Investigation of chronic endemic nephropathy in Yugoslavia

Hall, Phillip M.; Dammin, Gustave J.; Griggs, R.C.; Fajgelj, A.; Zimonjic, B.; Gaon, J.

doi:10.1016/0002-9343(65)90043-4

Cited by 28 publications

(7 citation statements)

References 6 publications

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“…, in the endemic region of Croatia, specific mortality from these carcinomas was 14 times higher than in Brodsko-Posavska county, and as many as 55 times higher than in the rest of Croatia [18]. In BEN, the early symptoms of UTT are tubular and/or glomemular lesions followed by parenchymal damage and fibrosis and marked membrane thickening and hyalinisation [27,28]. There may also be an association with increased urinary bladder cancer incidence [29], although many confounding factors such as tobacco smoking may interfere in the analysis of data for this organ.…”

Section: Balkan Endemic Nephropathy (Ben)mentioning

confidence: 96%

Ochratoxin A: An overview on toxicity and carcinogenicity in animals and humans

Pfohl‐Leszkowicz¹,

Manderville²

2006

Molecular Nutrition Food Res

867

525

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Ochratoxin A (OTA) is a ubiquitous mycotoxin produced by fungi of improperly stored food products. OTA is nephrotoxic and is suspected of being the main etiological agent responsible for human Balkan endemic nephropathy (BEN) and associated urinary tract tumours. Striking similarities between OTA-induced porcine nephropathy in pigs and BEN in humans are observed. International Agency for Research on Cancer (IARC) has classified OTA as a possible human carcinogen (group 2B). Currently, the mode of carcinogenic action by OTA is unknown. OTA is genotoxic following oxidative metabolism. This activity is thought to play a central role in OTA-mediated carcinogenesis and may be divided into direct (covalent DNA adduction) and indirect (oxidative DNA damage) mechanisms of action. Evidence for a direct mode of genotoxicity has been derived from the sensitive 32P-postlabelling assay. OTA facilitates guanine-specific DNA adducts in vitro and in rat and pig kidney orally dosed, one adduct comigrates with a synthetic carbon (C)-bonded C8-dG OTA adduct standard. In this paper, our current understanding of OTA toxicity and carcinogenicity are reviewed. The available evidence suggests that OTA is a genotoxic carcinogen by induction of oxidative DNA lesions coupled with direct DNA adducts via quinone formation. This mechanism of action should be used to establish acceptable intake levels of OTA from human food sources.

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Section: Balkan Endemic Nephropathy (Ben)mentioning

confidence: 96%

Ochratoxin A: An overview on toxicity and carcinogenicity in animals and humans

Pfohl‐Leszkowicz¹,

Manderville²

2006

Molecular Nutrition Food Res

867

525

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“…This in itself does not rule out a mycotoxin, including ochratoxin A, since little is known about age and species susceptibility, magnitude and duration of exposure required, or the variability of the response by different species to the several mycotoxins. There is also disagreement about the absence of renal interstitial fibrosis in cases of endemic Balkan nephropathy; HALL et al [15] described renal interstitial fibrosis as one of the major alterations of the disease. CUPPAGE and TATE [6] described interstitial fibrosis that spontaneously decreased in amount as the repair process progressed in rats poisoned with mercuric chloride.…”

Section: Discussionmentioning

confidence: 99%

Ochratoxicosis in Beagle Dogs

1974

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Abstract. Three young male Beagle dogs were given daily oral doses of 0.3 mg/kg body weight of crystalline ochratoxin A. Three untreated Beagle dogs served as controls. The principals survived for 11-1 5 days and were killed. Cytomorphologic alterations were seen primarily in the endomembrane system of the renal epithelial cells of the proximal convoluted tubules. Increased amounts of smooth-surfaced membranes were present as linear and concentric arrays and as large and small vesicles in many proximal tubular epithelial cells. Few basilar infoldings of the plasma membrane were present in proximal tubular epithelial cells of the principals, but extracellular basilar labyrinth was extensive in proximal tubular epithelial cells of the control kidney. Many tubular epithelial cells contained lipid droplets and cytoplasmic accumulations of phospholipids. The mitochondria usually appeared normal. Prominent ultrastructural alterations of the interstitium included separation between tubular basement membranes, increase in the number of interstitial cells, well-developed secretory apparatuses in many interstitial cells, and the presence of collagen and amorphous material. Few alterations were found in the epithelial cells of the distal convoluted tubules, but some contained more lipid droplets than normally. No consistent alterations were found in other parts of the nephron.Ochratoxin A is a nephrotoxic fungal metabolite elaborated by certain strains of Aspergillus ochruceus [41], Penicillium viridicatum [42], and other members of the A . ochruceus group [17, 191. These fungi are common contaminants of agricultural commodities [3,4,10,11,24,29,3 11, and the natural occurrence of ochratoxin A has been reported in cereal grains in the United States [12,33,34], Canada [30,31], and Denmark [18]. Although ochratoxin A was primarily a nephrotoxin in the species studied [9,18,23,26,27,37-391,

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“…This consideration is based upon studies of cystic changes in the kidneys of rats experimentally produced by feeding them diphenylamine (Kime et al, 1962) and observations of clinical and histological similarities of Balkan endemic toxic nephropathy to those of cystic disease of the renal medulla (Hall et al, 1965). Because of the familial occurrence of cystic disease, it can be surmised that there is a genetically common enzyme defect leading to accumulation of nephrotoxic material produced endogenously.…”

Section: Discussionmentioning

confidence: 99%

Medullary cystic disease of the kidney: its occurrence in two siblings

Handa

Tennant

1968

Postgraduate Medical Journal

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Summary Two cases of medullary cystic disease of the kidney in two siblings are presented. In both siblings there was an insidious onset of azotaemia and anaemia at an early age. The urinalyses were normal except for a trace of proteinuria and persistent low specific gravity. The kidneys were small by radiological studies and this was proved at necropsy. The gross microscopic appearances of the kidneys were consistent with medullary cystic disease. The literature on this subject and current views on the similarities between familial juvenile nephronophthisis and this condition are discussed.

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Investigation of chronic endemic nephropathy in Yugoslavia

Cited by 28 publications

References 6 publications

Ochratoxin A: An overview on toxicity and carcinogenicity in animals and humans

Ochratoxin A: An overview on toxicity and carcinogenicity in animals and humans

Ochratoxicosis in Beagle Dogs

Medullary cystic disease of the kidney: its occurrence in two siblings

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