RESUMO
PURPOSE: New-onset diabetes after transplantation (NODAT) is a frequent metabolic complication associated with podocyte damage and renal allograft dysfunction. Thus, Wilm's tumor-1 (WT-1) protein, as a podocyte marker, holds promise as an option to evaluate renal allograft dysfunction in NODAT. Therefore, the study aimed to investigate urinary WT-1 levels in NODAT patients during the first year after kidney transplantation (KTx). MATERIALS AND METHODS: KTx patients were categorized into non-NODAT and NODAT groups. Fasting blood glucose, glycated hemoglobin (HbA1c), urinary albumin/creatinine ratio (ACR), serum creatinine, estimated glomerular filtration rate (eGFR), and urinary WT-1 were measured at 3, 6, 9, and 12-months post-KTx. RESULTS: The NODAT group manifested elevated levels of blood glucose and HbA1c during the first year post-KTx. Also, exhibited elevations in ACR and serum creatinine levels at 6, 9, and 12-months post-KTx when compared to non-NODAT group. Conversely, eGFR values in the NODAT group demonstrated significant declines at 3, 6, and 9-months post-KTx relative to non-NODAT. Furthermore, NODAT group exhibited a median annual eGFR of 47 âmL/min/1.73 âm2. Urinary WT-1 levels at 3, 6, 9, and 12-months post-KTx were significantly higher in the NODAT group compared to non-NODAT. Additionally, noteworthy positive correlations were identified between urinary WT-1 and HbA1c levels, along with significant negative correlations between urinary WT-1 and eGFR at the 3, 6, 9, and 12-months post-KTx. CONCLUSION: The increased urinary WT-1 levels from 3-months post-KTx in NODAT patients may indicate the first sign of podocyte injury, predicting a renal allograft dysfunction in these patients.
Assuntos
Diabetes Mellitus , Taxa de Filtração Glomerular , Transplante de Rim , Proteínas WT1 , Humanos , Transplante de Rim/efeitos adversos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Proteínas WT1/urina , Diabetes Mellitus/urina , Biomarcadores/urina , Biomarcadores/sangue , Aloenxertos , Prognóstico , Seguimentos , Hemoglobinas Glicadas/metabolismoRESUMO
BACKGROUND: Proteinuria after kidney transplantation (KTx) has been a frequent problem due to several factors, high protein intake being one of them. Individualized nutritional intervention in the late post-KTx period can promote the improvement or the reduction of risks associated with the parameters of evaluation of kidney function, body composition, and quality of life in individuals submitted to KTx. METHODS: This is a single-center, randomized and stratified clinical trial. The study will be conducted in a university hospital in northeastern Brazil with 174 individuals aged ≥19 years submitted to KTx and followed up for 12 months. Assessments will take place at 3-month intervals (T0, T3, T6, T9, and T12). The patients will be allocated to intervention and control groups by random allocation. The intervention group will receive individualized nutritional interventions with normoproteic diets (1.0 g/kg) after 60 days of KTx whereas the controls will receive the standard nutritional guidance for the post-KTx period. The primary efficacy variable is the change from baseline in log proteinuria assessed with the urinary albumin/creatinine ratio. Secondary efficacy variables include body composition, anthropometry, quality of life assessment and physical activity, lipid profile and glycemic control. Ninety-two subjects per group will afford 70% power to detect a difference of 25% between groups in log proteinuria. Primary efficacy analysis will be on the modified intention-to-treat population with between-groups comparison of the change from baseline in log proteinuria by analysis of covariance. DISCUSSION: The study will assess the effects of an individualized nutritional intervention on proteinuria 12 months after KTx. TRIAL REGISTRATION: REBEC (RBR-8XBQK5).
Assuntos
Transplante de Rim , Composição Corporal , Humanos , Rim , Proteinúria , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Interleukin 18 (IL-18) is a proinflammatory cytokine that plays a role in host defense by upregulating both innate and acquired immune responses. Analysis of IL18 polymorphisms may be clinically important since their roles have been recognized in a variety of inflammatory and autoimmune disorders. However, the role of this cytokine polymorphisms in kidney transplant still remains unclear. In this study, we evaluated the associations between IL18 polymorphisms and graft function assessed by creatinine clearance in kidney transplant recipients. A total of 82 kidney transplant recipients and 183 healthy controls were enrolled, and frequencies of alleles, genotypes and haplotypes for IL18 polymorphisms were determined and compared with creatinine clearance. The -607C/A (rs1946518) and -137C/G (rs187238) variant alleles in the IL18 gene were determined by polymerase chain reaction. In our study, no significant association was found between the IL18 variants and creatinine clearance (p > 0.05). Nonetheless, polymorphism analysis revealed an increase in the frequency of the IL18 major haplotype -607C/-137G in kidney transplant patients (odds ratio 2.57, 95% confidence interval 1.45-4.55, p = 0.0014). Finally, we found that IL18 polymorphisms did not influence the renal function and that IL18 haplotype -607C/-137G seems to be associated with kidney transplant recipients.
RESUMO
BACKGROUND: The widespread use of prophylactic ganciclovir and anti-lymphocyte/thymocyte therapies are associated with increased induction of ganciclovir-resistant cytomegalovirus (CMV) strains. The use of sirolimus has been associated with a lower incidence of CMV infection in transplant recipients. We questioned whether it could also be effective as a therapeutic treatment of resistant CMV infection. METHODS: Patients with ganciclovir-resistant CMV infections determined clinically and by DNA sequencing analysis were enrolled. Antigenaemia and DNA sequencing were used to diagnosis and follow the mutations. RESULTS: Nine transplant patients were given sirolimus plus mycophenolate mofetil (n = 4) or a calcineurin inhibitor (n = 5). Seven out of nine recipients were CMV IgG negative before transplantation. We observed a rapid decrease in antigenaemia levels, reaching zero in eight out of nine (88.9%) patients within a median of 20.3 +/- 10.1 d. Graft function remained stable and no patient presented acute rejection or recurrence of the CMV infection. CONCLUSIONS: This suggests that the use of sirolimus plus ganciclovir therapy could be useful in ganciclovir-resistant CMV infections.
Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Transplante de Rim/efeitos adversos , Sirolimo/uso terapêutico , Adulto , Farmacorresistência Viral/genética , Ganciclovir/farmacologia , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Carga ViralRESUMO
Chronic cyclosporine (CsA) nephrotoxicity is a relevant factor in the pathogenesis of chronic allograft nephropathy. Pioglitazone is an agonist of PPARgamma, capable of reducing chronic inflammation. We investigated the capacity of pioglitazone in preventing renal dysfunction. Adult male Wistar rats were assigned to: Vehicle (olive oil 1 ml/kg/day), CsA (10 mg/kg/day) alone and with pioglitazone (5 or 10 mg/kg/day). The animals were sacrificed at 28 days, where blood (serum creatinine ratio, CR) and kidney samples (arteriolopathy analyses) were collected. The mRNA transcripts of TGF-beta1, PAI-1, Smad3 and 7 were evaluated by real-time PCR. As expected, CsA treatment significantly decreased renal function that peaked at day 28, compared with vehicle (CR=1.29+/-0.03 vs. 0.95+/-0.14, p<0.05). In contrast, the administration of pioglitazone 5 or 10 mg/kg combined with CsA resulted in better renal function (CR=1.09+/-0.05 and 1.14+/-0.14, respectively, p<0.05). Animals treated with CSA showed relevant arteriolopathy (49.5+/-2.86%) and pioglitazone administration significantly limited it (37.0+/-3.59% and 36.6+/-1.72%, respectively, 5 or 10 mg/kg, p<0.05). In CsA-treated animals (alone and with pioglitazone), TGF-beta1 and Smad3 increased significantly. In animals treated with CsA and pioglitazone (5 mg/kg), PAI-1 was significantly lower than CsA alone (3.96+/-0.92 vs. 7.53+/-1.38, p<0.05). Interestingly, the administration of pioglitazone 5 or 10 mg/kg was associated with an increase in Smad7 (1.79+/-0.25 and 1.75+/-0.19, respectively), compared to vehicle and to CsA-treated groups (1.08+/-0.17 and 1.17+/-0.19, respectively, p<0.05). These data provide evidence that pioglitazone acts through down regulation of pro-fibrotic cytokine PAI-1 and overexpression of the regulatory Smad7.
Assuntos
Ciclosporina/toxicidade , Nefropatias/prevenção & controle , Rim/efeitos dos fármacos , Tiazolidinedionas/farmacologia , Animais , Arteríolas/efeitos dos fármacos , Arteríolas/patologia , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Creatinina/sangue , Interações Medicamentosas , Expressão Gênica/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Imunossupressores/toxicidade , Rim/metabolismo , Rim/fisiopatologia , Nefropatias/induzido quimicamente , Nefropatias/genética , Masculino , Pioglitazona , Inibidor 1 de Ativador de Plasminogênio/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Proteína Smad3/genética , Proteína Smad7/genética , Fator de Crescimento Transformador beta1/genéticaRESUMO
O objetivo deste trabalho foi avaliar a função e a sobrevida do enxerto em pacientes com alto risco para NTA (necrose tubular aguda) e determinar o impacto dessa lesão na função do enxerto renal em pacientes utilizando protocolo de indução com timoglobulina. Timo foi usado com monitoramento da contagem de células CD3+. Avaliaram-se a sobrevida e a função do enxerto ao final de um ano. Setenta e oito pacientes que receberam rim de doador cadáver com o referido protocolo foram avaliados em dois anos de acompanhamento. Tempo de isquemia fria foi de 19,9 ± 4,89 horas. O total de doses de timoglobulina foi 7,48 ± 3,79. Contagem de CD3+: 19,3 ± 22,5. Ocorreu rejeição aguda em 14,1% dos casos, NTA em 66,6% e infecção pelo CMV em 55,1%. A sobrevida do enxerto em um ano foi de 95,9%, com creatinina de 1,56 ± 0,53 mg/dl. Pacientes que apresentaram NTA tiveram maior tempo de hospitalização (18,8 ± 6,1 x 10,4 ± 4,3dias p = < 0,001) e pior creatinina sérica ao fim de um ano (1,66 ±0,47 x 1,39 ± 0,6 mg/dl, p = 0,003). A única variável relacionada com a função do enxerto foi a idade do doador (> 38 anos, RR = 3,43 p <0,001). A indução com timoglobulina conferiu excelente sobrevida ao enxerto, com baixo índice de rejeição aguda e preservação da função do enxerto até o segundo ano após o transplante, a despeito da elevada prevalência de NTA.