Vol. 9, No 1, 2002 pp. 92 - 94
UC 616.61-004 616.611 616.612
DAMAGE TO KIDNEY IN BALKAN ENDEMIC NEPHROPATHY:
INITIAL LESION, TARGET STRUCTURES AND PATHOMORPHOGENESIS
Vojin Savić1, Rade Čukuranović1,
Natalija Stefanović2, Vladisav Stefanović1
1Institute of Nephrology and Hemodialysis,
Faculty of Medicine, Niš, Serbia
2Institute of Anatomy, Faculty of Medicine,
Niš, Serbia
E-mail: stefan@ni.ac.yu
Summary. Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial
kidney disease of unknown etiology. Not only the etiology of the disease
but even the initial lesion, target nephron structure and morphogenesis
remain unresolved. We have previously performed quantitative morphometric
analysis on kidney biopsy specimens of patients in different stages of
BEN (without renal failure, with initial and advanced renal failure). In
the initial stage of the disease, when glomerular filtration rate is normal,
the increase of cortical interstitium and a reduction of glomerular volume
are demonstrated. A significant reduction of the tubular epithelium volume
density is characteristic of the advanced stage. The number of renal interstitial
capillaries per 0.1 mm2, and the lenght density expressed per mm2, both
significantly decreased in BEN patients with normal kidney function (p<0.01)
and with renal failure (p<0.001).
We have also investigated the immunolocalization of laminin, cytokeratin
and vimentin in the kidney of patients in different stages of BEN. In the
early stages of BEN a marked overexpression of laminin in renal interstitial
capillaries was observed with a moderately increased expression in tubules.
Later stages were characterized by intensive expression of laminin in atrophic
tubules, much more in proximal than in distal ones. The coexpression of
vimentin and cytokeratin in proximal tubular cells was also demonstrated.
Evidence is presented that renal vascular changes occur early in BEN.
A significant role of tubular injury in the pathogenesis of BEN was supported
by the finding of vimentin and cytokeratin coexpression in the tubular
epithelial cells. Interstitial sclerosis could result from the overproduction
of extracellular matrix by injured proximal tubular epithelium and interstitial
capillary endothelial cells. The changes described, particularly those
taking place at the level of interstitium, bear the key responsability
for the BEN progression.
Key words: Balkan endemic nephropathy, cortical interstitium,
interstitial capillaries, interstitial sclerosis, glomeruli, proximal tubules
