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1.
Hyperuricemia is common after renal and cardiac transplantations, but it is rarely reported after liver transplantations. The aim of this study is to determine the frequency of hyperuricemia in children following orthotopic liver transplantation and the effects of calcineurin inhibitors tacrolimus and cyclosporine) on blood uric acid levels. Between September 1997 to January 2004, 76 liver transplantations were performed in 70 children (male/female; 39/31) at Ege University, Organ Transplantation Center (37 deceased donation and 39 live donors). Patients who had been transplanted within the last three months and patients who died within six months after liver transplantation were excluded from the study. Finally 59 patients were included in this study. Uric acid levels were measured before transplantation and after transplantation within six months intervals for two yr. In these series 17 cases had increased uric acid levels after liver transplantation (28.8%). Serum uric acid levels in both groups (tacrolimus or cyclosporine) were detected to be significantly higher than initial values at 12th months (p < 0.05). Hyperuricemia developed in eight patients receiving cyclosporine (eight of 11; 72%) whereas nine patients receiving tacrolimus developed hyperuricemia (nine of 48; 18%). However, the rate of having high uric acid levels was significantly higher in cyclosporine group compared tacrolimus group (p = 0.001, OR: 11.5, CI 95% 2.5-52.4). Uric acid levels were also significantly higher in cyclosporine group in 12th and 18th months (respectively, p = 0.003 and p = 0.003). Serum creatinine levels at 12th, 18th and 24th months were significantly higher in cyclosporine group than tacrolimus group (respectively, p = 0.009, p = 0.04 and p = 0.02). Hyperuricemia is a common complication after liver transplantation in children. Cyclosporine may cause hyperuricemia more often in respect to tacrolimus and this may be related to the impairment of renal functions. Complications developing because of hyperuricemia such as gout disease or renal calculi are quite rare in children.  相似文献   

2.
Increasingly, food allergy associated with tacrolimus after pediatric living‐donor liver transplantation (LT) has been reported. Tacrolimus prevents the activation of T cells by blocking calcineurin, thus producing an immunosuppressive effect, but tacrolimus induces an imbalance in T‐helper type 1 (Th1) and Th2 cells in the food allergy process. This report describes a case of tacrolimus‐associated food allergy after pediatric living‐donor LT. The patient was a 7‐year‐old Japanese girl who had undergone living‐donor LT at 12 months of age, and whom we first saw in the clinic at age 18 months. She received immunosuppressive therapy by tacrolimus after transplantation. Atopic dermatitis developed in post‐transplant month 18. Stridor, facial edema, lip swelling, and skin erythema after consuming tempura udon containing wheat occurred in post‐transplant month 39, and she was subsequently diagnosed with anaphylactic shock. Eosinophilic leukocyte and serum immunoglobulin (Ig)E increased, and specific IgE was positive for some food allergens. Pharmacotherapy was therefore changed from tacrolimus to cyclosporine A, after which eosinophilic leukocyte and serum IgE decreased and atopic dermatitis improved.  相似文献   

3.
Pneumatosis intestinalis is an uncommon finding beyond the neonatal period, but it has been reported in immunocompromized pediatric patients. The association of pneumatosis intestinalis in children following renal transplantation has to the best of our knowledge been only reported once in children. We describe a 4-year-old female who developed intermittent emesis, weight loss, and intermittently loose bloody stools after cadaveric renal transplantation at age 3.5 years. An abdominal x-ray demonstrated extensive pneumatosis in the colon. The infectious work-up was negative. Histologically, she had increased eosinophils throughout the lamina propria in the rectum. A glucose breath test was suggestive of small bowel bacterial overgrowth. She was treated with 10 days of metronidazole with resolution of the diarrhea and occult blood in stools. One month after the treatment she had radiologic resolution of her pneumatosis. Based on this report, pneumatosis intestinalis should be considered in the differential diagnosis of children after organ transplant suffering from diarrhea, abdominal pain, or blood in the stool.  相似文献   

4.
Predose monitoring of tacrolimus levels is standard practice in the care of pediatric renal transplant patients. This is despite a paucity of data investigating the ideal target range in children, and controversy as to whether tacrolimus levels correlate with renal transplant outcomes. We performed a retrospective cohort analysis of 48 renal transplant patients at a single Canadian pediatric transplant center following the initiation of a tacrolimus–mycophenolate–prednisone‐based IS protocol. We analyzed the relationship of graft function, as defined by GFR up to five yr post‐transplant, to the preceding mean tacrolimus level. There was no significant correlation between absolute GFR and mean tacrolimus levels (r = 0.206, p = 0.38). However, a higher mean tacrolimus level, particularly ≥10 ng/mL in the first three months after transplantation, was associated with a slower rate of decline in GFR with time (r = 0.608, p = 0.004) and with a less likelihood of developing CKD five yr after transplant. We suggest that the optimal target range for tacrolimus levels may be at the upper end of what is currently practiced and that further research to validate these findings would be useful.  相似文献   

5.
Recipient lymphocytes are crucial for direct and indirect pathways of allorecognition. We proposed that the administration of alemtuzumab several weeks pretransplantation could eradicate peripheral lymphatic cells and promote donor‐specific acceptance. This was a single‐center, retrospective review of 101 consecutive living donor kidney transplantations in pediatric patients (age 7 months—18 years), performed between September 2006 and April 2010. IS protocol included two 30 mg doses of alemtuzumab: The first was given 12‐29 days prior to transplantation, and the second at the time of transplantation. Maintenance IS was based on combination of low‐dose CNI and mycophenolate, with steroids tapered over the first 5 days post‐transplantation. Patients were followed for 7.8±1.3 years, and protocol biopsies were taken 1 month, 1, 3, and 5 years post‐transplant. The Kaplan‐Meier 8‐year patient and graft survival rates in the cyclosporine‐treated patients were 82.0±7.3% and 71.6±7.3, and in the tacrolimus‐treated patients were 97.2±5.4 and 83.8±6.0%. Biopsy‐proven acute rejection developed in 35% of cyclosporine‐treated patients and in 8% of tacrolimus‐treated patients. Alemtuzumab pretreatment prior to LRD kidney transplantation, followed by maintenance immunosuppression with tacrolimus and MMF, is associated with reasonable long‐term results in pediatric patients.  相似文献   

6.
In a 24‐month, multicenter, single‐arm, prospective study, 56 pediatric liver transplant patients with or without basiliximab induction were converted at 1‐6 months post‐transplant from standard calcineurin inhibitor (CN) therapy (± mycophenolic acid), to everolimus with reduced exposure to CNI (tacrolimus n=50, cyclosporine n=6). Steroid therapy was optional. Recruitment was stopped prematurely due to high rates of PTLD, treatment‐related serious infections leading to hospitalization and premature study drug discontinuation. Subsequently, patients aged <7 years reverted to local standard‐of‐care immunosuppression. Mean tacrolimus concentration was above or near the upper end of the maintenance target range (2‐5 ng/mL) until after month 6 post‐enrollment. The primary variable, mean (SD) change in eGFR from baseline to month 12 (last observation carried forward), was +6.2 (19.5) mL/min/1.73 m2. Two patients experienced treated biopsy‐proven acute rejection. No graft losses or deaths occurred. PTLD occurred in five patients (8.9%) (3/25 [12.0%] patients <2 years, 2/31 aged 2‐18 years [6.5%]). Adverse events, serious adverse events, and discontinuation due to adverse events were reported in 100.0%, 76.8%, and 44.6% of patients, respectively. In conclusion, everolimus with reduced CNI improved renal function while maintaining antirejection potency in pediatric liver transplant patients but safety outcomes suggest that patients were overimmunosuppressed.  相似文献   

7.
ALA induction in transplantation has been shown to reduce the need for maintenance immunosuppression. We report the outcome of 25 pediatric renal transplants between 2007 and 2010 using ALA induction followed by tacrolimus maintenance monotherapy. Patient ages were 1–19 yr (mean 14 ± 4.1 yr). Time of follow‐up was 7–51 months (mean 26 ± 13 months). Tacrolimus monotherapy was maintained in 48% of patients, and glucocorticoids were avoided in 80% of recipients. Mean plasma creatinine and GFR at one yr post‐transplant were 0.88 ± 0.3 mg/dL and 104.4 ± 25 mL/min/1.73m2, respectively. One, two, and three‐yr actuarial patient and graft survival rates were 100%. The incidence of early AR (<12 months after transplantation) was 12%, while the incidence of late AR (after 12 months) was 16%. Forty‐four percent of the recipients recovered normal, baseline renal function after an episode of AR, and 44% had persistent renal dysfunction (plasma creatinine 1.0–1.8 mg/dL). One graft was lost four yr after transplantation due to medication non‐compliance. Four (16%) patients developed BK or CMV infection. In our experience, ALA induction with tacrolimus monotherapy resulted in excellent short‐ and mid‐term patient and graft survival in low‐immunologic risk pediatric renal transplant recipients.  相似文献   

8.
Hourigan SK, Anders RA, Mitchell SE, Schwarz KB, Lau H, Karnsakul W. Chronic diarrhea, ascites, and protein‐losing enteropathy in an infant with hepatic venous outflow obstruction after liver transplantation. Abstract: An 18‐month‐old female status post‐orthotopic liver transplant for biliary atresia presented nine months after transplant with severe diarrhea and intolerance of feeds. She was found to have a PLE as evidenced by a low serum albumin and a persistent elevation of fecal A1AT. Investigation eventually revealed that the cause of the PLE was a stricture at the anastomosis site between the hepatic vein and inferior cava, supported by resolution of the PLE after venoplasty of the stricture. The patient has subsequently required several repeat venoplasties for recurrence of her symptoms correlating with recurrence of the stricture. This is a very rare presentation of hepatic venous outflow obstruction. Moreover, normal duplex ultrasound imaging of liver vasculature and her unusual presentation led to a delay in her diagnosis highlighting the need for an increased index of suspicion.  相似文献   

9.
Autoimmune‐mediated bowel disease has been reported after pediatric heart transplantation. Recognition and treatment of these patients has been difficult. We describe a patient who responded to steroids and basiliximab therapy after an inflammatory process secondary to abnormal T‐cell activation. Our patient is a 28‐month‐old female who received a heart transplant at five wk of age. At 24 months post‐transplant, she developed fever and bloody stools. Initial investigations were significant for an elevated ESR (>120) and CRP (15.2). Symptoms persisted despite bowel rest and mycophenolate discontinuation. Endoscopic evaluation revealed discontinuous ulcerative disease involving esophagus, terminal ileum, right and left colon, necessitating extensive bowel resection. She had additional airway inflammation leading to a TEF at the site of esophageal ulceration, requiring tracheostomy. Immune evaluation revealed autoimmune dysregulation that responded to parenteral methylprednisolone. Chronic basiliximab therapy allowed for successful weaning of steroids with sustained remission. She has been transitioned to sirolimus and tacrolimus maintenance immunosuppression with plans to discontinue basiliximab once off steroids. In conclusion, bowel disease in the setting of pediatric heart transplantation can be severe and refractory to traditional treatment methods. Tailoring immune therapy to activated T cells can result in remission. Basiliximab therapy was used in our patient to maintain steroid‐induced remission, but long‐term complications of this disease process are unknown.  相似文献   

10.
PTE is defined as hematocrit >51% or hemoglobin >17 g/dL after renal transplantation. Risk factors include native kidneys with adequate erythropoiesis pretransplant, smoking, renal artery stenosis, and cyclosporine treatment. We report the case of a 14‐yr‐old female kidney transplant patient, with triple therapy immunosuppression and stable graft function who developed PTE at 12 months post‐transplant with hemoglobin 17.3 g/dL, hematocrit 54.2%, stable graft function, and normotensive with normal cardiac echocardiogram and erythropoietin levels. The only risk factor found was tobacco use. As she had no spontaneous improvement, enalapril treatment was started at 19 months post‐transplant with a hemoglobin level of 17.5 g/dL and hematocrit 53%; by 23 months post‐transplant, hemoglobin lowered to 15 g/dL and hematocrit to 44.5% and continued to be in normal range thereafter. PTE is a rare condition in childhood and can be successfully treated with enalapril.  相似文献   

11.
De novo hepatocellular carcinoma (HCC) post‐transplantation in patients without viral hepatitis is extremely rare, with only three reported adult cases in the English literature. Here, we present a case of de novo HCC that developed in a 7‐year‐old female, who at 8 months of age received a liver, small bowel, spleen, and pancreas transplantation 6.5 years ago for gastroschisis and total parenteral nutrition (TPN)‐related cirrhosis. The post‐transplant course was complicated by Epstein‐Barr virus (EBV) infection, post‐transplant lymphoproliferative disease, and subsequent development of multifocal EBV‐associated post‐transplant smooth muscle tumors (EBV‐PTSMT) in the small bowel 1 year and 10 months after transplantation, respectively. This was managed by reducing immunosuppression with rituximab and EBV‐specific cytotoxic T‐cell therapy. She was noted to have a new lesion in her transplanted liver graft 6.5 years post‐transplantation that was diagnosed as HCC. The HCC was resected, and the patient remained clinically stable for 7 months. At that time, recurrence of the HCC was discovered on MRI. She passed away 6 months after. To the best of our knowledge, this is the first reported occurrence of de novo HCC post‐transplantation in the pediatric population that is unrelated to viral hepatitis in either recipient or donor.  相似文献   

12.
Kidney transplantation remains the treatment of choice for children with ESRD. Optimal perioperative management is critical in small recipients of ASK to assure adequate graft perfusion. We present a single‐center experience outlining management for patients weighing <20 kg who underwent primary renal transplantation with ASKs between 2007 and 2016. Sixty‐three patients met study criteria and underwent 34 living‐related, six living‐unrelated, and 23 deceased donor kidney transplants. Median age and weight at transplant were 25 months (IQR 18‐37 months; range 11 months‐6 years) and 11.0 kg (IQR 9.2‐14.5 kg; range 7.1‐19.5 kg). Eighty‐nine percent of patients required vasoactive agents intra‐operatively, with twenty patients requiring prolonged vasoactive agents post‐operatively. Intra‐operatively, patients received 51.9 mL/kg of crystalloid, 27.3 mL/kg of 5% albumin, and 13.6 mL/kg of packed red blood cells. Most (93.7%) patients were extubated on POD#0. Weights peaked on post‐operative days three through five. Over a median follow‐up of 49 months (IQR 31‐86 months; range 0‐130 months), four grafts were lost, two due to thrombosis and two secondary to chronic rejection. There was one patient death six months post‐transplant due to causes unrelated to transplantation. Graft survival at 1, 5, and 10 years was 98.4%, 96.6%, and 84.2%, respectively. Of surviving allografts, the median 1, 5, and 10 years post‐transplant eGFR was 122.9, 90.0, and 59.2 mL/min/1.73 m2 as determined by the 2009 Schwartz formula. Renal transplantation in small children using ASKs requires meticulous perioperative management including adequate fluid resuscitation and judicious use of pressors to assure adequate graft perfusion. The use of ASKs from living or deceased donors results in satisfactory short and long‐term outcomes.  相似文献   

13.
De novo PTAID may develop in pediatric solid organ transplant recipients, have a diverse spectrum, and are occasionally treatment resistant. Previous reports showed resolution of immune cytopenias in solid organ transplant recipients following replacement of the calcineurin inhibitor tacrolimus with the mTOR inhibitor sirolimus. Herein we describe a retrospective review (2000‐2017) of subjects who developed PTAID in whom immunosuppression was changed to sirolimus. Eight recipients (6 males) of either liver (n = 7) or multivisceral transplant (n = 1) suffered from severe, treatment‐resistant PTAID and were switched from tacrolimus to sirolimus. The median age at transplant was 1 year (range 0.5‐2.4 years). Six (75%) recipients developed de novo allergy and 2 immune‐mediated diseases. The median age at presentation of PTAID was 2.7 (1.4‐9) years at a median of 1.3 (0.25‐8) years after transplantation. The median time from PTAID presentation to conversion to sirolimus was 1.8 (0.45‐10) years. Complete resolution of symptoms was seen in 4 (50%) patients after a median of 12 (range 4‐24) months including 2 patients with immune‐mediated disease, 1 eczema, and 1 with eosinophilic colitis. One patient with multiple food allergies had a partial response and 3 (38%) had no response. None of the 8 recipients developed sirolimus‐attributed adverse events or acute rejection during a median follow‐up of 5 (0.6‐8) years after the conversion. Immunosuppression conversion from tacrolimus to sirolimus can be an effective therapy in patients suffering severe or treatment‐resistant PTAID, suggesting a potential role for tacrolimus in the pathogenesis of PTAID.  相似文献   

14.
PTLDs are a well‐recognized and potentially fatal complication after intestinal transplantation. We analyzed the incidence, clinical features, and outcome in a 63 intestinal transplantation series performed in our unit between October 1999 and July 2011. Types of graft included ISB (n = 23), LSB (n = 20), and MV (n = 20). Patients were categorized into three groups of immunosuppression: I (n = 43) received basiliximab, tacrolimus, and steroids; II (n = 11) thymoglobulin and tacrolimus, and III (n = 9) alemtuzumab and tacrolimus. EBV status was serially assessed. All PTLD cases were biopsied to establish histopathological diagnosis. The incidence of PTLD was 14.2% (9/63). Median onset of PTLD after transplant was four months (range: 0.5–28), within first postoperative year in 6 (66.6%) patients. Fever was the most common symptom. Graft removal was needed in four patients (44%). The patient survival rate was 66.6% (6/9). We have not found any association between PTLD and immunosuppression regimen or transplant type. However, there was a statistical association with EBV active infection.  相似文献   

15.
Tacrolimus granules were developed for patients who are unable to swallow capsules. Therapeutic drug monitoring (TDM) is required to optimize efficacy and safety, which is based on Ctrough for tacrolimus capsules. Pharmacokinetic (PK) data for tacrolimus granules are required to establish the basis for TDM in those who are unable to swallow capsules. In this phase IV study (NCT01371331) of children undergoing liver, kidney, or heart transplantation, patients received tacrolimus granules 0.15 mg/kg twice daily; first dose was administered within 24 hours of reperfusion. PK analysis samples were collected after reperfusion, after first dose of tacrolimus (Day 1), and at steady state (Day 7; >4 days stable dose). Of the 52 transplant recipients enrolled, 38 had two evaluable PK profiles. Mean AUCtau after first dose of tacrolimus was 211, 97, and 224 hour*ng/mL in liver, kidney, and heart transplant recipients, respectively; corresponding mean AUCtau at steady state was 195, 208, and 165 hour*ng/mL. Ctrough and AUCtau were positively correlated after first dose of tacrolimus and at steady state (Pearson's coefficients: r = 0.81 and r = 0.87, respectively). This study demonstrated that Ctrough is a reliable marker for TDM in pediatric transplant recipients treated with tacrolimus granules, consistent with TDM for other tacrolimus formulations.  相似文献   

16.
HPS is a life‐threatening condition in patients with end‐stage liver disease, in which intrapulmonary vascular dilatations result in intrapulmonary shunts and hypoxemia. The only successful treatment is liver transplantation. Hypoxemia may be severe prior to transplantation; however, it can worsen or become refractory after liver transplantation and result in increased post‐operative mortality. Here, we present the case of a 10‐month‐old female infant with progressive end‐stage liver disease and severe HPS, who developed refractory hypoxemia after a successful liver transplantation. After 19 days of unsuccessful attempts to reverse the hypoxemia using conventional mechanical ventilation and HFOV, the patient responded dramatically to APRV, with rapid improvement in her PaO2 and sharp decline in her OI. She was able to begin weaning from APRV two days later and was extubated within seven days. APRV was successful in treating refractory hypoxemia in this patient with severe HPS after liver transplantation, possibly by modifying distribution of pulmonary blood flow. Although we cannot rule out coincidental natural resolution of the HPS, APRV could be a useful rescue therapy in patients with HPS and refractory hypoxemia.  相似文献   

17.
aUCBT is a valuable curative option in pediatric patients with refractory idiopathic SAA and no available matched sibling or unrelated donors. Experience in the use of autologous cord blood units in patients with SAA is limited and private for‐profit cord blood‐banking programs are controversial. We report the successful treatment of two patients with SAA, aged 15 and 24 months, with autologous cord blood combined with immunosuppression. After conditioning with 200 mg/kg cyclophosphamide and ATG, 7.5 mg/kg, 32.2 × 107/kg, and 3.8 × 107/kg autologous cord blood nucleated cells were infused, respectively. One of our patients underwent transplantation after failure of IST. Both patients received post‐transplant immunosuppression with cyclosporine for 12 months. They remain disease‐free 6 years post‐transplantation.  相似文献   

18.
The BK virus (BKV) can be reactivated with immunosuppressive treatment in renal allograft recipients, which can result in interstitial nephritis (BKV‐associated nephropathy, BKVAN) and lead to renal allograft failure. Recently, leflunomide has been reported in some case series of BKVAN with favorable results. Most studies have included only adult patients, we herein report a pediatric case and include a literature review. The patient was a nine‐yr‐old female with end‐stage renal disease due to hypoxic kidney injury. A deceased donor renal transplant was performed and good initial allograft function was achieved following treatment with prednisolone, tacrolimus and mycophenolate mofetil. The serum Cr level increased to 1.6 mg/dL over the following four‐month period. A kidney biopsy revealed pathologic findings of acute cellular rejection and BK nephropathy. After methylprednisolone pulse therapy was administered to control acute rejection, the tacrolimus dose was reduced, and intravenous immunoglobulin treatment and leflunomide therapy were administered to control the BKVAN. Over the following 18 months, the viral load steadily decreased and remained below 100 copies/mL in the plasma. Leflunomide therapy in addition to a reduction of the immunosuppressive therapies resulted in a significant decline in the BK viral load without further deterioration of renal function.  相似文献   

19.
Food allergy is increasingly reported after paediatric liver transplantation. The underlying physiopathological mechanism remains incompletely understood. Therefore, we aimed to determine the incidence, clinical presentation, possible risk factors, and prognosis of post-transplant food allergy in children currently followed after liver and renal transplantation. The study population consists of 49 liver and 21 renal transplant patients transplanted between the age of 22 months and 15 years. Data were collected retrospectively from medical records and via a doctor’s questionnaire taken from the parents in a monocentric setting. Post-transplant food allergy has developed in 13 liver transplant patients and in none of the renal transplant recipients. Within the liver transplant group, median age at liver transplantation is significantly lower in the food-allergic (10 months) versus non-food-allergic group (3.3 years; p?=?0.002). The use of tacrolimus as primary maintenance immunosuppression is associated with food allergy (p?=?0.032) and mean donor age is significantly lower in the food-allergic group (p?=?0.009). Compared to the renal transplant group, median age at transplantation is significantly lower in the liver patients (p?<?0.001). No significant differences are found in primary immunosuppressive regimens between renal and liver transplant patients. Conclusion: Post-transplant food allergy is an important clinical problem in children after liver transplantation which does not affect renal transplant patients despite similar immunosuppressive regimens. Within the group of liver transplant recipients, tacrolimus use, young age at time of transplant and younger donor age were associated with the development of food allergy.  相似文献   

20.
ObjectivesTo evaluate the effect of patient, surgical, and medical factors on surgical complications and graft function following renal transplantation (Tx) in children weighing ≤20 kg, because the number of this challenging group of children is increasing.Patients and methodsBetween June 2009 and October 2013, 26 patients received living donor renal allotransplant using the extraperitoneal approach (EPA). The immunosuppression regimen was composed of prednisolone, mycophenolate mofetil, and ciclosporin or tacrolimus.ResultsThe mean weight was 16.46 ± 2.61 kg. Mean cold ischemia time was 53.85 ± 12.35 min. The graft survival rate (GSR) and patient survival rate (PSR) were 96% at 3 years. Acute rejection episodes (AREs) occurred in eight patients (30%). Postoperative surgical complications were ureteral leakage (3), vesicoureteric reflux (2), and renal vein thrombosis (2) (with one graft nephrectomy). Mean follow-up was 37.5 ± 7.4 months.ConclusionExcellent PSR and GSR can be achieved in low weight (<20 kg) recipients. Even in very low weight patients, the EPA was used. No cases were reported with primary graft non-function due to use of living donors, increasing pre-Tx body weight to at least 10 kg and maintaining adequate filling pressure before graft reperfusion. The presence of related donors and use of induction therapy and tacrolimus decreased the rate of ARE while the presence of pre-Tx lower urinary tract surgical interventions increased the rate of ureteric complications, but this was statistically insignificant.  相似文献   

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