Balkan endemic nephropathy

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Balkan endemic nephropathy
Other namesDanubian endemic familial nephropathy
Balkan endemic nephropathy map.svg
Areas in the Balkans with high prevalence
Specialty Nephrology   OOjs UI icon edit-ltr-progressive.svg

Balkan endemic nephropathy [1] (BEN) is a form of interstitial nephritis causing kidney failure. It was first identified in the 1920s among several small, discrete communities along the Danube River and its major tributaries, in the modern countries of Croatia, Bosnia and Herzegovina, Serbia, Kosovo, Romania, and Bulgaria. It is caused by small long-term doses of aristolochic acid in the diet. The disease primarily affects people 30 to 60 years of age. Doses of the toxin are usually low and people moving to endemic areas typically develop the condition only when they have lived there for 10–20 years. People taking higher doses of aristolochic acid (as Chinese herbal supplements) have developed kidney failure after shorter durations of exposure. [2]

Contents

Signs and symptoms

The patients are distinguished from those suffering from other causes of end-stage renal disease by showing an absence of high blood pressure, xanthochromia of palms and soles (Tanchev's sign), early hypochromic anemia, absence of proteinuria, and slow progression of kidney failure. [3] There is no specific therapy; BEN causes end-stage renal disease, for which the only effective treatments are dialysis or a kidney transplant. In endemic areas BEN is responsible for up to 70% of end-stage renal disease. At least 25,000 individuals are known to have this form of the disease. [4]

Patients with BEN have a greatly increased rate of transitional cell carcinoma of the upper urothelial tract, (the renal pelvis and ureters). (In populations without BEN, most urothelial cancer occurs in the bladder. [5] )

Causes

Dietary exposure to aristolochic acid is the cause of BEN and its attendant transitional cell cancers. [6] [2] Former hypotheses that included roles for ochratoxin, poisoning by organic compounds leached from lignite or by heavy metals, viruses, and trace-element deficiencies, are not supported by current evidence. [2] Genetic factors may be involved in determining which persons exposed to aristolochic acid suffer from BEN and which do not. [7]

In the Balkan region, dietary aristolochic acid exposure may come from the consumption of the seeds of Aristolochia clematitis (European birthwort), a plant native to the endemic region, which grows among wheat plants and whose seeds mingle with the wheat used for bread. [6] [8] Aristolochic-acid-containing herbal remedies used in traditional Chinese medicine are associated with a related—possibly identical—condition known as "Chinese herbs nephropathy". [9]

Exposure to aristolochic acid is associated with a high incidence of uroepithelial tumorigenesis. [10] [11]

Diagnosis

Biopsy - For definitive diagnosis[ citation needed ]

History

The first official published description of the disease was made by the Bulgarian nephrologist Dr. Yoto Tanchev (1917–2000) and his team in 1956 in the Bulgarian Journal Savremenna Medizina, [12] a priority generally acknowledged by the international nephrological community. [3]

The disease was originally called "Vratsa nephritis," and became known as "Balkan endemic nephropathy" later, after people living in Yugoslavia and Romania were found to be suffering from it as well. [3]

See also

Related Research Articles

<span class="mw-page-title-main">Aristolochic acid</span> Chemical compound

Aristolochic acids are a family of carcinogenic, mutagenic, and nephrotoxic phytochemicals commonly found in the flowering plant family Aristolochiaceae (birthworts). Aristolochic acid (AA) I is the most abundant one. The family Aristolochiaceae includes the genera Aristolochia and Asarum, which are commonly used in Chinese herbal medicine. Although these compounds are widely associated with kidney problems, liver and urothelial cancers, the use of AA-containing plants for medicinal purposes has a long history. The FDA has issued warnings regarding consumption of AA-containing supplements.

<span class="mw-page-title-main">Kidney disease</span> Damage to or disease of a kidney

Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can be diagnosed by blood tests. Nephrosis is non-inflammatory kidney disease. Nephritis and nephrosis can give rise to nephritic syndrome and nephrotic syndrome respectively. Kidney disease usually causes a loss of kidney function to some degree and can result in kidney failure, the complete loss of kidney function. Kidney failure is known as the end-stage of kidney disease, where dialysis or a kidney transplant is the only treatment option.

<span class="mw-page-title-main">IgA nephropathy</span> Disease of the kidney

IgA nephropathy (IgAN), also known as Berger's disease, or synpharyngitic glomerulonephritis, is a disease of the kidney and the immune system; specifically it is a form of glomerulonephritis or an inflammation of the glomeruli of the kidney. Aggressive Berger's disease can attack other major organs, such as the liver, skin and heart.

<i>Aristolochia</i> Genus of plants in the family Aristolochiaceae

Aristolochia is a large plant genus with over 500 species that is the type genus of the family Aristolochiaceae. Its members are commonly known as birthwort, pipevine or Dutchman's pipe and are widespread and occur in the most diverse climates. Some species, like A. utriformis and A. westlandii, are threatened with extinction.

Nephrotoxicity is toxicity in the kidneys. It is a poisonous effect of some substances, both toxic chemicals and medications, on kidney function. There are various forms, and some drugs may affect kidney function in more than one way. Nephrotoxins are substances displaying nephrotoxicity.

<span class="mw-page-title-main">Transitional epithelium</span> A type of tissue

Transitional epithelium is a type of stratified epithelium. Transitional epithelium is a type of tissue that changes shape in response to stretching. The transitional epithelium usually appears cuboidal when relaxed and squamous when stretched. This tissue consists of multiple layers of epithelial cells which can contract and expand in order to adapt to the degree of distension needed. Transitional epithelium lines the organs of the urinary system and is known here as urothelium. The bladder, for example, has a need for great distension.

<span class="mw-page-title-main">Ochratoxin</span> Group of chemical compounds

Ochratoxins are a group of mycotoxins produced by some Aspergillus species and some Penicillium species, especially P. verrucosum. Ochratoxin A is the most prevalent and relevant fungal toxin of this group, while ochratoxins B and C are of lesser importance.

<span class="mw-page-title-main">Interstitial nephritis</span> Medical condition

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<span class="mw-page-title-main">Analgesic nephropathy</span> Medical condition

Analgesic nephropathy is injury to the kidneys caused by analgesic medications such as aspirin, bucetin, phenacetin, and paracetamol. The term usually refers to damage induced by excessive use of combinations of these medications, especially combinations that include phenacetin. It may also be used to describe kidney injury from any single analgesic medication.

<i>Aristolochia clematitis</i> Species of plant

Aristolochia clematitis, the (European) birthwort, is a twining herbaceous plant in the family Aristolochiaceae, which is native to Europe. The leaves are heart shaped and the flowers are pale yellow and tubular in form. The plant seeks light by ascending the stems of surrounding plants.

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References

  1. ↑ Online Mendelian Inheritance in Man (OMIM): 124100
  2. 1 2 3 Stiborová, M., Arlt, V.M. & Schmeiser, H.H. Balkan endemic nephropathy: an update on its aetiology. Arch Toxicol 90, 2595–2615 (2016). https://doi.org/10.1007/s00204-016-1819-3
  3. 1 2 3 Tanchev Y, Dorossiev D (1991). "The first clinical description of Balkan endemic nephropathy (1956) and its validity 35 years later". IARC Sci. Publ. (115): 21–8. PMID   1820335.
  4. ↑ The Epidemiology, Diagnosis, and Management of Aristolochic Acid Nephropathy: A Narrative Review Annals of Internal Medicine 19 March 2013, Vol 158, No. 6
  5. ↑ Elif Batuman (August 12, 2013). "Poisoned Land: On the trail of a mystery disease in the Balkans". The New Yorker. Retrieved August 23, 2013.
  6. 1 2 Grollman AP, Shibutani S, Moriya M, et al. (2007). "Aristolochic acid and the etiology of endemic (Balkan) nephropathy". Proc. Natl. Acad. Sci. U.S.A. 104 (29): 12129–34. Bibcode:2007PNAS..10412129G. doi: 10.1073/pnas.0701248104 . PMC   1913550 . PMID   17620607.
  7. ↑ Balkan endemic nephropathy. U.S. Department of Health & Human Services. National Institutes of Health, National Center for Advancing Translational Sciences. https://rarediseases.info.nih.gov/diseases/8576/balkan-endemic-nephropathy
  8. ↑ Julia C. Mead (2007). "Manna from hell". The Scientist. 21 (11): 44. Archived from the original on 2008-09-06. Retrieved 2007-11-07.
  9. ↑ De Broe ME (March 2012). "Chinese herbs nephropathy and Balkan endemic nephropathy: toward a single entity, aristolochic acid nephropathy". Kidney Int. 81 (6): 513–5. doi: 10.1038/ki.2011.428 . PMID   22373701.
  10. ↑ Ronco, Claudio; et al., eds. (2008). Critical care nephrology. Elsevier Health Sciences. p. 1699. ISBN   978-1-4160-4252-5.
  11. ↑ Chen CH, Dickman KG, Moriya M, Zavadil J, Sidorenko VS, Edwards KL, Gnatenko DV, Wu L, Turesky RJ, Wu XR, Pu YS, Grollman AP (May 2012). "Aristolochic acid-associated urothelial cancer in Taiwan". Proc. Natl. Acad. Sci. U.S.A. 109 (21): 8241–6. doi: 10.1073/pnas.1119920109 . PMC   3361449 . PMID   22493262.
  12. ↑ Tanchev Y, Evstatiev Z, Dorossiev D, Pencheva J, Tzvetkova G. Studies on the nephritides in the District of Vratza. Savremena Medicina 1956; 7: 14–29 (Bulgarian).
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