Balkan nephropathy

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Abstract

Balkan (or endemic) nephropathy is a chronic tubulointerstitial disease of unknown, presumably exotoxic etiology. It has been shown to exist only in some parts of the southeastern Europe.

While there have been many meetings and papers [1, 2] concerning both cause and treatment of Balkan nephropathy, sociopolitical turmoil, including wars, and economical hardship prevented any meaningful research on the problem during the 1990’s. Thus, despite numerous proceedings and a large number of publications on the subject, many features of Balkan nephropathy, its etiology and natural history in particular, remained nearly as mysterious as when described in the mid-fifties.

Meetings organized by international organizations [3-7] had a key role in informing the international scientific community on the disease. A recent source of information is a bilingual (in English and Serbian) monograph published in 2000 [8].

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Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs.

R Vanhaelen-Fastre, M Jadoul, C Richard Boland … (1993)

Two similar cases of rapidly progressive fibrosing interstitial nephritis in young women who followed the same slimming regimen prompted us to conduct an epidemiological survey of the nephrology centres of Brussels and to further investigate the exact nature of this slimming treatment. Seven other women under the age of 50 in terminal or preterminal renal failure were admitted for dialysis in 1991 and 1992. They had all followed a slimming regimen in the same medical clinic. Renal biopsy samples in eight of the nine cases showed extensive interstitial fibrosis without glomerular lesions. Two of the patients were seen for the first time in terminal renal failure and were started immediately on dialysis. For the seven other women, the nephropathy was characterised by a rapid deterioration in renal function, with initial serum creatinine doubling within about 3 months. The clinic had specialised in slimming treatments for the previous 15 years without any problems. In May, 1990, therapy was changed, with the introduction of two Chinese herbs (Stephania tetrandra and Magnolia officinalis). In June, 1992, three of twenty-five randomly selected women who had followed the same regimen during at least 3 months from 1990 had impaired renal function. Chemical analysis of some brands of these Chinese herbs did not show nephrotoxic contaminants of fungal or plant origin (ochratoxin or aristolochic acid) or adulteration by diuretics or antiinflammatory drugs. However, the medicinal preparation of the capsules taken by patients had different alkaloid profiles from those expected in Chinese plants. The striking relation between a specific type of fibrosing interstitial nephritis in young women and a slimming treatment involving Chinese herbs adds support to the arguments against uncontrolled therapy with herbal preparations.

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Aristolochic acid and the etiology of endemic (Balkan) nephropathy.

A P Grollman, S Shibutani, M Moriya … (2007)

Endemic (Balkan) nephropathy (EN), a devastating renal disease affecting men and women living in rural areas of Bosnia, Bulgaria, Croatia, Romania, and Serbia, is characterized by its insidious onset, invariable progression to chronic renal failure and a strong association with transitional cell (urothelial) carcinoma of the upper urinary tract. Significant epidemiologic features of EN include its focal occurrence in certain villages and a familial, but not inherited, pattern of disease. Our experiments test the hypothesis that chronic dietary poisoning by aristolochic acid is responsible for EN and its associated urothelial cancer. Using (32)P-postlabeling/PAGE and authentic standards, we identified dA-aristolactam (AL) and dG-AL DNA adducts in the renal cortex of patients with EN but not in patients with other chronic renal diseases. In addition, urothelial cancer tissue was obtained from residents of endemic villages with upper urinary tract malignancies. The AmpliChip p53 microarray was then used to sequence exons 2-11 of the p53 gene where we identified 19 base substitutions. Mutations at A:T pairs accounted for 89% of all p53 mutations, with 78% of these being A:T --> T:A transversions. Our experimental results, namely, that (i) DNA adducts derived from aristolochic acid (AA) are present in renal tissues of patients with documented EN, (ii) these adducts can be detected in transitional cell cancers, and (iii) A:T --> T:A transversions dominate the p53 mutational spectrum in the upper urinary tract malignancies found in this population lead to the conclusion that dietary exposure to AA is a significant risk factor for EN and its attendant transitional cell cancer.

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Chinese herbs nephropathy: a clue to Balkan endemic nephropathy?

Jean-Pierre Cosyns, Michel Jadoul, Jean-Paul Squifflet … (1994)

Rapidly progressive interstitial renal fibrosis has recently been reported in young women who have been on a slimming regimen including Chinese herbs. We examined four nephroureterectomies performed in three patients prior to or at the time of transplantation to determine the nature and topography of the kidney and urinary tract lesions in Chinese herbs nephropathy (CHN). Extensive, hypocellular, interstitial sclerosis, tubular atrophy and global sclerosis of glomeruli decreasing from the outer to the inner cortex, including the columns of Bertin, were observed in the four kidney specimens, together with severe fibromucoid to fibrous intimal thickening, mainly of interlobular arteries, normal or collapsed residual glomeruli, and mild to moderate atypia and atypical hyperplasia of the urothelium. In addition, bilateral pelvi-ureteric sclerosis was observed in one case. With the exception of the latter, these lesions are very similar to those described in Balkan endemic nephropathy (BEN). The clinical presentation of the patients was also similar to that observed in BEN: normal blood pressure, aseptic leukocyturia, low grade low molecular weight proteinuria, early and severe anemia. In conclusion, on morphological and clinical grounds, CHN appears similar to BEN. A common etiologic agent, aristolochic acid, is suspected. The known carcinogenic potential of this compound, taken together with our finding of multiple foci of cellular atypia of the urothelium suggest that CHN patients should undergo a regular follow-up for urothelial malignancy.

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Journal

Journal ID (publisher-id): 978-0-387-84843-3

Journal ID (doi): 10.1007/978-0-387-84843-3

Journal ID (nlm-ta): Clinical Nephrotoxins

Title: Clinical Nephrotoxins

Subtitle: Renal Injury from Drugs and Chemicals

ISBN (Print): 978-0-387-84842-6

ISBN (Electronic): 978-0-387-84843-3

Publication date (Print): 2008

Pages: 843-858

Affiliations

[1 ]GRID grid.5284.b, ISNI 0000000107903681, Laboratory of Pathophysiology Universiteitsplein 1, , University of Antwerp, ; Wilrijk, B-2610 Belgium

[2 ]GRID grid.5288.7, ISNI 0000000097585690, Division of Nephrology, Hypertension and Clinical Pharmacology, , Oregon Health Sciences University, ; 3181 SW Sam Jackson Park Road, Portland, OR 97201 USA

[3 ]GRID grid.240094.b, ISNI 000000040443077X, Legacy Good Samaritan Hospital, ; 1015 NW 22nd Avenue, W004, Portland, OR 97201 USA

[4 ]GRID grid.418247.c, Groupe Hôspitalier Pitié Salpétrière Service De Néphrologie 83, , Boulevard de l′Hôpital, ; Paris, F-75013 France

[5 ]GRID grid.418577.8, ISNI 0000 0000 8743 1110, Clinical Centre of Serbia, , Institute of Urology and Nephrology, ; Pasterova 2, Beograd, 11000 Serbia

[6 ]GRID grid.411196.a, ISNI 0000000112403921, Faculty of Medicine, Department of Community Medicine and Behavioural Sciences, , Kuwait University, ; POB 24923, Safat, 13110 Kuwait

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Publisher ID: 38

DOI: 10.1007/978-0-387-84843-3_38

PMC ID: 7121851

SO-VID: 386d9ad2-7c49-46dc-842d-8a2a4c6a4799

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This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

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Keywords: aristolochic acid,balkan endemic nephropathy,analgesic nephropathy,endemic focus,tubular proteinuria

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Keywords: aristolochic acid, balkan endemic nephropathy, analgesic nephropathy, endemic focus, tubular proteinuria

Balkan nephropathy

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Most cited references 93

Rapidly progressive interstitial renal fibrosis in young women: association with slimming regimen including Chinese herbs.

Aristolochic acid and the etiology of endemic (Balkan) nephropathy.

Chinese herbs nephropathy: a clue to Balkan endemic nephropathy?

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