Balkan Endemic Nephropathy: An Autopsy Case Report

Abstract

Balkan endemic nephropathy (BEN) is a form of interstitial nephritis seen only in certain geographical areas in the Balkan peninsula. Herein we describe the gross and histological changes in a diseased 42-year-old male Caucasian patient with BEN. All the changes fit the classically described alterations, with copper hue discoloration of the skin of the torso and orange discoloration of the soles and palms. Grossly, the kidneys were atrophic, with the left one weighing 31 grams and the right one 32 grams. Their surface was predominantly smooth with areas of fine granulations and cystic transformations. Histology revealed hyalinization of the glomeruli, predominantly in the external part of the cortex, severe vascular changes, interstitial fibrosis, and scant inflammatory cell infiltrate. The renal pelvis and ureters revealed multiple urothelial papillomas and atypical urothelial hyperplasia. BEN is only one geographical variant of interstitial nephritis caused by exposure to aristolochic acid. Other forms of this condition include Chinese herb nephropathy/aristolochic acid nephropathy, as well as several similar endemic conditions with a yet unestablished link to aristolochic acid.

Unusual Urothelial Tumors and Refractory Uremia Due to Balkan Endemic Nephropathy: A Case Report

“…A literature search reveals that while there are some studies about epidemiological characteristics or proposed biomarkers/metabolic changes, 8 , 9 there is only 1 clinical case report about a patient with BEN referred post-mortem for autopsy. 10 This was a 34-year-old male who presented with anemia, HTN, and uremia—similar co-morbidities found in our patient’s presentation (though our patient did have concomitant MDS); he eventually had an arterio-venous fistula and for routine hemodialysis but unfortunately developed progressively worsening HTN and recurrent thrombotic events of the fistula. The patient then had a hospital admission for planned removal of the thrombotic fistula, and due to an inability to undergo appropriate hemodialysis, the uremia and anemia worsened and the patient passed away at age 41.…”

“…The renal biopsy of the patient in this case report in particular revealed urothelial atypia, which was found in our patient as urothelial carcinoma of the bladder wall (as confirmed in biopsy) and another site of likely urothelial carcinoma in the left UPJ (this site was not biopsied, but was stented). Interestingly, while the patient in the case report seems to have undergone 7 years of hemodialysis, 10 our patient did not have any hemodialysis until the last 4 days of hospital admission in which shortly after she passed away from likely refractory fluid overload and hypoxemia/hypotension.…”

“…We present this case to demonstrate a rare entity of CKD that can only be elucidated by a very careful social and epidemiological history, and that unfortunately, with prolonged disease, there is a real chance of late-stage ESRD and tumorigenesis refractory to aggressive medical management. 1 - 3 As seen in 1 other case report though, 10 it does appear that hemodialysis is an option for those that do go on to develop ESRD, provided that they are diagnosed in a timely fashion.…”

Aristolochic acid I as an emerging biogenic contaminant involved in chronic kidney diseases: A comprehensive review on exposure pathways, environmental health issues and future challenges

“…The clinical features of BEN differentiating it from other types of CKDs are: significantly decreased kidney size (>50 g); interstitial nephritis; association with urinary tract urothelial carcinoma (UTUC); anemia; albuminuria; glycosuria; tubular proteinuria and acidosis; lack of high blood pressure and a 1.5:1 female to male gender distribution (Stoyanov et al, 2021). Another peculiarity of BEN was discovered by Grollman's research, who was the first one to detected aristolochic acid-nuclear DNA (AA-DNA) adducts in kidney tissues and UTUC from Fig.…”

Alimentary Risk of Mycotoxins for Humans and Animals

“…OTA causes a dangerous disease called Balkan endemic nephropathy [37,38]. Moreover, for several years now, attention has been paid to the OTA contamination of white and red wines in Italy and other Mediterranean regions.…”