Balkan Endemic Nephropathy. a Reaprrisal after Forty Years

Balkan endemic nephropathy (BEN) was described in 1957, and this review gives an account of research forty years later. The etiology remains the main unanswered problem in BEN despite broad investigations conducted into the possible role of genetic factors, environmental agents and immune mechanisms.The evidence accumulated so far indicates that BEN is an environmentally-induced disease. A continuous, but cyclic, effect of environmental factors upon kidneys of children from the endemic settlements and endemic families in particular was demonstrated. Weathering of low-rank coals nearby the endemic villages produces water soluble polycyclic aromatic hydrocarbons and aromatic amines, similar to metabolic products of acetaminophen that has a causal relationship with analgesic nephropathy. Many of these compounds are known to be carcinogenic and could also cause urothelial cancer. The similarity of the morphological and clinical pattern of BEN and Chinese herb nephropathy has raised the possibility of a common etiologic agent, aristolochic acid. Genetic studies have landed support for genetic predisposition to BEN. Kidney morphology in early stages of the disease is peculiar and resembles that of aging with pronounced renal vascular changes. The histopathology is predominantly tubulointerstitial sclerosis without infiltrates. Humoral immune mechanisms do not appear to play a pathogenic role in BEN. An increased incidence of tumors of renal pelvis and ureter in patients with BEN and in population from endemic settlements has been observed. Recently the frequency of urinary bladder tumors in endemic settlements was also found increased compared with the nonendemic villages and cities. The geographic correlation between BEN and urinary tract tumors supports the speculation that these diseases share a common etiology.