RESUMEN
BACKGROUND: The risk of invasive pneumococcal disease is significant among solid organ transplant (SOT) recipients. The optimal pneumococcal vaccination strategy for SOT patients is not known. METHODS: The potential kidney transplant recipients in dialysis were randomized into two arms: to receive a 23-valent pneumococcal polysaccharide vaccine (PPV23) before transplantation or to receive a 13-valent pneumococcal conjugate vaccine (PCV13) before transplantation and a second dose of PCV13 six months after the transplantation. Serotype-specific antibody concentrations and opsonophagocytic activity (OPA) were measured before and after the first vaccination (visits V1,V2) and six and seven months after the transplantation, for example, before and after the second PCV13 (visits V3,V4). RESULTS: Out of 133 participants, 48 (PCV13 arm) and 46 (PPV23 arm) received a kidney transplant, and 37 + 37 in both arms completed the study. After the first vaccination, the geometric mean concentrations (GMCs) in the PCV13 arm were significantly higher for 9/13 serotypes and the OPA geometric mean titers (GMTs) were significantly higher for 4/13 serotypes. At V3, the antibody levels had declined but OPA remained significantly higher for 7/13 (PCV13) vs 4/13 (PPV23) serotypes. At V4, the GMCs for 9/13 serotypes and the GMTs for 12/13 serotypes were significantly higher in the PCV13 arm. The GMCs but not GMTs were lower than at V2. There was no difference in adverse effects. No vaccine-related allograft rejection was detected. CONCLUSIONS: The immunogenicity of PCV13 was better in dialysis patients, and revaccination with PCV13 was immunogenic and safe.
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Anticuerpos Antibacterianos/sangre , Inmunogenicidad Vacunal , Trasplante de Riñón/efectos adversos , Vacunas Neumococicas/inmunología , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Inmunización Secundaria , Masculino , Persona de Mediana Edad , Vacunas Neumococicas/administración & dosificación , Diálisis Renal , Receptores de TrasplantesRESUMEN
INTRODUCTION: Electrocardiographic (ECG) changes before and after kidney transplantation are not well-defined. Our aim was to describe the evolution of ECG in patients on dialysis before and after successful kidney transplantation and to explore the association between ECG findings and major cardiovascular (CV) events and mortality after kidney transplantation. PATIENTS AND METHODS: Electrocardiographics were collected retrospectively 3 times: at entry to the transplantation waiting list, at transplantation, and 1 year after the transplantation from 212 kidney transplantation recipients. Altogether 19 ECG variables were analyzed. RESULTS: Left ventricular hypertrophy was present in 10.2% by the Cornell voltage-duration product criteria and 10.7% by the Sokolow-Lyon voltage criteria before kidney transplantation. The presence of ST depression (OR 3.12, 95% CI 1.12 -8.7 and P = .03) at entry to the waiting list and Q wave at the time of transplantation (OR 3.28, 95% CI 1.06-10.10 and P = .04) were both independently associated with major CV events after the transplantation. In addition, the presence of Q wave at entry to the waiting list was a risk factor of premature death after the transplantation (OR 2.92, 95% CI 1.06-8.05 and P = .04). DISCUSSION: Careful analysis of the ECG before transplantation can be used to estimate cardiovascular events and mortality risk after kidney transplantation.
Asunto(s)
Sistema Cardiovascular/fisiopatología , Electrocardiografía/métodos , Hipertrofia Ventricular Izquierda/mortalidad , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Complicaciones Posoperatorias/mortalidad , Femenino , Estudios de Seguimiento , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Hipertrofia Ventricular Izquierda/diagnóstico , Hipertrofia Ventricular Izquierda/etiología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
BACKGROUND/AIMS: Ischemia-reperfusion injury (IRI) and innate immune response augment adaptive immunity and may also trigger repair processes that lead to uncontrolled fibrosis and atherosclerosis as seen in chronic allograft injury. Simvastatin has been shown to protect from renal IRI in several experimental studies. The aim of this study was to examine the effect of donor simvastatin pretreatment and early initiation of recipient simvastatin treatment on chronic kidney allograft injury. METHODS: A rat renal transplantation model was used. Simvastatin was administered perorally for donor (5 mg/kg) and/or for recipient (2 mg/kg) 2 hours before transplantation and/or as daily treatment starting on the first postoperative day (2 mg/kg/day). The study included 5 groups: (1) no simvastatin, (2) donor pretreatment, (3) daily recipient treatment, (4) donor pretreatment + daily recipient treatment and (5) donor pretreatment + recipient pretreatment + daily recipient treatment. The grafts were recovered at day 90 for histopathological and immunohistochemical analysis. Kidney function was followed weekly with serum creatinine, and 24-hour urine protein was measured 60 and 90 days after transplantation. RESULTS: We found that donor and recipient simvastatin pretreatment combined with daily recipient treatment reduced graft inflammation and chronic allograft injury. Treatment using only statins started after transplantation reduced inflammation to some extent, but did not affect chronic kidney allograft injury. Pretreatment using only donor statins impaired graft function and increased proteinuria. CONCLUSION: Our data suggest that perioperative recipient statin treatment reduces inflammation and may protect the graft in the long term.
Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Trasplante de Riñón/métodos , Atención Perioperativa/métodos , Proteinuria/prevención & control , Insuficiencia Renal Crónica/prevención & control , Daño por Reperfusión/prevención & control , Simvastatina/uso terapéutico , Aloinjertos , Animales , Creatinina/sangre , Ratas , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/orina , Daño por Reperfusión/sangre , Daño por Reperfusión/orina , Donantes de Tejidos , Receptores de TrasplantesRESUMEN
The influence of dialysis modalities on HRQoL before and after kidney transplantation (KT) and the role of adherence to medication on HRQoL have not been fully studied. Sixty four dialysis patients who answered the 15D HRQoL survey during dialysis were surveyed again after KT. Adherence and employment were also investigated. The mean 15D score was highest among home hemodialysis patients (HHD) and lowest among in-center hemodialysis patients (icHD). After KT, the mean 15D score improved significantly in 78.6% of peritoneal dialysis patients (PD), 47.6% of HHD, and 53.8% of icHD. Then, mean 15D score remained unchanged in 28.6% of HHD and in 23.1% of icHD patients. A deterioration in the 15D score occurred in 14.3% of PD, 23.1% of icHD, and 23.8% of HHD patients, and this was influenced by the number of pills (P = 0.04). Adherence to medication was the lowest in PD, timing being the most challenging task showing a connection to higher creatinine concentration (never forgot 1.41 mg/dl vs. forgot 2.08 mg/dl P = 0.05). Employed patients had a higher mean 15D score. The icHD and PD patients benefited the most from KT and HHD the least. Low pill burden and employment were linked to a better HRQoL.
Asunto(s)
Trasplante de Riñón , Calidad de Vida , Adulto , Anciano , Recolección de Datos , Escolaridad , Empleo , Femenino , Hemodiálisis en el Domicilio , Humanos , Fallo Renal Crónico/cirugía , Fallo Renal Crónico/terapia , Estudios Longitudinales , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Diálisis Peritoneal , Diálisis RenalRESUMEN
The first simultaneous pancreas-kidney transplantation in Finland was performed in 2010. On a global scale, already more than 45,000 pancreatic transplantations have been performed. Pancreatic transplantation restores the blood glucose level to normal, but only at the cost of possible adverse effects due to surgery and anti-rejection drugs. Based on our experience with 24 patients, this operation has met the expectations and shown that simultaneous pancreas-kidney transplantation is a good alternative for selected type 1 diabetics instead of mere kidney transplantation. In the future we aim to conduct approximately 15 combined transplantations per year.
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Diabetes Mellitus Tipo 1/cirugía , Trasplante de Riñón/estadística & datos numéricos , Trasplante de Páncreas/estadística & datos numéricos , Femenino , Finlandia , Humanos , Masculino , Selección de Paciente , Resultado del TratamientoRESUMEN
Lymphangiogenesis occurs in renal allografts and it may be involved in the maintenance of the alloreactive immune response and thus participate in the development of chronic kidney allograft injury. Sirolimus (SRL) has been shown to inhibit lymphangiogenesis. The aim of this study was to describe lymphangiogenesis and its regulation during the development of chronic kidney allograft injury and to investigate the effect of SRL on allograft lymphangiogenesis and chronic kidney allograft injury. A rat renal transplantation model was used. Allografts treated with cyclosporine A or with SRL were analyzed in various time points. Syngenic transplantations were used as controls. Kidney function was followed with serum creatinine. Histology was analyzed by Chronic Allograft Damage Index (CADI). Immunohistochemistry was used to detect lymphatic vessels, VEGF-C and VEGFR-3. In cyclosporine-treated allografts VEGF-C/VEGFR-3 pathway was strongly upregulated leading to extensive lymphangiogenesis 60 days after transplantation. Lymphangiogenesis correlated positively with the CADI score. Sirolimus efficiently inhibited lymphangiogenesis, improved graft function and attenuated the development of chronic kidney allograft injury when compared with cyclosporine. In conclusion, lymphangiogenesis is associated with chronic kidney allograft injury and SRL is a potent inhibitor of lymphangiogenesis in renal allografts. Inhibition of lymphatic proliferation could mediate the nephroprotective properties of SRL.
Asunto(s)
Trasplante de Riñón/patología , Linfangiogénesis/fisiología , Insuficiencia Renal/terapia , Sirolimus/farmacología , Animales , Enfermedad Crónica , Ciclosporina/uso terapéutico , Rechazo de Injerto , Inmunohistoquímica , Inmunosupresores/uso terapéutico , Riñón/lesiones , Masculino , Microscopía Fluorescente , Ratas , Ratas Wistar , Factores de Tiempo , Trasplante Homólogo , Factor C de Crecimiento Endotelial Vascular/metabolismo , Receptor 3 de Factores de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The annual number of kidney transplantations in Finland is 150 to 200. Successful kidney transplantation improves the patient's quality of life and prognosis and is cost-effective as compared with dialytic therapy. Only a few per cent of transplantations are made from a living donor. Waiting times for kidney transplantations have become longer in the last few years. Whereas attempts should be made to better identify potential brain-dead organ donors in order to increase kidney transplantations, transplantations from living donors could also reduce the disproportion between the availability and the need of organs.
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Trasplante de Riñón/estadística & datos numéricos , Donadores Vivos , Muerte Encefálica , Análisis Costo-Beneficio , Finlandia , Humanos , Trasplante de Riñón/economía , Pronóstico , Calidad de Vida , Diálisis Renal/economía , Obtención de Tejidos y Órganos/organización & administración , Listas de EsperaRESUMEN
BACKGROUND: Associations between mode of renal replacement therapy and employment rate have not been well characterized. STUDY DESIGN: Cross-sectional registry analysis. SETTING & PARTICIPANTS: The employment status of all prevalent 15- to 64-year-old dialysis and kidney transplant patients in Finland at the end of 2007 (N = 2,637) was analyzed by combining data from the Finnish Registry for Kidney Diseases with individual-level employment statistics of the Finnish government. PREDICTOR: Prevalence rate ratios (PRRs) of employment according to treatment modality with adjustment for age, sex, cause of end-stage renal disease (ESRD), duration of ESRD, and comorbid conditions were estimated using Cox regression with a constant time at risk. OUTCOME: Employment status of patients on dialysis therapy or after transplant. MEASUREMENTS: Clinical data were collected from the Finnish Registry for Kidney Diseases, and employment data were acquired from Statistics Finland. RESULTS: 19% of hemodialysis patients, 31% of peritoneal dialysis patients, and 40% of patients with a functioning transplant were employed; the overall employment rate for the Finnish population aged 15-64 years is 67%. Home hemodialysis patients and those treated with automated peritoneal dialysis had employment rates of 39% and 44%, respectively. In adjusted analysis, patients on home hemodialysis therapy (PRR, 1.87), on automated peritoneal dialysis therapy (PRR, 2.14), or with a kidney transplant (PRR, 2.30) had higher probabilities of employment than in-center hemodialysis patients. Patients with type 1 or 2 diabetes as the cause of ESRD had the lowest probability of employment (PRR, 0.48-0.60 compared with glomerulonephritis). Patients aged 25-54 years more frequently were employed than those younger than 25 or older than 54 years. Sex did not predict employment. For transplant recipients, longer time since transplant was associated with higher employment in addition to the mentioned factors. LIMITATIONS: Cross-sectional design. CONCLUSIONS: Employment rate of home dialysis patients was similar to that of transplant recipients and higher than that of in-center hemodialysis patients. Patients with diabetes were less likely to be employed.
Asunto(s)
Empleo/estadística & datos numéricos , Fallo Renal Crónico/terapia , Trasplante de Riñón , Diálisis Renal , Adolescente , Adulto , Estudios de Cohortes , Estudios Transversales , Femenino , Finlandia , Humanos , Fallo Renal Crónico/epidemiología , Masculino , Persona de Mediana Edad , Sistema de Registros , Terapia de Reemplazo Renal/métodos , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: The recurrence of IgA nephropathy (IgAN) in the allograft is common. Factors related to IgA recurrence are unclear. The aims of this study were to determine the incidence of IgAN recurrence as assessed by protocol biopsies and to identify predictive factors for recurrence. METHODS: We identified 65 protocol biopsies taken before the second year post-transplantation in patients with IgAN as primary renal disease. Diagnosis of recurrence of IgA was based on the detection of at least 1+ mesangial deposits of IgA. Pathological findings and clinical characteristics were retrospectively compared between recurrent and non-recurrent cases. RESULTS: IgAN recurrence rate was 32%. Mesangial C3 was detected in 83% of recurrent cases versus 17% in non-recurrent patients (P < 0.001). Normal urinalysis was observed in 52%. Non-recurrent patients had arteriolar hyalinosis in 31% of the cases versus none in IgAN recurrence (P = 0.006). Seventy-nine per cent of cyclosporine users were free of recurrence, whereas 45% of the patients without cyclosporine experienced recurrence (P = 0.03). The odds ratio (OR) for IgAN recurrence in patients using cyclosporine was 0.3 (confidence interval 0.1-0.9). Zero HLA-DR mismatch was associated with non-recurrence (P < 0.01). The OR for IgA recurrence was 6.7 if any degree of DR mismatch was present. IgAN recurrent patients had better glomerular filtration rate, but after censoring delayed graft function, the differences disappeared. Graft loss due to IgA recurrence was only 3%. CONCLUSIONS: IgAN recurrence rate was 32%. The histological diagnosis was not accompanied by abnormalities in the urinalysis in one-half of the patients. Full DR match and cyclosporine were associated with non-recurrence.
Asunto(s)
Biopsia , Glomerulonefritis por IGA/diagnóstico , Glomerulonefritis por IGA/etiología , Rechazo de Injerto/etiología , Fallo Renal Crónico/complicaciones , Trasplante de Riñón/efectos adversos , Adulto , Femenino , Estudios de Seguimiento , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Pronóstico , RecurrenciaRESUMEN
The incidence and clinical course of polyomavirus-associated nephropathy (PyVAN) in our well-HLA-matched kidney transplant population mainly on low-dose cyclosporine-based triple-drug immunosuppression has not been described in detail. We aimed to characterize our patients with PyVAN and BK virus (BKV) viremia. Among 166 kidney transplantations between January 2007 and February 2011 followed up at Helsinki University Hospital nephrology clinic, 136 were screened for BKV viremia by quantitative analysis of BKV DNA in plasma. PyVAN was diagnosed by biopsy histopathology and SV40 T-antigen detection. BKV viremia or PyVAN were treated by reducing immunosuppression. BKV viremia was detected in 12 (9%) patients. PyVAN was diagnosed in six patients (4%). In the six patients with no PyVAN, four had low-level viremia (<10,000 copies/mL) of short duration (<2 months), one had high-level viremia, and one had sustained low-level viremia. After reduction of immunosuppression, all except one patient were able to clear viremia. No grafts were lost due to PyVAN. Even in a low-risk population, BKV viremia and PyVAN occur, highlighting the importance of monitoring viral loads. Reduction of immunosuppression was successful, and no grafts were lost due to PyVAN.
Asunto(s)
Virus BK/aislamiento & purificación , Ciclosporina/efectos adversos , Rechazo de Injerto/prevención & control , Trasplante de Riñón/efectos adversos , Infecciones por Polyomavirus/virología , Infecciones Tumorales por Virus/virología , Viremia/virología , Ciclosporina/administración & dosificación , Femenino , Estudios de Seguimiento , Rechazo de Injerto/epidemiología , Rechazo de Injerto/inmunología , Antígenos HLA/inmunología , Humanos , Terapia de Inmunosupresión , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Enfermedades Renales/cirugía , Masculino , Persona de Mediana Edad , Infecciones por Polyomavirus/epidemiología , Infecciones por Polyomavirus/inmunología , Prevalencia , Pronóstico , Estudios Retrospectivos , Infecciones Tumorales por Virus/epidemiología , Infecciones Tumorales por Virus/inmunología , Viremia/epidemiología , Viremia/inmunologíaRESUMEN
BACKGROUND: Lymphatic network and chemokine-mediated signals are essential for leukocyte traffic during the proximal steps of alloimmune response. We aimed to determine the role of lymphatic vessels and their principal growth signaling pathway, vascular endothelial growth factor (VEGF)-C/D/VEGFR-3, during acute and chronic rejection in cardiac allografts. METHODS AND RESULTS: Analysis of heterotopically transplanted rat cardiac allografts showed that chronic rejection increased VEGF-C(+) inflammatory cell and hyaluronan receptor-1 (LYVE-1)(+) lymphatic vessel density. Allograft lymphatic vessels were VEGFR-3(+), contained antigen-presenting cells, and produced dendritic cell chemokine CCL21. Experiments with VEGFR-3/LacZ mice or mice with green fluorescent protein-positive bone marrow cells as cardiac allograft recipients showed that allograft lymphatic vessels originated almost exclusively from donor cells. Intraportal adenoviral VEGFR-3-Ig (Ad.VEGFR-3-Ig/VEGF-C/D-Trap) perfusion was used to inhibit VEGF-C/D/VEGFR-3 signaling. Recipient treatment with Ad.VEGFR-3-Ig prolonged rat cardiac allograft survival. Ad.VEGFR-3-Ig did not affect allograft lymphangiogenesis but was linked to reduced CCL21 production and CD8(+) effector cell entry in the allograft. Concomitantly, Ad.VEGFR-3-Ig reduced OX62(+) dendritic cell recruitment and increased transcription factor Foxp3 expression in the spleen. In separate experiments, treatment with a neutralizing monoclonal VEGFR-3 antibody reduced arteriosclerosis, the number of activated lymphatic vessels expressing VEGFR-3 and CCL21, and graft-infiltrating CD4(+) T cells in chronically rejecting mouse cardiac allografts. CONCLUSIONS: These results show that VEGFR-3 participates in immune cell traffic from peripheral tissues to secondary lymphoid organs by regulating allograft lymphatic vessel CCL21 production and suggest VEGFR-3 inhibition as a novel lymphatic vessel-targeted immunomodulatory therapy for cardiac allograft rejection and arteriosclerosis.
Asunto(s)
Arteriosclerosis/prevención & control , Quimiocina CCL21/biosíntesis , Trasplante de Corazón/inmunología , Inmunomodulación/efectos de los fármacos , Vasos Linfáticos/metabolismo , Receptor 3 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Animales , Anticuerpos Monoclonales/farmacología , Anticuerpos Monoclonales/uso terapéutico , Células Presentadoras de Antígenos , Arteriosclerosis/tratamiento farmacológico , Movimiento Celular/inmunología , Rechazo de Injerto/inmunología , Ratones , Ratones Noqueados , Ratas , Transducción de Señal/inmunología , Receptor 3 de Factores de Crecimiento Endotelial Vascular/inmunologíaRESUMEN
BACKGROUND: Chronic allograft nephropathy (CAN), now defined as interstitial fibrosis and tubular atrophy not otherwise specified, is a near universal finding in kidney grafts by the end of the first decade posttransplantation. Platelet-derived growth factor (PDGF) is a major mitogen mediating mesenchymal cell proliferation in CAN. Here, we investigated whether early short-term PDGF inhibition with imatinib could prevent CAN. METHODS: Kidney transplantations were performed from Dark-Agouti (DA) to Wistar-Furth (WF) rats and syngenic controls were done between DA rats. Allografts were immunosuppressed with cyclosporine. One group was also treated with imatinib for the first 30 days after transplantation. Serum creatinine levels were measured once a week. Grafts were harvested 90 days after transplantation. RESULTS: In control allografts, moderate to intense chronic changes were seen, whereas in syngenic grafts, no changes were seen. The early imatinib treatment prevented the development of CAN significantly compared to control allografts. Only few histological changes were seen. Fibrogenic growth factor ligand and receptor induction as well as inflammatory cell response was significantly inhibited by imatinib. Creatinine values of imatinib-treated allografts were also significantly lower compared to controls. CONCLUSIONS: We show that short-term imatinib treatment is sufficient to prevent CAN significantly, indicating that early PDGF induction has an important role in the pathogenesis of CAN. Here, we provide preclinical work that will need to be confirmed in patients with CAN.
Asunto(s)
Antineoplásicos/uso terapéutico , Enfermedades Renales/prevención & control , Trasplante de Riñón , Piperazinas/uso terapéutico , Pirimidinas/uso terapéutico , Animales , Benzamidas , Enfermedad Crónica , Ciclosporina/uso terapéutico , Mesilato de Imatinib , Técnicas para Inmunoenzimas , Inmunosupresores/uso terapéutico , Enfermedades Renales/metabolismo , Enfermedades Renales/patología , Masculino , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Ratas , Ratas Endogámicas , Factores de Tiempo , Trasplante HomólogoRESUMEN
Recurrent cytomegalovirus (CMV) infections commonly occur after kidney transplantation. We studied the impact of secondary prophylaxis and other factors on the risk of CMV recurrence. All kidney transplant recipients between 2004 and 2009 in our institution were analyzed (N = 254). Patients with CMV infection were included (N = 62). CMV infections were diagnosed with quantitative PCR. CMV D+/R- recipients received 6 months valganciclovir prophylaxis, after which DNAemia was monitored. After treatment, secondary prophylaxis with valganciclovir was given at the clinician's discretion for 2-26 weeks and CMV DNAemia was monitored. Altogether 43 reactivations and 19 primary infections occurred. Antiviral treatment with valganciclovir or ganciclovir was given to 45 patients; 34/62 (55%) patients received secondary prophylaxis for mean 62 days (range 14-180 days). CMV recurrence occurred in 14/43 (33%) seropositive patients and in 4/19 (21%) patients after primary infection. In logistic regression, delayed graft function (OR 3.4) and high viral load (>100 000 copies/ml) at initial diagnosis (OR 5.9) predicted recurrence. Use or length of secondary prophylaxis, CMV serostatus, level of immunosuppression, HLA mismatch, antiviral treatment, or time to clearance of viremia during treatment did not predict recurrence of CMV. CMV recurrences occur commonly despite secondary prophylaxis. High viral load at diagnosis predicted the risk of recurrent CMV infection.
Asunto(s)
Infecciones por Citomegalovirus/etiología , Trasplante de Riñón/efectos adversos , Adulto , Anticuerpos Antivirales/sangre , Antivirales/uso terapéutico , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/prevención & control , Infecciones por Citomegalovirus/virología , Funcionamiento Retardado del Injerto/complicaciones , Femenino , Ganciclovir/análogos & derivados , Ganciclovir/uso terapéutico , Humanos , Trasplante de Riñón/inmunología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Donantes de Tejidos , Valganciclovir , Carga ViralRESUMEN
OBJECTIVE: Chronic rejection is the main reason for the poor long-term survival of heart transplant recipients and is characterized by cardiac allograft inflammation, fibrosis, and arteriosclerosis. We examined the specific roles of different platelet-derived growth factor (PDGF) ligands (A-D)--potent mesenchymal cell mitogens--in rat cardiac allografts. METHODS AND RESULTS: PDGFR-alpha mRNA was upregulated in acutely-rejecting, and PDGF-A and PDGF-C mRNA in chronically-rejecting cardiac centhatn allografts. In acute rejection, PDGFR-alpha immunoreactivity increased in the media of arteries. In chronically-rejecting allografts, immunoreactivity of all PDGF ligands and receptors--except that of PDGF-B ligand--was found in the intima of arteries, and the expression of PDGF-A and PDGF-C was seen in cardiomyocytes. Intracoronary adeno-associated virus-2 (AAV2)-mediated PDGF-A and -D gene transfer enhanced cardiac allograft inflammation. AAV2-PDGF-A, AAV2-PDGF-C, and AAV2-PDGF-D significantly upregulated profibrotic TGF-beta1 mRNA and accelerated cardiac fibrosis and arteriosclerosis. In contrast, AAV2-PDGF-B did not aggravate chronic rejection. CONCLUSIONS: We found that alloimmune response induces PDGF-A, PDGF-C, and PDGF-D expression in the graft vasculature. PDGF-A, PDGF-C, and PDGF-D mediated profibrotic and proarteriosclerotic effects in transplanted hearts involving the TGF-beta1 pathway. Inhibition of signaling of all PDGF-ligands except that of PDGF-B may thus be needed to inhibit chronic rejection in cardiac allografts.
Asunto(s)
Arteriosclerosis/inmunología , Rechazo de Injerto/metabolismo , Trasplante de Corazón/inmunología , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Animales , Modelos Animales de Enfermedad , Fibrosis/inmunología , Rechazo de Injerto/inmunología , Rechazo de Injerto/patología , ARN Mensajero/metabolismo , Ratas , Transducción de Señal , Trasplante Homólogo , Regulación hacia ArribaRESUMEN
The impact of post-transplant diabetes (PTDM) on kidney transplant histopathology has been poorly described. We examined the association of glucose metabolism abnormalities on the progression of histopathological changes in serial protocol biopsies. Helsinki University Hospital kidney transplant recipients during 2004-2006 were followed up. Patients with pre-existing diabetes or 2-h oral glucose tolerance test (OGTT) performed at 3 months, and protocol biopsies taken at 0 and 12 months were analyzed (n = 76). Diabetes was defined according to WHO/ADA. Histology was analyzed with chronic allograft damage index (CADI). Altogether 32 patients had pre-existing diabetes. In OGTT at 3 months, four showed PTDM, eight impaired glucose tolerance (IGT), two impaired fasting glucose, and 30 normal glucose tolerance. Patients with impaired glucose metabolism were older (P = 0.005), received grafts from older donors (P = 0.04), and had reduced renal function at 12 months (P = 0.003). In patients with IGT or PTDM, 2-h postload glucose values in OGTT correlated with CADI at 12 months (R = 0.84, P = 0.001) and with the change in CADI score between 0 and 12 months (R = 0.67, P = 0.025). Graft survival was reduced in patients with pre-existing diabetes (P = 0.01). Glucose abnormalities were associated with the progression of histopathological changes, especially in patients with already compromised kidneys, supporting the harmful role of PTDM to the kidney allograft.
Asunto(s)
Biopsia/métodos , Diabetes Mellitus/inmunología , Glucosa/metabolismo , Trasplante de Riñón/efectos adversos , Adulto , Glucemia/metabolismo , Diabetes Mellitus/etiología , Progresión de la Enfermedad , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Factores de Riesgo , Factores de Tiempo , Trasplante HomólogoRESUMEN
In the treatment of end-stage renal disease, kidney transplantation is the best and most cost-effective alternative with regard to both prognosis and quality of life. Problems arise from the disproportion between the number of available allografts and the patients waiting for the transplantation. There are few absolute contraindications to kidney transplantation. In the assessment of the eligibility for transplantation of patients on dialysis the most important factors include cardiovascular diseases, cancer diseases, other diseases affecting operability and life expectancy, age, excess weight and possible infections.
Asunto(s)
Fallo Renal Crónico/cirugía , Trasplante de Riñón , Comorbilidad , Contraindicaciones , Finlandia , Humanos , Selección de Paciente , Pronóstico , Calidad de Vida , Diálisis Renal , Factores de RiesgoRESUMEN
Although the results of kidney transplantation have improved markedly, the long-term survival of renal allografts is still a major challenge. The long-term exposure of recipients to chronic renal failure and chronic immunosuppression increases the burden of infections, cardiovascular diseases, malignancies, and renal bone disease. The prevention and adequate treatment of these complications have become increasingly important. During the first months after kidney transplantation patients are followed carefully with short intervals; in stable patients the follow-up frequency is reduced later. Most important laboratory tests in the follow-up include parameters of graft function and pharmacokinetic monitoring of the immunosuppressive drugs.
Asunto(s)
Continuidad de la Atención al Paciente , Fallo Renal Crónico/cirugía , Trasplante de Riñón , Complicaciones Posoperatorias/terapia , Comorbilidad , Supervivencia de Injerto , Humanos , Inmunosupresores/uso terapéutico , Fallo Renal Crónico/complicacionesRESUMEN
BACKGROUND: The occurrence and clinical course of late primary CMV infections developing after valganciclovir prophylaxis in high-risk renal transplant recipients are poorly described. METHODS: Helsinki University Hospital district kidney allograft recipients between January 2004 and March 2007 (N = 175) were prospectively investigated. Patients with D+/R- CMV serostatus and 1-year follow-up were included (N = 25). After 6 months of oral valganciclovir prophylaxis, the patients were monitored for CMV-DNAemia with real-time quantitative plasma PCR at 2-6 weeks interval and if CMV infection was suspected. Infections were treated with i.v. ganciclovir or high-dose valganciclovir, followed by 1-3 months of secondary valganciclovir prophylaxis. RESULTS: CMV infection developed in 12/25 patients a mean of 107 days (range 26-330 days) after prophylaxis ended. Two were asymptomatic. In 10 patients symptoms included fever (N = 7), gastrointestinal (N = 5), upper respiratory tract (N = 3) and hepatopathy (N = 2). One patient with infection had prophylaxis terminated after 5 months (leukopenia). The mean viral load at diagnosis was 49 517 (range 490-325 300), and peak viral load was 84 654 (range 1250-527 400) copies/ml. Five infections were treated with valganciclovir and six with i.v. ganciclovir resulting with negative PCR results. One mild infection with low viral load was treated successfully with minimization of immunosuppression. Infection relapse developed in three patients a mean of 31 (range 15-61) days after the end of the therapy. Relapses were treated with valganciclovir. CONCLUSIONS: CMV primary infections were common after 6 months of valganciclovir prophylaxis and mostly symptomatic. Relapses commonly occurred. Primary infections seem to be delayed, but were not efficiently prevented by 6 months of prophylaxis.
Asunto(s)
Antivirales/uso terapéutico , Infecciones por Citomegalovirus/prevención & control , Ganciclovir/análogos & derivados , Trasplante de Riñón/efectos adversos , Adulto , Infecciones por Citomegalovirus/etiología , Infecciones por Citomegalovirus/transmisión , Finlandia , Estudios de Seguimiento , Ganciclovir/uso terapéutico , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Factores de Tiempo , Donantes de Tejidos , ValganciclovirRESUMEN
Since 2003, only one case of polyomavirus-associated nephropathy (PVAN) has occurred in our clinic despite screening protocols. In contrast to BK virus, the role of JC virus in PVAN is unclear. We studied the incidence and impact of polyomavirus BK and JC viruria and PVAN in well-matched Finnish kidney transplant recipients. All Helsinki University Hospital kidney transplant recipients between 2004 and 2006 were prospectively followed (n = 163). Patients with a 12-month protocol-biopsy taken and polyomavirus urinary secretion screened by PCR were studied (n = 68). Cyclosporine-based triple-drug immunosuppression was usually used. BK or JC viruria was detected in 18 (27%) and 14 (21%) patients after transplantation respectively. Persistent BK or JC viruria was found in 5 (7%) and 9 (13%) patients. No cases of PVAN were diagnosed from protocol biopsies or from biopsies taken for clinical indications. A positive BK or JC viruria or persistent viruria was not associated with reduced renal function at follow-up, histopathologic changes in 12-month protocol biopsies, or acute rejections. The incidence of BK and JC viruria was similar to what has been previously reported, but no cases of polyomavirus-associated nephropathy were seen in our well-matched kidney transplant population.