Antibody response to the non-adjuvanted and adjuvanted influenza A H1N1/09 monovalent vaccines in renal transplant recipients.

BACKGROUND: The 2009 pandemic influenza A (H1N1) virus spread rapidly throughout Brazil. Non-adjuvanted and the adjuvanted influenza A H1N1/09 monovalent vaccine were recommended as a single dose to persons at risk including renal transplant recipients (RTR). We analyzed the safety and the immune response of 2 influenza A H1N1/09 monovalent vaccines in RTR, and identified factors influencing the immune response. METHODS: A total of 78 RTR received a single dose of either influenza A H1N1 2009 monovalent AS03-adjuvanted vaccine or a non-adjuvanted vaccine, and 58 healthy controls received a single dose of non-adjuvanted vaccine. Antibody responses to influenza A H1N1 were measured by hemagglutination inhibition assay and were compared between groups on the day of vaccination and 21-30 days thereafter, using geometric mean titer (GMT), and seroprotection (SP) and seroconversion (SC) rates. RESULTS: Among RTR, after adjuvanted and non-adjuvanted H1N1 vaccination, the SP rate increased from 16.7% to 61.7% (P < 0.001) and to 50% (P < 0.001), and SC rates were 61.7% and 50%, respectively. For healthy controls, SP rate increased from 25.8% to 89.7% (P < 0.001), and SC rate was 87.9% after vaccination. Pre-vaccination GMT for the adjuvanted and non-adjuvanted RTR vaccine groups and healthy controls was 9.7 (95% confidence interval [CI] 7.3-13.1), 8.9 (95% CI 5.4-14.7), and 12.5 (95% CI8.7-18.2), and significantly increased to 49.8 (95% CI 31.3-79.4, P < 0.001), 43.2 (95% CI 16.3-114.4, P < 0.001), and 323.8 (95% CI 213.9-490.2, P < 0.001), respectively. Deceased-donor type transplant significantly reduced SP (odds ratio [OR] = 4.62, 95% CI 1.36-15.69, P = 0.014) and SC (OR = 6.29, 95% CI 1.89-20.98, P = 0.003) rates, and younger age positively affected SP (OR = 0.11; 95% CI 0.03-0.04, P = 0.001). Adverse events were mild, and renal function showed no change post vaccination. CONCLUSION: RTR vaccinated with either an adjuvanted or non-adjuvanted monovalent influenza vaccine presented poor response compared with healthy controls. Post-vaccination adverse events were mild, and no rejection episode or renal dysfunction was observed.

Evaluation of neutrophilic activity in patients submitted to kidney transplantation.

BACKGROUND: Cryoglobulinemia is frequent in renal transplant patients. The mononuclear and polymorphonuclear neutrophil (PMN) phagocytic systems are important for the clearance of cryoglobulin immune complexes. There might be a reduced phagocytic activity in transplant patients with cryoglobulinemia (CRYO+). METHODS: We studied the phagocytic activity by PMNs, in the presence of immune complexes in renal transplant patients, with or without hepatitis C virus (HCV) infection. Thirty-seven patients subjected to kidney transplant were evaluated, and for the control group, healthy blood donors were chosen. The presence of cryoprecipitate was evaluated, as well as HCV infection, phagocytic activity by neutrophils during the ingestion and digestion phase. RESULTS: The presence of cryoprecipitate was detected in 75.7% of the patients, 39.28% of which had HCV infection. IgG, IgM, IgA, and C3 and C4 complement components were identified in the cryoprecipitate. There was a reduction in the ingestion phase of phagocytosis by PMNs in renal transplant CRYO+ though the digestion phase was preserved. CONCLUSION: We concluded that there was a decreased PMN activity in transplanted patients presenting cryoglobulinemia.

Gamma-glutamyltransferase activity in chronic dialysis patients and renal transplant recipients with hepatitis C virus infection.

The prevalences of chronic infection by hepatitis C virus (HCV) and its genotypes vary among countries and ethnic groups. Among patients with end-stage renal disease (ESRD) and transplant recipients, the evolution of hepatic disease seems atypical and has not been established. In this study we compared the prevalence and HCV genotypic distribution among Brazilian patients with ESRD on dialysis or with transplantations. Moreover, we sought to compare the behavior of biochemical markers of hepatic activity of HCV infection in both groups. We prospectively evaluated 87 ESRD patients on dialysis and 105 transplant patients. Blood samples were obtained to perform qualitative HCV-RNA, genotyping, and, periodically, serum levels of aminotransferases (ALT, AST), gamma-glutamyltransferase (GGT), alpha-fetoprotein (AFT), and albumin. The prevalence of HCV in ESRD patients was similar to recipients (19.5% vs 25.7%; P = NS) and the most frequent genotype was 1a. There was no difference in the mean values of ALT, GGT, AFT, and serum albumin between both groups with HCV infection. The mean values of aminotransferases were slightly elevated and a high frequency of patients evolved with persistently normal parameters. In contrast, the mean values of the GGT were 3 or 4 times above the reference limit and a greater frequency of patients evolved with values persistently elevated in the 2 groups. In conclusion, in the 2 groups the prevalence of HCV infection was elevated; the most frequent genotype was 1a. Among the biochemical parameters, GGT seemed to be useful as an indirect marker of liver disease.

Oral manifestation of cytomegalovirus associated with herpes simplex virus in renal transplant recipient.

We report a case of a renal transplant recipient who presented with oral lesions associated with cytomegalovirus (CMV) and herpes simplex virus (HSV). This female patient, who underwent a living donor renal transplant 26 months prior, presented with a painful buccal lesion after an episode of leukopenia. The search for CMV antigen was negative. A biopsy incision was made in the mucous membrane and the material collected by scarification was sent for polymerase chain reaction PCR, anatomic, pathological, and cytological exams. The lab results showed infections with CMV, HSV, and Candida albicans. Thus, the treatment involved the use of acyclovir (1 g a day for 10 days), topical Nystatin gargles (six times a day), and an aqueous solution of chlorexidine (0.12%), as well as laser therapy. After the adoption of these therapeutic modalities, there was complete remission of the buccal lesions. The odontological routine follow-up and early treatment of oral complications deriving from the immunosuppressive therapy contributed to a significant outcome.

Gingival overgrowth in renal transplant recipients: a study concerning prevalence, severity, periodontal, and predisposing factors.

Gingival overgrowth (GO) is the main oral manifestation in transplant recipients who use calcineurin inhibitors. In the present study, factors for GO development were investigated in Brazilian renal transplant recipients who were prescribed cyclosporine (CsA) or tacrolimus (TAC). Demographic, pharmacological, clinical, and periodontal data were obtained from 83 patients, as well as HLA expression in 51 of them. The prevalence of GO was high (47%), but its severity was low according to periodontal indices. The prevalence of GO was greater among patients who used CsA (n = 49) than those receiving used TAC (n = 34) namely, 61% versus 26.5% (P = .003). Comparisons between patients with versus without GO were performed independent of the administered immunossupressant. The group with GO showed a greater degree of gingival inflammation index. HLA-A68 had greater expression among patients without GO (P = .04). The risk factors for GO occurrence were evaluated using a multivariate analysis that identified gingival inflammation and HLA-A24 expression as risk factors. Increased age and use of TAC were identified as protective factors. GO showed a high prevalence, yet a light intensity. Patients who were younger, men, or received CsA showed a greater occurrence of GO. The risk factors identified for GO development were the presence of gingival inflammation and HLA-A24 expression.

Human herpesvirus-8 infection in hemodialysis patients from São Paulo, Brazil: preliminary results.

Epidemiological studies conducted in endemic areas of human herpesvirus 8 (HHV-8) infection have shown iatrogenic Kaposi's sarcoma in renal transplant recipients. Hemodialysis has not yet been demonstrated to be a route of virus transmission/acquisition, although recently blood transfusion has been suggested as a vehicle of HHV-8 transmission. The present study searching HHV-8 antibodies among serum samples from 70 hemodialysis patients disclosed a high prevalence of infection (22.9%). There was an association between HHV-8 seroreactivity and previous transfusions and transplantation, as well as with a black/pardum ethnic background of patients. These results emphasized that chronic renal patients are at risk of developing HHV-8-related diseases.

Efeito do treinamento funcional do assoalho pélvico associado ou não à eletroestimulação na incontinência urinária após prostatectomia radical / Effect of functional training for the pelvic floor muscles with or without electrical stimulation in cases of urinary incontinence following radical prostatectomy

INTRODUÇÃO: A literatura sobre fisioterapia do assoalho pélvico no tratamento da incontinência urinária após prostatectomia radical é escassa e relata técnicas diferentes de tratamento fisioterapêutico. OBJETIVO: Avaliar o efeito do tratamento fisioterapêutico na recuperação da continência urinária de pacientes submetidos a prostatectomia radical utilizando treinamento funcional do assoalho pélvico acompanhado ou não da eletroestimulação. MÉTODO: Foram selecionados 20 pacientes com incontinência urinária pós-prostatectomia radical. Os pacientes foram distribuídos ao acaso em grupos controle e de investigação. O grupo de investigação, composto por 10 pacientes, recebeu como tratamento fisioterapêutico o treinamento funcional do assoalho pélvico e a eletroestimulação. O grupo controle, composto por 10 pacientes, recebeu como tratamento fisioterapêutico o treinamento funcional do assoalho pélvico. Todos os pacientes foram reavaliados 3 meses, 6 meses e 12 meses após o início do tratamento por meio de "pad test", Escala Visual Análoga (EVA) da incontinência, Escala Visual Análoga (EVA) do problema e número de fraldas utilizadas. RESULTADOS: Houve diminuição estatisticamente significante entre a avaliação inicial e o 12º mês do "pad test", da EVA incontinência, da EVA problema e do número de fraldas no grupo controle e no grupo de investigação. Entretanto, não foi encontrada diferença estatisticamente significante quando comparadas as mesmas variáveis entre os dois grupos. DISCUSSÃO E CONCLUSÃO: Não houve melhora adicional no tratamento com treinamento funcional do assoalho pélvico associado à eletroestimulação quando comparado com o tratamento apenas com treinamento funcional do assoalho pélvico. Entretanto, nos dois grupos, houve melhora significante da incontinência urinária.

INTRODUCTION: Literature on physical therapy for the pelvic floor muscles to treat urinary incontinence following radical prostatectomy is scarce, with descriptions of differing techniques for physical therapy treatment. OBJECTIVE: To evaluate the effect of physical therapy treatment for recovering urinary continence among patients who had undergone radical prostatectomy, by using functional training of the pelvic floor muscles with or without electrical stimulation. METHOD: Twenty patients with urinary incontinence following radical prostatectomy were selected. The patients were randomly allocated to a control or to an experimental group. The experimental group was composed of ten patients who received physical therapy treatment consisting of functional training of the pelvic floor muscles and electrical stimulation. The control group was composed of ten patients who received physical therapy treatment consisting only of functional training of the pelvic floor. All of the patients were reevaluated three, six and twelve months after beginning treatment, by using the pad test, visual analog scale (VAS) for incontinence, VAS for the problem and counting the number of diapers (nappies) used. RESULTS: There was a statistically significant decrease between the initial and 12th month evaluations of the pad test, VAS for incontinence, VAS for the problem and numbers of diapers of the control group and experimental group. However, no statistically significant difference was found when the same variable was compared between the two groups. CONCLUSION: There was no additional improvement from treatment with functional training of the pelvic floor muscles associated with electrical stimulation, in relation to treatment only using functional pelvic floor training. However, there was a significant improvement in urinary incontinence in both groups.

A preliminary study revealing a new association in patients undergoing maintenance hemodialysis: manganism symptoms and T1 hyperintense changes in the basal ganglia.

BACKGROUND AND PURPOSE: Patients undergoing parenteral nutrition and those with portosystemic encephalopathy secondary to chronic liver disease and acquired and congenital portosystemic venous shunts frequently present manganese deposition in the basal ganglia, detected by MR imaging as hyperintense areas on T1-weighted sequences. We also observed similar abnormalities in the basal ganglia of patients with chronic renal failure undergoing maintenance hemodialysis. Our aim was to evaluate the pallidal signal intensity on T1-weighted images in a series of patients undergoing hemodialysis, with further evaluation of serum manganese levels and neurologic correlation, comparing them with patients with chronic renal failure without dialytic treatment. MATERIALS AND METHODS: We performed MR imaging examinations in 9 patients with chronic renal failure, 5 of whom were undergoing hemodialysis. An experienced neuroradiologist scrutinized the presence of symmetric hyperintensities in the basal ganglia on T1-weighted sequences. We also determined the serum manganese levels and performed the neurologic evaluations in all patients. RESULTS: All patients undergoing hemodialysis presented elevated serum manganese levels and symmetric hyperintensities within the globus pallidus. In this group, 4 patients presented with parkinsonian symptoms, myoclonus, and syndromes with vestibular and vestibular-auditory symptoms. The patients without dialytic treatment presented with neither bilaterally increased T1 MR imaging signal intensity within the globus pallidus nor symptoms of manganism. CONCLUSION: Our preliminary results demonstrated the occurrence of bilateral pallidal hyperintensity on T1-weighted images in all patients undergoing hemodialysis associated with high serum manganese levels, revealing a new association.

Association between polymorphisms of the renin-angiotensin system and more severe histological forms of lupus nephritis.

AIMS: The pathogenesis of lupus nephritis (LN) has not been fully understood. The renin-angiotensin system (RAS) is implicated in various immunological and non-immunological phenomena, and the polymorphism of the RAS genes has been associated with cardiovascular and renal disease onset and outcome. Therefore, we evaluated the possible association between the polymorphism of the renin-angiotensin system genes and the development of the different types of histological lesions of lupus nephritis in Brazilian patients. METHODS: 72 LN patients and 65 healthy subjects (sex-and ethnic-matched) were enrolled and compared in this study. Following the extraction of genomic DNA from the leukocytes of the peripheral blood, the genotypes of the angiotensin converting enzyme (ACE I/D), of the angiotensinogen (AGT M235T) and of the angiotensin II type 1 receptor (AGTR1 A1166C) were determined by the polymerase chain reaction. The renal lesions of the patients with LN were classified by the histological findings according to the WHO criteria. In addition, the activity and chronicity indices were used to assess the severity of renal involvement. RESULTS: Among the 72 patients with LN, there were 17 class II, 8 class III, 40 class IV and 7 class V, according to the WHO criteria. Individuals with the III and IV classes of LN (WHO) showed a significantly increased DD genotype frequency of ACE I/D genes when compared to the control group (48% vs. 27.7%, chi2 = 4.885, df = 1, p = 0.0442). No difference was found in the distribution of the AGT M235T and AGTR1 A1166C genotype frequencies among the LN of the different histological classes (WHO) and healthy controls. There was no association between genetic polymorphism of ACE, AGT M235T and AGTR1 A1166C and susceptibility to lupus nephritis, nor histological activity and chronicity indices in renal biopsy among the patients studied. CONCLUSIONS: This study suggests that the DD genotype of the ACE may be associated with the development of the more severe histological forms of lupus nephritis.

Polymorphisms of the renin-angiotensin system genes in Brazilian patients with lupus nephropathy.

Genetic polymorphisms of the renin-angiotensin system (RAS) has been associated with cardiovascular events and the progression of nephropathy in several diseases. The objective of this study was to evaluate a possible association of the genetic polymorphisms of RAS with the development and/or progression of lupus nephritis in a Brazilian population. Seventy-five SLE patients with lupus nephropathy (LN group) were compared to 72 SLE patients without LN (SLE group) and 65 healthy individuals (CONTROL group), of sex and ethnic matched, in a Brazilian population sample. Mean global follow-up was 9 +/- 6 years for lupus without nephropathy and 11 +/- 7 years for lupus nephropathy. Following the extraction of genomic DNA from the leukocytes in the peripheral blood, angiotensin converting enzyme (ACE I/D), angiotensinogen (AGT M(235)T) and angiotensin II type 1 receptor (AGTR1 A(1166)C) genotypes were determined by the polymerase chain reaction. No significant difference of ACE, AGT and AGTR1 genotypes distribution between groups was observed in this study. There was no significant association between the variables of the RAS genotypes and the presence of hypertension in SLE. However, an increased frequency ofDD genotype (ACE I/D) was observed in SLE patients with LN who progressed to CRF compared to healthy controls (DD 60%, DI 26.7%, II 13.3% versus 27.7%, 60% and 12.3%, respectively; chi2 = 6.299, P = 0.0429). In the population studied, there was no influence of the RAS genetic polymorphisms in the development of lupus nephropathy, but the progression to CRF was associated with ACE DD polymorphism.

Cryoglobulinemia in kidney transplant recipients.

The aim of this study was to assess the presence of cryoglobulins, the constitution of the cryoprecipitate, as well as the possible etiology and clinical features in kidney transplant recipients. We excluded patients with clinical or laboratory evidence of autoimmune, liver or neoplasm disease, infections, blood transfusions or immunizations in the previous 3 months. Detection of cryoglobulins was obtained from the peripheral venous blood. In cases of cryoprecipitate formation it was analyzed using anti-IgG, anti-IgM, anti-IgA, anti-C3, and anti-C4 antibodies. The hepatitis C virus (HCV) was detected by the polymerase chain reaction. Thirty-nine patients were selected, of whom 23 were men and the overall mean age was 40.6 +/- 12.7 years. Cryoprecipitate was detected in 74.4% (29/39) patients. Among patients with or without cryoprecipitate formation, the serum creatinine values, the percentage of patients with proteinuria, and the posttransplantation times were similar. In patients with cryoglobulins, 37.9% (11/29) were HCV positive. The etiology was not determined for the other patients. The IgG, IgM, and IgA immunoglobulins and the complement fractions C3 and C4 were found in the cryoprecipitate. Their compositions were similar among patients with or without HCV. Few clinical features were associated with the presence of cryoglobulins, including deep venous thrombosis, cutaneous purpura and peripheral neuropathy. In conclusion, cryoglobulinemia was prevalent in kidney transplant recipients, but appeared to not affect graft function. HCV infection was the most frequently associated etiology and clinical features were infrequent.

Posttransplant diabetes mellitus in renal transplant patients with hepatitis C virus.

The aim of this study was to assess the possible association between posttransplant diabetes mellitus (DM) and hepatitis C virus (HCV) infection in renal transplant recipients. This study included 124 patients who underwent renal transplantation between 1997 and 2002. Inclusion criteria were patients who were not diabetic prior to transplantation and posttransplant follow-up longer than 6 months. DM was defined as fasting blood glucose levels higher than 126 mg/dL on at least two occasions. HCV infection was detected using second- or third-generation ELISA methods and/or polymerase chain reactions for HCV-RNA. Twenty-five HCV positive (HCV+) patients were compared with 25 consecutive HCV negative (HCV-) transplant patients. Demographic and clinical data of the groups were compared. Posttransplantation DM was observed in 24% of the HCV+ patients. There were no statistical differences in age, gender, race, family history of DM, follow-up, or body mass index between the two groups. There was a higher prevalence of posttransplantation DM in HCV+ patients, but the difference did not reach statistical significance (24% vs 12%, P = NS). Alternatively, comparing patients of the two groups (n = 50) who did versus not develop DM, the incidence of posttransplantation DM was higher among HCV+ patients, but the difference did not reach statistical significance (66.6% vs 46.3%, P = NS). In conclusion, there was no association between HCV infection and the development of posttransplantation DM in this cohort of renal transplant recipients. However, there was a trend that suggested an association.

Infection by Cryptosporidium parvum in renal patients submitted to renal transplant or hemodialysis.

The frequency of infection by Cryptosporidium parvum was determined in two groups of renal patients submitted to immunosuppression. One group consisted of 23 renal transplanted individuals, and the other consisted of 32 patients with chronic renal insufficiency, periodically submitted to hemodialysis. A third group of 27 patients with systemic arterial hypertension, not immunosuppressed, was used as control. During a period of 18 months all the patients were submitted to faecal examination to detect C. parvum oocysts, for a total of 1 to 6 tests per patient. The results showed frequencies of C. parvum infection of 34.8%, 25% and 17.4%, respectively, for the renal transplanted group, the patients submitted to hemodialysis and the control group. Statistical analysis showed no significant differences among the three groups even though the frequency of C. parvum infection was higher in the transplanted group. However, when the number of fecal samples containing C. parvum oocysts was taken in account, a significantly higher frequency was found in the renal transplanted group.

Acute renal failure due to hemolytic uremic syndrome in adult patients.

Hemolytic uremic syndrome is characterized by the simultaneous occurrence of hemolytic anemia, thrombocytopenia, and renal failure. Clinical/ pathologic data, along with the treatment and outcome of 8 adult patients with HUS, are described. There were 7 females and 1 male, age 30.7 +/- 12 years; 7 were White and 1 Black. Three patients were kidney graft recipients, 2 of whom were receiving cyclosporine; 2 patients were postpartum; 1 case followed an abortion; 1 occurred with prodromic infection; and 1 case was without a causal factor. All patients presented with hematuria and 6 with oligoanuria. Laboratory data showed hemolytic anemia with schistocytes, LDH values were 2584 +/- 2191 U/L, platelets were 79,000 +/- 40,000/mL, creatinine concentrations were 5.9 +/- 2.5 mg/dL. Renal biopsy showed thrombotic microangiopathy. Two had predominant glomerular involvement. 2 showed renal cortical necrosis, 4 were marked by predominant arteriolar involvement. In 5 patients dialytic therapy was performed. All were treated with fresh-frozen plasma infusion and 6 with plasmapheresis. Three patients died, 2 without recovery of renal function. In conclusion, the trigger events were related to renal transplant in 3.2 of them taking cyclosporine; 3 with pregnancy; 1 to precedent infection; and 1 with no causal factor. There was no correlation between histological form and outcome in this group of patients. The benefit of plasmapheresis was evident in the recovery of the extrarenal manifestations, although it did not change the renal outcome. The prognosis is poor, with a high mortality (37.5%) and/or end-stage renal failure (37.5%). Complete recovery of renal function was obtained in 25%.