Publications by authors named "Radovan Hojs"

93 Publications

Polymorphism in the Locus Associated with Dialysis-Independent Chronic Kidney Disease but Not Dialysis-Dependent Kidney Failure.

Genes (Basel) 2021 May 28;12(6). Epub 2021 May 28.

Center for Human Molecular Genetics and Pharmacogenomics, Faculty of Medicine, University of Maribor, Taborska ul. 8, 2000 Maribor, Slovenia.

The ten most statistically significant estimated glomerular filtration rate (eGFRcrea)-associated loci from genome-wide association studies (GWAs) are tested for associations with chronic kidney disease (CKD) in 208 patients, including dialysis-independent CKD and dialysis-dependent end-stage renal disease (kidney failure). The allele A of intergenic SNP rs2453533 (near ) is more frequent in dialysis-independent CKD patients ( = 135, adjusted = 0.020) but not dialysis-dependent kidney failure patients ( = 73) compared to healthy controls ( = 309). The allele C of intronic SNP rs4293393 () is more frequent in healthy controls (adjusted = 0.042) than in CKD patients. The Allele T of intronic SNP rs9895661 () is associated with decreased eGFRcys (adjusted = 0.001) and eGFRcrea (adjusted = 0.017). Our results provide further evidence of a genetic difference between dialysis-dialysis-independent CKD and dialysis-dependent kidney failure, and add the gene locus to the list of loci associated only with dialysis-independent CKD. risk allele carriers in the dialysis-independent group may have a genetic susceptibility to higher creatinine production rather than increased serum creatinine due to kidney malfunction, and therefore, do not progress to dialysis-dependent kidney failure. When using eGFRcrea for CKD diagnosis, physicians might benefit from information about creatinine-increasing loci.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/genes12060834DOI Listing
May 2021

CHA2DS2-VASc Score as a Predictor of Cardiovascular and All-Cause Mortality in Chronic Kidney Disease Patients.

Am J Nephrol 2021 May 11:1-8. Epub 2021 May 11.

Department of Nephrology, Clinic for Internal Medicine, University Medical Centre Maribor, Maribor, Slovenia.

Introduction: Chronic kidney disease (CKD) is a risk factor for cardiovascular and all-cause mortality. Recognition of high-risk patients is important and could lead to a different approach and better treatment. The CHA2DS2-VASc score was originally used to predict cerebral infarction in patients with atrial fibrillation (AF), but it is also a useful predictor of outcome in other cardiovascular conditions, independent of AF. Therefore, the aim of our research was to assess the role of CHA2DS2-VASc score in predicting cardiovascular and all-cause mortality in CKD patients.

Methods: Stable nondialysis CKD patients were included. At the time of inclusion, medical history data and standard blood results were collected and CHA2DS2-VASc score was calculated. Patients were followed till the same end date, until kidney transplantation or until their death.

Results: Eighty-seven CKD patients were included (60.3 ± 12.8 years, 66% male). Mean follow-up time was 1,696.5 ± 564.6 days. During the follow-up, 21 patients died and 11 because of cardiovascular reasons. Univariate Cox regression analysis showed that CHA2DS2-VASc score is a significant predictor of cardiovascular and all-cause mortality. In multivariate Cox regression analysis, in which CHA2DS2-VASc score, serum creatinine, urinary albumin/creatinine, hemoglobin, high-sensitivity C-reactive protein, and intact parathyroid hormone were included, CHA2DS2-VASc score was an independent predictor of cardiovascular (HR: 2.04, CI: 1.20-3.45, p = 0.008) and all-cause mortality (HR: 2.06, CI: 1.43-2.97, p = 0.001). The same was true after adding total cholesterol, triglycerides, and smoking status to both the analyses.

Conclusion: The CHA2DS2-VASc score is a simple, practical, and quick way to identify the risk for cardiovascular and all-cause mortality in CKD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000516121DOI Listing
May 2021

Subclinical atherosclerosis in patients with relapsing-remitting multiple sclerosis.

Wien Klin Wochenschr 2021 Apr 26. Epub 2021 Apr 26.

Department of Neurology, University Medical Centre Maribor, Ljubljanska 5, 2000, Maribor, Slovenia.

Background: Multiple sclerosis is an inflammatory disorder of the central nervous system. Inflammation may create high susceptibility to subclinical atherosclerosis. The purpose of this study was to compare subclinical atherosclerosis and the role of inflammatory cytokines between the group of patients with relapsing-remitting multiple sclerosis (RRMS) and healthy controls matched for age and sex.

Methods: The study group consisted of 112 non-diabetic and non-hypertensive RRMS patients treated with disease modifying drugs (DMD) and the control group was composed of 51 healthy subjects. The common carotid artery (CCA) intima media thickness (IMT) was investigated. Serum levels of risk factors for atherosclerosis and inflammatory cytokines were also determined.

Results: The mean CCA IMT (0.572 ± 0.131 mm vs. 0.571 ± 0.114 mm) did not differ (p > 0.05) between patients and controls. The RRMS patients' CCA IMT was significantly correlated with serum interleukin 6 (IL-6) (p = 0.027), high-sensitivity C-reactive protein (hs-CRP) (p = 0.027), cystatin C (p < 0.0005), glucose (p = 0.031), cholesterol (p = 0.008), LDL (p = 0.021), erythrocyte sedimentation rate (p = 0.001) and triglyceride (p = 0.018) level. We fitted generalized linear models in order to assess the relationship between CCA IMT and IL‑6 with adjustment for sex and age. The obtained results showed that adjusted for age (p < 0.001) and sex (p = 0.048) IL‑6 serum levels statistically significantly (p = 0.009) predict CCA IMT only in the RRMS group.

Conclusion: The findings of the present study suggest that when treated with DMD RRMS might not be an independent risk factor for early atherosclerosis presenting with arterial wall thickening; however, the results suggest a significant association of IL‑6 serum levels with CCA IMT only in the RRMS group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00508-021-01862-7DOI Listing
April 2021

Early Detection of Arteriovenous Fistula Stenosis in Hemodialysis Patients through Routine Measurements of Dialysis Dose (Kt/V).

Blood Purif 2021 Mar 30:1-8. Epub 2021 Mar 30.

Medical Faculty, University of Maribor, Maribor, Slovenia.

Background: Monitoring of arteriovenous (AV) fistula to detect hemodynamically important stenosis is crucial for the prevention of AV fistula thrombosis. The aim of our study was to analyze the importance of dialysis dose (Kt/V) during online postdilution hemodiafiltration (HDF) for early detection of AV fistula stenosis.

Methods: Hemodialysis patients with AV fistula were included in this study. We compared a group of 44 patients who have undergone fistulography and subsequently percutaneous transluminal angioplasty (PTA) of significant AV fistula stenosis (active group) with a group of 44 age- and sex-matched patients without PTA (control group). Observational time in both groups was the same.

Results: All patients had postdilution online HDF using a F5008 dialysis machine, which can measure online single-pool Kt/V. All data were analyzed during the performance of 2056 HDF procedures. In the active group, we found statistically significantly lower values of Kt/V, all 8 weeks before PTA. In the active group, there was a significant improvement in Kt/V in the first (p < 0.001) and second week (p = 0.049) after PTA. Three and 8 weeks after PTA, we did not find any statistically significant difference in Kt/V between both groups (p = 0.114; p = 0.058). Patients in the active group had statistically significantly lower substitution volumes and blood pump flow rates during HDF over the whole observation period before and after PTA. In contrast, there were no differences in venous pressure in the dialysis circuit between both groups throughout the observation period.

Conclusion: In hemodialysis patients with AV fistula, treated with online HDF, routine measurements of Kt/V during each HDF are a beneficial, quick, and straightforward method for early detection of hemodynamically significant AV fistula stenosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000514939DOI Listing
March 2021

Review on Inflammation Markers in Chronic Kidney Disease.

Biomedicines 2021 Feb 11;9(2). Epub 2021 Feb 11.

Department of Nephrology, Clinic for Internal Medicine, University Medical Centre Maribor, Ljubljanska Ulica 5, 2000 Maribor, Slovenia.

Chronic kidney disease (CKD) is one of the major health problems of the modern age. It represents an important public health challenge with an ever-lasting rising prevalence, which reached almost 700 million by the year 2017. Therefore, it is very important to identify patients at risk for CKD development and discover risk factors that cause the progression of the disease. Several studies have tackled this conundrum in recent years, novel markers have been identified, and new insights into the pathogenesis of CKD have been gained. This review summarizes the evidence on markers of inflammation and their role in the development and progression of CKD. It will focus primarily on cytokines, chemokines, and cell adhesion molecules. Nevertheless, further large, multicenter studies are needed to establish the role of these markers and confirm possible treatment options in everyday clinical practice.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/biomedicines9020182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917900PMC
February 2021

The association between pulse wave analysis, carotid-femoral pulse wave velocity and peripheral arterial disease in patients with ischemic heart disease.

BMC Cardiovasc Disord 2021 01 13;21(1):33. Epub 2021 Jan 13.

Department of Dialysis, Clinic for Internal Medicine, University Medical Centre Maribor, Ljubljanska ulica 5, 2000, Maribor, Slovenia.

Introduction: Functional changes in peripheral arterial disease (PAD) could play a role in higher cardiovascular risk in these patients.

Methods: 123 patients who underwent elective coronary angiography were included. Ankle-brachial index (ABI) was measured and arterial stiffness parameters were derived with applanation tonometry.

Results: 6 patients (4.9%) had a previously known PAD (Rutherford grade I). Mean ABI was 1.04 ± 0.12, mean subendocardial viability ratio (SEVR) 166.6 ± 32.7% and mean carotid-femoral pulse wave velocity (cfPWV) 10.3 ± 2.4 m/s. Most of the patients (n = 81, 65.9%) had coronary artery disease (CAD). There was no difference in ABI among different degrees of CAD. Patients with zero- and three-vessel CAD had significantly lower values of SEVR, compared to patients with one- and two-vessel CAD (159.5 ± 32.9%/158.1 ± 31.5% vs 181.0 ± 35.2%/166.8 ± 27.8%; p = 0.048). No significant difference was observed in cfPWV values. Spearman's correlation test showed an important correlation between ABI and SEVR (r = 0.196; p = 0.037) and between ABI and cfPWV (r = - 0.320; p ≤ 0.001). Multiple regression analysis confirmed an association between cfPWV and ABI (β = - 0.210; p = 0.003), cfPWV and mean arterial pressure (β = 0.064; p < 0.001), cfPWV and age (β = 0.113; p < 0.001) and between cfPWV and body mass index (BMI (β = - 0.195; p = 0.028), but not with arterial hypertension, dyslipidemia, diabetes mellitus or smoking status. SEVR was not statistically significantly associated with ABI using the same multiple regression model.

Conclusion: Reduced ABI was associated with increased cfPWV, but not with advanced CAD or decreased SEVR.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12872-021-01859-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807526PMC
January 2021

Accelerated atherosclerosis in premenopausal women with rheumatoid arthritis - 15-year follow-up.

Bosn J Basic Med Sci 2020 Nov 25. Epub 2020 Nov 25.

Division of Internal Medicine, Department of Rheumatology, University Medical Centre Maribor, Maribor, Slovenia; Medical Faculty, University of Maribor, Maribor, Slovenia.

Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with increased mortality and morbidity due to the higher cardiovascular risk in these patients. Traditional risk factors are not the only answer for the accelerated atherosclerosis. In a long-term prospective study, we investigated the relationship between asymptomatic atherosclerosis and traditional risk factors and inflammatory markers in patients with RA and matched healthy controls. We studied the laboratory test results, the concentrations of inflammatory mediators, matrix metalloproteases (MMP), and inflammation markers in the total of 70 (60 at follow-up) premenopausal healthy women with RA and 40 (34 at follow-up) matched controls. We used the B-mode ultrasound imaging of carotid arteries for the detection of asymptomatic atherosclerosis. Correlation with different factors was evaluated. Statistically significant higher values of inflammatory markers such as selective adhesion molecules ICAM and VCAM, interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and MMP-3 in patients group were found in the follow-up study. More plaques were found in the patients group (42.4% vs. 12.9%; p=0.005), as compared with the controls group. The patients had also higher values of cIMT (p=0.001). Using bivariate regression analysis only VCAM was found as a prognostic factor for plaque occurrence (r=0.341, p=0.016), but not for cIMT (r=-0.130, p=0.327) in premenopausal female patients with RA after the follow-up. Therefore, asymptomatic atherosclerosis is accelerated in premenopausal women with RA. The results of our follow-up study showed the association between inflammation and accelerated atherosclerosis. Furthermore, VCAM was found to have a statistically significant correlation with plaque occurrence in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17305/bjbms.2020.5176DOI Listing
November 2020

Oxidative Stress Markers in Chronic Kidney Disease with Emphasis on Diabetic Nephropathy.

Antioxidants (Basel) 2020 Sep 27;9(10). Epub 2020 Sep 27.

Dept. of Nephrology, Clinic for Internal Medicine, University Medical Centre Maribor, Ljubljanska 5, 2000 Maribor, Slovenia.

Diabetes prevalence is increasing worldwide, especially through the increase of type 2 diabetes. Diabetic nephropathy occurs in up to 40% of diabetic patients and is the leading cause of end-stage renal disease. Various factors affect the development and progression of diabetic nephropathy. Hyperglycaemia increases free radical production, resulting in oxidative stress, which plays an important role in the pathogenesis of diabetic nephropathy. Free radicals have a short half-life and are difficult to measure. In contrast, oxidation products, including lipid peroxidation, protein oxidation, and nucleic acid oxidation, have longer lifetimes and are used to evaluate oxidative stress. In recent years, different oxidative stress biomarkers associated with diabetic nephropathy have been found. This review summarises current evidence of oxidative stress biomarkers in patients with diabetic nephropathy. Although some of them are promising, they cannot replace currently used clinical biomarkers (eGFR, proteinuria) in the development and progression of diabetic nephropathy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antiox9100925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600946PMC
September 2020

Hyperuricemia, the heart, and the kidneys - to treat or not to treat?

Ren Fail 2020 Nov;42(1):978-986

Department of Nephrology, Clinic for Internal Medicine, University Medical Centre Maribor, Maribor, Slovenia.

Background: Hyperuricemia is a state in which the serum levels of uric acid are elevated. As such it has a pronounced effect on vascular and renal function with their consequences, while also showing some antioxidant effects that show to be beneficial.

Summary: Hyperuricemia has shown to have a J-shaped relationship with mortality, is frequently associated with development and progression of heart and kidney disease, and is correlated with malnutrition-inflammation-atherosclerosis syndrome, although several Mendelian studies have failed to show an association with morbidity and mortality. Hyperuricemia is usually associated with gout flares and tophi development but can also present as asymptomatic hyperuricemia. It is still uncertain whether asymptomatic hyperuricemia is an independent risk factor for cardiovascular or renal disease and as such its treatment is questionable.

Key Messages: Some possible tools for future decision making are the use of noninvasive techniques such as pulse wave analysis, urinary sediment analysis, and joint ultrasound, which could help identify individuals with asymptomatic hyperuricemia that could benefit from urate lowering therapy most.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/0886022X.2020.1822185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534372PMC
November 2020

Inflammation is an amplifier of lung congestion by high lv filling pressure in hemodialysis patients: a longitudinal study.

J Nephrol 2020 Jun 8;33(3):583-590. Epub 2020 Jan 8.

Aristotle University, Thessaloniki, Greece.

Introduction: Since inflammation alters vascular permeability, including vascular permeability in the lung, we hypothesized that it can be an amplifier of lung congestion in a category of patients at high risk for pulmonary oedema like end stage kidney disease (ESKD) patients.

Objective And Methods: We investigated the effect modification by systemic inflammation (serum CRP) on the relationship between a surrogate of the filling pressure of the LV [left atrial volume indexed to the body surface area (LAVI)] and lung water in a series of 220 ESKD patients. Lung water was quantified by the number of ultrasound B lines (US-B) on lung US. Six-hundred and three recordings were performed during a 2-year follow up. Longitudinal data analysis was made by the Mixed Linear Model.

Results: At baseline, 88 had absent, 101 had mild to moderate lung congestion and 31 severe congestion. The number of US B lines associated with LAVI (r = 0.23, P < 0.001) and serum CRP was a robust modifier of this relationship (P < 0.001). Similarly, in fully adjusted longitudinal analyses US-B lines associated with simultaneous estimates of LAVI (P = 0.002) and again CRP was a strong modifier of this relationship in adjusted analyses (P ≤ 0.01). Overall, at comparable LAVI levels, lung congestion was more pronounced in inflamed than in non-inflamed patients.

Conclusion: In ESKD systemic inflammation is a modifier of the relationship between LAVI, an integrate measure of LV filling pressure, and lung water. For any given pressure, lung water is increased with higher CRP levels, likely reflecting a higher permeability of the alveolar-capillary barrier.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40620-019-00696-xDOI Listing
June 2020

Anemia on admission and long-term mortality risk in patients with acute ischemic stroke.

Adv Clin Exp Med 2019 Oct;28(10):1419-1424

Clinic of Internal Medicine, Department of Nephrology, University Medical Centre, Maribor, Slovenia.

Background: Anemia is associated with adverse outcomes in patients with acute myocardial infarction and congestive heart failure. Additionally, it has been shown that anemia increases the short-term mortality risk in patients with acute stroke.

Objectives: The aim of our study was to determine the importance of anemia as a long-term mortality risk factor by itself or in combination with other risk factors.

Material And Methods: We included 390 Caucasian patients with acute ischemic stroke in our study. Their progress was followed from the day of their admission until their death or a max. of 1,669 days. Stroke and anemia were defined according to the World Health Organization (WHO) criteria.

Results: Anemia was present in 57 (14.6%) patients. The patients with anemia were older (p < 0.01) and more likely to be female (p < 0.001). They had higher NIHSS scores on admission (p < 0.001) and discharge (p < 0.001), lower estimated glomerular filtration rates (eGFRs) (p < 0.001), lower serum LDL cholesterol (p < 0.01) and lower serum albumin levels (p < 0.001), while their serum C-reactive protein (CRP) levels were higher (p < 0.001). The Kaplan-Meier curves showed that patients with anemia had higher mortality (p < 0.001). Cox's regression analysis revealed that anemia at admission was a predictor of long-term mortality in these patients (hazard ratio (HR) = 2.448, 95% confidence interval (95% CI) = 1.773-3.490; p < 0.001). Anemia remained a strong predictor of mortality after adjusting for other risk factors as well.

Conclusions: Anemia was frequent among our patients and was an independent predictor of long-term mortality even after adjusting for other risk factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17219/acem/104540DOI Listing
October 2019

Collagen type III nephropathy as a systemic disease? - A case report.

Nefrologia (Engl Ed) 2020 Jan - Feb;40(1):106-108. Epub 2019 Jul 31.

University Medical Centre Maribor, Division of Internal Medicine, Department of Nephrology, Ljubljanska 5, Maribor, Slovenia; University of Maribor, Faculty of Medicine, Taborska 5, Maribor, Slovenia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.nefro.2019.04.008DOI Listing
March 2021

Asymptomatic hyperuricemia and cardiovascular mortality in patients with chronic kidney disease who progress to hemodialysis.

Int Urol Nephrol 2019 Jun 24;51(6):1013-1018. Epub 2019 Apr 24.

Department of Nephrology, Clinic for Internal Medicine, University Medical Centre Maribor, Ljubljanska ulica 5, 2000, Maribor, Slovenia.

Purpose: Hyperuricemia has been associated with higher mortality in the general population, but less is known about CKD patients. The aim of our study was to determine the impact of elevated serum uric acid on cardiovascular mortality of CKD patients who later progress to hemodialysis.

Methods: In this retrospective study, 120 CKD patients (entire population of patients with ESKD on January 1st, 2012) were observed from their first visit at the Nephrology outpatient clinic, while transitioning to hemodialysis, and until their death or January 1, 2016. After non-cardiovascular death exclusion, 83 CKD patients (33 female, 50 male) were left for further analysis. The average time of observation was 8.8 ± 4.2 years. Serum uric acid was measured regularly (every 3 months). No patients were treated for hyperuricemia. Mean uric acid of 420 µmol/L was set as a cut-off between normouricemic and hyperuricemic patients as per the laboratory's reference values. Survival rates were analyzed using Kaplan-Meier survival curves. Three Cox regression models were used to assess the influence of uric acid on survival.

Results: Mean uric acid was 379.8 ± 71.6 µmol/L (range 220-574). Sixty-three (75.9%) patients were normouricemic and 20 (24.1%) were hyperuricemic. Cholesterol was the only variable to show statistically significant difference (p = 0.004) between the groups. Bivariate analysis revealed an association between death and age, hyperuricemia, arterial hypertension, and history of cardiovascular disease. Kaplan-Meier survival analysis showed higher risk of cardiovascular death for hyperuricemic patients (log rank test; p < 0.0005). In Cox regression models, hyperuricemia remained a predictor of cardiovascular mortality (SE = 0.500, Exp(B) = 14.120, 95% CI 5.297-37.640) in our patients next to age and arterial hypertension.

Conclusion: The results indicate an association between hyperuricemia and cardiovascular mortality in CKD patients who transition to hemodialysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11255-019-02154-wDOI Listing
June 2019

The effect of high-flux hemodialysis and post-dilution hemodiafiltration on platelet closure time in patients with end stage renal disease.

Hemodial Int 2019 07 29;23(3):319-324. Epub 2019 Mar 29.

Department of Nephrology, Clinic for Internal Medicine, University Medical Centre Maribor, Maribor, Slovenia.

Introduction: We aimed to compare prospectively the effect of high-flux hemodialysis and post-dilution hemodiafiltration on platelets.

Methods: Twenty-two hemodialysis patients were treated with one high-flux hemodialysis and one post-dilution hemodiafiltration procedure. PFA-100 closure times (collagen/epinephrine-CEPI and collagen/adenosine diphosphate-CADP) were measured before and after the procedure, as well as platelet count, hemoglobin, hematocrit, and red blood cell count. All pre-dialysis and post-dialysis samples were taken from the afferent line.

Findings: The platelet count after vs. before hemodialysis did not change significantly (229.3 ± 55.0 x10 /L vs. 233.6 ± 55.8 × 10 /L; P = 0.269), but was significantly lower after post-dilution hemodiafiltration (215.5 ± 51.7 × 10 /L vs. 245.3 ± 59.9 × 10 /L; P < 0.0001). CEPI after vs. before hemodialysis was not significantly prolonged (192.9 ± 60.8 s vs. 173.4 ± 52.5 s; P = 0.147), and the same applied to CADP (143.6 ± 40.3 s vs. 142.6 ± 38.4 s; P = 0.897). CEPI after vs. before post-dilution hemodiafiltration was significantly prolonged (268.3 ± 41.3 s vs. 176.4 ± 54.0 s; P < 0.0001) as was CADP (221.0 ± 53.9 s vs.133.9 ± 31.1 s; P < 0.0001).

Discussion: Only after post-dilution hemodiafiltration, we found a lower platelet count and prolonged platelet closure times.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/hdi.12756DOI Listing
July 2019

SGLT-2 inhibitors and GLP-1 receptor agonists for nephroprotection and cardioprotection in patients with diabetes mellitus and chronic kidney disease. A consensus statement by the EURECA-m and the DIABESITY working groups of the ERA-EDTA.

Nephrol Dial Transplant 2019 02;34(2):208-230

Department of Nephrology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark.

Chronic kidney disease (CKD) in patients with diabetes mellitus (DM) is a major problem of public health. Currently, many of these patients experience progression of cardiovascular and renal disease, even when receiving optimal treatment. In previous years, several new drug classes for the treatment of type 2 DM have emerged, including inhibitors of renal sodium-glucose co-transporter-2 (SGLT-2) and glucagon-like peptide-1 (GLP-1) receptor agonists. Apart from reducing glycaemia, these classes were reported to have other beneficial effects for the cardiovascular and renal systems, such as weight loss and blood pressure reduction. Most importantly, in contrast to all previous studies with anti-diabetic agents, a series of recent randomized, placebo-controlled outcome trials showed that SGLT-2 inhibitors and GLP-1 receptor agonists are able to reduce cardiovascular events and all-cause mortality, as well as progression of renal disease, in patients with type 2 DM. This document presents in detail the available evidence on the cardioprotective and nephroprotective effects of SGLT-2 inhibitors and GLP-1 analogues, analyses the potential mechanisms involved in these actions and discusses their place in the treatment of patients with CKD and DM.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/ndt/gfy407DOI Listing
February 2019

Beta Cell Functional Adaptation and Dysfunction in Insulin Resistance and the Role of Chronic Kidney Disease.

Nephron 2019 16;143(1):33-37. Epub 2019 Jan 16.

Institute of Physiology, Faculty of Medicine, University of Maribor, Maribor, Slovenia.

Background: Beta cells are central in the pathophysiology of diabetes, since their functional adaptation maintains euglycemia in insulin-resistant individuals and beta cell dysfunction is required for the clinical picture of frank diabetes. The pathophysiological mechanisms driving compensation and decompensation are incompletely understood and little is known about the influence of chronic kidney disease (CKD) on beta cell function.

Summary: In compensated insulin resistance, beta cells enhance their function at all stages in the stimulus-secretion coupling cascade, from the most proximal membrane depolarization to the intermediate increase in intracellular calcium concentration and the most distal granule fusion. Intercellular coupling is not disrupted at this early stage during disease progression. Later during progression, when hyperglycemia becomes more apparent owing to insufficient beta cell compensation, intracellular stimulus-secretion coupling becomes enhanced to an even larger degree, but intercellular coupling becomes disrupted, indicating that ineffective cell-to-cell signal transmission may be the earliest event in progression to frank diabetes. CKD can negatively affect beta cell function through increased levels of urea that reduce beta cell glucose utilization and impair insulin secretion, and possibly also through factors other than urea. It remains to be investigated whether urea and other factors of CKD can also affect intercellular coupling. Key messages: Beta cells enhance intracellular stimulus-secretion coupling in early insulin resistance. With worsening insulin resistance, intracellular coupling enhances even more, but intercellular coupling becomes disrupted. CKD negatively impacts beta cell function, but its influence on intercellular coupling awaits further studies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000495665DOI Listing
July 2020

MicroRNA-142-3p improves vascular relaxation in uremia.

Atherosclerosis 2019 01 10;280:28-36. Epub 2018 Nov 10.

Department of Internal Medicine, Clinical Division of Nephrology, Medical University of Graz, Graz, Austria.

Background And Aims: Chronic kidney disease (CKD) is strongly associated with a high burden of cardiovascular morbidity and mortality. Therefore, we aimed to characterize the putative role of microRNAs (miR)s in uremic vascular remodelling and endothelial dysfunction.

Methods: We investigated the expression pattern of miRs in two independent end-stage renal disease (ESRD) cohorts and in the animal model of uremic DBA/2 mice via quantitative RT-PCR. Moreover, DBA/2 mice were treated with intravenous injections of synthetic miR-142-3p mimic and were analysed for functional and morphological vascular changes by mass spectrometry and wire myography.

Results: The expression pattern of miRs was regulated in ESRD patients and was reversible after kidney transplantation. Out of tested miRs, only blood miR-142-3p was negatively associated with carotid-femoral pulse-wave velocity in CKD 5D patients. We validated these findings in a murine uremic model and found similar suppression of miR-142-3p as well as decreased acetylcholine-mediated vascular relaxation of the aorta. Therefore, we designed experiments to restore bioavailability of aortic miR-142-3p in vivo via intravenous injection of synthetic miR-142-3p mimic. This intervention restored acetylcholine-mediated vascular relaxation.

Conclusions: Taken together, we provide compelling evidence, both in humans and in mice, that miR-142-3p constitutes a potential pharmacological agent to prevent endothelial dysfunction and increased arterial stiffness in ESRD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.atherosclerosis.2018.11.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591123PMC
January 2019

Medical and surgical co-management - A strategy of improving the quality and outcomes of perioperative care.

Eur J Intern Med 2019 03 15;61:44-47. Epub 2018 Nov 15.

Internal Medicine Department, Centro Hospitalar Lisboa Ocidental, NOVA Medical School/Faculdade de Ciências Médicas, Lisboa, Portugal.

With the increase of ageing population, rates of chronic diseases and complex medical conditions, the management of high-risk surgical patients is likely to become a great concern in most countries. Considering all these factors, it is certainly rational and intuitive that internists should be included into a collaborative model of medical and surgical co-management, where their multi-potentiality and synthesis capacity require them to coordinate the multidisciplinary team and to be the leading agent of change. In this regard, our aim was to present the official position and approach of the Working Group on Professional Issues and Quality of Care of the European Federation of Internal Medicine (EFIM), for implementation of this strategy of care, encouraging internists to assume an important role and to provide continuity of multidisciplinary care, from the decision to operate through to rehabilitation and recovery. Moving from the traditional model of medical care of the surgical patients to the co-management model, from a reactive simple consultation to a new pro-active continued service, may optimize the quality and perioperative care, improving the survival, shortening hospital stays, replacing the old strategy of late and complication treatment to an early and preventive one.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejim.2018.10.017DOI Listing
March 2019

Derived Subendocardial Viability Ratio and Cardiovascular Events in Patients with Chronic Kidney Disease.

Cardiorenal Med 2019 8;9(1):41-50. Epub 2018 Nov 8.

Medical Faculty, University of Maribor, Maribor, Slovenia.

Background: Chronic kidney disease (CKD) is a well-known mortality risk factor. The subendocardial viability ratio (SEVR) is one of the pulse wave analysis parameters that constitutes a non-invasive measure of coronary perfusion. We aimed to assess the prognostic value of the SEVR for cardiovascular outcome in non-dialysis CKD patients.

Methods: A total of 98 CKD patients (mean age 60 years) were prospectively followed up from the date of the SEVR measurement until their death or the start of dialysis/transplantation, maximally up to 7.1 years (mean 5 years). According to the manufacturer's instructions regarding normal SEVR values, the patients were divided into a low SEVR group (SEVR ≤130%, n = 26) and a normal SEVR group (SEVR > 130%, n = 72).

Results: During the follow-up period, 13 patients (13.3%) suffered fatal and 23 patients (23.5%) suffered combined (non-fatal and fatal) cardiovascular events. In the patients who died of cardiovascular causes, the SEVR values were statistically significantly lower (130 vs. 154%; p = 0.017) than in those who survived. A Kaplan-Meier survival analysis showed that the cardiovascular survival rate in the low SEVR group of patients was statistically significantly lower (log-rank test: p < 0.001). Using an unadjusted Cox regression analysis, the patients in the low SEVR group had a 5.6-fold higher risk (95% CI: 1.8-17.3; p = 0.002) of fatal cardiovascular events and a 2.7-fold higher risk (95% CI: 1.1-6.3; p = 0.024) of combined fatal and non-fatal cardiovascular events. In the adjusted Cox regression model, the patients in the low SEVR group had a 16-fold higher risk (95% CI: 1.2-9.7; p = 0.004) of fatal cardiovascular events and a 7-fold higher risk (95% CI: 1-9.7; p = 0.009) of combined fatal and non-fatal cardiovascular events.

Conclusions: An SEVR < 130% predicts fatal and non-fatal cardiovascular events in non-dialysis CKD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000493512DOI Listing
May 2019

Impact of KDIGO-Defined Acute Kidney Injury on Mortality after Percutaneous Coronary Intervention for Acute Myocardial Infarction.

Cardiorenal Med 2018 17;8(4):332-339. Epub 2018 Sep 17.

Department of Nephrology, University Medical Center Maribor, Maribor, Slovenia.

Background: There are limited data regarding the incidence and long-term impact of acute kidney injury (AKI) according to the KDIGO guidelines on the outcome in patients with myocardial infarction (MI) treated with percutaneous coronary intervention (PCI). The aim of the study was to evaluate the prevalence of AKI, as classified by the KDIGO criteria, and its association with long-term mortality.

Methods: Data from 5,859 MI patients undergoing PCI at our institution were analyzed. We compared the group without and with AKI according to the KDIGO criteria in relation to long-term mortality.

Results: AKI was documented in 499 (8.5%) patients. AKI stage 1 occurred in 6.2% of patients, AKI stage 2 in 0.9% of patients, and AKI stage 3 in 1.5% of patients. Patients with AKI had a higher long-term mortality (57.3 vs. 20.6%; p < 0.0001). The mortality was 50.3% in AKI stage 1, 56.9% in AKI stage 2, and 87.2% in AKI stage 3. The hazard ratios for all-cause mortality for AKI stages 1-3 were 1.77, 1.85, and 6.30 compared to patients with no AKI. Cardiogenic shock, bleeding, heart failure, age, renal dysfunction, diabetes, hyperlipidemia, ST-elevation MI, contrast volume/glomerular filtration ratio, P2Y12 receptor antagonists, and radial access were associated with the development of AKI.

Conclusion: A slight increase in serum creatinine was associated with a progressive increase in long-term mortality in patients with AKI according to the KDIGO definition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000492287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6477518PMC
March 2019

Women and acute kidney injury in myocardial infarction.

J Nephrol 2018 Oct 12;31(5):713-719. Epub 2018 Jun 12.

Division of Internal Medicine, Department of Cardiology and Angiology, University Medical Center Maribor, Ljubljanska Ulica 5, 2000, Maribor, Slovenia.

Background: Data on the relationship between gender and acute kidney injury (AKI) in patients with myocardial infarction (MI) undergoing percutaneous coronary intervention (PCI) are conflicting and inconclusive. The contrast volume-to-estimated glomerular filtration rate ratio (CV/GFR) was shown to predict AKI in patients with MI undergoing PCI. We assessed gender-based differences in AKI and evaluated the association between the CV/GFR and AKI in MI patients undergoing PCI.

Methods: We retrospectively studied 4675 consecutive patients with MI who underwent PCI between January 2007 and December 2015. The incidence of AKI and CV/GFR in men and women were compared. Data were analyzed using descriptive statistics.

Results: Women suffered more AKI than men [152 (10.5%) women suffered AKI compared to 252 (7.8%) men; p = 0.003]. After adjustment for potential confounders, female gender was identified as an independent predictive factor for AKI. CV/GFR was higher in women (2.57 ± 1.95 in women vs. 2.25 ± 1.60 in men; p < 0.0001) and predicted AKI.

Conclusion: AKI occurs more often in women than men with MI undergoing PCI. Female gender independently predicted AKI in our analysis. A high CV/GFR denotes a group of patients who are at higher risk of AKI after PCI. CV/GFR was significantly higher in women, which may help to explain their worse outcome as regards AKI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40620-018-0504-4DOI Listing
October 2018

Cystatin C as a predictor of mortality in elderly patients with chronic kidney disease.

Aging Male 2019 Mar 18;22(1):62-67. Epub 2018 Jun 18.

a Department of Nephrology, Clinic for Internal Medicine , University Clinical Centre Maribor , Maribor , Slovenia.

Background: The prevalence of chronic kidney disease (CKD) in the elderly is high. Serum cystatin C is an accurate marker of kidney function and it also has prognostic utility in CKD patients. The aim of our study was to determine the prediction of serum cystatin C and other markers of kidney function on long-term survival in elderly CKD patients.

Methods: Fifty eight adult Caucasian patients, older than 65 years, without known malignancy, thyroid disease and/or not on steroid therapy were enrolled in the study. In each patient, CrEDTA clearance, serum creatinine, serum cystatin C, and estimated glomerular filtration rate using different equations were determined on the same day and patients were then followed for 11 years or until their death.

Results: The means are as follows: CrEDTA clearance 53.3 ± 17.4 ml/min/1.73 m, serum creatinine 1.62 ± 0.5 mg/dl, serum cystatin C 1.79 ± 0.5 mg/l, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation 40.1 ± 14 ml/min/1.73 m, Berlin Initiative Study 2 (BIS2) equation 38.9 ± 10.7 ml/min/1.73 m, full age spectrum (FAS) creatinine equation 43.8 ± 13.8 ml/min/1.73 m, FAS cystatin C equation 40.1 ± 11.7 ml/min/1.73 m. In the follow up period, 47 (81%) patients died. Cox regression analysis showed different hazard ratios (HRs) for death: for CrEDTA clearance HR 1.022 (95% CI 1.004-1.042; p = .015), serum creatinine HR 1.013 (95% CI 1.006-1.019; p = .001), serum cystatin C HR 2.028 (95% CI 1.267-3.241; p = .003), CKD-EPI creatinine equation HR 1.048 (95% CI 1.019-1.076; p = .001), BIS2 equation HR 1.055 (95% CI 1.021-1.088; p = .001), FAS creatinine equation HR 1.046 (95% CI 1.017-1.074; p = .001), FAS cystatin C equation HR 1.039 (95% CI 1.010-1.071; p = .009).

Conclusions: Our results showed the highest HR for serum cystatin C among kidney function markers for prediction of outcome in elderly CKD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/13685538.2018.1479386DOI Listing
March 2019

Hospital ambulatory medicine: A leading strategy for Internal Medicine in Europe.

Eur J Intern Med 2018 08 14;54:17-20. Epub 2018 Apr 14.

Internal Medicine Department, Hospital São Francisco Xavier, Lisboa, Portugal.

Addressing the current collision course between growing healthcare demands, rising costs and limited resources is an extremely complex challenge for most healthcare systems worldwide. Given the consensus that this critical reality is unsustainable from staff, consumer, and financial perspectives, our aim was to describe the official position and approach of the Working Group on Professional Issues and Quality of Care of the European Federation of Internal Medicine (EFIM), for encouraging internists to lead a thorough reengineering of hospital operational procedures by the implementation of innovative hospital ambulatory care strategies. Among these, we include outpatient and ambulatory care strategies, quick diagnostic units, hospital-at-home, observation units and daycare hospitals. Moving from traditional 'bed-based' inpatient care to hospital ambulatory medicine may optimize patient flow, relieve pressure on hospital bed availability by avoiding hospital admissions and shortening unnecessary hospital stays, reduce hospital-acquired complications, increase the capacity of hospitals with minor structural investments, increase efficiency, and offer patients a broader, more appropriate and more satisfactory spectrum of delivery options.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejim.2018.04.010DOI Listing
August 2018

Renal dysfunction predicts mortality in type 2 diabetic patients suffering from an acute ischemic stroke.

Eur J Intern Med 2018 06 2;52:e22-e24. Epub 2018 Apr 2.

Clinic for Internal Medicine, Dept. of Nephrology, University Medical Centre, Maribor, Slovenia; University of Maribor, Maribor, Slovenia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejim.2018.03.013DOI Listing
June 2018

Students as partners: Our experience of setting up and working in a student engagement friendly framework.

Med Teach 2018 06 11;40(6):589-594. Epub 2018 Mar 11.

a Faculty of Medicine , University of Maribor , Maribor , Slovenia.

Background: Student engagement (SE) in the curriculum is a positive indicator in the development of students deeply involved in their learning. It also has several benefits for the schools' level of educational innovation and quality assurance.

Method: In order to identify the most important pearls from the last decade of educational developments within the field of SE at the Faculty of Medicine University of Maribor, we searched through our school's archives, publications and research in the field of medical education.

Results: Three areas were identified as the most important SE complements: (i) peer teaching, (ii) school governance, and (iii) extracurricular activities. The paper highlights how many student-driven initiatives move from informal frameworks toward a formal structure, elective courses, and, in the end, compulsory components of the curriculum.

Discussion: As demonstrated by the three educational achievements at our school, fostering a high level of SE can lead to innovative curricular changes, benefit the whole school and enable students to deliver highly impactful extracurricular projects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/0142159X.2018.1444743DOI Listing
June 2018

Newer glomerular filtration rate estimating equations for the full age spectrum based on serum creatinine and cystatin C in predicting mortality in patients with ischemic stroke.

Eur J Intern Med 2018 06 9;52:67-72. Epub 2018 Feb 9.

Clinic for Internal Medicine, Dept. of Nephrology, University Medical Centre, Maribor, Slovenia; Faculty of Medicine, University of Maribor, Maribor, Slovenia. Electronic address:

Background: Renal dysfunction is associated with increased risk of mortality. The novel Full Age Spectrum (FAS) equations estimating the glomerular filtration rate (GFR) based on serum creatinine (FAScrea) and cystatin C (FAScysC) are validated across the entire age spectrum and are superior markers of renal function compared to other equations. Possible association of these equations with mortality in patients with ischemic stroke is not known.

Patients And Methods: We included 390 patients (207 men, 183 women) in our observational cohort study who had suffered from an ischemic stroke and followed-up on for 3 years. Serum creatinine and cystatin C were measured at admission; GFR was estimated according to the FAScrea, CKD-EPIcrea, FAScysC and CKD-EPIcysC equations. The values of estimated GFRs were divided into quintiles.

Results: During the follow-up period, 173 (44.4%) patients died. The association of hazard ratios for FAScrea and CKD-EPIcrea with all-cause mortality was J-shaped and only significantly higher when comparing the fifth quintile hazard ratio for mortality with the first quintile (P < 0.001). For FAScysC and CKD-EPIcysC, hazard ratios increased from the first to the fifth quintile linearly. In an adjusted analysis, FAScrea and CKD-EPIcrea were not associated with all-cause mortality and the hazard ratios of the fifth quintile of FAScysC (P = 0.008) and CKD-EPIcysC (P = 0.042) were significantly associated with mortality compared to the first quintile.

Conclusions: In patients with an ischemic stroke, estimated GFR based on serum cystatin (FAScysC and CKD-EPIcysC) was a better predictor of all-cause and cardiovascular mortality than estimated GFR based on serum creatinine.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejim.2018.02.005DOI Listing
June 2018

Introduction to the special issue on acutely ill patients.

Eur J Intern Med 2017 11 8;45. Epub 2017 Nov 8.

Clinic for Internal Medicine, Department of Nephrology, University Medical Centre Maribor, Maribor, Slovenia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejim.2017.10.021DOI Listing
November 2017

The assessment of acute kidney injury in critically ill patients.

Eur J Intern Med 2017 Nov 2;45:54-58. Epub 2017 Oct 2.

Clinic for Internal Medicine, Department of Nephrology, University Medical Centre Maribor, Maribor, Slovenia; Faculty of Medicine, University of Maribor, Maribor, Slovenia. Electronic address:

Acute kidney injury (AKI) is common in critically ill patients and is associated with high morbidity and mortality. The availability of several biomarkers of kidney injury offers new tools for its early recognition and management. The early identification of high-risk patients provides an opportunity to develop strategies for the prevention, early diagnosis and treatment of AKI. Despite progress in critical care medicine over the past decade, the treatment strategies for AKI in critically ill patients, such as when to start renal replacement therapy, remain controversial. A recently proposed risk prediction score for AKI, based on routinely available clinical variables, presents a new means of identifying patients at high risk of AKI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejim.2017.09.041DOI Listing
November 2017