), and tremor (5.4%). Treatment‐related serious AEs were reported for nine patients (16.1%) and six withdrew due to AEs. Viremia was centrally confirmed in 10 patients; there was no confirmed CMV disease. One patient tested positive for a resistance mutation (UL97 L595F). Biopsy‐proven acute rejection occurred in six patients (10.7%), but no graft loss or deaths occurred. In conclusion, up to 200 days of valganciclovir prophylaxis in pediatric kidney allograft recipients showed a safety profile consistent with that established in adult transplant patients.