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1.
Pediatr Transplant ; 28(7): e14872, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39385715

RESUMEN

BACKGROUND: Due to the low incidence of pediatric liver transplantations, short- and long-term data regarding their outcome, details on early postoperative complications and their risk factors are under-represented in the literature. METHODS: We retrospectively reviewed 1645 LTx performed at Hannover Medical School between January 2005 and December 2021. Of these, 421 transplantations were performed in 405 pediatric recipients. Univariate and multivariate binary logistic regressions were performed to identify independent risk factors for the onset of selected perioperative complications requiring intervention within the first 30 days following transplantation and their influence on graft and patient survival. RESULTS: Pleural effusions represent the most common postoperative complication observed in 49.4% (n = 208) of cases, followed by vascular complications in 22.6% (n = 95) and biliary complications in 20.0% (n = 84) of cases. Donor age (OR: 1.019; p = 0.010) and recipient age between 3 and 12 years (OR: 1.849; p = 0.008) were identified as independent risk factors for the onset of pleural effusions. Retransplantations within the first year after LTx were necessary in 11.4% of all cases (n = 48). Twenty (4.8%) patients died within the first year after LTx. CONCLUSION: Pleural effusions requiring postoperative intervention were observed in approximately half of the pediatric recipients. Therefore, the preemptive intraoperative placement of a chest drain under sterile conditions and general anesthesia should be considered. Our data further indicate that a two-stage procedure for biliary reconstruction may be the preferred procedure in patients at risk of early bile duct complications and retransplantation within the first year.


Asunto(s)
Trasplante de Hígado , Derrame Pleural , Complicaciones Posoperatorias , Humanos , Estudios Retrospectivos , Trasplante de Hígado/efectos adversos , Masculino , Femenino , Niño , Preescolar , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Factores de Riesgo , Adolescente , Lactante , Derrame Pleural/etiología , Derrame Pleural/epidemiología , Supervivencia de Injerto , Modelos Logísticos , Reoperación
2.
Am J Transplant ; 22(2): 519-531, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34455702

RESUMEN

Graft survival beyond year 1 has not changed after orthotopic liver transplantation (OLT) over the last decades. Likewise, OLT causes comorbidities such as infection, renal impairment and cancer. We evaluated our single-center real-world individualized immunosuppression program after OLT, based on 211 baseline surveillance biopsies (svLbx) without any procedural complications. Patients were classified as low, intermediate and high rejection risk based on graft injury in svLbx and anti-HLA donor-specific antibodies. While 32% of patients had minimal histological inflammation, 57% showed histological inflammation and 23% advanced fibrosis (>F2), which was not predicted by lab parameters. IS was modified in 79% of patients after svLbx. After immunosuppression reduction in 69 patients, only 5 patients showed ALT elevations and three of these patients had a biopsy-proven acute rejection, two of them related to lethal comorbidities. The rate of liver enzyme elevation including rejection was not significantly increased compared to a svLbx control cohort prior to the initiation of our structured program. Immunosuppression reduction led to significantly better kidney function compared to this control cohort. In conclusion, a biopsy guided personalized immunosuppression protocol after OLT can identify patients requiring lower immunosuppression or patients with graft injury in which IS should not be further reduced.


Asunto(s)
Trasplante de Hígado , Biopsia , Rechazo de Injerto/patología , Supervivencia de Injerto , Humanos , Terapia de Inmunosupresión , Inmunosupresores/uso terapéutico , Trasplante de Hígado/efectos adversos
3.
Liver Transpl ; 28(9): 1463-1474, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35447015

RESUMEN

This study aims to evaluate the long-term efficacy and reintervention rate after primary percutaneous portal vein stent angioplasty for portal vein stenosis (PVS) in pediatric liver transplantation (LT) recipients. From 2004 to 2020, a total of 470 pediatric LTs were performed in our center. All cases were screened for interventional PVS treatment and analyzed retrospectively. We identified 44 patients with 46 percutaneous angioplasties for posttransplantation PVS. The median interval from LT to percutaneous catheter intervention was 5 months (16 days-104 months) with a median follow-up (f/u) period after catheter intervention of 5.7 years (2-156 months). In 40 patients, an endovascular stent was placed as primary (n = 38) or secondary (n = 2) intervention. The median age at stent placement was 23 (6-179) months with a median weight of 10 kg (6-46 kg). Technical success and relief of PVS were achieved in all patients irrespective of age or weight. Adverse events occurred peri-interventionally in two patients and were resolved with standard care. All primary portal vein (PV) stents remained patent until the end of f/u. Reinterventions have been successfully performed in 10 patients for suspected or proven restenosis, resulting in a primary patency rate of 75% and an assisted patency rate of 25%. The median time to reintervention was 6.2 years (range 1-10 years). The need for reintervention was independent of age or weight at both transplantation and initial angioplasty as well as of additional risk factors due to portal hypertension. Percutaneous transhepatic PV stent angioplasty in children is safe and effective in all age groups, with excellent long-term patency. Primary stent angioplasty should be considered as first-line treatment for PVS after pediatric LT.


Asunto(s)
Angioplastia de Balón , Trasplante de Hígado , Angioplastia/efectos adversos , Angioplastia de Balón/métodos , Niño , Constricción Patológica/etiología , Constricción Patológica/cirugía , Humanos , Trasplante de Hígado/efectos adversos , Vena Porta/diagnóstico por imagen , Vena Porta/cirugía , Estudios Retrospectivos , Stents , Resultado del Tratamiento
4.
Liver Transpl ; 28(11): 1766-1775, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35666175

RESUMEN

Leukocyte telomere length (LTL) is a marker for biological age. Pediatric liver transplant recipients show a high rate of subclinical atherosclerosis, indicated by elevated intima-media thickness (IMT). We hypothesized that atherosclerosis is associated with biological age in these patients and investigated the course of LTL over time. We measured LTL from peripheral blood leukocytes by quantitative polymerase chain reaction and IMT from 97 pediatric patients after liver transplantation in a prospective cohort study. Of the patients, 71% (n = 69) had two or more assessments (total, 228 observations; median follow-up, 1.1 years). Lower LTL was associated with higher IMT (ß = -0.701, p = 0.01) and higher aspartate aminotransferase (ß = -0.001, p = 0.02), adjusted for age, sex, and age at transplantation. Of the patients, 45% showed decreasing LTL over time, whereas 55% exhibited stable LTL. Patients with stable LTL showed a decrease in IMT (median, -0.02 mm/year) and a decrease of tacrolimus trough levels (median, -0.08 µg/L/year). LTL is associated with IMT independent of age in pediatric liver transplant patients, suggesting that early aging contributes to the high burden of subclinical cardiovascular damage and may furthermore negatively affect the graft.


Asunto(s)
Aterosclerosis , Trasplante de Hígado , Aspartato Aminotransferasas , Aterosclerosis/epidemiología , Aterosclerosis/etiología , Grosor Intima-Media Carotídeo , Niño , Humanos , Leucocitos , Trasplante de Hígado/efectos adversos , Estudios Prospectivos , Tacrolimus , Telómero
5.
Liver Transpl ; 27(6): 887-899, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33641215

RESUMEN

Recurrence or de novo infection of hepatitis C virus (HCV) after liver transplantation (LT) has been associated with progressive graft hepatitis that can be improved by treatment with novel direct-acting antivirals. Cases of rejection episodes have been described during and after HCV treatment. The evolution of innate and adaptive immune response during and after cure of HCV LT is unknown. We studied 74 protein biomarkers in the plasma of LT patients receiving antiviral therapy. In addition, deep immune phenotyping of both the myeloid and lymphoid immune cell subsets in peripheral blood mononuclear cells was performed. We found that LT patients with active HCV infection displayed distinct alterations of inflammatory protein biomarkers, such as C-X-Cmotif chemokine 10 (CXCL10), caspase 8, C-C motif chemokine 20 (CCL20), CCL19, interferon γ, CUB domain-containing protein 1 (CDCP1), interleukin (IL)-18R1, CXCL11, CCL3, IL8, IL12B, tumor necrosis factor-beta, CXCL6, osteoprotegerin, IL10, fms-related tyrosine kinase 3 ligand, hepatocyte growth factor, urokinase-type plasminogen activator, neurotrophin-3, CCL4, IL6, tumornecrosis factor receptor superfamily member 9, programmed death ligand 1, IL18, and monocyte chemotactic protein 1, and enrichment of peripheral immune cell subsets unlike patients without HCV infection who received transplants. Interestingly, patients who cleared HCV after LT did not normalize the altered inflammatory milieu nor did the peripheral immune cell subsets normalize to what would be seen in the absence of HCV recurrence. Overall, these data indicate that HCV-specific imprints on inflammatory analytes and immune cell subsets after LT are not completely normalized by therapy-induced HCV elimination. This is in line with the clinical observation that cure of HCV after LT did not trigger rejection episodes in many patients.


Asunto(s)
Hepatitis C Crónica , Hepatitis C , Trasplante de Hígado , Antígenos de Neoplasias/uso terapéutico , Antivirales/uso terapéutico , Moléculas de Adhesión Celular/uso terapéutico , Hepacivirus , Hepatitis C/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Humanos , Leucocitos Mononucleares , Trasplante de Hígado/efectos adversos
6.
J Pediatr Gastroenterol Nutr ; 73(3): 385-390, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34091543

RESUMEN

OBJECTIVES: Cystic fibrosis-related liver disease (CFLD) with consecutive cirrhosis is the third most common cause of death in CF patients. The aim of this study was to identify the potential long-term benefits of liver transplantation (LTx) in a match-control comparison. METHODS: Retrospective single-center data analysis of all pediatric LTx for CFLD between 1998 and 2014. A control group was selected from the local CF patient registry. Data were collected from case report forms and included clinical and laboratory data, lung function tests, the indication for LTx, and details of surgical procedures. RESULTS: At our institution, 23 patients with severe CFLD median age 13.8 years (range 8.7-17.4; 16 boys) underwent LTx between 1998 and 2014. In all patients, normalization of hepatic CF manifestations were achieved after LTx. But obviously there was no significant positive influence on nutritional status. Signs of posttransplant liver steatosis were documented by ultrasound in 17 patients. Liver biopsies after LTx were performed in 19 patients, in 42% (n = 8) of these biopsies a fatty degeneration was observed. Five patients died after LTx, none because of primary hepatic dysfunction (1 because of posttransplant proliferative disorder, 4 because of infection). Analysis of matched control pairs revealed that liver function, anthropometry, pulmonary function, and life expectancy of CFLD patients with LTx are comparable with matched CF peers without CFLD. CONCLUSIONS: Isolated LTx normalizes the hepatic manifestation of CF disease. LTx enables children and adolescents with severe CFLD to have a comparable prognosis in terms of growth, life expectancy, and lung function as CF patients without advanced liver involvement. Our data clarifies the long-term perspectives of affected patients.


Asunto(s)
Fibrosis Quística , Trasplante de Hígado , Adolescente , Niño , Fibrosis Quística/complicaciones , Fibrosis Quística/cirugía , Humanos , Cirrosis Hepática , Masculino , Análisis por Apareamiento , Estudios Retrospectivos
7.
Pediatr Transplant ; 25(4): e13989, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33689189

RESUMEN

Growth failure persists after pediatric liver transplantation and impairs pediatric development and quality of life. Steroid dose minimization attempts to prevent growth impairment, yet long-term assessment in pediatric liver recipients is lacking. We identified risk factors for impaired linear growth after pediatric liver transplantation, with a special focus on low-dose steroid therapy. This is a single-center retrospective analysis of height development in pediatric liver recipients up to 5 years after transplantation. Risk factors for impaired linear growth (height Z-scores≤-2) at transplantation, after two (n = 347) and five years (n = 210) were identified by univariate and multivariate logistic regression. At transplantation, growth retardation was found in 52.2%, predominantly younger children. Height Z-scores improved from -2.23 to -1.40 (SE 0.11; 95%CI 0.74-1.16; p < .001) two years and -1.19 (SE 0.07;0.08-0.34; p = .017) five years post-transplant. Multivariate analysis showed previous growth impairment (OR=1.484; 95%-CI=1.107-1.988; p = .004), graft loss (49.006;2.232-1076; p = .006), and prolonged cold ischemic time (1.034;1.007-1.061; p = .011) as main long-term risk factors; steroid use was a significant predictor of 2-year but not 5-year growth impairment. In univariate analysis, impaired growth after 2 and 5 years was associated with continuous low-dose (2.5 mg/m2 BSA) steroid therapy (OR=3.323;1.578-6.996; p < .001/OR=8.352;1.089-64.07; p = .006)and graft loss (OR=2.513;1.395-4.525; p = .003/OR=3.378;1.815-7.576; p < .001). Furthermore, indication and era of transplantation affected growth. Our results show significant catch-up growth after pediatric liver transplantation, yet growth failure strongly affects particularly young liver recipients. The main influenceable long-term risk factor is pre-existing growth failure, emphasizing the importance of early aggressive nutritional therapy. Moreover, low-dose steroid therapy might impair growth and should therefore be critically questioned in long-term immunosuppression.


Asunto(s)
Estatura/efectos de los fármacos , Trastornos del Crecimiento/prevención & control , Inmunosupresores/administración & dosificación , Trasplante de Hígado , Complicaciones Posoperatorias/prevención & control , Prednisolona/administración & dosificación , Adolescente , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Trastornos del Crecimiento/etiología , Humanos , Inmunosupresores/efectos adversos , Lactante , Recién Nacido , Modelos Logísticos , Masculino , Complicaciones Posoperatorias/etiología , Prednisolona/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
8.
Pediatr Transplant ; 25(2): e13871, 2021 03.
Artículo en Inglés | MEDLINE | ID: mdl-33053269

RESUMEN

The field of pediatric kidney transplantation remains challenging due to an ongoing lack of size-matched grafts and anatomical peculiarities. In the current study, we investigated the incidence of surgical complications in pediatric recipients, with a focus on risk factors and effects on graft outcome. We retrospectively reviewed all 2386 kidney transplantations at our institution from January 2005 until December 2018. Of these, 221 transplants were performed in pediatric recipients, defined as under the age of 18 years. Donor-recipient body surface area ratios were calculated to evaluate the effects of size mismatching. Regression analyses were performed to identify independent risk factors for surgical complications and graft survival, respectively. Perioperative surgical complications requiring revision were observed in 34 (15.4%) cases. Leading cause for revision were vascular complications such as thrombosis or stenosis (n = 15 [6.8%]), which were significantly more frequent in case of young donors, (ie, donor age <6 years; OR: 4.281; CI-95%:1.385-13.226; P = .012), previous nephrectomy (OR: 3.407; CI-95%:1.019-11.387; P = .046), and en-bloc grafts (OR: 4.923; CI-95%:1.355-17.884; P = .015), followed by postoperative hemorrhage (n = 10 [4.5%]), ureteral complications (n = 8 [3.6%]), and lymphoceles (n = 7 [3.2%]). Median follow-up was 84.13 (0.92-175.72) months. One-, 5-, and 10-year graft survival rates were 97.1%, 88.9%, and 65.1%, respectively. Except for vascular complications (HR: 4.727; CI-95%:1.363-16.394; P = .014), none of the analyzed surgical morbidities significantly influenced graft survival. In conclusion, pediatric kidney transplantation achieves excellent long-term results. However, meticulous surgical technique and continuous postoperative monitoring are imperative for early detection and treatment of imminent vascular complications, especially in case of young donors and en-bloc grafts.


Asunto(s)
Supervivencia de Injerto , Trasplante de Riñón , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/cirugía , Reoperación/estadística & datos numéricos , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Modelos Logísticos , Masculino , Evaluación de Resultado en la Atención de Salud , Complicaciones Posoperatorias/etiología , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo
9.
BMC Nephrol ; 22(1): 258, 2021 07 09.
Artículo en Inglés | MEDLINE | ID: mdl-34243724

RESUMEN

BACKGROUND: In spite of renal graft shortage and increasing waiting times for transplant candidates, simultaneous heart and kidney transplantation (HKTx) is an increasingly performed procedure established for patients with combined end-stage cardiac and renal failure. Although data on renal graft outcome in this setting is limited, reports on reduced graft survival in comparison to solitary kidney transplantation (KTx) have led to an ongoing discussion of adequate organ utilization. METHODS: This retrospective study was conducted to evaluate prognostic factors and outcomes of 27 patients undergoing HKTx in comparison to a matched cohort of 27 patients undergoing solitary KTx between September 1987 and October 2019 in one of Europe's largest transplant centers. RESULTS: Median follow-up was 100.33 (0.46-362.09) months. Despite lower five-year kidney graft survival (62.6% versus 92.1%; 111.73 versus 183.08 months; p = 0.189), graft function and patient survival (138.90 versus 192.71 months; p = 0.128) were not significantly inferior after HKTx in general. However, in case of prior cardiac surgery requiring sternotomy we observed significantly reduced early graft and patient survival (57.00 and 94.09 months, respectively) when compared to patients undergoing solitary KTx (183.08 and 192.71 months; p < 0.001, respectively) or HKTx without prior cardiac surgery (203.22 and 203.22 months; p = 0.016 and p = 0.019, respectively), most probably explained by the significantly increased rate of primary nonfunction (33.3%) and in-hospital mortality (25.0%). CONCLUSIONS: Our data demonstrates the increased rate of early kidney graft loss and thus significantly inferior graft survival in high-risk patients undergoing HKTx. Thus, we advocate for a "kidney-after-heart" program in such patients to ensure responsible and reasonable utilization of scarce resources in times of ongoing organ shortage crisis.


Asunto(s)
Supervivencia de Injerto , Trasplante de Corazón , Trasplante de Riñón , Adulto , Anciano , Femenino , Alemania , Trasplante de Corazón/efectos adversos , Trasplante de Corazón/mortalidad , Mortalidad Hospitalaria , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/mortalidad , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias , Estudios Retrospectivos , Factores de Riesgo , Facultades de Medicina , Resultado del Tratamiento
10.
Zentralbl Chir ; 146(4): 382-391, 2021 Aug.
Artículo en Alemán | MEDLINE | ID: mdl-33761573

RESUMEN

Machine perfusion of donor livers is currently regarded as the most important innovation in transplant surgery to address the continuing shortage of organs in liver transplantation. Hypothermic machine perfusion (HMP) is safe to use and appears to reduce the risk of biliary complications and improve the long-term survival of transplanted organs following preservation by cold static storage - even in donors after cardiac death. A potential functional test of donor organs during HMP uses flavin mononucleotide and is still under clinical investigation. Normothermic machine perfusion (NMP) has a greater risk of technical problems, but functional testing using conventional laboratory parameters during NMP allows significant expansion of the donor pool, even though no prospective randomised study has been able to demonstrate a survival advantage for transplanted organs after NMP. In addition, the preservation time of the donor organs can be significantly extended with the help of NMP, which is particularly advantageous for complex recipient operations and/or logistics. Both methods could be applied for various scenarios in transplantation medicine - theoretically also in combination. The majority of German transplant centres regard machine perfusion as an important innovation and already actively perform perfusions or are in preparation for doing so. However, the overall practical experience in Germany is still relatively low, with only 2 centres having performed more than 20 perfusions. In the coming years, multi-centre efforts to conduct clinical trials and to develop national guidelines on machine perfusion will therefore be indispensable in order to define the potential of these technological developments objectively and to exploit it optimally for the field of transplantation medicine.


Asunto(s)
Trasplante de Hígado , Humanos , Hígado , Preservación de Órganos , Perfusión , Estudios Prospectivos , Donantes de Tejidos
11.
Liver Transpl ; 25(5): 752-762, 2019 05.
Artículo en Inglés | MEDLINE | ID: mdl-30742355

RESUMEN

Cardiovascular (CV) events account for 8%-13% of deaths after liver transplantation (LT) in adulthood. Although CV risk factors (RFs) are present, little is known about the prevalence of subclinical CV target organ damage (TOD) in children after LT. The aim of this prospective observational study was to assess the prevalence of subclinical CV TOD in children after LT and to identify RFs contributing to CV damage as potential targets for clinical intervention. In this study, 104 children after LT (54% female, 46% male; aged 11.5 ± 3.8 years) underwent cross-sectional assessment of subclinical TOD by carotid-femoral pulse wave velocity (PWV), carotid intima-media thickness (IMT), and left ventricular mass index (LVMI). Results were correlated with the presence of CV RFs (obesity, hypertension, dyslipidemia, renal impairment, anemia, and microinflammation). Of the patients, 22% were exposed to 2 CV RFs, and 36% displayed 3 or more CV RFs. Pathological results for PWV, IMT, and LVMI were found in 21.9%, 57.0%, and 11.1% of patients, respectively. In the multivariate analysis, diastolic blood pressure (P = 0.01) and estimated glomerular filtration rate (eGFR; P = 0.03) were independently associated with PWV, eGFR (P = 0.005), and age at LT (P = 0.048) with IMT and body mass index with LVMI (P = 0.004). In conclusion, patients after pediatric LT carry a substantial burden of subclinical CV TOD. Identification of modifiable CV RFs opens opportunities for targeted intervention in order to reduce CV morbidity and mortality in the future.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Trasplante de Hígado/efectos adversos , Adolescente , Presión Sanguínea/fisiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/fisiopatología , Grosor Intima-Media Carotídeo , Niño , Estudios Transversales , Femenino , Tasa de Filtración Glomerular/fisiología , Ventrículos Cardíacos/fisiopatología , Humanos , Masculino , Prevalencia , Estudios Prospectivos , Análisis de la Onda del Pulso , Factores de Riesgo
12.
Transpl Int ; 32(12): 1277-1285, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31188498

RESUMEN

Only few centers have reported their observations on patients with very long-term kidney graft survival of more than 25 years. Eighty-six subjects were identified in our center with graft survival of >25 years. Donor age was 31.3 ± 18.5 years. Mean duration of transplantation was 30.3 ± 3.6 years. At last follow-up, the cystatin C clearance was 47 ± 23 ml/min. Transplant biopsies for cause were performed in 30 subjects at a median of 28.4 years (19.1-40.3) after transplantation. Acute or chronic active T cell-mediated rejection was present in five cases and histological characteristics of acute or chronic active humoral rejection in eight cases. More than 80% of biopsies had inflammatory infiltrates in nonatrophic or atrophic cortical areas. The number of HLA mismatches were higher in biopsied subjects (3.0 ± 1.8 vs. 2.2 ± 1.7 without biopsy). Immunosuppressive therapy was adapted in most biopsied subjects; impaired graft function and proteinuria was unchanged at last follow-up. Sixty percent of all subjects had hyperparathyroidism (iPTH of the whole group: 132 ± 157 pg/ml), which was predominantly secondary, as judged by serum calcium and graft function. Young donor age was certainly a prerequisite of longterm graft survival. Nonetheless, inflammation or rejection in most biopsied patients suggests an important role of alloreactivity even in this late course.


Asunto(s)
Supervivencia de Injerto , Trasplante de Riñón , Riñón/patología , Adolescente , Adulto , Biopsia , Niño , Preescolar , Femenino , Tasa de Filtración Glomerular , Rechazo de Injerto , Humanos , Inmunosupresores/uso terapéutico , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangre , Adulto Joven
13.
Pediatr Transplant ; 22(5): e13207, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29729061

RESUMEN

Immunosuppressive combination therapy with MMF can reduce CNI associated nephrotoxicity. We investigated effectiveness and safety of de novo MMF-tacrolimus based immunosuppression after pLTx. Patients after pLTx receiving immunosuppression with MMF/tacrolimus (MMF/TAC) were compared to retrospectively selected age- and diagnosis-matched patients with tacrolimus monotherapy (TAC) and cyclosporine/prednisolone therapy (CSA) (19 patients each, n = 57). Effectiveness, renal function and side effects were analyzed for 1 year after pLTx. Tacrolimus reduction in combination therapy (0.7 µg/L over the year) was lower than aspired (2 µg/L). Acute BPAR occurred equally in MMF/TAC and TAC groups (31.6% each), being slightly higher in CSA group (42.1%; OR = 1.5; 95% CI = 0.42-5.44; P = .5). GFR deteriorated comparably in all 3 groups (P < .01 each) without significant differences between the groups. Septicemia was detected significantly more often in MMF/TAC (73.6%) than in TAC (31.6%) (OR 4.17; 1.07-16.27; P = .04). EBV reactivation occurred more often in CSA patients (84.2%) than in MMF/TAC (47.4%; OR 5.16; 0.98-27.19; P = .05) and TAC patients (52.6%; OR 8.16; 1.48-44.89; P = .02) the same was true for other viral infections (47.4% (CSA) vs 15.8% (TAC); OR 4.21; 0.95-18.55; P = .05). Our study does not provide additional evidence for a benefit of initial use of MMF/TAC over TAC regarding renal function, but raises concerns regarding a potentially increased risk of serious infections under MMF/TAC compared to TAC monotherapy at equivalent renal outcome; our study is, however, limited by the minor CNI reduction in combination therapy.


Asunto(s)
Inhibidores de la Calcineurina/uso terapéutico , Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Trasplante de Hígado , Ácido Micofenólico/uso terapéutico , Insuficiencia Renal/prevención & control , Tacrolimus/uso terapéutico , Adolescente , Niño , Preescolar , Ciclosporina/uso terapéutico , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Lactante , Modelos Logísticos , Masculino , Análisis por Apareamiento , Prednisolona/uso terapéutico , Insuficiencia Renal/inducido químicamente , Estudios Retrospectivos , Resultado del Tratamiento
14.
J Magn Reson Imaging ; 44(1): 112-21, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26778459

RESUMEN

PURPOSE: To combine diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) for detection of allograft dysfunction in patients early after kidney transplantation and to correlate diffusion parameters with renal function and renal histology of allograft biopsies. MATERIALS AND METHODS: Between day 4 and 11 after kidney transplantation 33 patients with initial graft function and 31 patients with delayed graft function (DGF) were examined with a 1.5T magnetic resonance imaging (MRI) scanner. DTI and DWI sequences were acquired and fractional anisotropy (FA), apparent diffusion coefficient (ADCmono), pure diffusion (ADCdiff ), and the perfusion fraction (Fp) were calculated. Kidney biopsies in 26 patients were analyzed for allograft pathology, ie, acute tubular injury, inflammation, edema, renal fibrosis, and rejection. Histological results were correlated with MRI parameters. RESULTS: In the renal medulla FA (0.25 ± 0.06 vs. 0.29 ± 0.06, P < 0.01) and ADCmono (1.73 ± 0.13*10(-3) vs. 1.93 ± 0.16*10(-3) mm(2) /s, P < 0.001) were significantly reduced in DGF patients compared with patients with initial function. For ADCdiff and Fp similar reductions were observed. FA and ADCmono significantly correlated with renal function (r = 0.53 and r = 0.57, P < 0.001) and were inversely correlated with the amount of renal fibrosis (r = -0.63 and r = -0.65, P < 0.05). CONCLUSION: Combined DTI and DWI detected allograft dysfunction early after kidney transplantation and correlated with allograft fibrosis. J. Magn. Reson. Imaging 2016;44:112-121.


Asunto(s)
Imagen de Difusión por Resonancia Magnética/métodos , Imagen de Difusión Tensora/métodos , Rechazo de Injerto/diagnóstico por imagen , Rechazo de Injerto/etiología , Trasplante de Riñón/efectos adversos , Riñón/patología , Imagen Multimodal/métodos , Femenino , Fibrosis , Rechazo de Injerto/patología , Humanos , Riñón/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
15.
Clin Transplant ; 30(6): 741-8, 2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27160359

RESUMEN

BACKGROUND: The 12-month (M) PROTECT study showed that de novo liver transplant recipients (LTxR) who switched from a calcineurin inhibitor (CNI)-based immunosuppression to a CNI-free everolimus (EVR)-based regimen showed numerically better renal function. Here, we present the five-yr follow-up data. METHODS: PROTECT was a randomized controlled study in which LTxR received basiliximab and CNI-based immunosuppression ± corticosteroids. Patients were randomized 1:1 to receive EVR or continue CNI. Patients completing the core study could enter the extension study on their randomized treatment. RESULTS: A total of 81 patients entered the extension study (41, EVR; 40, CNI). At M59 post-randomization, the adjusted mean eGFR was significantly higher in the EVR group, with a benefit of 12.4 mL/min using Cockcroft-Gault (95% CI: 1.2; 23.6; p = 0.0301). Also, there was a significant benefit for adjusted and unadjusted eGFR using the four-variable Modification of Diet in Renal Disease (MDRD4) or Nankivell formula. During the extension period, treatment failure rates were similar. SAEs occurred in 26 (63.4%) and 28 (70.0%) of the patients in EVR and CNI groups, respectively. CONCLUSION: Compared with the CNI-based treatment, EVR-based CNI-free immunosuppression resulted in significantly better renal function and comparable patient and graft outcomes after five-yr follow-up.


Asunto(s)
Inhibidores de la Calcineurina/administración & dosificación , Everolimus/administración & dosificación , Rechazo de Injerto/tratamiento farmacológico , Supervivencia de Injerto/efectos de los fármacos , Hepatopatías/cirugía , Trasplante de Hígado/efectos adversos , Privación de Tratamiento , Adulto , Femenino , Estudios de Seguimiento , Rechazo de Injerto/etiología , Humanos , Inmunosupresores/administración & dosificación , Pruebas de Función Renal , Masculino , Estudios Prospectivos , Resultado del Tratamiento
16.
Am J Physiol Renal Physiol ; 308(12): F1444-51, 2015 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-25925250

RESUMEN

Delayed graft function (DGF) after kidney transplantation is not uncommon, and it is associated with long-term allograft impairment. Our aim was to compare renal perfusion changes measured with noninvasive functional MRI in patients early after kidney transplantation to renal function and allograft histology in biopsy samples. Forty-six patients underwent MRI 4-11 days after transplantation. Contrast-free MRI renal perfusion images were acquired using an arterial spin labeling technique. Renal function was assessed by estimated glomerular filtration rate (eGFR), and renal biopsies were performed when indicated within 5 days of MRI. Twenty-six of 46 patients had DGF. Of these, nine patients had acute rejection (including borderline), and eight had other changes (e.g., tubular injury or glomerulosclerosis). Renal perfusion was significantly lower in the DGF group compared with the group with good allograft function (231 ± 15 vs. 331 ± 15 ml·min(-1)·100 g(-1), P < 0.001). Living donor allografts exhibited significantly higher perfusion values compared with deceased donor allografts (P < 0.001). Renal perfusion significantly correlated with eGFR (r = 0.64, P < 0.001), resistance index (r = -0.57, P < 0.001), and cold ischemia time (r = -0.48, P < 0.01). Furthermore, renal perfusion impairment early after transplantation predicted inferior renal outcome and graft loss. In conclusion, noninvasive functional MRI detects renal perfusion impairment early after kidney transplantation in patients with DGF.


Asunto(s)
Funcionamiento Retardado del Injerto/patología , Funcionamiento Retardado del Injerto/fisiopatología , Supervivencia de Injerto/fisiología , Trasplante de Riñón , Riñón/fisiopatología , Imagen por Resonancia Magnética , Adulto , Anciano , Femenino , Tasa de Filtración Glomerular/fisiología , Rechazo de Injerto/patología , Humanos , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Perfusión/métodos , Trasplante Homólogo/efectos adversos , Trasplante Homólogo/métodos
17.
Liver Transpl ; 21(2): 195-203, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25504770

RESUMEN

Living related liver transplantation (LRLT) is a valuable transplant option for children with end-stage liver disease who face long waiting times on regular waiting lists. The subjection of a healthy adult to a potentially life-threatening operation can raise issues of freedom of choice, fear, and family conflict for the potential donors. We examined attitudes, fears, and influencing factors in the decision-making process for living liver donation for children in order to identify factors to improve support for living liver donors in the future. In a retrospective, questionnaire-based survey of 93 adults evaluated for living liver donation between 1997 and 2010, 47 of whom actually proceeded to donation, we asked about attitudes, motivation, fears, influencing factors, and well-being during the LRLT evaluation process and during the donation period. Answers were recorded on Likert scales and compared with Pearson's rho correlation and the Mann-Whitney U test as appropriate. Although there was a strong sense of a lack of alternatives among the donors, the majority of the donors felt free in their decision to donate. Donors who were asked to donate for a relative who was not their own child appeared at higher risk of lacking support and of feeling coerced. Family and social support and good and empathic information about the donation process were identified as key factors for donor well-being. In conclusion, potential living liver donors need to have adequate, sufficient, and empathic information, and they need to be provided a supportive framework, including family support, in order to promote their well-being. Care needs to be taken in identifying and counseling potential donors at risk of feeling coerced into donation.


Asunto(s)
Toma de Decisiones , Enfermedad Hepática en Estado Terminal/cirugía , Trasplante de Hígado/psicología , Adolescente , Adulto , Anciano , Actitud Frente a la Salud , Niño , Preescolar , Colestasis Intrahepática/cirugía , Empatía , Salud de la Familia , Miedo , Femenino , Humanos , Lactante , Donadores Vivos , Masculino , Persona de Mediana Edad , Motivación , Riñón Poliquístico Autosómico Recesivo/cirugía , Encuestas y Cuestionarios , Obtención de Tejidos y Órganos/métodos , Resultado del Tratamiento , Adulto Joven
19.
Ann Transplant ; 29: e944603, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39350474

RESUMEN

BACKGROUND Kidney transplantation is still the best therapy for patients with end-stage renal disease, but the demand for donor organs persistently surpasses the supply. A prognostic model using pre-transplant data for the prediction of renal graft function would be helpful to optimize organ allocation and avoid futile transplantations. MATERIAL AND METHODS Retrospective data of 2431 patients who underwent kidney transplantation between January 01, 2000, and December 31, 2012 with subsequent ten-year clinical follow-up in our transplant center were analyzed. Of these, 1172 patients met the inclusion criteria. Multivariable regression modelling was used to develop a prognostic model for the prediction of graft function after 1 year utilizing only pre-transplant data. The final model was assessed with the area under the receiver operating characteristic (AUROC) curve. RESULTS Donor age, donor serum creatinine, recipient body mass index, re-transplantations beyond the second kidney transplantation, and cold ischemia time had an independent, significant influence on graded renal graft function 1 year after kidney transplantation. AUROC analysis of the prognostic model was >0.700 for all GFR categories except KDIGO G5, indicating high sensitivity and specificity of prediction. CONCLUSIONS For improvement of renal graft function, organs from older donors or donors with high serum creatinine should not be used in obese recipients and for re-transplantations beyond the second one. Cold ischemia time should be as short as possible.


Asunto(s)
Trasplante de Riñón , Humanos , Femenino , Masculino , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Pronóstico , Supervivencia de Injerto , Donantes de Tejidos , Fallo Renal Crónico/cirugía , Tasa de Filtración Glomerular , Isquemia Fría , Creatinina/sangre
20.
Discov Oncol ; 15(1): 224, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38865024

RESUMEN

The rapidly aging population in industrialized countries comes with an increased incidence of intrahepatic cholangiocarcinoma (iCC) which presents new challenges for oncological treatments especially in elderly patients. Thus, the question arises to what extent the benefit of surgical resections, as the only curative treatment option, outweighs possible perioperative risks in patients ≥ 80 years of age (octogenarians). We therefore retrospectively analyzed 311 patients who underwent resection for iCC at Hannover Medical School between January 1996 and December 2022. In total, there were 11 patients older than 80 years in our collective. Despite similar tumor size, octogenarians underwent comparatively less extensive surgery (54.5% major resections in octogenarians vs. 82.7% in all other patients; p = 0.033) with comparable rates of lymphadenectomy and tumor-free resection margins. Furthermore, we did not observe increased major postoperative morbidity (Clavien-Dindo ≥ IIIa complications: 27.3% vs. 34.3% in all other patients; p = 0.754) or mortality (estimated 1-year OS of 70.7% vs. 72.5% in all other patients, p = 0.099). The length of intensive care unit (ICU) or intermediate care unit (IMC) stay was significantly longer in octogenarians, however, with a comparable length in total hospital stay. The estimated overall survival (OS) did also not differ significantly, although a trend towards reduced long-term survival was observed (14.5 months vs. 28.03 months in all other patients; p = 0.099). In conclusion, primary resection is a justifiable and safe therapeutic option even in octogenarians but requires an even more thorough preoperative patient selection.

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