Renal function, protein excretion, and pathology of Balkan endemic nephropathy. III. Light and electron microscopic...

This study was performed to evaluate histomorphological features of BEN in 50 kidney biopsies from patients who met the epidemiologic, clinical and laboratory criteria for BEN. This is the first such study reported in detail. The patients were divided into three groups based on the DTPA clearance values: group 1, greater than 99 ml/min, group 2, 51 to 99 ml/min, and group 3, 29 to 50 ml/min. All patients in all groups had an increase in proteinuria consisting of proteins less than 25,000 daltons. Multifocal interstitial sclerosis spreading from the superficial into the deep cortex was found in 49 (98%), tubular atrophy in 48 (96%), and global glomerular sclerosis with microvascular hyalinosis/sclerosis of sclerotic and atrophic changes were significantly increased when compared to age-related standards. An accelerated aging process may be assumed to occur in BEN. More peculiar additional findings with much lower incidence and extent included multifocal vascular and glomerular capillary changes resembling the chronic form of thrombotic microangiopathy group of diseases. These findings, together with the presence of arteriolar hyalinosis and tubulointerstitial sclerosis seen in patients with cyclosporine nephrotoxicity suggest that the mechanism of toxicity may be similar to BEN. We conclude that the histopathology is predominantly tubulointerstitial sclerosis without infiltrates. The combination of the histology, tubular proteinuria, geographic distribution, familial occurrence, and the remarkable association with papillary transitional cell carcinoma of the renal pelvis and ureters, qualifies BEN as a unique disease.