Faculty of Medicine

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    Podocalyxin and kidney diseases
    (Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine, 2025-04)
    Kostovska, Irena
    Selectivity of blood filtration by the renal glomerulus is largely determined by the presence in its visceral epithelium of the terminally differentiated “octopus-like” cells called podocytes. Podocalyxin (PoDXL) is a major transmembrane glycoprotein located on the podocytes’ apical surface. Recently, the appearance of PoDXL in urine has been considered a marker of nephropathy. the purpose of this review article is to analyze the data of studies on the structural and functional features of podocalyxin and its value in diagnostic, prognostic and potential therapeutic relevance in most common kidney diseases.
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    LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A2 (Lp‐PLA2) AS A PREDICTOR OF END-STAGE RENAL DISEASE IN PATIENTS WITH DIABETIC NEPHROPATHY
    (Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, 2024-12-11)
    Kostovska, Irena
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    Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a specific biomarker for vascular inflammation. It is associated with microvascular complications such as diabetic nephropathy (DN) in patients with type 2 diabetes mellitus. To determine the predictive value of Lp-PLA2 concentration/activity for end-stage renal disease (ESRD) in patients with DN. A total of 94 patients included in this cross-sectional study with DN were divided into four stages of chronic kidney disease (CKD) according to CKD-EPI: Stage II (n=20), Stage IIIa (n=29), Stage IIIb (n=38), and Stage IV (n=7). Forty-four healthy subjects were used as a control group. In addition to anamnestic data (age, gender, body weight, height, glycemic control), we measured the concentration of glucose, total cholesterol, triacylglycerols, blood urea, and creatinine in the blood serum using standard photometric methods. Lp-PLA2 concentration/activity was measured by chemiluminescence immunoassay-CLIA. Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) serum creatinine was used to determine the GFR and CKD stages. We found significant differences among subgroups of patients with DN divided according to CKD stage and healthy subjects regarding age, body mass index, duration of disease, blood glucose, glycated hemoglobin, total cholesterol, triacylglycerols, blood urea, serum creatinine, GFR, and Lp-PLA2. A significant negative correlation was found between Lp‐PLA2 and GFR. ROC analysis showed that Lp-PLA2 had a positive predictive value of 98.3% in patients with DN. Lp-PLA2 gradually increased in stages of DN. Lp-PLA2 could be considered as a potential predictive biomarker for the progression of DN to ESRD.
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    DIAGNOSTIC ACCURACY OF MICROALBUMINURIA IN SECONDARY NEPHROPATHIES
    (Central Medical Library Medical University – Sofia, Bulgaria, Sciendo, 2024-10)
    Kostovska, Irena
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    Introduction: Microalbuminuria is an initial indicator of kidney damage in diabetic nephropathy (DN), hypertensive nephropathy (HN), and pre-eclampsia (PE). This study aims to assess the diagnostic accuracy of urinary microalbumin to creatinine ratio (UM/CR) as an early diagnostic tool in patients with DN, HN, and PE.
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    NEPHROPROTECTIV EFFECTS OF CANDESARTAN ON DIABETIC NEPHROPATHY IN RATS
    (Macedonian Association of Anatomists and Morphologists, 2023)
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    Kolovchevski, Nikola
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    Shikole, Emilija
    Diabetic nephropathy (DN) stands out as a primary contributor to end-stage kidney damage. The renin-angiotensin system (RAS) plays a pivotal role in the advancement of DN, making angiotensin receptor blockers (ARBs) particularly noteworthy due to their influence on angiotensin II in DN development. This study investigated the impact of the angiotensin receptor blocker candesartan (CAN) on rats with streptozotocin (STZ)-induced DN, characterized by albuminuria, renal hypertrophy, and mild glomerulosclerosis.DN was induced in normotensive Wistar rats through a single injection of STZ (60 mg/kg ip). STZ administration led to diabetes mellitus (DM) symptoms and DN indicators, such as poor general condition, weight loss, increased kidney weight, elevated serum creatinine levels and BUN, augmented diuresis, and notable albuminuria. These manifestations were prominent at 4 weeks, intensifying further at 8 and 12 weeks post-STZ injection. Commencing candesartan treatment (5 mg/kg BW) at the 4-week mark post-STZ injection significantly alleviated all DN symptoms, reducing serum creatinine values and BUN, albuminuria, and diuresis. Histopathological examination at 8 and 12 weeks revealed that candesartan effectively mitigated glomerulopathy progression, improved the glomerulosclerotic index, and attenuated renal histological abnormalities induced by STZ. In conclusion, candesartan treatment ameliorates STZ-induced nephropathic changes in DM rats.
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    The role of TGF-β1 in the development of diabetic nephropathy experimentally induced by Streptozotocin and the nephroprotective effects of Candesartan
    (Macedonian Association of Anatomists and Morphologists, 2023-12)
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    Shikole Emilija
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    Kolovchevski, Nikola
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    Labachevski, Bojan
    Diabetic nephropathy (DN) stands as a prevalent and severe complication of diabetes mellitus (DM), lacking adequate medical therapy. The molecular mechanisms contributing to glomerular membrane damage involve the overactivity of angiotensin II, heightened expression of nephrin, vascular endothelial growth factor (VEGF), and notably, intraglomerular transforming growth factor TGF-β1. Pharmaceutical treatments targeting hemodynamic disturbances in diabetic nephropathy, such as ACE inhibitors and angiotensin receptor blockers (ARBs), hold promise for DN therapy. This study aimed to assess the role of intraglomerular TGF-β expression in experimentally induced DN in rats and explore the nephroprotective effects of candesartan. Diabetes mellitus was induced through a single intraperitoneal injection of streptozotocin (STZ) at 60 mg/kg, and DN was allowed to develop over four weeks. DM rats were randomly assigned to two groups: STZ (untreated) and STZ+CAN (treated with candesartan at 5 mg/kg/day from week 4 to week 12). STZ administration led to a substantial increase in TGF-β1 expression in the glomeruli, exceeding control levels by 5-6 times. Candesartan treatment demonstrated a significant reduction in glomerular proliferation and subsequent expansion of the mesangial matrix, suggesting a potential mechanism by which these drugs achieve therapeutic effects.
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    NGAL and Cystatin C: Two possible early markers of diabetic nephropathy in patients with type 2 diabetes mellitus
    (Македонско лекарско друштво = Macedonian Medical Association, 2020-12)
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    Introduction. Diabetic nephropathy (DN) is a progressive renal impairment characterized by impaired renal architecture and function and is one of the leading causes of permanent renal impairment. Patients with DN have a high mortality rate, which is primarily due to cardiovascular complications. In everyday practice in the Republic of North Macedonia, serum creatinine, microalbuminuria and glomerular filtration rate are used to detect DN. However, these standard tests do not always allow for detection of initial DN damage. Aim. The aim of this study was to investigate the role of NGAL (in urine) and Cystatin C (in serum) values as adjunctive testing of existing markers (microalbuminuria and creatinine) in unmasking early structural and functional renal impairment in asymptomatic patients with type 2 diabetes mellitus (DM type 2). Methods. This was a prospective, observational (6-month follow-up) study, involving 60 patients aged 35-70 years. The first two groups were patients with diagnosed DM type 2 for a minimum of 5 years, 15 patients diagnosed with DM type 2 with diabetic nephropathy and 15 patients without diabetic nephropathy. The third group consisted of healthy respondents (30). In addition to standard biochemical analyses, the three groups were also examined for body fluid concentrations of NGAL (architect urine NGAL) and Cystatin C (nephelometry), as well as standard biomarkers for renal nephropathy (serum creatinine and microalbumin). Results. The respondents from the three analyzed groups did not differ significantly in terms of gender structure (p=0.71) and age (p=0.068). The study found that (the core values) baseline creatinine, microalbuminuria, NGAL and Cystatin C serum levels were higher in patients diagnosed with DM type 2 and diabetic nephropathy (DN) compared to those with diabetes and without diabetic nephropathy in healthy trials. Also, after 6 months of follow-up, it was proven that in patients diagnosed with DM type 2 and DN all four parameters were higher with confirmed significance unlike the group of patients with DM type 2 without DN. In the group with diabetes and diabetic nephropathy, during the re-evaluation after 6 months of monitoring we registered a non-significant increase in the biomarker NGAL p=0.16), and a significant increase in the biomarker Cystatin C (p=0.016). There was a statistically significant correlation between baseline creatinine values and baseline control values of Cystatin C (p<0.0001), creatinine and NGAL values after a 6-month re-evaluation (p=0.014), all of which were positive. The correlation between the two biomarkers NGAL and Cystatin C were statistically insignificant in the first measurements (p=0.160), and were significant and direct positive on the second measurements, after 6 months (r=0.536, p=0.039). The two markers changed in direct proportion to the serum, with the increasing of one marker in the serum. Also, the other biomarker increased, and vice versa. Conclusion. NGAL and Cystatin C, biomarkers of renal impairment, are correlated with decreased renal function in patients with DM type 2, suggesting that NGAL and Cystatin C may be used as adjunctive tests to existing ones (creatinine and microalbuminuria) to unmask early renal dysfunction.