American Journal of Kidney Diseases
Volume 52, Issue 3 , Pages 606-616 , September 2008

Balkan Nephropathy: Evolution of Our Knowledge

  • Giorgos Bamias, MD

      Affiliations

    • First Department of Propaedeutic Medicine, Laikon Hospital, Athens, Greece
    • ,
  • John Boletis, MD

      Affiliations

    • Department of Nephrology and Transplant Center, Laiko Hospital, Athens, Greece
    • Corresponding Author InformationAddress correspondence to John Boletis, MD, 17 Agiou Thoma St, Athens, Greece

Received 26 February 2008 ,Accepted 8 May 2008.

References 

  1. Tanchev Y, Evstatiev Z, Dorossiev D, Pencheva J, Zvetkov G. Studies on the nephritides in the District of Vratza. Savremenna Medicina. 1956;7:14–29
  2. Danilovic V, Djurisic M, Mokranjac M, Stojimirovic B, Zivojinovic J, Stojakovic P. Porodicna oboljenia bubrega u selu Sopic izvazvana hronicnom intoksikacijom olovom. Srpski Arh Tcelok Lek. 1957;85:1115–1125
  3. Fortza N, Negoescu M. Nefrita cronica azotemia endo-epidemica. Stud Cercet Med. 1961;1:217–221
  4. World Health Organization. Memorandum: The endemic nephropathy of South-Eastern Europe. Bull World Health Org. 1965;32:441–448
  5. In:  Wolstenholme GE,  Knight J editor. CIBA Foundation Study Group No. 30: The Balkan Nephropathy. Boston, MA: CIBA Foundation; 1967;
  6. Georgiev G. Clinical and genealogical investigation of Balkan endemic nephropathy [in Bulgarian]. In: Sophia, Bulgaria: Bulgarian Academy of Science; 1979;p. 1–55
  7. Radonic M, Radosevic Z. Clinical features of Balkan endemic nephropathy. Food Chem Toxicol. 1992;30:189–192
  8. Stefanovic V, Cosyns JP. Balkan nephropathy. In:  Davison AM,  Cameron JS,  Grunfeld JP,  Ponticelli C editor. Oxford Textbook of Clinical Nephrology. New York, NY: Oxford University; 2005;p. 1095–2101
  9. Pavlović-Kentera V, Clemons GK, Trbojević S, Dimković N, Djukanović L. Erythropoietin and anemia in the progression of Balkan endemic nephropathy and other renal diseases. Nephron. 1990;54:139–143
  10. Plestina R. Some features of Balkan endemic nephropathy. Food Chem Toxicol. 1992;30:177–181
  11. Hall PW, Piscator M, Vasiljevic M, Popović N. Renal function studies in individuals with the tubular proteinuria of endemic Balkan nephropathy. Q J Med. 1972;41:385–393
  12. Djukanovic L, Bukvic D, Maric I. Creatinine clearance and kidney size in Balkan endemic nephropathy patients. Clin Nephrol. 2004;61:384–386
  13. Vukelic M, Sostaric B, Belicza M. Pathomorphology of Balkan endemic nephropathy. Food Chem Toxicol. 1992;30:193–200
  14. Vukelic M, Sostaric B, Fuchs R. Some pathomorphological features of Balkan endemic nephropathy in Croatia. In:  Castegnaro M,  Plestina R,  Dirheimer G,  Chernozemsky IN,  Bartsch H editor. Mycotoxins, Endemic Nephropathy and Urinary Tract Tumors (IARC Scientific Publications No 115). Lyon, France: International Agency for Research on Cancer; 1991;p. 37–42
  15. Nadasdy T, Sedmak D. Acute and chronic tubulointerstitial nephritis. In:  Jennette JC,  Olson JL,  Schwartz MM,  Silva FG editor. Heptinstall's Pathology of the Kidney. ed 6. Philadelphia, PA: Lippincott Williams & Wilkins; 2006;p. 1124–1126
  16. Hall PW, Batuman V. Balkan endemic nephropathy—Introduction. Kidney Int Suppl. 1991;34:S1–S3
  17. Hall PW, Dammin GJ. Balkan nephropathy. Nephron. 1978;22:281–300
  18. Ceovic S, Hrabar A, Saric M. Epidemiology of Balkan endemic nephropathy. Food Chem Toxicol. 1992;30:183–188
  19. Cracium E, Rosculescu I. On Danubian endemic familial nephropathy (Balkan nephropathy). Am J Med. 1970;49:774–779
  20. Austwick PKC. Balkan nephropathy. Practitioner. 1981;225:1031–1038
  21. Ceović S, Hrabar A, Radonić M. An etiological approach to Balkan endemic nephropathy based on the investigation of two genetically different populations. Nephron. 1985;40:175–179
  22. Tatu CA, Orem WH, Finkelman RB, Feder GL. The etiology of Balkan endemic nephropathy: Still more questions than answers. Environ Health Perspect. 1998;106:689–700
  23. Sattler TA, Dimitrov T, Hall PW. Relation between endemic (Balkan) nephropathy and urinary tract tumours. Lancet. 1977;1:278–280
  24. Petkovic S, Mutavdzic M, Petronic V, Markovic V. Les tumeurs du bassinet et de l'uretère (Recherches cliniques et étiologiques). J Urol Néphrol. 1971;77:429–439
  25. Chernozemsky IN, Stoyanov IS, Petkova-Bocharova TK, et al. Geographic correlation between the occurrence of endemic nephropathy and urinary tract tumours in Vratza district, Bulgaria. Int J Cancer. 1977;19:1–11
  26. Stoyanov IS, Chernozemsky IN, Nicolov IG, Stoichev II, Petkova-Bocharova TK. Epidemiologic association between endemic nephropathy and urinary system tumors in an endemic region. J Chronic Dis. 1978;31:721–724
  27. Markovic N, Ignjatovic I, Cukuranovic R, Petrovic B, Kocic B, Stefanovic V. Decreasing incidence of urothelial cancer in a Balkan endemic nephropathy region in Serbia (A surgery-based study from 1969 to 1998). Pathol Biol. 2005;53:26–29
  28. Danilovic V, Djurisic M, Mokranjac M, Stojimirovic B, Zivojinovic J, Stojakovic P. Chronic nephritis caused by poisoning with lead via the digestive tract (flour). Presse Med. 1957;65:2039–2040
  29. Krogh P, Hald B, Plestina R, Ceovic S. Balkan (endemic) nephropathy and foodborn ochratoxin A: Preliminary results of a survey of foodstuffs. Acta Pathol Microbiol Scand B. 1977;85:238–240
  30. Krogh P. Mycotoxic porcine nephropathy: A possible model for Balkan endemic nephropathy. In:  Puchlev A editors. Proceedings of the Second International Symposium on Endemic Nephropathy. Sofia, Bulgaria: Bulgarian Academy of Sciences; 1974;p. 26–270
  31. Lioy PJ. Measurement methods for human exposure analysis. Environ Health Perspect. 1995;103:S35–S43(suppl 3)
  32. Long DT, Voice TC. Role of exposure analysis in solving the mystery of Balkan endemic nephropathy. Croat Med J. 2007;48:300–311
  33. Kuiper-Goodman T, Scott PM. Risk assessment of the mycotoxin ochratoxin A. Biomed Environ Sci. 1989;2:179–248
  34. Stefanaki I, Foufa E, Tsatsou-Dritsa A, Dais P. Ochratoxin A concentrations in Greek domestic wines and dried vine fruits. Food Addit Contam. 2003;20:74–83
  35. Petkova-Bocharova T, Castegnaro M. Ochratoxin A contamination of cereals in an area of high incidence of Balkan endemic nephropathy in Bulgaria. Food Addit Contam. 1985;2:267–270
  36. Abouzied MM, Horvath AD, Podlesny PM, et al. Ochratoxin A concentrations in food and feed from a region with Balkan endemic nephropathy. Food Addit Contam. 2002;19:755–764
  37. Vrabcheva T, Petkova-Bocharova T, Grosso F, et al. Analysis of ochratoxin A in foods consumed by inhabitants from an area with Balkan endemic nephropathy: A 1 month follow-up study. J Agric Food Chem. 2004;52:2404–2410
  38. Radic B, Fuchs R, Peraica M, Lucic A. Ochratoxin A in human sera in the area with endemic nephropathy in Croatia. Toxicol Lett. 1997;91:105–109
  39. Maaroufi K, Achour A, Betbeder AM, et al. Foodstuffs and human blood contamination by the mycotoxin ochratoxin A: Correlation with chronic interstitial nephropathy in Tunisia. Arch Toxicol. 1995;69:552–558
  40. Maaroufi K, Achour A, Hammami M, et al. Ochratoxin A in human blood in relation to nephropathy in Tunisia. Hum Exp Toxicol. 1995;14:609–614
  41. Godin M, Fillastre J-P, Simon P, Francois A, Le Roy F, Morin J-P. Is ochratoxin A a nephrotoxic in human beings?. Adv Nephrol Necker Hosp. 1997;26:181–206
  42. Grollman AP, Jelakovic B. Role of environmental toxins in endemic (Balkan) nephropathy (October 2006, Zagreb, Croatia). J Am Soc Nephrol. 2007;18:2817–2823
  43. Kazantzis G. Comment in the general discussion: Possible nephrotoxic agents. In:  Wolstenholme GE,  Knight J editor. The Balkan Nephropathy. Boston, MA: CIBA Foundation; 1967;p. 114
  44. Ivić M. Etiology of endemic nephropathy. Lijec Vjesn. 1969;91:1273–1281
  45. Dumic A. Horse poisoning with Aristolochia clematitis [in Croatian]. In: Zagreb: Izdanje Vojno tehnickog glasnika; 1954;p. 3–45
  46. Martincic M. Toxic effects of Aristolochia clematitis on horses' kidneys [in German]. Vetererinarski Arhiv. 1957;27:51–59
  47. Ivić M, Lovriæ B. Carcinogenic action of Aristolochia [in Serbian]. Acta Medica Med. 1967;5:1–3
  48. Vanherweghem JL, Depierreux M, Tielmans C, et al. Rapidly progressive interstitial renal fibrosis in young women: Association with slimming regimen including Chinese herbs. Lancet. 1993;341:387–391
  49. Cosyns JP, Jadoul M, Squifflet JP, van Cangh PJ, van Ypersele de Strihou C. Chinese herbs nephropathy: A clue to Balkan endemic nephropathy?. Kidney Int. 1994;45:1680–1688
  50. Tanaka A, Nishida R, Sawai K. Traditional remedy-induced Chinese herbs nephropathy showing rapid deterioration of renal function [in Japanese]. Nippon Jinzo Gakkai Shi. 1997;39:794–797
  51. Cosyns JP, Jadoul M, Squifflet JP, Wese FX, van Ypersele de Strihou C. Urothelial lesions in Chinese herb nephropathy. Am J Kidney Dis. 1999;33:1011–1017
  52. Nortier JL, Muniz MC, Schmeiser HH, et al. Urothelial carcinoma associated with the use of a Chinese herbs (Aristolochia species). N Engl J Med. 2000;342:1686–1692
  53. Arlt VM, Pfohl-Leszkowicz A, Cosyns J, Schmeiser HH. Analyses of DNA adducts formed by ochratoxin A and aristolochic acid in patients with Chinese herbs nephropathy. Mutat Res. 2001;494:143–150
  54. Grollman AP, Shibutani S, Moriya M, et al. Aristolochic acid and the etiology of endemic (Balkan) nephropathy. Proc Natl Acad Sci U S A. 2007;104:12129–12134
  55. Lemy A, Wissing KM, Rovire S, et al. Late onset of bladder urothelial carcinoma after kidney transplantation for end-stage aristolochic acid nephropathy: A case series with 15-year follow-up. Am J Kidney Dis. 2008;51:471–477
  56. Hranjec T, Kovač A, Kos J, et al. Endemic nephropathy: The case for chronic poisoning by aristolochia. Croat Med J. 2005;46:116–125
  57. Feder GL, Radovanovi Z, Finkelman RB. Relationship between weathered coal deposits and the aetiology of Balkan endemic nephropathy. Kidney Int Suppl. 1991;34:S9–S11
  58. Orem WH, Feder GL, Finkelman RB. A possible link between Balkan endemic nephropathy and the leaching of toxic organic compounds from Pliocene lignites by groundwater. Int J Coal Geol. 1999;40:237–252
  59. Orem WH, Tatu CA: Health Effects of Toxic Organic Compounds from Coal—The Case of Balkan Endemic Nephropathy (BEN), in USGS: USGS Fact Sheet FS–004–01. Reston, VA, April 2001
  60. Goldberg MC, Feder GL, Radovanovic Z. Correlation of Balkan endemic nephropathy with fluorescent organic compounds in shallow ground water. Appl Hydrogeol. 1994;2:15–23
  61. Niagolova N, McEllmurry SP, Voice TC, et al. Nitrogen species in drinking water indicate potential exposure pathway for Balkan endemic nephropathy. Envir Pollut. 2005;134:229–237
  62. Voice TC, McElmurry SP, Long DT, Dimitrov P, Ganev VS, Petropoulos EA. Evaluation of the hypothesis that Balkan endemic nephropathy is caused by drinking water exposure to contaminants leaching from Pliocene coal deposits. J Expo Sci Environ Epidemiol. 2002;16:515–524
  63. Palca J. Eastern Europe: Missing an opportunity. Science. 1991;248:20–22
  64. Uzelac-Keserović B, Spasić P, Bojanić N, et al. Isolation of a coronavirus from kidney biopsies of endemic Balkan nephropathy patients. Nephron. 1999;81:141–145
  65. Riquelme C, Escors D, Ortego J, et al. Nature of the virus associated with endemic Balkan nephropathy. Emerg Infect Dis. 2002;8:869–870
  66. Toncheva D, Dimitrov T, Stojanova S. Etiology of Balkan endemic nephropathy: A multifactorial disease?. Eur J Epidemiol. 1998;14:389–394
  67. Toncheva D, Dimitrov T, Tzoneva M. Cytogenetic studies in Balkan endemic nephropathy. Nephron. 1988;48:18–21
  68. Stefanović V. Balkan endemic nephropathy: A need for novel aetiological approaches. Q J Med. 1998;91:457–463
  69. Toncheva D, Dimitrov T. Genetic predisposition to Balkan endemic nephropathy. Nephron. 1996;72:564–569
  70. Toncheva DI, Gergov TD, Tzoneva MT, Bouchakliev ZP. Spontaneous and induced chromosome aberrations in Balkan endemic nephropathy. Kidney Int Suppl. 1991;34:S97–S101
  71. Dimitrov PS, Simeonov VA, Ganev VS, Karmaus WJ. Is the incidence of Balkan endemic nephropathy decreasing?. Pathol Biol (Paris). 2002;50:38–41
  72. Cukuranovic R, Petrovic B, Cukuranovic Z, Stefanovic V. Balkan endemic nephropathy: A decreasing incidence of the disease. Pathol Biol (Paris). 2000;48:558–561
  73. Djukanovic L, Radovic M, Bakovic J, et al. Epidemiology of end-stage renal disease and current status of hemodialysis in Yugoslavia. Int J Artif Organs. 2002;25:852–859
  74. Stefanovic V, Toncheva D, Atanasova S, Polenakovic M. Etiology of Balkan endemic nephropathy and associated urothelial cancer. Am J Nephrol. 2006;26:1–11
  75. Abid S, Hassen W, Achour A, et al. Ochratoxin A and human chronic nephropathy in Tunisia: Is the situation endemic?. Hum Exp Toxicol. 2003;22:77–84
  76. Orem W, Tatu C, Pavlovic N, et al. Health effects of toxic organic substances from coal: Toward “panendemic” nephropathy. Ambio. 2007;36:98–102

PII: S0272-6386(08)00993-1

doi: 10.1053/j.ajkd.2008.05.024

American Journal of Kidney Diseases
Volume 52, Issue 3 , Pages 606-616 , September 2008

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