Abstract

Balkan endemic nephropathy (BEN) represents a chronic tubulointerstitial nephropathy which is followed by the progression of kidney fibrosis to end-stage kidney failure. The critical involvement of poisons in food (aristolochic acid (AA), ochratoxin, and heavy metals) and selenium deficiency are among nutritive factors which contribute to the pathogenesis of BEN, due to reactive oxygen species (ROS) liberation and/or decreased antioxidative defence system. The aim of the study is to distinguish a possible systemic and local origin of ROS through the measurement of xanthine oxidase (XO) activity in urine and plasma, along with the determination of the oxidative changes in lipids and proteins. The study included 50 patients with BEN and 38 control healthy subjects. We noted increased levels of both thiobarbituric acid-reactive substances (TBARS) and advanced oxidation protein products (AOPPs) in the plasma of patients with BEN, compared to the control group (p < 0.001). The urinary levels of AOPPs were higher in patients with BEN in comparison to the control (p < 0.001). The specific activity of XO was significantly lower in plasma and urine in BEN samples, compared to controls (p < 0.005). Based on these results, we hypothesize that XO might not be considered a direct systemic or local contributor to ROS production in BEN, most probably because of the diminished kidney functional tissue mass and/or AA-induced changes in purine nucleotide conformation. The increased AOPP and TBARS level in both plasma and urine in BEN may predict ROS systemic liberation with toxic local effects.

Highlights

  • Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial nephropathy characterized by an unpredictable onset and a gradual progression to end-stage renal disease

  • The level of advanced oxidation protein products (AOPPs) in plasma and urine is shown in Figure 2, whereas Figure 3 shows the difference in plasma/urine AOPP ratio among groups

  • Compared to those in controls, plasma and urine levels of AOPPs and plasma/urine AOPP ratio were significantly increased in BEN patients (p < 0:05, p < 0:001, and p < 0:001, respectively)

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Summary

Introduction

Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial nephropathy characterized by an unpredictable onset and a gradual progression to end-stage renal disease. It has been reported that kidney transplantation in BEN patients, partially restores renal function, does not reduce the risk of developing UUC [5]. This disease was first discussed over sixty years ago [6, 7]. It is similar to all tubulointerstitial nephritic diseases and is characterized by progressive kidney atrophy and sclerosis [9].

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