NUTRITIONAL STATUS OF PATIENTS ON MAINTENANCE HEMODIALYSIS WITH BALKAN (ENDEMIC) NEPHROPATHY

The aim of this study was to ascertain the nutritional status of patients with Balkan (Endemic) Nephropathy (BEN) on maintenance hemodialysis (HD). The specimen of examines included 14 patients with BEN and 178 patients with another diagnosis on hemodialysis in Institute of Nephrology and Hemodialysis, Clinical Center Nis in 2002. Body mass index (BMI) of male patients with BEN was 25.7±5.0 kg/m2; normal body weight was present in 66.7% of cases and obese in 33.3% of cases. BMI of female patients with BEN was 24.5±4.3 kg/m2; malnutrition was present in 12.5% of cases, normal body weight in 50.0% and obese in 37.5% of cases. Anthropometric indexes (BMI, lean body mass, body height, relative body weight, biceps, triceps, sub-scapular and iliac skinfold thickness, as well as, percent of body fat, mid-arm circumference and mid-arm muscle circumference) of another HD patients was slight lower then HD patients with BEN, but differences was not statistically significant

THE AVERAGE VOLUME OF FETAL KIDNEY DURING DIFFERENT PERIODS OF GESTATION

Early antenatal diagnostics and importance of genetic consultation are of great interest for echosonographical evaluation of normal fetus’ anatomy. The research was carried out on kidneys of 100 fetuses of both sexes, ages ranging from IV to X lunar months. Each of the fourth and fifth lunar month was subdivided in two groups because of very progressive kidney growth. All fetuses were fixed in formaldehyde for a period of 30 days, at least. Macrodissection was used to extract both kidneys en block. After separation from the surrounding tissue, their volumes were measured by the method of sinking into the glass gauge. The corrections were made on the results of the procedure by means of the shrinkage factor.Average volume of fetal kidney in the first half of IV lunar month was 0,33 ml and continually increased up to 8,68 ml (left kidney) and 9,53 ml (right kidney) in X lunar month.The kidney shows statistically significant (p<0,05) increase of volume in the second half of IV lunar month and in VI lunar month.The highest value ratio volume/crown-rump length displays in X lunar month when the kidney is physically prepared for full taking over of all its functions after birth

TUMORS OF THE KIDNEY AND URINARY TRACT IN ENDEMIC AREA OF VILLAGE BRESTOVAC

During the twenty- five-year period the incidence of urothelial tumors was followed in the endemic village Brestovac. Thirty patients (3 of which with confirmed endemic nephropathy and 15 persons with suspected nephropathy) were investigated. Our retrograde study showed that there is a relationship between endemic nephropathy and urothelial cancer, and this association persisted with marked tendency to rise. Tumors were more common among males, aged from 50 to 70 years, with upper urinary tract urothelial cancer, papillary or trancellular forms, predominantly. Clinical feature showed classic triad of hematuria, flank pain and, rarely, flank mass, accompanied with non-specific symptomatology. Normal renal function was observed in 25 patients, but chronic renal failure was proven in five. Ten patients were treated by surgery, while 20 patients were treated by conservative therapy. There are no marked risk factors

Whole genome methylation array analysis reveals new aspects in Balkan endemic nephropathy etiology

Background Balkan endemic nephropathy (BEN) represents a chronic progressive interstitial nephritis in striking correlation with uroepithelial tumours of the upper urinary tract. The disease has endemic distribution in the Danube river regions in several Balkan countries. DNA methylation is a primary epigenetic modification that is involved in major processes such as cancer, genomic imprinting, gene silencing, etc. The significance of CpG island methylation status in normal development, cell differentiation and gene expression is widely recognized, although still stays poorly understood. Methods We performed whole genome DNA methylation array analysis on DNA pool samples from peripheral blood from 159 affected individuals and 170 healthy individuals. This technique allowed us to determine the methylation status of 27 627 CpG islands throughout the whole genome in healthy controls and BEN patients. Thus we obtained the methylation profile of BEN patients from Bulgarian and Serbian endemic regions. Results Using specifically developed software we compared the methylation profiles of BEN patients and corresponding controls and revealed the differently methylated regions. We then compared the DMRs between all patient-control pairs to determine common changes in the epigenetic profiles. SEC61G, IL17RA, HDAC11 proved to be differently methylated throughout all patient-control pairs. The CpG islands of all 3 genes were hypomethylated compared to controls. This suggests that dysregulation of these genes involved in immunological response could be a common mechanism in BEN pathogenesis in both endemic regions and in both genders. Conclusion Our data propose a new hypothesis that immunologic dysregulation has a place in BEN etiopathogenesis. Keywords: Epigenetics; Whole genome array analysis; Balkan endemic nephropath

MORPHOMETRIC CHARACTERISTICS OF THE PINEAL ACERVULI DURING THE HUMAN AGING

Acervuli of 30 human pineal gland, were investigated during our research. They were collected during the autopsies at the Institut for forensic medicine of the Faculty of Medicine in Niš. Pineal tissue was processed with standard histologic procedure. Then, it was cut into 10 mm thick sections which were stained with HE, PAS, AB PAS and Mallory’s trichrome connective tissue stain. After that they were analyzed with light microscope. Morphometric analysis was performed by astereologic method. The B100 double square lattice test system was used. Average area, average perimeter, average diameter and contour index were calculated for the pineal acervuli of each age group. Obtained morphometric parameters were statisticaly analyzed. Acervuli were colored blue on HE stained sections. They were PAS and AB PAS positive structures which had red colored center and blue colored periphery on Mallory’s trichrome stained sections. Laminate structure was present, but it was not so concentric as it was in pineal capsula acervuli. Acervuli of the first age group had regular shape. They were localized at the pineal gland periphery. Acervuli of the second and the third age group obtained larger dimensions and more irregular shape, which finally led to mulberry structures formation in the core of the pineal gland. They were probably the result of the conglomeration of just formed with already formed ones. The increase of the average area, average parimeter, average diameter and contour index confirmed the increase of pineal acervuli dimensions and their shape irregularity during the aging process.Therefore, pineal acervuli show the increase of dimensions and shape irregularity. Finally, the process of conglomeration leads to mulberry like structures formation, in the second and the third age group which dominate pineal tissue in these age groups

Predictive Markers for Malignant Urothelial Transformation in Balkan Endemic Nephropathy: A Case–Control Study

Balkan endemic nephropathy (BEN) is a chronic tubulointerstitial disease frequently accompanied by urothelial carcinoma (UC). In light of the increased UC incidence and the markers observed in BEN patients with developed UC, the aim of the current case&ndash;control study is to assess survivin, p53 protein, growth factors and receptors (VEGF, VEGFR1, IGF I, IGF-1R and IGFBP5), tumor marker (TF)/CD142, circulating soluble Fas receptor and neopterin, as potentially predictive markers for UC in patients with BEN (52 patients), compared to healthy, age-matched subjects (40). A threefold increase was registered in both circulating and urinary survivin level in BEN patients. Especially noticeable was the ratio of U survivin/U Cr level five times the ratio of BEN patients associated with standard renal markers in multivariate regression models. The concentrations of VEGF, VEGFR1, (TF)/CD142, (sFas) were not significantly different in BEN patients, while urinary/plasma level demonstrated a significant decrease for VEGF. The levels of IGF I, IGFBP5 and IGF-1R were significantly reduced in the urine of BEN patients. Plasma concentration of neopterin was significantly higher, while urinary neopterin value was significantly lower in BEN patients compared to healthy controls, which reflected a significantly lower urine/plasma ratio and low local predictive value. As BEN is a slow-progressing chronic kidney disease, early detection of survivin may be proposed as potential predictor for malignant alteration and screening tool in BEN patients without the diagnosis of UC

Diagnostic criteria for Balkan endemic nephropathy: proposal by an international panel.

Balkan endemic nephropathy (BEN) is a familial chronic tubulointerstitial disease with insidious onset and slow progression to terminal renal failure. Diagnostic criteria for BEN have been described more than 40 years ago. Research groups on BEN use one of at least three described lists of criteria. Comparison of studies using such criteria is difficult, and a recent meeting of investigators (Zagreb, October 2006) has suggested that unified criteria have to be elaborated. In this paper, an International Panel of BEN Investigators agreed on criteria appropriate to epidemiologic studies and clinical investigations of BEN. A screening procedure of BEN in endemic settlements is proposed

MicroRNA Profiling in Patients with Upper Tract Urothelial Carcinoma Associated with Balkan Endemic Nephropathy

Balkan endemic nephropathy (BEN) is a disease that affects people that live in the alluvial plains along the tributaries of the Danube River in the Balkan region. BEN is a chronic tubulointerstitial disease with a slow progression to terminal renal failure and has strong association with upper tract urothelial carcinoma (UTUC). There are several hypotheses about the etiology of BEN, but only the toxic effect of aristolochic acid has been confirmed as a risk factor in the occurrence of the disease. Aberrantly expressed miRNAs have been shown to be associated with many types of cancers. A number of studies have investigated the expression of microRNAs in urothelial carcinoma, mainly on urothelial bladder cancer, and only a few have included patients with UTUC. Here we present the first study of microRNA profiling in UTUC tissues from patients with BEN (BEN-UTUC) and patients with UTUC from nonendemic Balkan regions (non-BEN-UTUC) in comparison to normal kidney tissues. We found 10 miRNAs that were differentially expressed in patients with BEN-UTUC and 15 miRNAs in patients with non-BEN-UTUC. miRNA signature determined in BEN-UTUC patients differs from the non-BEN-UTUC patients; only miR-205-5p was mutual in both groups