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Background: Over the past decade, diabetes mellitus (DM) has emerged as a growing epidemic, with a direct link to an increased risk of hospitalization and a strong effect of glycemic control on clinical outcomes. The aim of this document was to critically appraise and adapt existing clinical practice guidelines (CPGs) to provide specific recommendations for the management of hyperglycemia in hospitalized adults with and without previously known DM, in an attempt to provide a practical tool to reduce the risk of major in-hospital complications., Methods: The first step of the adaptation process was to identify unsolved clinical questions (PICOs) in hospitalized persons with hyperglycemia. This was followed by a critical appraisal of updated existing CPGs and the selection of recommendations that were most applicable to specific clinical situations., Results: From the four updated high-quality evidence-based CPGs, 75 recommendations were selected, focusing on five common clinical scenarios in real-world practice: 1) glycemic targets; 2) persons with comorbidities; 3) elderly adults with low consciousness or dementia with irregular feeding or parenteral/enteral nutrition; 4) special hyperglycemic scenarios (stress hyperglycemia, corticosteroid treatment, fasting); and 5) glucose-lowering therapy at discharge. Of the 75 selected recommendations (59 strong and 16 weak), 37 were based on high-quality evidence, 8 on moderate-quality evidence, and 17 on low-quality evidence, while 13 were based on consensus (best practice statements). The recommendations apply to adults who are hospitalized or discharged from the hospital., Conclusion: Using a systematic methodology, this guideline provides an updated and ease-to-use tool for the management of hospitalized adults with hyperglycemia., Competing Interests: Declaration of competing interest The authors declare that they have no financial and non-financial competing interests. The authors declare they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: This retrospective study aimed to evaluate the 30 and 60-day survival of critically ill patients with COVID-19 and AKI., Methods: Inflammatory and biochemical biomarkers, length of intensive care unit (ICU) stay and mortality at Day 30 and Day 60 after ICU admission were analyzed. A total of 44 patients treated with continuous renal replacement therapy (CRRT) with cytokine adsorber (CA group) were compared to 58 patients treated with CRRT alone (non-CA group)., Results: Patients in CA group were younger, had better preserved kidney function prior to the beginning of CRRT and had higher levels of interleukin-6. There were no statistically significant differences in their comorbidities and in other measured biomarkers between the two groups. The number of patients who died 60 days after ICU admission was statistically significantly higher in non-CA group (p = 0.029)., Conclusion: Treatment with CRRT and cytokine adsorber may have positively influenced 60-day survival in our COVID-19 ICU patients with AKI., (© 2024 The Author(s). Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis and Japanese Society for Apheresis.)

Kidney diseases are among the leading causes of death globally. With the increasing rates of acute kidney injury (AKI) requiring hospitalisation, a better understanding of pathophysiological mechanisms is needed to treat the patients more efficiently. Nephrotoxicity is one of the most common causes of AKI, mainly due to the high availability of over-the-counter drugs and natural supplements, which may interact with prescribed drugs at the level of pharmacokinetics, among other factors. The latter can lead to clinically relevant complications (including AKI), which is even more pronounced given the increasingly ageing population in the Western world and the associated increase in polypharmacy. Drug testing starts at the preclinical level, where a reliable model is needed to predict human response to a tested drug with sufficient accuracy. Recently, in-vitro kidney models of different complexities have been created to study various aspects of kidney diseases. Because the proximal tubule plays a vital role in several mechanisms, many models include proximal tubular epithelial cells (PTECs). Monocultures of PTECs do not represent in-vivo tissue accurately enough. Therefore, more complex models with more cell types are being built. To our knowledge, this is the first review focusing on co-culture models and cell types used alongside PTECs for studying the nephrotoxicity of drugs and other mechanisms of AKI and chronic kidney disease., (Creative Commons Attribution license.)

Factor XIII (FXIII), a plasma transglutaminase, is a coagulation factor that plays a crucial role in blood clotting and patient blood management. The studies have demonstrated that FXIII targets a wide range of additional substrates that have an important role in hemostasis, especially in posttraumatic patients, patients undergoing surgery or obstetrics, being involved in wound healing and tissue repair. Morover, FXIII deficiency has also been described and an extensive research has shown that FXIII deficiency is a rare coagulopathy that leads to longer bleeding time, perioperative and postoperative complications and slower wound healing. Present article aims to overview the diverse functions of FXIII and to highlight its role in patient blood management., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

International consensus supports the development of standardized protocols for measured glomerular filtration rate (mGFR) to facilitate the integration of mGFR testing in both clinical and research settings. To this end, the European Kidney Function Consortium convened an international group of experts with relevant experience in mGFR. The working group performed an extensive literature search to inform the development of recommendations for mGFR determination using 1-compartment plasma clearance models and iohexol as the exogenous filtration marker. Iohexol was selected as it is non-radio labeled, inexpensive, and safe, can be assayed at a central laboratory, and the other commonly used non-radio-labeled tracers have been (inulin) or are soon to be (iothalamate) discontinued. A plasma clearance model was selected over urine clearance as it requires no urine collection. A 1 compartment was preferred to 2 compartments as it requires fewer samples. The recommendations are based on published evidence complemented by expert opinion. The consensus paper covers practical advice for patients and health professionals, preparation, administration, and safety aspects of iohexol, laboratory analysis, blood sample collection and sampling times using both multiple and single-sample protocols, description of the mGFR mathematical calculations, as well as implementation strategies. Supplementary materials include patient and provider information sheets, standard operating procedures, a study protocol template, and support for mGFR calculation., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Advanced chronic lymphocytic leukemia (CLL) is accompanied by increased circulating regulatory T cells (Tregs) and increased susceptibility to severe infections, which were also shown to entail a striking induction of FOXP3 expression in Tregs. As homeostasis of the most suppressive CD45RA - FOXP3 high activated Treg (aTreg) subset differs, it is critical to analyse homeostatic signalling in Treg subsets., Materials and Methods: In this study, by using conventional and imaging flow cytometry, we monitored STAT5 signalling/phosphorylation (pSTAT5) and investigated Treg subsets in relation to the Binet stage, the total tumor mass score (TTM) and the disease course during a follow-up of 37 patients with CLL., Results: The aTreg percentage was significantly increased among CD4 + T cells from patients with advanced disease and significantly correlated with the TTM. A subgroup of patients with higher aTreg percentages among CD4 + FOXP3 + T cells at the start of therapy was characterised by more frequent episodes of severe infections during follow-up., Conclusions: The results suggesting that an aTreg fraction could represent a possible marker of a severe disease course with infectious complications. Augmented homeostatic STAT5 signalling could support aTreg expansion, as higher pSTAT5 levels were significantly correlated with an increased aTreg frequency among CD4 + FOXP3 + T cells during the follow-up of patients on therapy, as well as following SARS-CoV-2 antigen-specific stimulation in vitro.

Mineralocorticoid receptor antagonists (MRAs) are one of the renin-angiotensin-aldosterone system inhibitors widely used in clinical practice. While spironolactone and eplerenone have a long-standing profile in clinical medicine, finerenone is a novel agent within the MRA class. It has a higher specificity for mineralocorticoid receptors, eliciting less pronounced adverse effects. Although approved for clinical use in patients with chronic kidney disease and heart failure, intensive non-clinical research aims to further elucidate its mechanism of action, including dose-related selectivity. Within the field, animal models remain the gold standard for non-clinical testing of drug pharmacological and toxicological properties. Their role, however, has been challenged by recent advances in in vitro models, mainly through sophisticated analytical tools and developments in data analysis. Currently, in vitro models are gaining momentum as possible platforms for advanced pharmacological and pathophysiological studies. This article focuses on past, current, and possibly future in vitro cell models research with clinically relevant MRAs.

Diabetic kidney disease is a frequent microvascular complication of diabetes and is currently the leading cause of chronic kidney disease and end-stage kidney disease worldwide. Although the prevalence of other complications of diabetes is falling, the number of diabetic patients with end-stage kidney disease in need of kidney replacement therapy is rising. In addition, these patients have extremely high cardiovascular risk. It is more than evident that there is a high unmet treatment need in patients with diabetic kidney disease. Finerenone is a novel nonsteroidal mineralocorticoid receptor antagonist used for treating diabetic kidney disease. It has predominant anti-fibrotic and anti-inflammatory effects and exhibits several renal and cardiac protective effects. This review article summarizes the current knowledge and future prospects of finerenone in treating patients with kidney disease.

The Perceived Inventory of Technological Competency as Caring in Nursing (PITCCN) questionnaire has been designed to measure technological competency as caring in nursing practice. It incorporates the use of technology with the fundamental principles of caring that are central to nursing. As there were no psychometrically sound instruments to quantify the concept of technological competency as caring in the Slovene language, we adapted the English version of the questionnaire to the local environment. The goal was to assess the level of psychometric properties of the PITCCN investigated in Slovene hospitals., Methods: Content validity was conducted with eight experts and quantified by the content validity index (CVI) and the modified Cohen's kappa index. Face validity was assessed through discussions with participants from the target culture in the pilot study. To assess construct validity and internal consistency, a cross-sectional research methodology was used on a convenience sample of 121 nursing personnel from four hospitals. Principal component analysis (PCA) was used to examine construct validity, while Cronbach's alpha and adjusted item-total correlations were used to measure internal consistency., Results: The content and face validity of PITCCN were adequate. The scale validity index (S-CVI) was 0.97. Cronbach's α was 0.92, and subscale reliabilities ranged from 0.810 to 0.925. PCA showed four components, which explained more than 73.49% of the variance., Conclusions: The Slovenian version of PITCCN (PITCCN_SI) has good psychometric properties.

Introduction: The pathogenesis of renal disease in obesity and metabolic syndrome (MS) is mostly unknown. This is in part because of the limited information about renal morphological changes in these conditions. We evaluated renal histology in subjects with MS and those without MS, who are participants in the European Nephrectomy Biobank (ENBiBA) project., Methods: MS was defined with at least 3 of the following criteria: (i) body mass index (BMI) ≥27 kg/m 2 ; (ii) prediabetes: fasting glucose of 100-125 mg/dl or HbA1c >5.7%; (iii) systolic or diastolic blood pressure >140/90 mm Hg or the use of medications; and (iv) triglycerides >150 mg/dl or high-density lipoprotein cholesterol <40 (in men) or 50 mg/dl (in women). The absence of these criteria defined patients without MS. Exclusion criteria were diabetes or known causes of renal disease., Results: A total of 157 cases were evaluated: 49 without and 108 with MS. Those with MS were older (54 ± 16 vs. 66 ± 11, P  < 0.0001), had more prevalent chronic kidney disease (CKD, estimated glomerular filtration rate [eGFR] <60 ml/min): 24% (23%) versus 4% (8%) ( P  = 0.02), and had higher albumin-to-creatinine ratio (10 [4-68] vs. 4.45 [0-27], P  = 0.05) than those without MS. Global sclerosis (3% [1-7] vs. 7% [3-13], P  < 0.0001), nodular sclerosis, mesangial expansion, glomerulomegaly; moderate + severe hyalinosis, and arteriosclerosis were more frequent in those with MS than in those without (88 [82] vs. 29 [59]; 83 [77] vs. 30 [61]; P  < 0.05). These vascular changes were independent of differences in age., Conclusion: In MS, ischemic renal disease may play a role in renal disease. In addition, some patients may develop lesions compatible with diabetic nephropathy such as increased mesangial expansion and nodular sclerosis. Further analyses are needed to study the consequences of the pandemic of obesity on renal health., (© 2024 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.)

Introduction: Protein-energy wasting (PEW) is a common and serious co-morbidity in haemodialysis (HD) patients. Its importance as a prognostic factor has been increasingly recognised during the past decades. Much effort has been invested in the improvement of nutritional status and amelioration of consequences through different therapeutic approaches, either intradialytic parenteral nutrition or more commonly oral nutritional supplementation. In the article, we present the results of a prospective study in HD patients after 12 months of therapeutic intervention with oral nutritional supplements (ONS)., Methods: A total of 92 HD adult patients were enrolled in the study after 3 months of wash-out period. Baseline nutritional status was assessed using composite scores, laboratory markers, bioelectrical impedance analysis, and hand-grip strength test. Patients recognised as undernourished or at high risk for undernutrition received renal-specific commercially available ONS on HD day in addition to their regular diet. After 12 months, the effect of ONS on surrogate markers of undernutrition, serum albumin level, phase angle, and hand-grip strength was analysed in 71 surviving patients., Results: After 12 months, data for 71 patients, 39 (54.9%) men, 62.4 ± 12.9 years, and median haemodialysis vintage 53.3 (IQR 27.5-92.8) months, were available. Patients were divided into three groups: group A patients were with normal nutritional status at baseline not necessitating ONS; group B patients received ONS; and group C patients were entitled to receive but refused to take ONS. The baseline results showed statistically significant differences between the groups in serum albumin levels and phase angle but not hand-grip strength. Differences between the groups remained statistically significant at month 12; we did not find any statistically significant positive changes within the groups, indicating no positive effect of intervention with ONS., Conclusion: In a prospectively designed interventional single-centre study, we did not find a statistically significant change in surrogate markers of PEW in our cohort of HD patients, receiving ONS for 12 months. Since PEW is an independent risk factor influencing the survival of HD patients, efforts should be directed towards a timely and comprehensive nutritional approach, including intensive, personalised dietary counselling, increase in protein and energy intake and advocating tight control of nutritional status during HD treatment, possibly providing psychological support and motivation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ocepek, Ekart, Povalej Bržan and Bevc.)

Acute kidney injury and chronic kidney disease are among the most common non-communicable diseases in the developed world, with increasing prevalence. Patients with acute kidney injury are at an increased risk of developing chronic kidney disease. One of kidney injury's most common clinical sequelae is increased cardiovascular morbidity and mortality. In recent years, new insights into the pathophysiology of renal damage have been made. Oxidative stress is the imbalance favoring the increased generation of ROS and/or reduced body's innate antioxidant defense mechanisms and is of pivotal importance, not only in the development and progression of kidney disease but also in understanding the enhanced cardiovascular risk in these patients. This article summarizes and emphasizes the role of oxidative stress in acute kidney injury, various forms of chronic kidney disease, and also in patients on renal replacement therapy (hemodialysis, peritoneal dialysis, and after kidney transplant). Additionally, the role of oxidative stress in the development of drug-related nephrotoxicity and also in the development after exposure to various environmental and occupational pollutants is presented.

Background: Obesity is associated with several neurohumoral changes that play an essential role in organ damage. Increased arterial stiffness causes functional vessel wall changes and can therefore lead to accelerated target organ damage as well. Whether obesity causes an independent increase in central arterial stiffness is, however, not yet fully known., Methods: One hundred thirty-three patients (63.2% male) were included. Body Mass Index (BMI) was defined as body weight in kilograms, divided by the square of body height in meters. Chronic Kidney Disease Epidemiology Collaboration creatinine 2009 equation was used to estimate the glomerular filtration rate (eGFR). Non-invasive applanation tonometry was used for arterial stiffness measurements (Sphygmocor Atcor Medical, Sydney, Australia). All patients underwent coronarography., Results: The mean age of our patients was 65.0 ± 9.2 years. Their mean BMI was 28.5 ± 4.4 kg/m 2 , eGFR 75.5 ± 17.2 ml/min/1.73 m 2 and ankle-brachial index (ABI) 1.0 ± 0.1. Their arterial stiffness measurements showed mean carotid-femoral pulse wave velocity (cfPWV) 10.3 ± 2.7 m/s, subendocardial viability ratio (SEVR) 164.4 ± 35.0%, and pulse pressure (PP) 47.8 ± 14.5 mmHg. Spearman's correlation test revealed a statistically significant correlation between BMI and SEVR (r = -0.193; p = 0.026), BMI and cfPWV (r = 0.417; p < 0.001) and between BMI and PP (r = 0.227; p = 0.009). Multiple regression analysis confirmed an independent connection between BMI and cfPWV (B = 0.303; p < 0.001) and between BMI and SEVR (B = -0.186; p = 0.040). There was no association between BMI and kidney function, ABI, or coronary artery disease., Conclusion: Increased BMI is independently associated with augmented central arterial stiffness and reduced subendocardial perfusion but not with coronary artery disease, kidney function, or ABI., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Increased frequency of CD4 + CD25 + regulatory T-cells (Treg) has been associated with disease progression in chronic lymphocytic leukemia (CLL). Flow cytometric methods, which allow for the simultaneous analysis of their specific transcription factor Foxp3 and activated STAT proteins, together with proliferation can help to elucidate the signaling mechanisms driving Treg expansion and suppression of FOXP3- conventional CD4 + T-cells (Tcon). Herein, we first report a novel approach in which STAT5 phosphorylation (pSTAT5) and proliferation (BrdU-FITC incorporation) could be analyzed specifically in FOXP3+ and FOXP3- responding cells after CD3/CD28 stimulation. The addition of magnetically purified CD4 + CD25 + T-cells from healthy donors to cocultured autologous CD4 + CD25 - T-cells resulted in suppression of Tcon cell cycle progression accompanied by a decrease in pSTAT5. Next, a method using imaging flow cytometry is presented for the detection of cytokine-dependent pSTAT5 nuclear translocation in FOXP3-expressing cells. Finally, we discuss our experimental data obtained by combining Treg pSTAT5 analysis and antigen-specific stimulation with SARS-CoV-2 antigens. Applying these methods on samples from patients revealed Treg responses to antigen-specific stimulation and significantly higher basal pSTAT5 in CLL patients treated with immunochemotherapy. Thus, we speculate that through the use of this pharmacodynamic tool, the efficacy of immunosuppressive drugs and their possible off-target effects can be assessed.