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Introduction: Pre-eclampsia (PE) is characterized by new-onset hypertension and proteinuria. Damage of podocyte cells has been reported in pre-eclamptic women, thus podocyte specific proteins such as nephrin and podocalyxin could be useful biomarkers in PE. Aim: To investigate the role of urinary nephrin (u-nephrin) and urinary podocalyxin (u-PDX) levels in predicting PE in women with a high-risk pregnancy. Materials and methods: We included 101 pregnant women in this study and allocated them into three groups: group 1 included pregnant women at high risk of developing PE (n=41), group 2 - pregnant women with PE (n=30), and group 3 was the controls including healthy pregnant women (n=30). The inclusion criteria for women with PE were de novo hypertension >140/90 mm Hg, proteinuria >300 mg/24 hours, and presence of edema after 20 weeks of gestation, while the exclusion criteria were a history of renal diseases and pregnant women younger than 18. Inclusion criteria for the group of women with a high-risk pregnancy was gestational week >15, a history of PE in a previous pregnancy, pre-existing diabetes type 1 or 2, pre-existing hypertension, multiple gestations, prior placental abruption, obesity women, nulliparity, maternal age >35 years, and a family history of PE. The study was conducted from March 2016 to May 2017 in the Medical Faculty at the Institute of Medical and Experimental Biochemistry in Skopje. Urine samples were used to measure the nephrin and podocalyxin levels using immunoenzyme assay, creatinine and microalbumin. Blood samples were collected for biochemical analyses. Results: U-nephrin levels were elevated in 96.7% of women with PE, and 73% of women with a high-risk pregnancy. U-PDX levels were elevated in 63% of the women with PE and 100% of the women with a high-risk pregnancy. U-nephrin and u-PDX levels were significantly increased in women with a high-risk pregnancy and women with PE compared with a control group (p Conclusions: U-nephrin and U-PDX levels could be useful as predictors of PE in women with a high-risk pregnancy.

Lipoprotein(a) – Lp(a) – is an independent risk factor for cardiovascular disease (CVD). Indeed, individuals with plasma concentrations of Lp(a) > 200 mg/l carry an increased risk of developing CVD. Circulating levels of Lp(a) are remarkably resistant to common lipid lowering therapies, currently available treatment for reduction of Lp(a) is plasma apheresis, which is costly and labour intensive. The Lp(a) molecule is composed of two parts: LDL/apoB-100 core and glycoprotein, apolipoprotein(a) – Apo(a), both of them can interact with components of the coagulation cascade, inflammatory pathways and blood vessel cells (smooth muscle cells and endothelial cells). Therefore, it is very important to determine the molecular pathways by which Lp(a) affect the vascular system in order to design therapeutics for targeting the Lp(a) cellular effects. This paper summarises the cellular effects and molecular mechanisms by which Lp(a) participate in atherogenesis, thrombogenesis, inflammation and development of cardiovascular diseases.

Urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary N-acetyl-bd-glucosaminidase (NAG), urinary α1-microglobulin/creatinine ratio and cystatin C have been suggested as potential early markers of delayed graft function (DGF) following kidney transplantation. We conducted a prospective study in 50 consecutive kidney transplant recipients to evaluate serial changes of these biomarkers within the first week after transplantation and assess their performance in predicting DGF (dialysis requirement during initial post-transplant week) and graft function throughout the first year. Urine samples were collected on post-transplantation days 0, 1, 2, 4, and 7. Statistical analysis: Linear mixed and multivariable regression models, receiver-operating characteristic (ROC), and areas under ROC curves were used. At all-time points, mean urinary NGAL levels were significantly higher in patients developing DGF. Shortly after transplantation (3-6 h), uNGAL and uNAG values were higher in DGF recipients (on average +242 ng/mL; NAG – 6.8 U/mmol creatinine, considering mean dialysis time of 4.1 years) and rose further in the following days, contrasting with prompt function recipients. On Day-1 uNGAL levels accurately predicted DGF (AUC-ROC = 0.93), with a performance higher than serum creatinine (AUC-ROC = 0.76), and similar to cystatin C (AUC-ROC = 0.95). Multivariable analyses revealed that uNGAL levels at days 4 and 7 were strongly associated with one-year serum creatinine level. Urinary NGAL, serum cystatin C is an early marker of graft injury and is independently associated with dialysis requirement within one week after transplantation and one-year graft function.

Fournier’s gangrene (FG) is a necrotizing fasciitis of the genital, perianal and perineal regions, caused by multiple anaerobic/aerobic infection. It is a rare but very serious condition with multiple long-term complications and high mortality rate. Early diagnosis and multidisciplinary approach in treatment of complicated cases of FG are crucial to the successful outcome. We report a case of an extensive FG in a 59-years-old female patient with multiple risk factors such as obesity, type 2 diabetes and hypertension. She was hospitalized as an emergency case with diabetic ketoacidosis, sepsis and extensive necrotic lesions located perineal, perianal, genital and spread to inguinal, hypogastric, gluteal and sacrococcygeal region. Fournier’s gangrene was diagnosed, and after prompt resuscitation, intravenous fluids, broad-spectrum antibiotics, insulin infusion, emergency aggressive surgical debridement was performed. Several aerobic and anaerobic bacteria were isolated from wound culture and hemoculture. Patient has second debridement after four days. After second debridement was applied metabolic control, broad-spectrum antibiotics coverage, dressing the wound and negative pressure wound therapy (NPWT). Patient was discharged home five weeks after a second debridement in good condition. One month later she underwent reconstructive surgical treatment. Besides extensive FG and multiple comorbidity she was successfully managed with good outcome. Fournier’s gangrene remains a life-threatening and fulminant disease which need urgent diagnosis and aggressive medical and surgical treatment, to achieve a reduction in long term complications and mortality rate.

BACKGROUND: Proteinuria, in addition to haematuria, is the most important laboratory parameter in patients with nephro-urological diseases. Low molecular weight proteinuria (LMWP) is of particular importance because some diseases genetic and tubulointerstitial are diagnosed based on its presence.AIM: The purpose of this study is to describe the clinical features, the course and outcome of pediatric patients with a renal disease associated with LMWP.MATERIAL AND METHODS: This retrospective observational study included 250 pediatric patients with various kidney diseases in which the type of proteinuria was defined by 4-20% gradient gel sodium dodecyl sulphate polyacrylamide gel (SDS-PAG) electrophoresis.RESULTS: Isolated LMWP was detected in 12% of patients, while mixed glomerulotubular proteinuria was detected in 18% of patients. It was detected in all patients with the Dent-1/2 disease, Lowe's syndrome and secondary Fanconi syndrome. Transient LMWP was also detected in a series of 12 patients with distal renal tubular acidosis. In patients with nephrotic syndrome, it was associated with corticoresistence and unfavourable clinical course.CONCLUSION: This study contributes to the understanding of the clinical spectrum of various kidney diseases associated with LMWP, their natural course, and the effect of therapy.

Objective: Febrile proteinuria is functional proteinuria and is seen as a transitory phenomenon during acute febrile illness, mainly viral infections. It is a benign phenomenon and clears promptly with resolution of the infection. Clinical Presentation and Intervention: In this report, we present a patient who was thought to have febrile proteinuria. Persistence of significant proteinuria after resolution of the infection prompted biochemical and genetic workup which led to the diagnosis of Dent-2 disease. Conclusion: We recommend the use of SDS-PAGE (sodium dodecyl sulfate electropheresis) for the detection of low molecular weight proteinuria.

Distal renal tubular acidosis (dRTA) (MIM #267300, #602722 and #179800) is a rare inherited tubulopathy characterized by the inability of the distal tubule to acidify the urine with consecutive systemic acidosis. The clinical features include polyuria, polydipsia, poor appetite, failure to thrive, short stature and rickets. Prominent biochemical features are hypokalemia, hypercalciuria and hypocitraturia. There are reports on patients who presented with unusual biochemical features such as low molecular proteinuria, hypophosphatemia, hypouricemia, generalized hyperaminioaciduria, hyperoxaluria and other making diagnostic confusion to the clinicians. In this work, we report on a series of 8 children with clinically, biochemically and genetically proven dRTA who present with low molecular proteinuria at the disease onset. With metabolic compensation of the disease, there was complete resolution of the low molecular weight protenuria and other proximal tubular abnormalities in all children. Late recognition of the disease with long standing hypokalemia and acidosis may result in abnormal expression and function of the transporters in the proximal tubules. Sodium dodecyl sulphate polyacrylamide gel electrophoeresis is an accurate method for detection and follow up of patients with low molecular weight proteinuria.

Objective: Acute kidney injury is common condition in the neonatal intensive care unit and it is associated with poor outcome. The incidence of neonatal AKI is the highest one followed by adults and children, depending on different factors such as the gestational age, birth weight, contributing conditions and the facilities of the neonatal intensive care unit. The aim of the study was to determine the incidence, risk factors and the outcome of the neonatal acute kidney injury. Subjects and Methods: This was a clinical, prospective study that was performed in a referent NICU at the University Children′s Hospital in Skopje. All neonates admitted from January 2012 to December 20014 with documented acute kidney injury were included. The medical data records of the admitted neonates with AKI were analyzed. The material was statistically processed using methods of the descriptive statistics. Results: During the study period 770 newborn infants were admitted to the NICU and 50 (6.5%) infants developed acute kidney injury. The male to female ratio was 2.1:1. Most of the neonates involved in the study were neonates born at term (62%). Oliguric AKI was found in 28 cases (56%) and no oliguric in 22 cases (44%). The prevalence of prerenal, renal and post renal AKI were 78.5%, 19.5% and 2.0% respectively. Perinatal asphyxia was the most common predisposing factor for AKI and was evaluated in 38% of the cases with predominance of term infants and male. The mortality rate was 32% and was significantly higher in the group of patients with congenital heart diseases. Conclusion: AKI is a life threatening condition with still high mortality rate. Early recognition of the risk factors and the rapid effective treatment of the contributing conditions will reduce AKI in the neonatal period.

Objectives: To examine the alterations in LDL and HDL subclass distribution in ESRD patients compared with a control group and to investigate the relationship of LDL particle size to the other plasma lipoproteins levels. Design and methods: Plasma lipids, LDL and HDL subclasses were determined in 63 hemodialysis patients (HD), 42 predialysis patients and 345 control subjects. Lipoprotein subclasses were separated by polyacrylamide 3 to 31% gradient gel electrophoresis. Results: In predialysis group, 88% subjects had small LDL particles compared with 58.5% of hemodialysis patients and 16.5% of control subjects. Mean LDL size particle diameter was significantly smaller in HD and predialysis patients in comparison with controls (p < 0,0005, p < 0,0001; respectively). Significant inverse correlation between LDL particle size and triglyceride level was observed for both patient groups. Decreased levels of the largest HDL2b subclass was found in both predialysis (16.5%) and in HD patients (30%) as compared with controls (50%), and increased levels of the small HDL3a subclass was found only in predialysis group (21%) in comparison with controls (4.5%). Conclusions: Alterations in LDL and HDL subclass distribution toward smaller particles is the main lipid abnormality associated with atherogensis found in ESRD. ESRD is associated with reduced levels of HDL2b subclass and increased levels of HDL3c subclass, which occurs in coronary artery disease (CAD) as well.

Background: Lipoprotein subclass determinations provide a more detailed reflection of lipoprotein metabolism and an accurate prediction for risk of cardiovascular disease. Gradient gel electrophoresis for lipoprotein separation on Pharmacia electrophoretic apparatus has been most commonly used for many years. Methods: In this paper, we describe a new method for separating LDL and HDL subclasses by nondenaturing polyacrylamide gradient (3–31%) gel electrophoresis, using BioRad Mini Protean II electrophoretic cells. Results: The mean particle diameters of cholesterol-stained LDL and HDL lipoproteins were estimated after calibrating the gels with size standards, using fractional absorbance profiles. For the first time in the Republic of Macedonia, lipoprotein distribution and size phenotyping were studied in 345 healthy individuals. Large LDL subclasses (phenotype A) were dominant in 88.5% of the population, whereas small LDL subclasses (phenotype B) were dominant in 11.5%. The mean dominant LDL size was 26.08±0.8 nm. Five HDL subclasses were separated on the same gels, and HDL2b and HDL2a (larger) were dominant in healthy Macedonians. Conclusion: Antiatherogenic, larger LDL and HDL particles are most commonly found in healthy populations in the Republic of Macedonia.

Cholesteryl ester transfer protein (CETP) plays a key role in reverse cholesterol transport and high density lipoprotein (HDL) metabolism. Predominance of small, dense LDL particles is associated with an increased risk of atherosclerosis and coronary heart disease (CHD). The aim of the study was to determine the potential relationship between the CETP concentration and low density lipoprotein (LDL) particle size and their association with intima media thickness (IMT) in patients with CHD. Lipid parameters, CETP concentration and LDL particle size were determined in 100 healthy subjects (control group) and in 100 patients with CHD, aged 43 to 77 years. Plasma CETP concentrations were measured by an enzyme-linked immuno-sorbent assay with two different monoclonal antibodies. LDL subclasses were separated by nondenaturing polyacrilamide 3-31% gradient gel electrophoresis. CETP concentration was higher in patients compared to controls (2.02 ± 0.75 mg/ml vs. 1.74 ± 0.63 mg/ml, p