RESUMEN
Drug-induced immunosuppression can predispose kidney transplant patients to different complications including chronic infections and oral lesions. We surveyed oral hygiene habits and conducted detailed periodontal examinations for status assessment. Appropriate oral hygiene and regular professional control can reduce number and severity of complications, which might be preventive for transplant rejection.
Asunto(s)
Terapia de Inmunosupresión/efectos adversos , Trasplante de Riñón/efectos adversos , Enfermedades de la Boca/epidemiología , Enfermedades de la Boca/etiología , Salud Bucal , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
BACKGROUND: The most common conditions leading to death after simultaneous pancreas-kidney transplantations (SPKs) are cardiovascular diseases. The aim of this study was to test the platelet aggregation inhibitor acetylsalicylic acid (ASA) resistance in patients after SPKs, including investigations into the triggering factors. METHODS: Thirty-two patients (22 men, 10 women; overall age, 47.4 ± 8.6 years) were involved in our study and took 100 mg ASA per day. We used optical platelet aggregometry to detect resistance. RESULTS: Resistance occurred in 40.6% of the study group. However, with the use of logistic regression analysis, the examined 24 factors did not show any significant correspondence with resistance. CONCLUSIONS: The incidence of ASA resistance seems to be higher compared with other groups, but the triggering effect is still unproved. Clarifying this question should be important regarding the mortality- and morbidity-reducing capacity of antiplatelet drugs in the management of cardiovascular conditions.
Asunto(s)
Aspirina/uso terapéutico , Resistencia a Medicamentos , Trasplante de Riñón/efectos adversos , Trasplante de Páncreas/efectos adversos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Adulto , Anciano , Enfermedades Cardiovasculares/prevención & control , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agregación Plaquetaria/efectos de los fármacosRESUMEN
Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with very diverse distribution and functions. Among others, PACAP is a potent cytoprotective peptide due to its antiapoptotic, anti-inflammatory, and antioxidant actions. This also has been shown in different kidney pathologies, including ischemia/reperfusion-induced kidney injury. Similar protective effects of the endogenous PACAP are confirmed by the increased vulnerability of PACAP-deficient mice to different harmful stimuli. Kidneys of homozygous PACAP-deficient mice have more severe damages in renal ischemia/reperfusion and kidney cell cultures isolated from these mice show increased sensitivity to renal oxidative stress. In our present study we raised the question of whether the partial lack of the PACAP gene is also deleterious, i.e. whether heterozygous PACAP-deficient mice also display more severe damage after renal ischemia/reperfusion. Mice underwent 45 or 60 minutes of ischemia followed by 2 weeks reperfusion. Histological evaluation of the kidneys was performed and individual histopathological parameters were graded. Furthermore, we investigated apoptotic markers, cytokine expression, and the activity of superoxide dismutase (SOD) enzyme 24 hours after 60 minutes of renal ischemia/reperfusion. We found no difference between the intact kidneys of wild-type and heterozygous mice, but marked differences could be observed following ischemia/reperfusion. Heterozygous PACAP-deficient mice had more severe histological alterations, with significantly higher histopathological scores for most of the tested parameters. Higher level of the proapoptotic pp38 MAPK and of some proinflammatory cytokines, as well as lower activity of the antioxidant SOD could be found in these mice. In conclusion, the partial lack of the PACAP gene results in worse outcomes in cases of renal ischemia/reperfusion, confirming that PACAP functions as an endogenous protective factor in the kidney.
Asunto(s)
Riñón/patología , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/genética , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/fisiología , Daño por Reperfusión/metabolismo , Animales , Antioxidantes/metabolismo , Apoptosis/efectos de los fármacos , Citocinas/metabolismo , Femenino , Marcación de Gen , Heterocigoto , Homocigoto , Inflamación , Enfermedades Renales/patología , Masculino , Ratones , Ratones Transgénicos , Neuropéptidos/química , Estrés Oxidativo/efectos de los fármacos , Daño por Reperfusión/patología , Superóxido Dismutasa/metabolismo , Factores de Tiempo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Pituitary adenylate cyclase activating polypeptide (PACAP ) is a multifunctional neuropeptide occurring in the nervous system as well as in the peripheral organs. Beneficial action of PACAP has been shown in different pathological processes. The strong protective effects of the peptide are probably due to its complex modulatory actions in antiapoptotic, anti-inflammatory and antioxidant pathways. In the kidney, PACAP is protective in models of diabetic nephropathy, myeloma kidney injury, cisplatin-, gentamycin- and cyclosporin-induced damages. Numerous studies have been published describing the protective effect of this peptide in renal ischemia/reperfusion. The present review focuses on the ischemia/reperfusion-induced kidney injury and gives a brief summary about the results published in this area.
Asunto(s)
Enfermedades Renales/prevención & control , Riñón/enzimología , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/metabolismo , Daño por Reperfusión/enzimología , Animales , Humanos , Enfermedades Renales/enzimología , Enfermedades Renales/patología , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/administración & dosificación , Receptores del Polipéptido Activador de la Adenilato-Ciclasa Hipofisaria/metabolismo , Daño por Reperfusión/patología , Transducción de SeñalRESUMEN
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a widespread neuropeptide with a diverse array of biological functions. Not surprisingly, the lack of endogenous PACAP therefore results in a variety of abnormalities. One of the important effects of PACAP is its neuroprotective and general cytoprotective role. PACAP protects neurons and other tissues against ischemic, toxic, and traumatic lesions. Data obtained from PACAP-deficient mice provide evidence that endogenous PACAP also has protective functions. Mice lacking PACAP are more vulnerable to different in vitro and in vivo insults. The present review summarizes data on the increased sensitivity of PACAP-deficient mice against harmful stimuli. Mice lacking PACAP respond with a higher degree of injury in cerebral ischemia, autoimmune encephalomyelitis, and axonal lesion. Retinal ischemic and excitotoxic injuries also produce increased cell loss in PACAP-deficient mice. In peripheral organs, kidney cell cultures from PACAP-deficient mice are more sensitive to oxidative stress and in vitro hypoxia. In vivo, PACAP-deficient mice have a negative histological outcome and altered cytokine response in kidney and small intestine ischemia/reperfusion injury. Large intestinal inflammation, toxic lesion of the pancreas, and doxorubicin-induced cardiomyopathy are also more severe with a lack of endogenous PACAP. Finally, an increased inflammatory response has been described in subacute endotoxin-induced airway inflammation and in an oxazolone-induced allergic contact dermatitis model. In summary, lack of endogenous PACAP leads to higher vulnerability in a number of injuries in the nervous system and peripheral organs, supporting the hypothesis that PACAP is part of the endogenous cytoprotective machinery.
Asunto(s)
Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/fisiología , Estrés Fisiológico/fisiología , Animales , Enfermedades Autoinmunes/fisiopatología , Cardiomiopatías/fisiopatología , Dermatitis Alérgica por Contacto/fisiopatología , Susceptibilidad a Enfermedades , Homeostasis/fisiología , Inflamación/fisiopatología , Isquemia/fisiopatología , Enfermedades Renales/fisiopatología , Enfermedades Pulmonares/fisiopatología , Ratones , Ratones Noqueados , Enfermedades del Sistema Nervioso/fisiopatología , Neurotoxinas/toxicidad , Noxas/efectos adversos , Enfermedades Pancreáticas/fisiopatología , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/deficiencia , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/genética , Heridas y Lesiones/fisiopatologíaRESUMEN
The prediction of graft rejection can play an important part in graft survival. Analysis of immune reactions has shown that graft rejection shares mechanisms with recurrent abortions during pregnancy. Progesterone-induced blocking factor (PIBF), a mediator of progesterone that blocks natural killer cell activity in peripheral blood, produces antiabortive effects. The aim of this study was to examine the PIBF concentration in the urine of transplanted recipients. The study included 116 white adults (70 men and 46 women) of median age 49.3 years, who had undergone kidney transplantations. The median duration after transplantation was 3.46 years. The average period between renal disease and our measurement was 12.3 years, and the median interval between graft rejection and our study was 1.75 years. Urine samples were used to measure PIBF concentrations by an enzyme-linked immunsorbent assay. PIBF urinary concentrations decreased significantly in patients who experienced ≥1 rejection episode (31.8±2.2 ng/mL) compared with those without any episode (22.7±1.2 ng/ml; P<.01). Moreover, the urinary PIBF level was significantly lower among patients who had increased creatinine and urea nitrogen levels in blood samples (P<.05 and P<.01, respectively). Decreased PIBF values in kidney transplant patients followed previous rejection episodes. A close negative correlation was observed between urinary PIBF concentrations and blood levels of creatinine and urea nitrogen. These findings suggested that PIBF detection may predict graft rejection in transplant recipients.
Asunto(s)
Rechazo de Injerto/etiología , Trasplante de Riñón/efectos adversos , Proteínas Gestacionales/orina , Factores Supresores Inmunológicos/orina , Biomarcadores/sangre , Biomarcadores/orina , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Rechazo de Injerto/orina , Humanos , Hungría , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Factores de Tiempo , Resultado del TratamientoRESUMEN
Pituitary adenylate cyclase activating polypeptide (PACAP), a multifunctional neuropeptide, has 2 active forms, PACAP38 and PACAP27. It is now well-established that PACAP has several actions also in peripheral organs, including renoprotective effects. The peptide itself has not been previously identified in the rat kidney. The first aim of our study was to identify PACAP in the rat kidney using mass spectrometry and radioimmunoassay (RIA). Receptor mRNA and binding studies revealed the existence of all 3 PACAP receptors (PAC1, VPAC1, and VPAC2) in the kidney, but their exact localization in histologic sections was not evident. Because most of the cytoprotective effects of PACAP relate to its specific PAC1 receptor, our second aim was to identify the cell types wherein the PAC1 receptor is expressed in the rat kidney. Mass spectrometry revealed the presence of PACAP38 in the kidney. RIA measurements showed both PACAP38- and PACAP27-like immunoreactivities in kidney homogenates, with PACAP38 being dominant. Immunohistochemistry revealed PAC1 receptor-like immunoreactivity in kidney sections, mainly expressed in cortical tubular epithelial cells. These results showed PACAP to be endogenously present in the kidney. The tubular localization of the PAC1 receptor provides the basis for the renal effects of the peptide under physiologic and pathologic conditions.
Asunto(s)
Riñón/química , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/análisis , Receptores del Polipéptido Activador de la Adenilato-Ciclasa Hipofisaria/análisis , Animales , Inmunohistoquímica , Riñón/citología , Radioinmunoensayo , Ratas , Ratas Wistar , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
PACAP (pituitary adenylate cyclase-activating polypeptide) occurs in two biologically active forms, with 38 and 37 amino acid residues (PACAP38 and PACAP27). In mammalian tissues, PACAP38 is the dominant form. Diverse effects have been described in the cardiovascular, respiratory, gastrointestinal, and urogenital systems. PACAP is known for its strong cytoprotective effects, which are present endogenously as well, as proven by knockout studies and results showing that PACAP is up-regulated following diverse injuries. Little is known about such effects in the kidney. We have previously shown that PACAP is protective in renal ischemia-reperfusion injury. Therefore, the aim of the present study was to investigate the changes of endogenous PACAP following 60-minute renal ischemia using radioimmunoassay. Changes were observed within 24 hours following renal vessel clamping. In the cortex, an acute decrease was followed by an increase on the intact side, and levels returned to original ones on the operated side. In the medulla, changes were only observed on the clamped side: a marked up-regulation was detected in PACAP38-like immunoreactivity within the first 24 hours. The present study showed that PACAP38- and PACAP27-like immunoreactivities sensitively react to renal ischemia-reperfusion, the physiological importance of which awaits further investigation.
Asunto(s)
Enfermedades Renales/metabolismo , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/metabolismo , Receptores del Polipéptido Activador de la Adenilato-Ciclasa Hipofisaria/metabolismo , Daño por Reperfusión/prevención & control , Animales , Corteza Renal/metabolismo , Corteza Renal/patología , Enfermedades Renales/patología , Médula Renal/metabolismo , Médula Renal/patología , Masculino , Radioinmunoensayo , Ratas , Ratas Wistar , Reperfusión , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patologíaRESUMEN
One of the well-known effects of pituitary adenylate cyclase activating polypeptide (PACAP) is its neuroprotective and cytoprotective actions including renoprotective effects. Mice deficient in endogenous PACAP exhibit several behavioral, metabolic, and developmental alterations. Furthermore, PACAP-deficient mice have larger infarct volume in a model of cerebral ischemia, delayed axonal regeneration, and increased cell death in cerebellar oxidative stress. We have previously demonstrated that PACAP-deficient mice have increased susceptibility to in vitro oxidative stress, which can be counteracted by exogenous PACAP treatment. These results demonstrate that endogenous PACAP has a protective role against various stressors. The objective of the present study was to investigate whether endogenous PACAP has a protective effect in the kidney against in vitro hypoxia. Kidney cell cultures were isolated from wild-type and PACAP-deficient mice, and cell viability was assessed after in vitro hypoxia induced using CoCl(2). The sensitivity of cells from PACAP-deficient mice was increased to hypoxia: both after 24 and 48 hours of exposure, cell viability was significantly reduced compared with that in control wild-type mice. These results show that endogenous PACAP protects against noxious stimuli in the kidney and that PACAP may act as a stress sensor in renal cells.
Asunto(s)
Enfermedades Renales/metabolismo , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/deficiencia , Animales , Isquemia Encefálica/genética , Muerte Celular , Supervivencia Celular , Cerebelo/patología , Hipoxia/genética , Hipoxia/patología , Infarto/genética , Riñón/metabolismo , Riñón/patología , Enfermedades Renales/genética , Enfermedades Renales/patología , Ratones , Ratones Endogámicos , Ratones Noqueados , Estrés OxidativoRESUMEN
There is increasing evidence that nonmelanoma skin cancers (NMSCs) are the most frequently observed tumors in transplant recipients. The incidence of posttransplantation NMSC was determined using our dermatologic screening program. Included in the study were 116 white adults (70 men and 46 women; median age, 49.3 years) who had undergone kidney or combined kidney-pancreas transplantation, with follow-up from September 2008 to December 2009. All patients underwent a full skin examination for NMSC, and completed a standardized questionnaire. Screening resulted in detection of 16 NMSCs in 11 patients out of 116 (9.5%). Lesions were equally distributed by sex, and were detected at a median of 4.1 years posttransplantation. Histologic analysis verified 13 basal cell carcinomas and 3 squamous cell carcinomas (ratio, 4:1). The incidence of NMSC was significantly greater in patients who received cyclosporine immunosuppression therapy (16 vs 1; P < .05), had experienced 2 or more painful sunburns before transplantation (10 vs 11), or worked outdoors (10 vs 11). These data indicate the relevance of skin cancer surveillance in transplant recipients. Our results correspond to international statistics except for the ratio of basal cell carcinoma to squamous cell carcinoma. Further studies are needed to elucidate the reasons for this difference.
Asunto(s)
Trasplante de Órganos/efectos adversos , Neoplasias Cutáneas/epidemiología , Carcinoma Basocelular/epidemiología , Carcinoma de Células Escamosas/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Hungría/epidemiología , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Trasplante de Páncreas/efectos adversos , Piel/patología , Neoplasias Cutáneas/clasificación , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
Transplant recipients are at high risk of nonmelanoma skin cancer (NMSC). Ultraviolet radiation can generate oxygen free radicals (OFRs), leading to oxidative stress and carcinogenesis, primarily during immunosuppression therapy. In the present study, changes in oxidative stress were examined in transplant recipients with and without NMSC. The study included 116 white adults who had undergone kidney or combined kidney-pancreas transplantation. Dermatologic follow-up revealed 16 NMSCs (13.8%). To monitor oxidative stress, peripheral blood samples were used to measure malondialdehyde (MDA), reduced glutathione, sulfhydryl (-SH) groups, OFRs, and activity of myeloperoxidase, superoxide dismutase, and catalase. The mean (SD) plasma MDA concentration was significantly greater in patients without NMSC compared with healthy control individuals (0.48+/-0.05 nmol/mL; P < .05), whereas MDA concentration in hemolysate was slightly increased. In peripheral blood samples, the MDA concentration in both plasma (0.71+/-0.03 nmol/mL) and hemolysate (87.74+/-1.25 nmol/mL) was significantly increased in the NMSC group compared with the healthy control group (0.24+/-0.05 nmol/mL vs 75.87+/-2.8 nmol/mL; P < .05) or patients without NMSC (0.48+/-0.04 nmol/mL vs 79.62+/-2.77 nmol/mL; P < .05). The reduced glutathione concentration was significantly decreased in the -SH groups compared with the healthy control group (P < .05). Antioxidant activity of myeloperoxidase (0.78+/-0.05 IU/mL) and catalase (1855.8+/-45.41 IU/mL) was significantly increased in the group without NMSC compared with the healthy control group (0.41+/-0.1 IU/mL vs 1642.07+/-82.96 IU/mL) and the NMSC group (0.93+/-0.03 IU/mL vs 2180.5+/-15.03 IU/mL). The superoxide dismutase activity was decreased slightly but not significantly. Total production of OFRs was significantly greater in the NMSC group compared with the non-NMSC group or the healthy control group (P < .05). These findings suggest that an imbalance exists between pro-oxidant and antioxidant status in transplant recipients, with a significant difference in patients with vs without NMSC.
Asunto(s)
Trasplante de Riñón/efectos adversos , Trasplante de Órganos/efectos adversos , Estrés Oxidativo , Trasplante de Páncreas/efectos adversos , Neoplasias Cutáneas/epidemiología , Catalasa/sangre , Femenino , Radicales Libres/sangre , Glutatión/sangre , Humanos , Masculino , Malondialdehído/sangre , Persona de Mediana Edad , Neoplasias Cutáneas/sangre , Neoplasias Cutáneas/fisiopatología , Compuestos de Sulfhidrilo/sangre , Superóxido Dismutasa/sangreRESUMEN
We have performed 115 "zero-hour" biopsies of transplanted kidneys since 1994. Donor kidneys were divided into five groups, based on the morphological findings of "zero-hour" biopsies. No morphological abnormalities were found in 38.26% of the cases (group 1). Arteriolosclerosis was present in 22.61% of donor kidneys (group 2). Specific morphological alterations, i.e. acute tubular necrosis (24.35%), tubulointerstitial nephritis (5.22%) or glomerulonephritis (9.56%) were detectable in the remaining cases (groups 3-5). During an average of 644 days after transplantation clinical and histological follow-up were performed. According to our observations: 1. Higher creatinine was found in patients with grafts with arteriolosclerosis (group 2). 2. There were more non-viable grafts and longer periods of delayed graft function in patients with acute tubular necrosis (group 3). 3. Higher serum creatinine, more frequent rejections with the need of secondary hemodialysis were observed in patients who received a kidney with "zero-hour" biopsy of tubulointerstitial nephritis (group 4). 4. The only complication observed in patients with glomerulonephritis donor kidneys was delayed functioning of the graft (group 5). Biopsies did not cause complication in any of our patients. In conclusion, "zero-hour" biopsies can be useful and safe tools to predict early graft function. Besides, "zero-hour" biopsies help histological interpretation of consecutive graft re-biopsies.
Asunto(s)
Biopsia/métodos , Enfermedades Renales/diagnóstico , Trasplante de Riñón , Riñón/patología , Arteriosclerosis/diagnóstico , Cadáver , Creatinina/sangre , Glomerulonefritis/diagnóstico , Rechazo de Injerto/etiología , Humanos , Riñón/fisiopatología , Enfermedades Renales/sangre , Enfermedades Renales/patología , Enfermedades Renales/fisiopatología , Necrosis Tubular Aguda/diagnóstico , Donadores Vivos , Nefritis Intersticial/diagnóstico , Valor Predictivo de las Pruebas , Pronóstico , Resultado del TratamientoRESUMEN
"Zero-hour" biopsies of 65 donors have been performed since 1994. Donor kidneys were categorized into five groups based on the morphological findings in "zero-hour" biopsies. No morphological abnormalities were found in 38% of the cases (group 1). Arteriosclerosis was present in 31% of donor kidneys (group 2). Specific morphological alterations, i.e. acute tubular necrosis [21.5%], tubulointerstitial nephritis [6.2%] or glomerulonephritis [3.1%] were detectable in the cases remained (group 3-5). During an average of 336 posttransplant days clinical and histological follow up was performed (50 rebiopsies). Statistical data of mismatch (1.4-2.0), average of donor/recipient age (35-42 years), cold and warm ischaemic time (1290 and 66 min) were comparable in all groups. According to our observations: 1. higher creatinin was found in grafts with arteriosclerosis (group 2) (p < 0.05), 2. there were more non-viable grafts and longer period of delayed graft function in acute tubular necrosis (group 3), 3 higher creatinin, rejections with the need of rehemodialysis were observed in four cases of tubulointerstitial nephritis (TIN-group 4). Glomerulonephritis (GN-group 5) grafts had only delayed graft function, however these groups were few for statistical evaluation. Biopsy complication in 1/115 cases was found (rebiopsy induced kidney haemorrhage). In conclusion, "zero-hour" biopsies can be useful and safe tools to predict early graft function. Besides "zero-hour" biopsies help the histological interpretation of consecutive graft rebiopsies.