Browsing by Author "Miloševski-Lomić, Gordana (20436011000)"

Introduction The causes of acute tubulointerstitial nephritis can be grouped into four broad categories: medications, infections, immunologic diseases, or idiopathic processes. Here we report a 17-year-old female who developed acute kidney injury (AKI) due to granulomatous interstitial nephritis (GIN) associated with influenza A: H1N1 infection. Case Outline The illness presented after two weeks of respiratory tract infection, skin rash and hypermenorrhea. On admission the patient was febrile, with bilateral pedal edema, macular skin rash, and auscultatory finding that suggested pneumonia. Laboratory investigations showed normocytic anemia, azotemia, hematuria and proteinuria. Renal ultrasound was normal. Antinuclear antibodies, antineutrophil cytoplasmic antibodies, lupus anticoagulant, antiphospholipid antibodies were negative with normal complement. Urine cultures including analysis for Mycobacterium tuberculosis were negative. The diagnosis of influenza A: H1N1 infection was made by positive serology. A kidney biopsy showed interstitial nephritis with peritubular granulomas. Glomeruli were normal. Staining for immunoglobulins A, M, G, and E was negative. The girl was treated with oseltamivir phosphate (Tamiflu; Genentech, Inc., South San Francisco, CA, USA) for five days, as well as with tapered prednisone after a starting dose of 2 mg/kg. The treatment resulted in a complete remission during two years of follow-up. Conclusion We present a severe but reversible case of GIN and AKI associated with influenza A: H1N1 infection. Although a causal effect cannot be confirmed, this case suggests that influenza A: H1N1 should be considered in the differential diagnosis of GIN manifested with AKI in children. © 2016, Serbia Medical Society. All rights reserved.

Introduction/Objective Jeune syndrome (JS) is a rare hereditary ciliopathy characterized by asphyxiating thoracic dystrophy, shortened limbs and brachydactyly. Extraskeletal anomalies such as chronic renal failure (CRF), hepatic fibrosis, and retinitis pigmentosa may be a part of the JATD phenotype. The aim of this study is to present long-term follow-up of JS patients with early progressive kidney disease. Methods This is a retrospective study of pediatric patients with JS and CRF who were treated at the University Children’s Hospital between January 1980 and December 2014. The patients’ data were retrospectively reviewed from the medical records. Results There were thirteen patients from 11 families, five girls and eight boys mean aged 4.3 years at the time of diagnosis. All of the patients had characteristic skeletal findings, retinal degeneration and an early onset of CRF at age range from 1.5 to 7 years. Five patients had neonatal respiratory distress and congenital liver fibrosis was diagnosed in five patients. One patient died due to complications of CRF, while others survived during follow-up of mean 11 years. IFT140 mutations were found in four genetically tested patients. Conclusion The average incidence rate of JS with renal phenotype in Serbia was about 0.2 per one million of child population. Long-term survival of JS patients depends on renal replacement therapy, while skeletal dysplasia, growth failure, respiratory and eyes problems have impact on the patients’ quality of life. © 2017, Serbia Medical Society. All rights reserved.

Introduction: The aim of this study was to investigate lipoprotein particle distributions and the likelihood of achieving cholesterol homeostasis in the remission phase of nephrotic syndrome (NS) in paediatric patients. We hypothesized that lipoprotein particle distributions moved toward less atherogenic profile and that cholesterol homeostasis was achieved. Materials and methods: Thirty-three children, 2 to 9 years old with NS were recruited. Blood sampling took place both in the acute phase and during remission. Serum low-density lipoprotein particles (LDL) and high-density lipoprotein particles (HDL) were separated using non-denaturing polyacrylamide gradient gel (3-31%) electrophoresis. Serum non-cholesterols sterols (NCSs), desmosterol, lathosterol, 7-dehydrocholesterol (7-DHC), campesterol and β-sitosterol were measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Results: All patients had desirable serum HDL cholesterol concentrations during remission. The dominant lipoprotein diameters and LDL subclass distribution did not change significantly during follow-up. In contrast, HDL lipoprotein particle distribution shifted towards larger particles. The absolute concentration of desmosterol was significantly lower during remission (P = 0.023). β-sitosterol concentration markedly increased during remission (P = 0.005). Desmosterol/β-sitosterol (P < 0.001) and 7-DHC/β-sitosterol (P = 0.005) ratios significantly declined during disease remission. Conclusions: Favourable changes in the serum lipid profiles, HDL particle subclass distribution and cholesterol metabolism in paediatric patients with NS during remission took place. For the first time, we found that cholesterol homeostasis changed in favour of increased cholesterol absorption during disease remission. Nevertheless, complete cholesterol homeostasis was not achieved during disease remission. © by Croatian Society of Medical Biochemistry and Laboratory Medicine.

Introduction: The aim of this study was to investigate lipoprotein particle distributions and the likelihood of achieving cholesterol homeostasis in the remission phase of nephrotic syndrome (NS) in paediatric patients. We hypothesized that lipoprotein particle distributions moved toward less atherogenic profile and that cholesterol homeostasis was achieved. Materials and methods: Thirty-three children, 2 to 9 years old with NS were recruited. Blood sampling took place both in the acute phase and during remission. Serum low-density lipoprotein particles (LDL) and high-density lipoprotein particles (HDL) were separated using non-denaturing polyacrylamide gradient gel (3-31%) electrophoresis. Serum non-cholesterols sterols (NCSs), desmosterol, lathosterol, 7-dehydrocholesterol (7-DHC), campesterol and β-sitosterol were measured by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Results: All patients had desirable serum HDL cholesterol concentrations during remission. The dominant lipoprotein diameters and LDL subclass distribution did not change significantly during follow-up. In contrast, HDL lipoprotein particle distribution shifted towards larger particles. The absolute concentration of desmosterol was significantly lower during remission (P = 0.023). β-sitosterol concentration markedly increased during remission (P = 0.005). Desmosterol/β-sitosterol (P < 0.001) and 7-DHC/β-sitosterol (P = 0.005) ratios significantly declined during disease remission. Conclusions: Favourable changes in the serum lipid profiles, HDL particle subclass distribution and cholesterol metabolism in paediatric patients with NS during remission took place. For the first time, we found that cholesterol homeostasis changed in favour of increased cholesterol absorption during disease remission. Nevertheless, complete cholesterol homeostasis was not achieved during disease remission. © by Croatian Society of Medical Biochemistry and Laboratory Medicine.

Background: The pathophysiological mechanisms crucial in the development of nephrotic syndrome (NS) in the pediatric population are still not fully understood. This study aimed to investigate the relationship between hypertension, oxidative stress, and inflammation in pediatric patients during the acute phase of the disease. Methods: The study included 33 children, aged 2 to 9 years, with nephrotic syndrome. Blood samples were collected during the acute phase and remission. Parameters of oxidative status were determined, including total oxidative status (TOS), advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB), sulfhydryl groups (- SH), paraoxonase 1 (PON1), and total antioxidant status (TAS) in serum, measured spectrophotometrically. Inflammatory parameters such as pentraxin 3 (PTX3), leptin, programmed cell death ligand 1 (PD-L1), and E-cadherin were determined using enzyme-linked immunosorbent assay (ELISA). Results: Patients with nephrotic syndrome and hypertension had significantly higher levels of advanced oxidation protein products and total antioxidant status (p=0.029 and p=0.003, respectively). During the acute phase of the disease, lower activity of sulfhydryl groups and paraoxonase 1 was observed compared to remission (p<0.001, for both). Pentraxin 3 levels were higher, while leptin levels were lower during the acute phase (p<0.001, for both). Pentraxin 3 correlated with advanced oxidation protein products and total antioxidant status during the acute phase but not in remission (rs=0.42, p=0.027 and rs=0.43, p=0.025, respectively). A negative correlation between Advanced oxidation protein products and leptin was observed during the acute phase, which disappeared in remission (rs=-0.42, p=0.028). Conclusions: Results of this study show that hypertension influences oxidative stress markers, and decreased antioxidant capacity may contribute to nephrotic syndrome development. Pentraxin 3 appears as a potential disease activity marker, indicating a dynamic connection between inflammation and oxidative stress. Leptin may also play a role in oxidative stress in nephrotic syndrome. © 2024 Society of Medical Biochemists of Serbia. All rights reserved.

Background: The pathophysiological mechanisms crucial in the development of nephrotic syndrome (NS) in the pediatric population are still not fully understood. This study aimed to investigate the relationship between hypertension, oxidative stress, and inflammation in pediatric patients during the acute phase of the disease. Methods: The study included 33 children, aged 2 to 9 years, with nephrotic syndrome. Blood samples were collected during the acute phase and remission. Parameters of oxidative status were determined, including total oxidative status (TOS), advanced oxidation protein products (AOPP), prooxidant-antioxidant balance (PAB), sulfhydryl groups (- SH), paraoxonase 1 (PON1), and total antioxidant status (TAS) in serum, measured spectrophotometrically. Inflammatory parameters such as pentraxin 3 (PTX3), leptin, programmed cell death ligand 1 (PD-L1), and E-cadherin were determined using enzyme-linked immunosorbent assay (ELISA). Results: Patients with nephrotic syndrome and hypertension had significantly higher levels of advanced oxidation protein products and total antioxidant status (p=0.029 and p=0.003, respectively). During the acute phase of the disease, lower activity of sulfhydryl groups and paraoxonase 1 was observed compared to remission (p<0.001, for both). Pentraxin 3 levels were higher, while leptin levels were lower during the acute phase (p<0.001, for both). Pentraxin 3 correlated with advanced oxidation protein products and total antioxidant status during the acute phase but not in remission (rs=0.42, p=0.027 and rs=0.43, p=0.025, respectively). A negative correlation between Advanced oxidation protein products and leptin was observed during the acute phase, which disappeared in remission (rs=-0.42, p=0.028). Conclusions: Results of this study show that hypertension influences oxidative stress markers, and decreased antioxidant capacity may contribute to nephrotic syndrome development. Pentraxin 3 appears as a potential disease activity marker, indicating a dynamic connection between inflammation and oxidative stress. Leptin may also play a role in oxidative stress in nephrotic syndrome. © 2024 Society of Medical Biochemists of Serbia. All rights reserved.

Introduction Frasier syndrome (FS) is a genetic form of glomerulopathy, which results from mutations in the Wilms' tumour suppressor gene (WT1). Proteinuria in FS has been traditionally considered unresponsive to any medication and FS inevitably progresses to end stage renal failure. Case Outline We present a patient with FS who had atypical clinical manifestation and unusual beneficial antiproteinuric response to renin-angiotensin system (RAS) inhibitors given in combination with indomethacin. After 13 years of follow-up, the patient is now 17-year old with normal renal functions and no proteinuria. Conclusion RAS inhibitors combined with indomethacin showed beneficial effect in our patient. Thus, this combination might be the initial treatment of patients with FS. If this treatment strategy was not satisfied for at least 3 months, then CsA would be considered to be administered taking account of the nephrotoxicity and the increased risk of malignancy. Further prospective study is required to clarify this issue.

Objective – To examine renal functional reserve (RFR) and blood pressure (BP) in children with a solitary functioning kidney (SFK) and stage 1-3 chronic kidney disease (CKD). Method – RFR was measured in 48 children with SFK and in 10 healthy children, as the difference between un-stimulated and stimulated clearance of endogenous cre-atinine by a meat-free oral protein load (OPL). Cimetidine was given 48 h prior to the measurement when the study subjects were on a diet free of meat, fish and poultry. Serum cystatin C and urinary protein (UPRT)/urinary creatinine (UCr) were examined before and 2 hours after OPL. BP was determined by office and by 24-h ambulatory BP monitoring (ABPM). Results – The majority of the patients (79.6%) had congenital SFK, while the remaining had acquired SFK due to unilateral nephrectomy. Sixteen patients had CKD1, 19 patients had CKD2 and 13 had CKD3. The patients and controls did not differ in terms of age, gender, body size, office and 24-h blood pressure read-ings and basal GFR. Kidney size was greater and serum cystatin C was higher in patients than in controls. Increased proteinuria and arterial hypertension were found in 24.3% and 18.9% of the patients, respec-tively. Nocturnal hypertension was more common than that during the daytime. After OPL, GFR significantly increased, more in controls than in patients. Among the patients, the RFR was the highest in the CKD3 group. Conclusion – OPL induced an increase in GFR above its basal value. This response was higher in healthy children than in those with SFK. The positive relationship between RFR and CKD stage and the highest RFR in CKD3 patients suggests well preserved renal functional reserve in patients with moderate renal failure. ABPM is necessary for BP evaluation in children with SFK. © 2017 by the University Clinical Centre Tuzla, Tuzla, Bosnia and Herzegovina.

Background: New renal biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) show promise in early diagnosis of contrast media induced acute kidney injury (CI-AKI). The purpose of our study was to compare the subclinical nephrotoxicity (a condition without changes in standard renal bio-markers) of gadolinium-based contrast media (Gd-DTPA, gadopentetate dimeglumine) and iodinated-based contrast media (iopromide) in pediatric patients with normal kidney function. Material/Methods: The first group (n=58) of patients included in the study were undergoing angiography with iopromide, and the second group (n=65) were undergoing magnetic resonance (MR) angiography/urography with Gd-DTPA admin-istration. The concentrations of NGAL and KIM-1 were measured four times in the urine (pre-contrast, then at four hours, 24 hours, and 48 hours after contrast administration), and serum NGAL was measured at 0 (base-line), 24 hours, and 48 hours after contrast exposure. Results: After 24 hours, serum NGAL increase of ³25% was noticed in 32.6% of the patients in the iopromide group and in 25.45% of the patients in the gadolinium group, with significantly higher average percent of this increase in first group (62.23% vs. 36.44%, p=0.002). In the Gd-DTPA group, we observed a statistically significant in-crease in urinary KIM-1 24 hours after the procedure. Normalized urinary KIM-1, 24 hours after contrast expo-sure, was a better predictive factor for CI-AKI than other biomarkers (AUC 0.757, cut off 214 pg/mg, sensitivi-ty 83.3%, specificity 54.2%, p=0.035). Conclusions: In children with normal renal function, exposure to iodinated-based and gadolinium-based media might lead to subclinical nephrotoxicity, which could be detected using serum NGAL and urinary KIM-1. © Med Sci Monit.

Introduction Renovascular hypertension is a rare cause of arterial hypertension in the pediatric population. The aim of this report was to present the treatment outcome in a girl with severe stenosis of the renal artery on a solitary kidney. Case outline A 6.5-year-old girl, otherwise healthy, was found to be highly hypertensive (up to 200/140 mmHg) during a systematic examination for school enrollment. The imaging evaluation revealed that she had a single kidney with critical renal artery stenosis. Medication with three antihypertensive drugs was unsuccessful. The angioplasty attempt was complicated by artery wall dissection and the pseudoaneurysm development. This complication was treated surgically with an autologous saphenous vein graft by-pass. Postoperatively, acute kidney injury developed, which required continuous renal replacement therapy for two days, followed by hemorrhagic shock and the need for reintervention with retroperitoneal hematoma evacuation. After three years, aneurismal dilated vein graft was replaced by a synthetic one (PTFE) in London. Angioplasty of the synthetic graft was performed twice due to the development of proximal stenosis and restenosis. After 11 years of follow-up, the girl has well controlled blood pressure under two antihypertensives, with normal renal function without proteinuria. Conclusion This case illustrates that angioplasty for single artery stenosis in children is a high-risk procedure, which may result in an aneurism formation or bleeding and a need for several kidney revascularization procedures. In order to preserve kidney function, it requires a serious multidisciplinary approach by nephrologists, interventional radiologists/cardiologists, and vascular surgeons. © 2024, Serbia Medical Society. All rights reserved.

Background: Acute kidney injury (AKI) is a common complication in pediatric oncology patients, most often caused by nephrotoxic drugs. We aimed to assess whether levels of urinary kidney injury molecule-1 (uKIM-1), neutrophil gelatinase-associated lipocalin (uNGAL), liver fatty acid binding protein (uL-FABP) and Vanin-1 (uVNN-1), individually and in combination-integrated could be early markers for cytotoxic treatment induced AKI. Methods: Children with different malignant diseases treated with cisplatin (CIS) or ifosfamide (IFO) were included. AKI was defined using pediatric KDIGO (Kidney Disease Improving Global Outcomes) criteria by comparing pretreatment serum creatinine (sCr) values with those acquired at 48 h after the first or second chemotherapy cycle. Five serum (at baseline, 2, 6, 24 and 48 h after treatment) and four urine samples (at baseline, 2, 6 and 24 h after treatment) were obtained. Urinary biomarkers (uBm) were normalized to urine creatinine. Results: Thirty-eight patients were assessed. Within 48 h following chemotherapy 6 (15.79%) patients experienced AKI. Patients with AKI were younger and tend to have lower baseline sCr values than patients without AKI, but these differences were not statistically significant. Compared to baselines, all uBm were significantly increased during the first 6 h while sCr concentrations did not change significantly during the study period. The median increases in uBm during the first 6 h after treatment were 529.8% (interquartile range – IQR, 63.9-1835.2%) – 2194.0% (IQR, 255.3-4695.5%) in AKI vs. 302.2% (IQR 114.6-561.2%) -429.8% (156.5–1467.0%) in non-AKI group depending of tested uBm. The magnitude of these changes over time didn’t differ significantly between groups. The area under receiver operator curve (AUC) for uL-FABP and uNGAL at 24 h after chemotherapy were 0.81 and 0.72, respectively. The ROC analysis revealed that the other individual biomarkers’ performance at any time-point wasn’t statistically significant (AUC < 0.7). A model of integrated-combined uBm, 2 h (AUC 0.78), 6 h (AUC 0.85) and 24 h after (AUC 0.92) treatment with CIS and/or IFO showed good utility for early AKI prediction. Conclusions: The results of this study support that the use of the uBm to improves early AKI prediction in patients receiving CIS and/or IFO containing chemotherapy. Further studies on larger comparable groups of patients are needed. © The Author(s) 2025.