Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common cause of chronic liver disease and is closely associated with metabolic abnormalities and cardiovascular risks. Butyrate, a short-chain fatty acid produced by gut microbiota, has the potential to enhance liver health by modulating inflammation and supporting gut barrier integrity. This study aimed to investigate and compare the effects of sodium butyrate and calcium butyrate in patients with MASLD. In this single-center, randomized clinical trial, 181 patients with MASLD were enrolled and assigned to receive either sodium butyrate (n = 121) or calcium butyrate (n = 60) supplementation at a daily dose of 1000 mg. The primary endpoint was the change in liver steatosis, measured using the Controlled Attenuation Parameter (CAP) via FibroScan^®. Secondary endpoints included liver stiffness, biochemical parameters, hepatic steatosis and fatty liver indices, fecal calprotectin levels, stool short-chain fatty acid levels, and microbiome composition. A subgroup analysis compared responders (a ≥ 5% reduction in CAP) to non-responders. There were no significant changes in CAP values for either group (ΔCAP: sodium butyrate, 0.84; calcium butyrate, −0.23; p = 0.70). Sodium butyrate significantly reduced serum trimethylamine N-oxide and fatty liver index, while calcium butyrate led to a decrease in fecal calprotectin levels. Responders demonstrated a lower body mass index, higher levels of high-sensitivity C-reactive protein and HbA1c, and distinct microbiome profiles, characterized by lower abundance of Subdoligranulum and higher abundance of Catenibacterium. Although butyrate supplementation did not significantly improve liver steatosis as measured by CAP, the differing effects on metabolic and inflammatory markers suggest that there may be potential benefits for specific subgroups of patients with MASLD.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common cause of chronic liver disease and is closely associated with metabolic ab-normalities and cardiovascular risks. Butyrate, a short-chain fatty acid produced by gut microbiota, has the potential to enhance liver health by modulating inflammation and supporting gut barrier integrity. This study aimed to investigate and compare the effects of sodium butyrate and calcium butyrate in patients with MASLD. Methods: In this single-center, randomized clinical trial, 181 patients with MASLD were enrolled and assigned to receive either sodium butyrate (n=121) or calcium butyrate (n=60) supplementation at a daily dose of 1000 mg. The primary endpoint was the change in liver steatosis, measured using the Controlled Attenuation Parameter (CAP) via Fi-broScan®. Secondary endpoints included liver stiffness, biochemical parameters, se-rum and fecal calprotectin levels, stool short-chain fatty acid levels, and microbiome composition. A subgroup analysis compared responders (a ≥5% reduction in CAP) to non-responders. Results: There were no significant changes in CAP values for either group (ΔCAP: sodium butyrate, 0.84; calcium butyrate, –0.23; p=0.70). Sodium butyrate significantly reduced serum trimethylamine N-oxide, while calcium butyrate led to a decrease in fecal calprotectin levels. Responders demonstrated a lower body mass in-dex, higher levels of high-sensitivity C-reactive protein and HbA1c, and distinct mi-crobiome profiles, characterized by lower abundance of Subdoligranulum and higher abundance of Catenibacterium. Conclusions: Although butyrate supplementation did not significantly improve liver steatosis as measured by CAP, the differing effects on metabolic and inflammatory markers suggest that there may be potential benefits for specific subgroups of patients with MASLD.

Ischemic heart disease (IHD) remains a leading cause of global morbidity and mortality despite advances in prevention, diagnosis, and therapy. Traditional clinical risk scores and biomarkers often fail to fully capture the complex molecular processes underlying atherosclerosis, myocardial infarction, and ischemic cardiomyopathy, leaving substantial residual risk. MicroRNAs have emerged as promising regulators and biomarkers of cardiovascular disease, among which microRNA-21 (miR-21) has attracted particular attention. MiR-21 is deeply involved in key pathophysiological mechanisms of IHD, including endothelial dysfunction, vascular inflammation, vascular smooth muscle cell proliferation, plaque development and vulnerability, cardiomyocyte survival, and myocardial fibrosis. Accumulating clinical evidence suggests that circulating miR-21 holds diagnostic value across the ischemic continuum, from stable coronary artery disease to acute coronary syndromes, myocardial infarction, and ischemic heart failure. Moreover, miR-21 demonstrates prognostic relevance, correlating with plaque instability, adverse remodeling, heart failure progression, and long-term cardiovascular outcomes. Preclinical studies further indicate that miR-21 represents a double-edged therapeutic target, offering cardio protection in acute ischemic injury while contributing to fibrosis and maladaptive remodeling if dysregulated. This narrative review summarizes current evidence on the diagnostic, prognostic, and therapeutic utility of miR-21 in IHD, highlighting its clinical promise as well as key limitations and future translational challenges.

Increased peritoneal protein loss has been associated with the fast transport of small molecules, diabetes mellitus (DM), and a reduced survival in patients on peritoneal dialysis (PD), although some studies did not confirm the association with survival. In this single-center retrospective study, we investigated the relationship of baseline peritoneal albumin and protein loss with transport status, comorbidities including DM, and survival in 106 incident PD patients during the period of July 2005–June 2014. Five-year survival rate was determined using Cox-regression analysis. There were not significant differences in D/Pcr or peritoneal protein and albumin loss between diabetics and non-diabetics. In the group of 66 non-diabetics, high and high-average transporters for creatinine had higher values for both peritoneal protein (11.85 ± 6.77 vs. 7.85 ± 4.36 g/day; p = 0.002) and albumin (5.03 ± 2.32 vs. 3.72 ± 1.54 g/day; p = 0.016) loss as compared to slow transporters. However, in the group of 40 diabetics, this association was not observed. Upon multivariable regression analysis, the independent association of D/PCr with peritoneal albumin (β = 0.313; p = 0.008) and protein (β = 0.441; p = 0.001) loss was found only in non-diabetics in whom ultrafiltration also appeared as a significant predictor of peritoneal protein loss (β = 0.330; p = 0.000). A high comorbidity grade, older age, and low serum albumin were associated with mortality, but both peritoneal protein and albumin loss as well as D/Pcr were not determinants of survival. Baseline peritoneal protein and albumin loss was not associated with DM and did not predict survival. The clinical significance of the absence of association between fast peritoneal transport status and peritoneal protein flux in diabetics should be evaluated in a prospective study comprising a greater number of diabetics with evaluation of overhydration as a main inducing variable of protein leak.

Background and Objectives: Anemia is a common complication of chronic kidney disease (CKD) and is associated with reduced quality of life, accelerated disease progression, and increased cardiovascular risk. Sodium–glucose cotransporter-2 inhibitors (SGLT2is) have demonstrated significant renal and cardiovascular benefits, and clinical trials have reported improvements in hematologic parameters during treatment. However, real-world evidence regarding their longitudinal effects on hemoglobin (Hb) and iron metabolism in patients with CKD remains limited. Materials and Methods: We conducted a pre–post analysis of 118 adult patients with CKD stages 1–4 treated with SGLT2is (empagliflozin or dapagliflozin) at the University Clinical Center of Serbia between January 2024 and June 2025. Patients received either agent at 10 mg once daily for 18 months. Hb, ferritin, C-reactive protein (CRP), albumin (Alb), daily proteinuria (Prt), and estimated glomerular filtration rate (eGFR) were assessed at baseline and at 18 months. Ferritin was adjusted for inflammatory and nutritional status using a residualization model incorporating CRP and Alb. Changes between the two time points were analyzed using repeated-measures general linear models (GLMs). Results: In unadjusted analyses, mean Hb increased modestly from 136.5 ± 17.9 g/L at baseline to 138.8 ± 18.9 g/L at follow-up (p = 0.028), while median ferritin decreased from 102.2 µg/L to 89.9 µg/L (p = 0.011). After adjustment for CRP and Alb, ferritin levels remained unchanged (p = 0.752). Repeated-measures analyses showed no significant longitudinal effect of time on Hb or ferritin and no significant interaction between time and SGLT2i type. Baseline eGFR, Prt, sex, and baseline ferritin significantly influenced longitudinal hematologic trajectories. Conclusions: SGLT2i therapy was associated with modest increases in Hb levels over 18 months, while inflammatory status remained stable and no significant reduction in ferritin levels was observed after adjustment for inflammatory and nutritional factors. Longitudinal Hb and ferritin trajectories did not differ significantly between empagliflozin and dapagliflozin, while baseline kidney function, Prt, iron status, and sex significantly influenced hematologic outcomes. Although causal inference is limited by the absence of a control group, these findings suggest a possible favorable effect of SGLT2is on anemia-related parameters in patients with CKD.

MicroRNA-21 (miR-21) has long been regarded as one of the most promising molecular targets in chronic kidney disease (CKD) because of its consistent upregulation across diverse renal disorders and its involvement in fibrosis, inflammation, oxidative stress, and metabolic dysfunction. Strong preclinical evidence demonstrated that inhibition of miR-21 reduced kidney injury, preserved renal function, and improved survival in multiple experimental models, particularly Alport syndrome, leading to the clinical development of the antisense oligonucleotide lademirsen. However, despite a compelling biological rationale and encouraging animal data, the phase 2 HERA trial failed to demonstrate a clinically meaningful effect on the rate of kidney function decline, resulting in discontinuation of the program. This review examines the biological functions of miR-21 in CKD, summarizes the experimental and clinical evidence that supported its therapeutic development, and critically analyzes the factors that may explain the discrepancy between preclinical success and clinical failure. Particular attention is given to the distinction between disease-associated biomarkers and true therapeutic drivers, the limitations of animal models, disease heterogeneity, timing of intervention, and the complex regulatory networks underlying progressive kidney fibrosis. Rather than representing the end of miR-21 research, the experience with lademirsen provides valuable insights into the challenges of translating RNA-based therapies into clinical practice. Future therapeutic strategies will likely require earlier intervention, improved patient selection, robust biomarkers of target engagement, and combination approaches that address the multifactorial nature of CKD. The lessons learned from the lademirsen program may help guide the development of the next generation of RNA therapeutics for kidney disease.