RESUMO
BACKGROUND: Vascular calcification has been widely recognized as a significant contributor to cardiovascular risk in patients with chronic kidney disease. Recent evidence suggests that BMP-7 decreases the vascular calcification observed in uraemic rats, while BMP-2 could also be participating in this process. Gremlin, a bone morphogenetic protein antagonist, has been detected in rat aortic vascular smooth muscle cells (VSMCs), and since the role of the VSMCs into vascular calcification in uraemia is considered critical in this process, we hypothesized that gremlin could be participating in its pathogenesis. With this aim, we studied its expression in aorta from uraemic rats with calcitriol-induced vascular calcification and in 16-vessel biopsies of uraemic patients undergoing kidney transplantation. METHODS: Gremlin was detected by in situ hybridization (ISH) and immunohistochemistry (IMH). BMP-7, BMP-2 and BMP-2 receptor (BMPR2) were detected by IMH. Vascular calcification was assessed by the von Kossa staining method. Sham-operated and 5/6 nephrectomized rats (NFX) (1.2%P) were treated with vehicle or calcitriol (80 ng/kg, intraperitoneally every other day). Rats were killed after 4 weeks of treatment, and abdominal aorta was dissected for assessment of gremlin expression and vascular calcification. Epigastric arteries were obtained from dialysis patients during kidney transplantation procedure. Arteries from kidney donors were also studied. RESULTS: NFX rats developed a mild vascular calcification, whereas NFX-calcitriol rats developed a severe vascular and tissue calcification. A marked overexpression of gremlin was observed in the vascular media of aorta from NFX-calcitriol rats as compared with NFX and sham-calcitriol groups (4.8 +/- 1.3 versus 0.59 +/- 0.17 versus 0.19 +/- 0.07 percentage/mm(2), P < 0.01), and correlated with the BMP-2 and BMPR2 expression. Sham rats showed minimal or null gremlin expression. BMP-7 was not found in sham or calcified arteries. In human studies, we observed strong expression of gremlin mRNA and protein in the media layer of vessels from uraemic patients as compared with those from normal humans (staining score 3.72 +/- 0.95 versus 0.91 +/- 0.08 percentage/mm(2), P < 0.05). CONCLUSION: We observed a marked gremlin overexpression in the media layer of vessels in uraemic rats and patients in association with vascular calcification and BMP-2 expression. We postulate that gremlin may play a role in the vascular calcification process in uraemia, and its interaction with BMP-7 or BMP-2 remains to be elucidated.
Assuntos
Doenças da Aorta/fisiopatologia , Proteínas Morfogenéticas Ósseas/antagonistas & inibidores , Calcinose/fisiopatologia , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Uremia/complicações , Animais , Doenças da Aorta/patologia , Modelos Animais de Doenças , Transplante de Rim , Masculino , Ratos , Ratos Sprague-Dawley , Uremia/cirurgiaRESUMO
BACKGROUND: The increasing use of living kidney donors requires knowledge about long-term effects, especially number and causes of donors with chronic renal failure (CRF), and discussion about a regular follow-up program for donors, policies giving priority to kidney donors on the waiting list for a kidney, and a national record of donors. METHODS: We performed a Retrospective analysis of 470 records of our kidney donors from the kidney transplantation unit between 1977 and 1997. RESULTS: Five out of the 470 donors developed CRF (1.1%), with a calculated incidence of 610 per million people a year. CONCLUSION: The data showed that the risk of a donor developing CRF may be higher than in the in general population. These results showed the necessity of creating an effective follow-up program for donors and a national record.
Assuntos
Transplante de Rim/estatística & dados numéricos , Doadores Vivos , Nefrectomia/efeitos adversos , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Uremia/epidemiologia , Seguimentos , Humanos , Seleção de Pacientes , Uremia/etiologia , Uremia/cirurgiaRESUMO
Drug-related hepatotoxicity is more common in renal transplant (RT) recipients with chronic liver disease because drug metabolism is not as efficient in these individuals. We describe a long-term survivor (30 years) of renal transplantation with hepatitis C virus (HCV) and drug-related hepatotoxicity. Our patient, a 26-year-old male, developed uremic syndrome in May 1976 and received a renal allograft from a related, living donor with an identical human leukocyte antigen genotype in August 1976. Maintenance immunosuppression treatment consisted of azathioprine (AZA) and prednisone. In 1993, the patient tested negative for HCV antibody v1.0 (anti-HCV). In 2000, the patient had elevated aminotransferases, which was attributed to pravastatin treatment. Remission of this abnormality was achieved once pravastatin was discontinued. In 2003, the patient again exhibited elevated levels of aminotransferases and AZA-related hepatotoxicity was suspected; therefore, AZA was discontinued and treatment with mycophenolate mofetil was initiated, which led to normal aminotransferase levels. The patient tested positive for anti-HCV v3.0 and HCV RNA and a liver biopsy showed chronic hepatitis with moderate activity. Currently, the patient's renal transplant and liver are functional. In conclusion, hepatotoxic drugs should be used with caution in renal transplant recipients and close monitoring of liver function in patients with chronic viral hepatitis is crucial.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/complicações , Rejeição de Enxerto/prevenção & controle , Hepatite C Crônica/complicações , Imunossupressores/efeitos adversos , Transplante de Fígado , Uremia/cirurgia , Adulto , Biópsia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Seguimentos , Rejeição de Enxerto/patologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Prognóstico , Fatores de TempoRESUMO
INTRODUCTION: Hepatitis B virus (HBV) and hepatitis C virus (HCV) coinfection results in more severe forms of liver disease in nonuremic patients; however, the impact of HCV coinfection is not clearly known in end-stage renal disease (ESRD) patients with HBV infection. We sought to determine the impact of HCV coinfection in HBV-infected ESRD patients. PATIENTS AND METHODS: The HBsAg-positive ESRD patients evaluated between March 1999 and May 2003 were divided into two groups: group B, HBV infection alone, and group BC, HBV-HCV coinfection (anti-HCV-positive). Both groups were compared regarding epidemiological, laboratory, and histological findings. A liver biopsy was obtained in cases with evidence of viral replication and/or elevated alanine aminotransferase. RESULTS: One hundred patients (73% men) with mean age of 42 +/- 11 years (55 patients in group B and 45 in group BC) were studied. Comparison between groups showed a difference in time on hemodialysis and duration of infection, which were higher in group BC (P < .001 and P = .001, respectively) and in history of blood transfusion, which was also more frequent in group BC (P = .04). Liver biopsies, obtained from 15 patients in group B and 28 patients in group BC, showed no difference in frequency of septal fibrosis (60% in group B vs 48% in group BC, P = .46) or interface hepatitis (73% vs 71%, P = .99). CONCLUSIONS: HBV-HCV coinfection was related to a longer time on hemodialysis, longer duration of infection, and history of blood transfusion. Contrary to nonuremic patients, HCV coinfection was not associated with more severe forms of liver disease in ESRD patients.