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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.

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.

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.

Aristolochic acid contamination in herbal remedies leads to interstitial fibrosis, tubular atrophy, and renal failure in humans. To study the cellular mechanisms contributing to the pathophysiology of this renal disease, we studied Wistar rats treated with aristolochic acid and measured tubular and interstitial cell proliferation, epithelial/mesenchymal cell marker expression, tubular membrane integrity, myofibroblast accumulation, oxidative stress, mitochondrial damage, tubular apoptosis, and fibrosis. Oxidative stress, a loss of cadherin concomitant with vimentin expression, basement membrane denudation with active caspase-3 expression, and mitochondrial injury within tubular cells were evident within 5 days of administration of the toxin. During the chronic phase, interstitial mesenchymal cells accumulated in areas of collagen deposits. Impaired regeneration and apoptosis of proximal tubular cells resulted in tubule atrophy with a near absence of dedifferentiated cell transmembrane migration. We suggest that resident fibroblast activation plays a critical role in the process of renal fibrosis during aristolochic acid toxicity.

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.

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.