Danubian Endemic Familial Nephropathy

The endemic nephropathy commonly called 'Balkan' is more properly called Danubian. It occurs in a relatively restricted rural area of Roumania, Bulgaria and Yugoslavia near the Danubian Iron Gates. Clinical, epidemiologic and laboratory investigations are thought to have excluded selected forms (although not necessarily all forms) of infection, parasitism, intoxication, and radiation. 'No genetic factors are evident. Of paramount importance are household factors and living conditions' (Craciun and Rosculescu, 1970). On the other hand these authors state that 'the disease in a family may disappear within two or three generations.' The histologic end stage of the kidney lesion is thought to be a form of primary amyloidosis.

Nephropathia epidemica (NE) is endemic in Scandinavia, European Russia, and the Balkans (Lee and van der Groen, 1989). Mustonen et al. (1996) stated that the causative agent, Puumala virus, is a member of the hantavirus genus. Korean hemorrhagic fever is caused by one hantavirus serotype and the Balkan form by another. The natural host of hantaviruses are chronically but asymptomatically infected rodents and insectivores, which transmit the virus to humans in their excretions. Transmission from human to human has not been reported. A hantavirus pulmonary syndrome was described by Duchin et al. (1994) in U.S. patients. There is considerable variability in the clinical severity of NE. As judged from the seroprevalence in Finland (6%), many infections must be subclinical or undiagnosed. In 74 adult patients with NE, Mustonen et al. (1996) found that patients with the most severe course of the disease had a very high frequency of HLA-B8 (142830), C4A*Q0 (120810), and DRB1*0301 (142857) alleles. HLA-B8 was found in all 7 cases (100%) with shock and in 9 of the 13 (69%) patients who required dialysis, versus only 25 of 74 (34%) in the entire population, and 14 of 93 (15%) controls.

Toncheva and Dimitrov (1996) performed chromosome studies of healthy relatives of patients with Balkan endemic nephropathy who were born in nonendemic areas and found a high frequency of abnormalities at 3q25. The authors concluded that an increased frequency of nonrandom 3q25 aberrations may be involved in the development of the disease even in the absence of exposure to a 'BEN' environment. Toncheva et al. (1988) observed mosaicism for t(1;3)(q11.2;q25) in a patient with BEN.

Stefanovic (1998) interpreted the accumulating evidence that BEN is an environmentally induced disease. Weathering of low-rank coals near the villages where BEN is endemic produces water-soluble polycyclic aromatic hydrocarbons and aromatic amines, similar to metabolic products of acetaminophen that cause analgesic nephropathy. Familial aggregation of BEN was first described by Danilovic et al. (1957). Stefanovic (1998) pointed out that the development of BEN in emigrants from the endemic region who resettled far away supports the role of inheritance in the disorder. An increased incidence of tumors of the renal pelvis and ureter in the population from endemic settlements has been observed. Familial clustering of urinary tract tumors was also reported from these areas.