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BACKGROUND/AIMS: Patients undergoing maintenance dialysis have an unsatisfactory response to vaccination, including to hepatitis B vaccine. A recombinant HB vaccine containing a new adjuvant system AS04 (HBV-AS04) has been recently developed; a few data exist on the immunogenicity and safety of HBV-AS04 among patients undergoing regular dialysis. All hepatitis B virus-seronegative patients with undetectable antibody against HBsAg undergoing maintenance dialysis at two units were prospectively included. METHODS: Patients received four 20-mcg doses of HBV-AS04 by intramuscular route (deltoid muscle) at months 0,1,2, and 3. Anti-HB surface antibody concentrations were measured at intervals of 1, 2, 3, 4, and 12 months. Univariate and multivariate analyses determined which parameters predicted immunologic response to HBV-AS04 vaccine. RESULTS: 102 patients were enrolled and 91 completed the study. At completion of the vaccination schedule, using per-protocol analysis, 76 of 91 (84%) had antibody titers ≥10 mIU/mL with anti-HBs geometric antibody concentrations (GMCs) of 385.25 mIU/mL. The sero-protection rate at month 12 was 84% (48/57) with lower GMCs (62.74 mIU/mL, P<0.0001). Multivariate analysis revealed a detrimental role of age on the immune response to HB-AS04 vaccine (F Ratio, 4.04; P<0.04). Tolerance to HBV-AS04 was good and only minor side-effects were observed. CONCLUSIONS: HBV-AS04 vaccine was highly immunogenic in our cohort of patients on maintenance dialysis even if a significant number of non-responders is still present. Prospective studies with HBV-AS04 on larger study groups and with longer follow-ups are under way.
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Vacunas contra Hepatitis B/inmunología , Lípido A/análogos & derivados , Diálisis Renal , Adyuvantes Inmunológicos , Adulto , Anciano , Envejecimiento/inmunología , Estudios de Cohortes , Femenino , Antígenos de Superficie de la Hepatitis B/sangre , Vacunas contra Hepatitis B/administración & dosificación , Vacunas contra Hepatitis B/efectos adversos , Humanos , Esquemas de Inmunización , Inyecciones Intramusculares , Lípido A/administración & dosificación , Lípido A/efectos adversos , Lípido A/inmunología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Seguridad , Vacunas SintéticasRESUMEN
BACKGROUND: Little information is available about the long-term outcome of renal transplantation in adults with Henoch-Schonlein purpura (HSP). METHODS: We compared the outcomes of 17 patients with HSP who received 19 renal transplants with those of 38 controls matched for time of transplantation, age, gender and source of donor. The mean post-transplant follow-up was 109 +/- 99 months for HSP patients and 110 +/- 78 months for controls. RESULTS: The actuarial 15-year patient survival was 80% in HSP patients and 82% in controls, and the death-censored graft survival was 64% in HSP patients and in controls. The risks of acute rejection, chronic graft dysfunction, arterial hypertension and infection were not different between the two groups. In eight grafts (42%) recurrence of HSP nephritis was found (0.05/patient/year). In spite of therapy, one patient died and four eventually restarted dialysis respectively 10, 32, 35 and 143 months after renal transplant. Seventy-one percent of grafts transplanted in patients with necrotizing/crescentic glomerulonephritis of the native kidney had HSP recurrence in comparison to 12% of recurrences in patients with mesangial nephritis (P = 0.05) CONCLUSIONS: Long-term patient and allograft survival of HSP patients was good. However, 42% of HSP patients, particularly those with necrotizing/crescentic glomerulonephritis of the native kidneys, developed a recurrence of HSP nephritis that eventually caused the loss of the graft function in half of them.
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Glomerulonefritis/cirugía , Vasculitis por IgA/cirugía , Trasplante de Riñón , Adolescente , Adulto , Femenino , Glomerulonefritis/etiología , Supervivencia de Injerto , Humanos , Vasculitis por IgA/complicaciones , Vasculitis por IgA/mortalidad , Masculino , Recurrencia , Estudios Retrospectivos , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Mixed cryoglobulinemia is a multisystem disorder associated strongly with hepatitis C virus (HCV) infection. The kidney frequently is involved, and glomerulonephritis represents the key factor affecting prognosis. METHODS: Clinical, serological, immunogenetic, and morphological data were collected retrospectively from medical records of 146 patients with cryoglobulinemic glomerulonephritis who underwent biopsies in 25 Italian centers and 34 cryoglobulinemic controls without renal involvement. RESULTS: Eighty-seven percent of patients were infected with HCV; genotype 1b was more frequent than genotype 2 (55% versus 43%). Diffuse membranoproliferative glomerulonephritis was the most prevalent histological pattern (83%). Type II cryoglobulin (immunoglobulin Mkappa [IgMkappa]/IgG) was detected in 74.4% of cases. The remainder had type III (polyclonal IgM/IgG) cryoglobulins. A multivariate Cox proportional hazard model showed that age, serum creatinine level, and proteinuria at the onset of renal disease were associated independently with risk for developing severe renal failure at follow-up. Overall survival at 10 years was about 80%. Kaplan-Meier survival curves were worsened by a basal creatinine value greater than 1.5 mg/dL (>133 mumol/L), but were unaffected by sex and HCV infection. Cardiovascular disease was the cause of death in more than 60% of patients. CONCLUSION: Data confirm the close association between mixed cryoglobulinemia and HCV infection and between glomerulonephritis and type II cryoglobulin. Survival profiles are better than previously reported in the literature, probably because of improvement in therapeutic regimens. Causes of death reflect this improvement in survival, with an increased prevalence of cardiovascular events compared with infectious complications and hepatic failure, which were predominant in the past.
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Crioglobulinemia/virología , Glomerulonefritis/virología , Hepatitis C/complicaciones , Adulto , Anciano , Crioglobulinemia/complicaciones , Femenino , Glomerulonefritis/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
A cohort of 201 kidney transplant recipients (KTR) including 7 patients with evidence of renal function deterioration (as defined by creatinine levels >20% over baseline values) was analyzed for polyomavirus DNA in blood and urine samples by a new quantitative polymerase chain reaction method. Of 201 patients, 14 (6.9%) were positive for polyomavirus DNA in blood (median level, 500 copies per milliliter of blood) including all 7 patients with renal function deterioration. Polyomavirus DNA detection in blood for diagnosis of renal function deterioration in KTR showed a sensitivity of 100% and a specificity of 96%, whereas positive and negative predictive values were 50% and 100%, respectively. Diagnostic value of decoy cells detection and polyomavirus DNA quantification in urine samples was negligible.
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Virus BK/aislamiento & purificación , ADN Viral/sangre , Virus JC/aislamiento & purificación , Trasplante de Riñón/efectos adversos , Infecciones por Polyomavirus/sangre , Infecciones por Polyomavirus/genética , Adolescente , Adulto , Anciano , Virus BK/genética , Niño , Estudios de Cohortes , ADN Viral/orina , Femenino , Humanos , Virus JC/genética , Masculino , Persona de Mediana Edad , Infecciones por Polyomavirus/orina , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: In renal allograft recipients, most cases of liver dysfunction are caused by hepatitis B virus and hepatitis C virus (HCV). The natural history of hepatitis C and B was studied in 286 renal allograft recipients who received a kidney allograft between 1972 and 1989 when tests for anti-HCV became available. METHODS: In all patients, hepatitis B (HB) surface (s) antigen (Ag) was tested before and anti-HCV (by enzyme-linked immunosorbent assay II) after transplantation. RESULTS: At enrollment in 1989 (5.5+/-4 years after transplantation), 209 patients were anti-HCV positive (C+), 42 patients were HBsAg-positive (B+), and 35 patients were both B+ and C+ (C+B+). One hundred four patients were receiving azathioprine (AZA) and 182 were on cyclosporine A (CsA). Since transplantation, the median follow-up was 18 years in AZA-treated and 13 years in CsA-treated patients. Liver biopsy showed chronic hepatitis in 73 patients, cirrhosis in 20 patients, and fibrosing cholestatic hepatitis in 2 patients. In 34 patients, liver biopsy was repeated, and progression of fibrosis was observed in 24 patients. The 12-year patient survival rate was similar in B+, C+, and B+C+ patients (67%, 78%, and 71%, respectively; P=not significant). Liver-related death was the first cause of death in B+ and B+C+ infected patients (58% and 72%, respectively), whereas cardiovascular disease was the leading cause of death in C+ patients (40%). Multivariate analysis showed that older age (>40 years) (relative risk [RR], 2.8), B+ status (RR, 2.36), and C+ status (RR, 1.65) were independently associated with a worse patient survival. CONCLUSIONS: In the long term, B+ patients had a higher risk of death related to liver disease than C+ patients, and co-infection did not worsen patient survival.
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Hepatitis B/fisiopatología , Hepatitis C/fisiopatología , Trasplante de Riñón/efectos adversos , Estudios de Seguimiento , Supervivencia de Injerto , Hepatitis B/epidemiología , Hepatitis B/mortalidad , Hepatitis C/epidemiología , Hepatitis C/mortalidad , Humanos , Inmunosupresores/uso terapéutico , Trasplante de Riñón/mortalidad , Hígado/patología , Hígado/virología , Estudios Retrospectivos , Análisis de Supervivencia , Factores de Tiempo , Trasplante HomólogoRESUMEN
BACKGROUND: It is still unknown whether it is better to administer cyclosporine (CsA) once or twice a day to renal-transplant patients. METHODS: Fifty-four patients were randomized to receive CsA once a day (OD group, 28 patients) or twice a day (BD group, 26 patients). Clinical parameters and pharmacokinetic studies were regularly monitored over the first year. RESULTS: Two patients lost their grafts because of renal vascular thrombosis. A patient in the BD group died. The other 51 patients were alive with graft functioning after a minimum follow-up of 1 year. Five patients per group had reversible acute rejection. There was a not significant trend toward a lower mean serum creatinine in OD than in BD (1.38 +/- 0.38 and 1.7 +/- 0.80 mg/dL at 1 year posttransplant, respectively). In 47 patients, 319 pharmacokinetic studies were performed. We measured the area under the concentration-time curve during the first 4 hours (AUC0-4) and CsA blood levels at 0, 2, and 4 hours after dosing. C0 was significantly lower in OD than in BD (P=0.0011), whereas C2 (P<0.0001) and C4 (P<0.0001) were significantly higher in OD than in BD. In OD, the AUC was higher than in BD (P<0.0001). OD allows us to reach high levels of C2 and AUC for several hours after dosing, whereas BD showed persistently high levels throughout the whole day. CONCLUSION: No difference in survival and rejection rates were observed between OD and BD groups.
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Ciclosporina/administración & dosificación , Ciclosporina/farmacocinética , Supervivencia de Injerto/inmunología , Inmunosupresores/farmacocinética , Trasplante de Riñón/fisiología , Adulto , Área Bajo la Curva , Creatinina/sangre , Ciclosporina/efectos adversos , Ciclosporina/uso terapéutico , Esquema de Medicación , Emulsiones , Femenino , Supervivencia de Injerto/efectos de los fármacos , Prueba de Histocompatibilidad , Humanos , Inmunosupresores/administración & dosificación , Inmunosupresores/efectos adversos , Inmunosupresores/uso terapéutico , Enfermedades Renales/clasificación , Enfermedades Renales/cirugía , Trasplante de Riñón/inmunología , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Little information is available about the role of oxidative stress in renal transplant patients. To evaluate the prevalence and severity of oxidative stress in renal transplantation, the authors conducted a cross-sectional study. METHODS: In 112 cadaver or living-donor kidney transplant recipients with a follow-up of at least 6 months and with plasma creatinine less than or equal to 2.5 mg/dL, complete blood count, serum vitamin B12, serum folate (s-F), reactive oxygen species (ROS), thiol groups (-SH), total antioxidant activity (TAOC), serum homocysteine (Hcy), and intraerythrocyte folate (ery-F) were measured. RESULTS: The mean levels of Hcy (21.1 microM vs. <10 microM), ROS (302.7 U. Carr (Carratelli units) vs. 250-300 U. Carr), and TAOC (410.6 micromol/HclO/mL vs. >350 micromol/HclO/mL), were higher than the reference interval, whereas -SH groups, vitamin B12, s-F, and ery-F were within the normal range. In the multivariate model, plasma creatinine (P=0.0062), vitamin B12 (P=0.0121), and TAOC (P=0.0007) were independently associated with oxidative stress. At multiple regression analysis, -SH groups and ROS were directly and inversely related to hematocrit (P=0.0007 and P=0.0073). There was also a negative correlation between -SH groups and blood pressure levels (P=0.0095). CONCLUSIONS: Renal transplant patients have a pattern of increased oxidant stress that is counterbalanced by an enhancement of the antioxidant mechanisms. Besides the well-known risk factors, the authors found that anemia is an independent risk factor for an increase of ROS. Further studies are needed to evaluate whether the correction of anemia might prevent or reduce the oxidative stress in renal transplant patients.
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Ácido Fólico/sangre , Homocisteína/sangre , Trasplante de Riñón/fisiología , Estrés Oxidativo , Adulto , Cadáver , Creatinina/sangre , Eritrocitos/metabolismo , Femenino , Estudios de Seguimiento , Hematócrito , Humanos , Donadores Vivos , Masculino , Especies Reactivas de Oxígeno/análisis , Valores de Referencia , Análisis de Regresión , Estudios Retrospectivos , Factores de Tiempo , Donantes de TejidosRESUMEN
A renal transplant patient treated with tacrolimus and mycophenolate-mofetil (MMF) developed progressive graft function deterioration 10 months after transplantation. Biopsy of the graft showed severe, focally accentuated interstitial inflammation with focal tubulitis and tubular necrosis, and medium-severe interstitial fibrosis with focal tubular atrophy. Glomerular and vascular structures were preserved. On careful examination, in some sections, tubular epithelial cells showed a definite increase with deformation of the nuclear shape, chromatin irregularities with peripheral dislocation and inclusion bodies. These cytopathic changes suggested polyoma virus infection ("decoy cells"). Subsequent screening of the urinary sediment confirmed the presence of many "decoy cells". Immunohistochemical analysis of the biopsy showed many tubular cells were strongly positive for the SV 40 antigen, specific for BK polyoma virus. A diagnosis of interstitial nephritis due to BK polyoma virus was made, though the coexistence of cellular rejection could not be excluded. At variance with previous reports, our patient had not had repeated episodes of rejection before biopsy or heavy immunosuppressive treatment, such as ALG, OKT3, after transplantation. This case shows that even in the absence of vigorous anti-rejection therapy an immunosuppressive regimen based on tacrolimus and MMF may involve the risk of BK polyoma virus- associated interstitial nephritis.
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Virus BK/aislamiento & purificación , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Nefritis Intersticial/etiología , Infecciones por Polyomavirus/complicaciones , Complicaciones Posoperatorias , Infecciones Tumorales por Virus/complicaciones , Adulto , Humanos , Fallo Renal Crónico/patología , Masculino , Nefritis Intersticial/patología , Infecciones por Polyomavirus/patología , Infecciones Tumorales por Virus/patologíaRESUMEN
INTRODUCTION: Mycobacterium gordonae is one of the least pathogenic of the mycobacteria. This pathogen may produce caseating or non-caseating granulomas, and skin lesions showing acute or chronic inflammation with scattered histiocytes and giant cells have been seen. The mortality rate is less than 0.1%. Mycobacterium gordonae may be a marker of severe immunosuppression in patients infected with human immunodeficiency virus. CASE PRESENTATION: We report a case of Mycobacterium gordonae infection in an 86-year-old woman and discuss the problems inherent to the identification and treatment of this emerging pathogen. Mycobacterium gordonae strain we isolated was resistant to trimethoprim-sulfamethoxazole but sensitive to ciprofloxacin, and long term administration (six months) induced complete healing of the cutaneous abscesses. CONCLUSION: Advanced laboratory diagnostic techniques have improved the isolation and identification of nontuberculous mycobacteria. The diagnosis requires a high index of clinical suspicion, as detection by conventional methods is difficult. To our knowledge, this patient is the first documented case of cutaneous infection from this pathogen in Italy.
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BACKGROUND: While graft survival rates in the short term have improved dramatically, only a modest improvement has been shown in long-term graft survival rates. We evaluated the causes of late failure in renal allograft recipients treated with cyclosporine A (CsA). METHODS: A total of 864 adults with a functioning graft at one year were evaluated. The end points were dialysis or death with a functioning graft. RESULTS: The 13-year patient and graft survival probabilities were 0.82 and 0.64, respectively. The graft half-life was 20.1 years and the pure graft half-life was 31.1 years. At multivariate analysis, plasma creatinine at one year (P = 0.0006; RR 1.72), low-density lipoproteins (LDL) at one year (P = 0.0014; RR 1.65), older age (P = 0.0128; RR 1.50) and delayed graft function (P = 0.0350; RR 1.45) were associated with the end point. Chronic allograft nephropathy was the cause of failure in 97 patients, death in 70, recurrence of glomerulonephritis in 24, other events in 6. Cardiovascular complications were the most frequent cause of death. Post-transplant cardiovascular events were associated with: pre-transplant cardiovascular events (P = 0.0012; RR 2.65), older age (P = 0.0001; RR 2.46), pre-transplant arterial hypertension (P = 0.0249; RR 1.57), smoking (P = 0.0235; RR 1.29), duration of dialysis (P = 0.0229; RR 1.28). Mean serum cholesterol, LDL and triglycerides were each significantly associated post-transplant cardiovascular events. CONCLUSIONS: The graft half-life was 20 years. Chronic allograft nephropathy was the leading cause of late failure, followed by death. If the data were censored by death, the projected pure graft half-life would be 31.1 years. Pre-transplant selection and preparation of the candidate as well as appropriate life style are recommended to improve life expectancy and extend graft survival.
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Supervivencia de Injerto , Fallo Renal Crónico/mortalidad , Trasplante de Riñón/mortalidad , Adolescente , Adulto , Anciano , Enfermedades Cardiovasculares/mortalidad , Ciclosporina/administración & dosificación , Femenino , Glomerulonefritis/mortalidad , Glomerulonefritis/cirugía , Humanos , Inmunosupresores/administración & dosificación , Fallo Renal Crónico/cirugía , Masculino , Persona de Mediana Edad , Recurrencia , Estudios Retrospectivos , Factores de Riesgo , Trasplante Homólogo , Insuficiencia del TratamientoRESUMEN
Only a few cases of acute post-infectious glomerulonephritis have been described in renal transplant patients. We report here three cases of acute post-bacterial glomerulonephritis in renal transplants. In contrast to the classic cases of post-streptococcal glomerulonephritis the type of infection was heterogeneous: respectively, Escherichia coli bacteremia, a skin abscess, and cholangitis. The clinical presentation was characterized by a deterioration of graft function in two of our three patients. Acute renal dysfunction recovered in both patients, but in the long term the outcome was severe; two of the three patients lost their graft function. It is difficult to ascertain whether progression was due to chronic allograft nephropathy, to glomerulonephritis, or both. It may be concluded that acute post-infectious glomerulonephritis is a possible, although rare, complication in renal transplant recipients. It has an unusual presentation and may have a poor outcome in the long term. The role of therapy, if any, is still undefined.
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Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Enfermedad Aguda , Adulto , Bacteriemia , Biopsia , Escherichia coli/metabolismo , Femenino , Glomerulonefritis/patología , Humanos , Enfermedades Renales/patología , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Insuficiencia Renal , Factores de Tiempo , Resultado del TratamientoRESUMEN
In this randomized controlled trial started in October 1990, 354 cadaveric kidney transplant recipients were assigned to receive either cyclosporine (CsA) monotherapy (115 patients), CsA + steroids (117 patients), or CsA + steroids + azathioprine (122 patients). The median follow-up was 85.1 mo. Thirty-one deaths occurred (infection, 12; cardiovascular disease, 11; neoplasia, 4; and others, 4), and 65 grafts were lost, mostly due to acute (15) or chronic rejection (50). The cumulative graft half-life was 18.1 yr. According to the "intention-to-treat," the 9-yr actuarial patient and graft survival were 94.0% and 73.3%, respectively, in monotherapy, 87.3% and 65.9% in dual therapy, and 87% and 72.2% in triple therapy (P = 0.647). At the last follow-up, the percentage of patients who remained with the original treatment was 51.2% in monotherapy, 81.7% in dual therapy, and 63.3% in triple therapy. At the seventh year, the mean creatinine clearances were 54.9 +/- 17.6 ml/min in monotherapy, 57.9 +/- 23.4 in dual therapy, and 60.6 +/- 20.7 in triple therapy (P = 0.375). Cataracts (P = 0.000), osteoporosis (P = 0.000), and cardiovascular complications (P = 0.000) were more frequent in dual or triple therapy than in monotherapy. Actuarial graft survival at 9 yr in patients on monotherapy who had to have steroids added was similar to that of the other two groups (62.2% versus 69.3%, P = 0.134). In conclusion, actuarial patient and graft survivals did not differ among the three schemes. The long-term renal function and survival were not affected in the patients on monotherapy who needed the addition of steroids. Monotherapy was associated with a lower incidence of extrarenal complications than the other two regimens.