TY  - JOUR
AU  - Mitrović, Miloš
AU  - Stanković-Popović, Verica
AU  - Tolinački, Maja
AU  - Golić, Nataša
AU  - Soković Bajić, Svetlana
AU  - Veljović, Katarina
AU  - Nastasijević, Branislav
AU  - Soldatović, Ivan
AU  - Svorcan, Petar
AU  - Dimković, Nada
PY  - 2023
UR  - https://www.sciencedirect.com/science/article/pii/S1051227622001522
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1753
AB  - ObjectiveAltering dysbiotic gut flora through synbiotic supplementation has recently been recognized as a potential treatment strategy to reduce the levels of gut-derived uremic toxins and decrease inflammation. Assessing its efficacy and safety has been the main goal of our randomized, double-blind, placebo-controlled study.MethodsA total of 34 nondialyzed chronic kidney disease patients, aged ≥18 years, with an estimated glomerular filtration rate between 15 and 45 mL/minute, were randomized either to an intervention group (n = 17), receiving synbiotic (Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium lactis, 32 billion colony forming units per day plus 3.2 g of inulin), or control group (n = 17), receiving placebo during 12 weeks. The impact of treatment on the dynamic of serum levels of gut-derived uremic toxins, total serum indoxyl sulfate, p-cresyl sulfate, and trimethylamine N-oxide, was defined as the primary outcome of the study. Secondary outcomes included changes in the stool microbiome, serum interleukin-6 levels, high-sensitivity C-reactive protein, estimated glomerular filtration rate, albuminuria, diet, gastrointestinal symptom dynamics, and safety. Serum levels of uremic toxins were determined using ultraperformance liquid chromatography. The stool microbiome analysis was performed using the 16S ribosomal ribonucleic acid gene sequencing approach.ResultsSynbiotic treatment significantly modified gut microbiome with Bifidobacteria, Lactobacillus, and Subdoligranulum genera enrichment and consequently reduced serum level of indoxyl sulfate (ΔIS –21.5% vs. 5.3%, P < .001), improved estimated glomerular filtration rate (ΔeGFR 12% vs. 8%, P = .029), and decreased level of high-sensitivity C-reactive protein (–39.5 vs. –8.5%, P < .001) in treated patients. Two patients of the intervention arm complained of increased flatulence. No other safety issues were noted.ConclusionSynbiotics could be available, safe, and an effective therapeutic strategy we could use in daily practice in order to decrease levels of uremic toxins and microinflammation in chronic kidney disease patients.
T2  - Journal of Renal Nutrition
T2  - Journal of Renal NutritionJournal of Renal Nutrition
T1  - The impact of synbiotic treatment on the levels of gut-derived uremic zoxins, inflammation, and gut microbiome of chronic kidney disease patients - a randomized trial
EP  - 288
IS  - 2
SP  - 278
VL  - 33
DO  - 10.1053/j.jrn.2022.07.008
ER  - 

@article{
author = "Mitrović, Miloš and Stanković-Popović, Verica and Tolinački, Maja and Golić, Nataša and Soković Bajić, Svetlana and Veljović, Katarina and Nastasijević, Branislav and Soldatović, Ivan and Svorcan, Petar and Dimković, Nada",
year = "2023",
abstract = "ObjectiveAltering dysbiotic gut flora through synbiotic supplementation has recently been recognized as a potential treatment strategy to reduce the levels of gut-derived uremic toxins and decrease inflammation. Assessing its efficacy and safety has been the main goal of our randomized, double-blind, placebo-controlled study.MethodsA total of 34 nondialyzed chronic kidney disease patients, aged ≥18 years, with an estimated glomerular filtration rate between 15 and 45 mL/minute, were randomized either to an intervention group (n = 17), receiving synbiotic (Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium lactis, 32 billion colony forming units per day plus 3.2 g of inulin), or control group (n = 17), receiving placebo during 12 weeks. The impact of treatment on the dynamic of serum levels of gut-derived uremic toxins, total serum indoxyl sulfate, p-cresyl sulfate, and trimethylamine N-oxide, was defined as the primary outcome of the study. Secondary outcomes included changes in the stool microbiome, serum interleukin-6 levels, high-sensitivity C-reactive protein, estimated glomerular filtration rate, albuminuria, diet, gastrointestinal symptom dynamics, and safety. Serum levels of uremic toxins were determined using ultraperformance liquid chromatography. The stool microbiome analysis was performed using the 16S ribosomal ribonucleic acid gene sequencing approach.ResultsSynbiotic treatment significantly modified gut microbiome with Bifidobacteria, Lactobacillus, and Subdoligranulum genera enrichment and consequently reduced serum level of indoxyl sulfate (ΔIS –21.5% vs. 5.3%, P < .001), improved estimated glomerular filtration rate (ΔeGFR 12% vs. 8%, P = .029), and decreased level of high-sensitivity C-reactive protein (–39.5 vs. –8.5%, P < .001) in treated patients. Two patients of the intervention arm complained of increased flatulence. No other safety issues were noted.ConclusionSynbiotics could be available, safe, and an effective therapeutic strategy we could use in daily practice in order to decrease levels of uremic toxins and microinflammation in chronic kidney disease patients.",
journal = "Journal of Renal Nutrition, Journal of Renal NutritionJournal of Renal Nutrition",
title = "The impact of synbiotic treatment on the levels of gut-derived uremic zoxins, inflammation, and gut microbiome of chronic kidney disease patients - a randomized trial",
pages = "288-278",
number = "2",
volume = "33",
doi = "10.1053/j.jrn.2022.07.008"
}

Mitrović, M., Stanković-Popović, V., Tolinački, M., Golić, N., Soković Bajić, S., Veljović, K., Nastasijević, B., Soldatović, I., Svorcan, P.,& Dimković, N.. (2023). The impact of synbiotic treatment on the levels of gut-derived uremic zoxins, inflammation, and gut microbiome of chronic kidney disease patients - a randomized trial. in Journal of Renal Nutrition, 33(2), 278-288.
https://doi.org/10.1053/j.jrn.2022.07.008

Mitrović M, Stanković-Popović V, Tolinački M, Golić N, Soković Bajić S, Veljović K, Nastasijević B, Soldatović I, Svorcan P, Dimković N. The impact of synbiotic treatment on the levels of gut-derived uremic zoxins, inflammation, and gut microbiome of chronic kidney disease patients - a randomized trial. in Journal of Renal Nutrition. 2023;33(2):278-288.
doi:10.1053/j.jrn.2022.07.008 .

Mitrović, Miloš, Stanković-Popović, Verica, Tolinački, Maja, Golić, Nataša, Soković Bajić, Svetlana, Veljović, Katarina, Nastasijević, Branislav, Soldatović, Ivan, Svorcan, Petar, Dimković, Nada, "The impact of synbiotic treatment on the levels of gut-derived uremic zoxins, inflammation, and gut microbiome of chronic kidney disease patients - a randomized trial" in Journal of Renal Nutrition, 33, no. 2 (2023):278-288,
https://doi.org/10.1053/j.jrn.2022.07.008 . .

TY  - JOUR
AU  - Stopić, Bojan
AU  - Dragičević, Sandra
AU  - Medić-Brkić, Branislava
AU  - Nikolić, Aleksandra
AU  - Stojanović, Marko
AU  - Budisavljević, Sreten
AU  - Dimković, Nada
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1463
AB  - Cardiovascular (CV) morbidity and mortality increase along with the progression of chronic kidney disease (CKD). The potential novel biomarkers of cardiotoxicity have been tested with the aim of the early detection of patients at high CV risk, and among them are markers of inflammation, oxidative stress, acute renal injury, and microRNAs. The study analyzed biomarkers in non-dialysis-dependent (NDD; stage 3a-4 CKD) and dialysis-dependent (DD) CKD patients. The prospective cohort study included 87 patients who were followed for 18 months, during which period newly occurred CV events were recorded. Cox regression analysis confirmed serum albumin, urea, interventricular septum thickness diameter (IVST), the use of calcium antagonist, and erythropoiesis-stimulating agent to be significant predictors of CV outcome. No significant difference was observed in biomarkers of inflammation, oxidative stress, acute kidney injury (IL-18, CRP, ferritin, IMA, SOD, NGAL, and KIM-1), and miR-133a, in regards to the presence/absence of CV event, CV death, and left ventricular hypertrophy. Serum albumin, urea, IVST, and the use of calcium antagonist and erythropoiesis-stimulating agents were confirmed to be factors associated with CV events in CKD patients. Apart from traditional risk factors, new research is needed to define novel and reliable biomarkers of cardiotoxicity in CKD patients.
PB  - MDPI, Basel
T2  - Toxins
T1  - Biomarkers of Uremic Cardiotoxicity
IS  - 9
VL  - 13
DO  - 10.3390/toxins13090639
ER  - 

@article{
author = "Stopić, Bojan and Dragičević, Sandra and Medić-Brkić, Branislava and Nikolić, Aleksandra and Stojanović, Marko and Budisavljević, Sreten and Dimković, Nada",
year = "2021",
abstract = "Cardiovascular (CV) morbidity and mortality increase along with the progression of chronic kidney disease (CKD). The potential novel biomarkers of cardiotoxicity have been tested with the aim of the early detection of patients at high CV risk, and among them are markers of inflammation, oxidative stress, acute renal injury, and microRNAs. The study analyzed biomarkers in non-dialysis-dependent (NDD; stage 3a-4 CKD) and dialysis-dependent (DD) CKD patients. The prospective cohort study included 87 patients who were followed for 18 months, during which period newly occurred CV events were recorded. Cox regression analysis confirmed serum albumin, urea, interventricular septum thickness diameter (IVST), the use of calcium antagonist, and erythropoiesis-stimulating agent to be significant predictors of CV outcome. No significant difference was observed in biomarkers of inflammation, oxidative stress, acute kidney injury (IL-18, CRP, ferritin, IMA, SOD, NGAL, and KIM-1), and miR-133a, in regards to the presence/absence of CV event, CV death, and left ventricular hypertrophy. Serum albumin, urea, IVST, and the use of calcium antagonist and erythropoiesis-stimulating agents were confirmed to be factors associated with CV events in CKD patients. Apart from traditional risk factors, new research is needed to define novel and reliable biomarkers of cardiotoxicity in CKD patients.",
publisher = "MDPI, Basel",
journal = "Toxins",
title = "Biomarkers of Uremic Cardiotoxicity",
number = "9",
volume = "13",
doi = "10.3390/toxins13090639"
}

Stopić, B., Dragičević, S., Medić-Brkić, B., Nikolić, A., Stojanović, M., Budisavljević, S.,& Dimković, N.. (2021). Biomarkers of Uremic Cardiotoxicity. in Toxins
MDPI, Basel., 13(9).
https://doi.org/10.3390/toxins13090639

Stopić B, Dragičević S, Medić-Brkić B, Nikolić A, Stojanović M, Budisavljević S, Dimković N. Biomarkers of Uremic Cardiotoxicity. in Toxins. 2021;13(9).
doi:10.3390/toxins13090639 .

Stopić, Bojan, Dragičević, Sandra, Medić-Brkić, Branislava, Nikolić, Aleksandra, Stojanović, Marko, Budisavljević, Sreten, Dimković, Nada, "Biomarkers of Uremic Cardiotoxicity" in Toxins, 13, no. 9 (2021),
https://doi.org/10.3390/toxins13090639 . .

TY  - CONF
AU  - Stopić, Bojan
AU  - Dragičević, Sandra
AU  - Medić Brkić. Branislava
AU  - Nikolić, Aleksandra
AU  - Budisavljević, Sreten
AU  - Marković Nikolić, Natasa
AU  - Dimković, Nada
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2080
AB  - Chronic kidney disease (CKD) is associated with a high incidence of cardiovascular (CV) disease and numerous risk factor have been implicated to play a role.  Recent studies have shown that the levels of various microRNAs in the serum of patients with CKD have been altered and there are reports that miR-133a serum levels correlated with left ventricular hypertrophy in hemodialysis patients.The aim of this study was to investigate association between circulating miR-133a levels and development of de novo CV events in patients with CKD stage 3-5HD.METHODS: This study included 51 patients with diagnosed CKD and 7 healthy individuals as controls. According to the estimated glomerular filtration ratio (eGFR) patients were divided into three equal subgroups (n=17): patients with CKD stage 3b, 4, and 5HD.  The level of miR-133a was measured in serum by quantitative real-time PCR. Echo parameters were measured by cardiac ultrasound at the beginning and after 12 months of follow-up. The following CV events were reported during 18 months of follow-up: cardiac death, myocardial infarction, cerebrovascular insult, exacerbation of existing and newly discovered angina pectoris and peripheral arterial disease.
PB  - Oxford University Press
C3  - Nephrology Dialysis Transplantation, 56th ERA-EDTA Congress Abstracts
T1  - Is miR-133a marker of progressive chronic kidney disease?
IS  - Supplement_1
SP  - FP177
VL  - 34
DO  - 10.1093/ndt/gfz106.FP177
ER  - 

@conference{
author = "Stopić, Bojan and Dragičević, Sandra and Medić Brkić. Branislava and Nikolić, Aleksandra and Budisavljević, Sreten and Marković Nikolić, Natasa and Dimković, Nada",
year = "2019",
abstract = "Chronic kidney disease (CKD) is associated with a high incidence of cardiovascular (CV) disease and numerous risk factor have been implicated to play a role.  Recent studies have shown that the levels of various microRNAs in the serum of patients with CKD have been altered and there are reports that miR-133a serum levels correlated with left ventricular hypertrophy in hemodialysis patients.The aim of this study was to investigate association between circulating miR-133a levels and development of de novo CV events in patients with CKD stage 3-5HD.METHODS: This study included 51 patients with diagnosed CKD and 7 healthy individuals as controls. According to the estimated glomerular filtration ratio (eGFR) patients were divided into three equal subgroups (n=17): patients with CKD stage 3b, 4, and 5HD.  The level of miR-133a was measured in serum by quantitative real-time PCR. Echo parameters were measured by cardiac ultrasound at the beginning and after 12 months of follow-up. The following CV events were reported during 18 months of follow-up: cardiac death, myocardial infarction, cerebrovascular insult, exacerbation of existing and newly discovered angina pectoris and peripheral arterial disease.",
publisher = "Oxford University Press",
journal = "Nephrology Dialysis Transplantation, 56th ERA-EDTA Congress Abstracts",
title = "Is miR-133a marker of progressive chronic kidney disease?",
number = "Supplement_1",
pages = "FP177",
volume = "34",
doi = "10.1093/ndt/gfz106.FP177"
}

Stopić, B., Dragičević, S., Medić Brkić. Branislava, Nikolić, A., Budisavljević, S., Marković Nikolić, N.,& Dimković, N.. (2019). Is miR-133a marker of progressive chronic kidney disease?. in Nephrology Dialysis Transplantation, 56th ERA-EDTA Congress Abstracts
Oxford University Press., 34(Supplement_1), FP177.
https://doi.org/10.1093/ndt/gfz106.FP177

Stopić B, Dragičević S, Medić Brkić. Branislava, Nikolić A, Budisavljević S, Marković Nikolić N, Dimković N. Is miR-133a marker of progressive chronic kidney disease?. in Nephrology Dialysis Transplantation, 56th ERA-EDTA Congress Abstracts. 2019;34(Supplement_1):FP177.
doi:10.1093/ndt/gfz106.FP177 .

Stopić, Bojan, Dragičević, Sandra, Medić Brkić. Branislava, Nikolić, Aleksandra, Budisavljević, Sreten, Marković Nikolić, Natasa, Dimković, Nada, "Is miR-133a marker of progressive chronic kidney disease?" in Nephrology Dialysis Transplantation, 56th ERA-EDTA Congress Abstracts, 34, no. Supplement_1 (2019):FP177,
https://doi.org/10.1093/ndt/gfz106.FP177 . .