RESUMO
Glomerular diseases may occur as primary manifestation of cancer, especially in patients older than 60 years. Among glomerulopathies, membranous nephropathy is preferentially associated with respiratory and gastrointestinal tract adenocarcinomas, whereas minimal change disease is most often seen in haematological malignancies. Though breast cancer is one of the most frequent malignancies in women, paraneoplastic glomerular disease is rarely observed. We describe the case of a 79-year-old female patient who presented with nephrotic syndrome and renal failure. Breast cancer was found. Pathological studies of kidney and breast biopsy revealed a minimal change disease and an infiltrating ductal carcinoma, respectively.
RESUMO
Eye disorders are frequently associated with renal diseases, mostly linked to underlying causes such as hypertension, diabetes or autoimmune diseases. Conversely, advanced uraemic states may also lead to progressive vision impairment. The present report concerns a 50-year-old patient who presented with a bilateral, painless, progressive vision loss, a moderate systemic inflammation and chronic renal failure due to hypertension nephrosclerosis. Steroids were given and haemodialysis was initiated, resulting in vision improvement. At 4 months later when the steroids were stopped, the patient developed dyspnoea, cough, fever and fatigue of unclear origin. A lung biopsy showed non-caseating granuloma consistent with pulmonary sarcoidosis. Re-challenge with steroids rapidly improved the respiratory disease. Ophthalmological examinations performed early and later in the course excluded anterior ischaemic optic neuropathy and ocular manifestations of sarcoidosis, leading to a diagnosis of uraemic optic neuropathy. This rare ophthalmological disorder should be promptly recognised since haemodialysis and steroid therapy are highly effective.
RESUMO
Aristolochic acid nephropathy (AAN), a progressive renal interstitial fibrosis frequently associated with urothelial malignancies, was initially reported in a Belgian cohort of more than 100 patients after the intake of slimming pills containing a Chinese herb, Aristolochia fangchi. Although botanicals known or suspected to contain aristolochic acid (AA) were no longer permitted in many countries, several AAN cases were regularly observed all around the world. The incidence of AAN is probably much higher than initially thought, especially in Asia and the Balkans. In Asian countries, where traditional medicines are very popular, the complexity of the pharmacopoeia represents a high risk for AAN because of the frequent substitution of the botanical products by AA-containing herbs. In the Balkan regions, the exposure to AA found in flour obtained from wheat contaminated with seeds of Aristolochia clematitis could be responsible for the so-called Balkan-endemic nephropathy. Finally, despite the Food and Drug Administration's warnings concerning the safety of botanical remedies containing AA, these herbs are still sold via the Internet.
Assuntos
Aristolochia/efeitos adversos , Ácidos Aristolóquicos/efeitos adversos , Medicamentos de Ervas Chinesas/efeitos adversos , Nefrite Intersticial/induzido quimicamente , Nefrite Intersticial/epidemiologia , Animais , Aristolochia/toxicidade , Ácidos Aristolóquicos/metabolismo , Ácidos Aristolóquicos/toxicidade , Nefropatia dos Bálcãs/induzido quimicamente , Nefropatia dos Bálcãs/epidemiologia , Nefropatia dos Bálcãs/metabolismo , Bélgica/epidemiologia , Transformação Celular Neoplásica/induzido quimicamente , Adutos de DNA/biossíntese , Surtos de Doenças , Medicamentos de Ervas Chinesas/toxicidade , Feminino , Saúde Global , Humanos , Incidência , Neoplasias Renais/induzido quimicamente , Neoplasias Renais/epidemiologia , Neoplasias Renais/metabolismo , Nefrite Intersticial/metabolismoRESUMO
BACKGROUND: Aristolochic acid (AA), the plant extract of Aristolochia species, is involved in the onset of progressive tubulointerstitial renal fibrosis in humans. Clinical and in vitro findings have previously suggested that the proximal tubule was the target of AA. METHODS: Using a rat model of AA nephropathy, the proximal tubular lesions induced by daily subcutaneous injections of AA for 35 or 5 days were characterized biochemically and histologically. Urinary excretion of proteins, albumin, low molecular weight proteins, N-acetyl-beta-d-glucosaminidase, alpha-glutathione S-transferase, leucine aminopeptidase and neutral endopeptidase (NEP) was determined and related to histological conventional findings and immunostainings of NEP and megalin. RESULTS: In both protocols, an acute phase of release of urinary markers was observed within the first 3 days of AA treatment in parallel with a significant increase of specific AA-related DNA adducts reflecting early tubular intoxication. A dramatic loss of the proximal tubule brush border was histologically confirmed, while the expression of megalin decreased at the damaged apical epithelium (mainly of the S3 segment). CONCLUSION: Proximal tubule injury occurs early after AA intoxication in rats, with a link between specific AA-DNA adduct formation, decreased megalin expression and inhibition of receptor-mediated endocytosis of low molecular weight proteins, bringing in vivo confirmation of previous in vitro studies.
Assuntos
Ácidos Aristolóquicos/toxicidade , Carcinógenos/toxicidade , Nefropatias/induzido quimicamente , Túbulos Renais Proximais/efeitos dos fármacos , Acetilglucosaminidase/urina , Albuminas/metabolismo , Animais , Biomarcadores/metabolismo , Cromatografia Líquida de Alta Pressão , Adutos de DNA/genética , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Glutationa Transferase/urina , Nefropatias/patologia , Nefropatias/urina , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Leucil Aminopeptidase/urina , Proteína-2 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Masculino , Neprilisina/urina , Ratos , Ratos WistarRESUMO
BACKGROUND: Experimental aristolochic acid nephropathy (AAN), characterized by interstitial fibrosis, tubular atrophy, and chronic renal failure, was reported after 35-day injections of aristolochic acids (AA) to salt-depleted male Wistar rats. The link between renal fibrosis and the renin-angiotensin system (RAS) in this model remains unknown. METHODS: We investigated the impact of sodium diets (low and normal), of RAS inhibition with enalapril (ENA) alone, or combined with candesartan (CSN) for 35 days, and ENA + CSN for 65 days on AAN development. At the end of each observation period, blood pressure and renal angiotensin-converting enzyme activity were measured, as well as renal functional impairment (plasma creatinine increase, proteinuria) and histologic lesions (interstitial fibrosis, monocytes/macrophages infiltration, myofibroblasts collagens type I and IV, proliferating cells). RESULTS: Sodium intake did not modify renal functional and morphologic impairment induced by AA. The RAS blockade by ENA or ENA + CSN in rats receiving AA did not result in any statistical difference in terms of renal failure, proteinuria, and interstitial fibrosis on day 35 or 65. On day 35, the monocytes/macrophages infiltration was significantly decreased by two-fold when ENA (P < 0.01) or ENA + CSN (P < 0.01) was given from day 0. CONCLUSION: Our data demonstrate that RAS modulation by salt depletion and pharmacologic blockade do not influence renal failure and interstitial fibrosis in the rat model of AAN. We suggest that pathways of interstitial renal fibrosis may be independent of RAS at least in some conditions.
Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Benzimidazóis/farmacologia , Enalapril/farmacologia , Nefropatias/induzido quimicamente , Nefropatias/prevenção & controle , Sistema Renina-Angiotensina/efeitos dos fármacos , Tetrazóis/farmacologia , Animais , Ácidos Aristolóquicos , Compostos de Bifenilo , Pressão Sanguínea/efeitos dos fármacos , Dieta Hipossódica , Sinergismo Farmacológico , Fibrose , Rim/metabolismo , Rim/patologia , Nefropatias/patologia , Nefropatias/fisiopatologia , Masculino , Peptidil Dipeptidase A/metabolismo , Ratos , Ratos WistarRESUMO
Chinese-herb nephropathy (CHN) is a rapidly progressive renal fibrosis associated with the intake of a Chinese herb (Aristolochia fangchi) containing nephrotoxic and carcinogenic aristolochic acids (AA). This study attempted to reproduce the main features of human CHN (renal failure, tubular atrophy, and interstitial fibrosis) in a rat model similar to that of cyclosporin-induced nephropathy. Salt-depleted male Wistar rats received daily subcutaneous injections of either 1 mg/kg body wt AA (low-dose AA group), 10 mg/kg body wt AA (high-dose AA group), or vehicle (control group) for 35 d. On days 10 and 35, assessment of renal function, measurements of urinary excretion of glucose, protein, and leucine aminopeptidase, and histologic analyses were performed (six rats euthanized/group). High-dose AA induced glucosuria, proteinuria, and elevated serum creatinine levels and reduced leucine aminopeptidase enzymuria on days 10 and 35, whereas low-dose AA had no significant effect. Tubular necrosis associated with lymphocytic infiltrates (day 10) and tubular atrophy surrounded by interstitial fibrosis (day 35) were the histologic findings for the high-dose AA-treated rats. In both AA groups, urothelial dysplasia was also observed, as well as fibrohistiocytic sarcoma at the injection site. A short-term model of AA-induced renal fibrosis was established in salt-depleted Wistar rats. These results support the role of AA in human CHN and provide a useful model for examination of the pathophysiologic pathways of renal fibrosis.