Search Results (2,615)

Background: The immune mechanism of diabetic kidney disease (DKD) has not yet been fully elucidated. This study aimed to characterize circulating lymphocyte subsets in patients with type 2 diabetes mellitus (T2DM), with a particular focus on DKD-related immune alterations and prognosis. Methods: Circulating T cells, B cells and NK cells were identified by flow cytometry. The primary endpoint was all-cause mortality, and overall survival was defined as the time from enrollment to death from any cause or last follow-up. Associations between lymphocyte subsets, inflammatory indices and renal function parameters were analyzed. Cox regression was used to identify factors associated with overall survival in patients with DKD and in the whole T2DM cohort. A prognostic nomogram was developed in the whole T2DM cohort to estimate 1-, 2-, 3-, and 5-year overall survival (OS) probabilities. Model performance was evaluated using the concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Mendelian randomization (MR) was performed as a further exploratory analysis to assess whether immune-related traits were genetically associated with DKD susceptibility, with inverse variance weighting (IVW) as the primary analytical method. Results: In total, 74 T2DM patients were divided into DKD (stage 3–4 of chronic kidney disease) and non-DKD groups. Median follow-up duration was 34.6 months. DKD patients exhibited elevated levels of NK cells, the monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). In patients with DKD, higher PLR and serum creatinine (SCr) were associated with poorer overall survival, whereas CD4⁺CD25⁺ T cell frequency was not significant after adjustment. In the whole T2DM cohort, higher frequency of circulating CD4⁺CD25⁺ T cells were associated with improved survival (HR 0.920, 95% CI 0.858–0.986, p = 0.019), whereas elevated PLR and SCr were linked to poorer outcomes. The exploratory nomogram incorporating CD4⁺CD25⁺ T cells, PLR, and SCr, showed acceptable internal performance in this cohort. As a separate exploratory analysis, MR suggested that genetically proxied CD4 expression on activated CD4 regulatory T cells was associated with a lower risk of DKD. Conclusions: DKD was associated with higher mortality and elevated MLR-, NLR-, PLR-, and NK cell levels in patients with T2DM. In patients with DKD, PLR and SCr were associated with overall survival, supporting the prognostic relevance of systemic inflammation and renal dysfunction. Individual lymphocyte subsets were not independently associated with survival in the DKD cohort after adjustment, whereas CD4⁺CD25⁺ T cell frequency provided additional prognostic information in the whole extended T2DM cohort analysis. Further validation is warranted. Full article

Background: Low-density lipoprotein cholesterol (LDL-C) is a central modifiable driver of atherosclerotic cardiovascular disease, yet cardiovascular risk in type 2 diabetes mellitus (T2DM) may be better captured by longitudinal LDL-C exposure than by a single LDL-C measurement. We examined the association of current LDL-C, cumulative LDL-C burden, and prior time below LDL-C targets with incident acute coronary syndrome (ACS) in patients with T2DM. Methods: We conducted a retrospective longitudinal cohort study using routinely collected electronic health-record data. Patients with T2DM and at least one valid LDL-C measurement between 1 January 2018 and 31 December 2023 were followed from the first eligible LDL-C measurement until incident ACS or administrative censoring on 31 March 2024. LDL-C was modeled using time-updated start–stop Cox regression. The primary exposure was current LDL-C category: <1.4, 1.4 to <1.8, 1.8 to <2.6, 2.6 to <3.4, 3.4 to <4.9, and ≥4.9 mmol/L. Secondary exposure metrics were cumulative LDL-C burden above prespecified thresholds and prior percentage of follow-up time below LDL-C targets. Models were adjusted for age, sex, hypertension, chronic kidney disease, HbA1c, T2DM duration, and calendar year of baseline LDL-C measurement; HbA1c and T2DM duration were multiply imputed. Results: The analytic cohort included 106,185 patients, 426,965 LDL-C intervals, and 5416 incident ACS events over 419,251.0 person-years. Compared with current LDL-C <1.4 mmol/L, adjusted ACS risk was higher for current LDL-C 3.4 to <4.9 mmol/L (HR 1.35, 95% CI 1.21–1.50) and ≥4.9 mmol/L (HR 1.94, 95% CI 1.63–2.32), whereas lower LDL-C categories were not clearly different from the reference category after adjustment. Each 1 mmol/L-year higher cumulative LDL-C burden was associated with higher ACS risk across evaluated thresholds, with HRs ranging from 1.04 to 1.13. Greater prior time below LDL-C targets was associated with lower ACS risk, with HRs of 0.97–0.98 per 10% higher time below target. Findings were consistent in sensitivity analyses restricted to patients with at least three LDL-C measurements, landmark analyses, and complete-case analysis. Conclusions: In patients with T2DM, incident ACS risk was associated with very high current LDL-C and with longitudinal LDL-C exposure captured by cumulative burden and time below target. These findings support sustained, target-oriented LDL-C control and suggest that longitudinal LDL-C metrics may complement single LDL-C values in cardiovascular risk assessment. Full article

Type 2 diabetes mellitus is a relevant cardio–renal–metabolic disorder in which chronic low-grade inflammation and oxidative stress have a crucial function in linking insulin resistance, endothelial dysfunction, β-cell impairment, and progressive organ injury. In this context, nutrition has emerged as a key modifiable determinant of metabolic homeostasis, capable of influencing inflammatory signalling, redox balance, mitochondrial function, and gut microbiota–host interactions. The objective of this review is to critically summarise the mechanistic connections among inflammation, oxidative stress, and diabetes progression, and to investigate how dietary factors and patterns, as well as nutrition-responsive biomarkers, influence these pathways and their cardiorenal consequences. We discuss the effects of macronutrient quality, dietary fibre, fatty acids, polyphenols, and specific micronutrients, including vitamin C, vitamin E, selenium, zinc, and magnesium, as well as the role of Mediterranean, DASH, and plant-based diets in improving glycaemic control, endothelial function, and cardio-renal risk profiles. We also summarise established and emerging biomarkers of inflammation and oxidative stress that may improve risk stratification and the evaluation of nutrition-based interventions. Overall, current evidence supports a shift from a purely glucose-centred approach toward an integrated model in which dietary modulation of inflammatory and oxidative pathways helps reduce cardiovascular and renal risk. However, heterogeneity of interventions, variability in biomarker assessment, and interindividual differences in dietary response represent major limitations. Future research should focus on biomarker-informed, precision-oriented nutritional approaches integrated within contemporary cardio–renal–metabolic care. Full article

Objective: Atherosclerotic renal artery stenosis (ARAS) is increasingly prevalent among aging populations and in patients with diabetes, hyperlipidemia, aortoiliac obstructive disease, coronary artery disease, and/or hypertension. Patients with severe ARAS are at a substantially elevated risk of cardiovascular disease, recurrent congestive heart failure, stroke, ischemic nephropathy, and chronic kidney disease. Therefore, the ARAS-TR study aims to evaluate the effect of renal artery stenting on the clinical outcomes in patients with severe ARAS and renovascular hypertension. Materials: This study was conducted as a multicenter, prospective study between July 2024 and September 2025. It encompassed 278 patients with angiographically confirmed severe ARAS who underwent renal artery stent implantation. Patients were subsequently monitored for 6 months. A paired-samples t-test was used to compare continuous variables pre- and post-intervention, while categorical variables were analyzed using the Pearson chi-square test and Fisher’s exact test. Results: The mean age of the patients was 63.6 [±13.4] years, and the male gender ratio was 52.5%. After renal artery stenting, systolic and diastolic blood pressures decreased significantly at the 6-month follow-up compared with the pre-procedure levels (SBP 166.99 [21.24] vs. 135.40 [15.69], p < 0.001; DBP 96.28 [13.03] vs. 80.39 [11.03], p < 0.001, respectively). GFR (61.23 [28.33] vs. 63.35 [26.36], p = 0.029) and creatinine (1.40 [0.93] vs. 1.29 [0.66], p = 0.004) levels improved compared to baseline. The mean number of antihypertensive drugs required for patients to remain normotensive decreased significantly (3.19 [1.04] vs. 2.48 [1.13], p < 0.001) during the follow-up period. Conclusions: Percutaneous renal artery intervention appears to be a promising and safe strategy for carefully selected high-risk patients presenting with severe ARAS, renovascular hypertension, and non-atrophic kidneys. In this specific clinical context, restoring renal artery patency through percutaneous stenting was associated with improved renal function and observed reduction in the burden of antihypertensive drugs required to sustain normotension. Full article

The COVID-19 pandemic has had a profound impact on global health, especially among patients with cardiovascular disease (CVD) and the existence of additional conditions such as diabetes (DM), hypertension (HT), and chronic kidney disease (CKD) can have a significant impact on survival rates. The aim of this study was to determine the mortality rate in patients with CVD and the impact of other comorbidities on the death of patients with COVID-19. This systematic review was conducted using PubMed, EMBASE, and Google Scholar databases from August 2020 to June 2025. Inclusion criteria were patients with cardiovascular disease and associated comorbidities during the COVID-19 pandemic. Article selection was limited to articles published in English and Polish. Statistical analysis using a random-effects model was performed using STATA software. Heterogeneity between studies was examined, and a funnel plot for publication bias was generated. The higher mortality rates (OR = 3.00, 95% CI: 2.06–4.38) for patients with cardiovascular disease were observed. In the group of patients with comorbidities such as hypertension and diabetes mellitus the risk of death was also determined and for HT was OR = 1.94, 95% CI, 1.50–2.52 and for DM OR = 2.17, 95% CI: 1.64–2.86. The mortality in the chronic kidney disease group was higher than for HT and DM (OR = 3.91, 95% CI: 2.50–6.10). The risk of death is three times higher for patients with COVID-19 and CVD. High mortality risk is also linked to diabetes and hypertension but for chronic kidney disease patients increased up to four times. Full article

Background/Objectives: Cystatin C-based and combined creatinine–cystatin C estimated glomerular filtration rate (eGFR) equations improve early chronic kidney disease (CKD) detection and prediction of adverse outcomes compared to creatinine alone. However, their role in predicting microvascular complications such as diabetic retinopathy (DR) is less clear. We examined the association between diabetic kidney disease (DKD), defined using creatinine-, cystatin C-, and combined eGFR measures, as well as albuminuria, and the risk of incident DR among Asian adults in Singapore. Methods: We analysed 1135 Chinese and Indian adults with diabetes aged ≥40 years from a population-based cohort study with baseline (2007–2011) and 6-year follow-up (2013–2017) data. DR was graded from retinal photographs, and incident DR was defined as new-onset at follow-up. DKD was defined as eGFR < 60 mL/min/1.73 m² using eGFRcr, eGFRcys, combined eGFRcr-cys, and albuminuria (UACR ≥ 30 mg/g), assessed individually and jointly. Modified Poisson regression models adjusted for age, sex, ethnicity, diabetes duration, HbA1c, and systolic blood pressure were used to estimate relative risks (RRs). Results: Overall, incident DR occurred in 13.0% of participants. Among those with DKD, incidence was 18.2% (eGFRcr), 16.7% (eGFRcys), 23.7% (eGFRcr-cys), and 18.3% (albuminuria). eGFRcr-DKD (RR = 2.18, 95% CI 1.33–3.58), eGFRcys-DKD (2.38 [1.51–3.78]), and eGFRcr-cys-DKD (3.15 [1.94–5.12]) were independently associated with incident DR, whereas albuminuria alone was not. Risk increased with increasing number of markers,2.00 (1.02–3.92) by dual and 4.91 (2.50–9.65) by triple markers. Conclusions: DKD defined using multiple kidney markers, particularly combined creatinine–cystatin C, was strongly associated with incident DR. These findings support the use of multiple kidney function markers to improve risk stratification for developing DR. Full article

This manuscript examines the total toxic releases from electric utilities and mining facilities in the United States in 2020, focusing on their relationships with human health outcomes. The research highlights the adverse effects of air and water pollution, linking exposure to toxic emissions to several health issues, such as low birth weight, respiratory and cardiovascular diseases, and cancers. It underscores the disproportionate impact of these pollutants on low-income and minority populations. This research project utilizes two sets of data: (1) environmental data, the EPA’s Toxic Release Inventory (TRI) data that records total emissions of all-electric and mining facilities, and (2) health data, the PLACES health data. The results of this study show that census tracts exposed to higher toxic releases are expected to have worse health outcomes. The coefficients for total toxic release indicate that higher toxic release corresponds to a higher rate of cancer, chronic obstructive pulmonary disease (COPD), diabetes, kidney diseases, arthritis, cardiac heart disorders (CHD), and stroke. Except for diabetes and kidney diseases, the associations are statistically significant. The analysis indicates the need for comprehensive public health strategies to mitigate the risks posed by toxic releases, particularly for vulnerable communities. Full article

Background and Objectives: Hepatic encephalopathy (HE) management becomes particularly challenging in older patients. This study aimed to evaluate the physician-reported diagnostic approaches, therapeutic strategies, and specific challenges in managing HE in older cirrhotic patients across Italy. Methods: A nationwide survey was conducted under the aegis of the Italian Association for the Study of the Liver (AISF). Forty-three hepatology centres participated. Data were analyzed using descriptive statistics. Results: Participating centers followed over 6000 older patients with cirrhosis, nearly one-third of whom experienced overt HE and/or minimal HE episodes in the previous year. Physicians reported that infections were the most frequently reported precipitating factor, followed by constipation and electrolyte disturbances for OHE. Half of patients with HE (50%; IQR 30.0–50.0%) experienced recurrent episodes, while 22% (IQR 10.0–30.0%) were reported to have persistent HE. In this setting, the diagnosis of HE was often complicated by cognitive decline. Treatment primarily consisted of a combination of lactulose and rifaximin, but adherence was often limited. Caregiver support emerged as a critical element in patient management. The management of comorbidities such as diabetes and chronic kidney disease was a major challenge, and nutritional screening was not routinely implemented across centres. Conclusions: This study highlights the need for better multidisciplinary management, improved caregiver support, and more consistent approaches to the diagnosis and treatment of HE in the elderly. The survey also explored how centres approach the differential diagnosis between HE and age-related cognitive disorders, the practical role of caregivers in outpatient management, and the impact of comorbidities, polypharmacy, and nutritional issues on everyday care. Marked heterogeneity emerged in psychometric assessment, multidisciplinary collaboration, and nutritional screening, indicating that several relevant aspects of care remain insufficiently standardized. Overall, the findings suggest that older patients with HE should be regarded as a distinct high-risk subgroup requiring tailored diagnostic pathways and integrated management models. Full article

Background: Magnesium is an essential dietary mineral, and low magnesium status has been associated with adverse cardiometabolic and renal outcomes. In chronic kidney disease (CKD), the prevalence of magnesium deficiency remains uncertain because serum magnesium alone may not accurately reflect overall magnesium status. We aimed to characterize magnesium status in a multi-ethnic Asian CKD cohort compared with healthy participants using combined serum and 24-h urinary magnesium (24U-Mg) measurements. Methods: This cross-sectional observational study included 232 adults with CKD and 103 healthy participants. Serum magnesium and 24-h urinary magnesium excretion were measured concurrently. Magnesium deficiency was defined as serum magnesium ≤0.75 mmol/L; probable magnesium deficiency was defined as serum magnesium 0.76–0.85 mmol/L with 24U-Mg ≤ 3.29 mmol/day; and possible magnesium deficiency was defined as either normal serum Mg with low 24U-Mg ≤ 1.65 mmol/day or serum Mg 0.76–0.85 mmol/L with 24U-Mg > 3.29 mmol/day. Associations with age, sex, body mass index, diabetes, blood pressure, and kidney function were examined. Results: CKD participants had lower mean serum magnesium (0.86 vs. 0.90 mmol/L, p < 0.001) and lower 24U-Mg (2.50 vs. 2.93 mmol/day, p = 0.006) compared with healthy participants. Using the proposed combined serum and 24U-Mg criteria, magnesium deficiency was present in 13.8% of CKD participants and 0% of healthy participants, while probable deficiency was observed in an additional 25.8% of CKD and 16.5% of healthy participants. Multivariate analysis demonstrated that CKD, older age, high BMI, and diabetes status were independently associated with lower serum magnesium levels, and female sex was associated with lower serum and urinary magnesium in healthy participants. Conclusions: Magnesium deficiency is common in non-dialysis CKD patients and is frequently not identified by serum magnesium alone. Combined assessment using serum and urinary magnesium may better identify individuals at risk of magnesium deficiency and inform future prospective studies in CKD. Full article

Background: Certain metabolites of the tryptophan-kynurenine (Trp-KYN) pathway, which are primarily cleared via tubular transport, have been linked to end-stage kidney disease (ESKD). Uromodulin—a protein expressed exclusively in the kidneys—is a key regulator of renal structure and function, as well as a direct marker of tubular health. This preliminary study explores the hypothesis that serum uromodulin correlates with Trp-KYN metabolites, potentially revealing new pathophysiological pathways in patients undergoing kidney replacement therapy (KRT). Given the link between serum uromodulin, Trp-KYN metabolites, and tubular function, we examined their correlation in KRT patients. Furthermore, we assessed how various clinical and dialysis parameters influence serum uromodulin levels. Methods: A total of 64 stable patients from a single dialysis center receiving hemodialysis (HD) or hemodiafiltration (HDF) were enrolled. Pre- and post-dialysis concentrations of uromodulin, Trp, KYN, kynurenic acid (KYNA), 3-hydroxykynurenine (3-OHKYN), and their reduction ratios (RRs) were established. High-performance liquid chromatography (HPLC) was used to estimate the KYN pathway metabolite levels, whereas uromodulin concentration was measured using an immunoenzymatic assay. Results: Detectable serum uromodulin was found in only 30 patients. This group was predominantly male (p < 0.001) and characterized by shorter dialysis vintage (p < 0.001), a higher prevalence of residual kidney function (RKF) (p = 0.001) and diabetes mellitus (p = 0.028), higher pre-dialysis serum phosphorus levels (p = 0.015), and more frequent use of loop diuretics (p = 0.004). Furthermore, univariate analysis revealed significantly higher pre-dialysis (p = 0.004) and post-dialysis (p = 0.025) serum Trp concentrations in the uromodulin-positive group. Pre-dialysis serum uromodulin concentration correlated positively with pre-dialysis Trp level (p < 0.001) and negatively with the pre-dialysis KYN/Trp ratio (p = 0.008), but not with other metabolites that are also subject to tubular transport mechanisms. Post-dialysis uromodulin levels correlated positively only with post-dialysis Trp level (p = 0.005). Patients treated with HDF had significantly higher RR for uromodulin than those treated with HD (p = 0.01). Conclusions: The presented data indicate that serum uromodulin levels are correlated with RKF. Additionally, the presence of detectable serum uromodulin may indicate reduced immunological activation, leading to diminished activity within the Trp-KYN pathway. Full article

Contrast-induced nephropathy (CIN), now more accurately referred to as contrast-induced acute kidney injury (CI-AKI), remains a major cause of hospital-acquired acute kidney injury (AKI) and is associated with increased morbidity and mortality, particularly in high-risk patients. This condition occurs following the intravascular administration of iodinated radiocontrast media (RCM), especially in individuals with pre-existing chronic kidney disease (CKD), diabetes mellitus, heart failure, advanced age, or exposure to high contrast volumes. The pathophysiology of CI-AKI is multifactorial and involves renal hemodynamic alterations, direct tubular toxicity, oxidative stress, inflammatory activation, and endothelial dysfunction, ultimately leading to tubular injury and reduced glomerular filtration rate (GFR). Traditional diagnostic markers such as serum creatinine (sCr) and estimated glomerular filtration rate (eGFR) are limited by low sensitivity and delayed response, prompting growing interest in novel biomarkers, including cystatin C (CysC), β-2 microglobulin (β-2M), Interleukin-18 (IL-18), Kidney Injury Molecule-1 (KIM-1), Neutrophil Gelatinase-Associated Lipocalin (NGAL), and osteopontin (OPN), which allow earlier detection and risk stratification. Preventive strategies remain the cornerstone of management and include optimizing hydration protocols, minimizing contrast dose, selecting low- or iso-osmolar agents, and individualized risk assessments. Despite extensive research into pharmacological and procedural interventions, no effective treatment for established CI-AKI exists, underscoring the critical importance of prevention and ongoing investigation into safer contrast agents and innovative prophylactic approaches. Full article

Background/Objectives: This study aimed to determine the incidence of herpes zoster (HZ) and risk factors associated with its occurrence in patients receiving Janus kinase inhibitors (JAKis) for immune-mediated inflammatory diseases (IMIDs), while evaluating preventive strategies and zoster vaccine uptake. Methods: We conducted a retrospective single-center cohort study including patients with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, inflammatory bowel disease, atopic dermatitis and alopecia areata treated with upadacitinib, baricitinib or tofacitinib. The primary outcome was incident HZ during JAKi exposure. Incidence rates (IRs) were calculated per 100 person-years (PY) and Cox regression identified factors associated with HZ. Results: A total of 292 patients contributed 565.5 PY of JAKi exposure. During follow-up, 23 patients (7.9%) developed HZ, corresponding to an overall IR of 4.07/100 PY (95% CI 2.40–5.73). Incidence rates were numerically lower with upadacitinib and varied across disease groups; differences were not statistically significant. Diabetes mellitus (HR 3.05, 95% CI 1.28–7.29) and chronic kidney disease (HR 3.24, 95% CI 1.17–8.95) were independently associated with HZ. Herpes simplex infection requiring systemic antiviral therapy was more frequent among patients who developed HZ. Recombinant zoster vaccine (RZV) uptake was low (9.9%), but higher among patients evaluated in a dedicated infectious risk consultation. No HZ events were observed among RZV-vaccinated patients. Although six HZ events (26.1%) were severe, all cases resolved completely. Conclusions: HZ remains a relevant complication of JAKi therapy across IMIDs. Diabetes mellitus and chronic kidney disease may help identify higher-risk patients, while structured infectious risk assessment could improve vaccine uptake. Full article

Diabetic kidney disease (DKD) is a primary cause of end-stage renal disease (ESRD), and while ferroptosis is known to contribute to DKD pathogenesis, the regulatory role of the NLRP3 inflammasome in this process remains elusive. To address this research gap, we explored whether NLRP3 inhibition alleviates DKD by suppressing ferroptosis using streptozotocin-induced diabetic wild-type and NLRP3-knockout C57BL/6 mice, alongside high-glucose-cultured (30 mM) human renal tubular epithelial (HK-2) cells with or without siNLRP3 transfection. Inflammatory cytokines (IL-6, TNF-α, and IL-1β) were measured using an ELISA; oxidative stress markers (CSSG, MDA, GSH, and ROS) and the iron ion content via colorimetric assays; mitochondrial morphology by transmission electron microscopy (TEM); and ferroptosis-related proteins (ACSL4, COX2, and GPX4) through Western blotting. Our findings demonstrate that NLRP3-knockout diabetic mice displayed markedly reduced urinary albumin excretion and serum creatinine levels (p < 0.01) compared with wild-type diabetic controls, concurrent with suppressed renal iron overload and ferroptosis, diminished inflammatory cytokine levels, and attenuated oxidative stress. Pathological assessments further revealed ameliorated renal fibrosis and preserved mitochondrial ultrastructure in NLRP3-deficient mice. In vitro, siNLRP3 transfection abrogated high-glucose-induced inflammation, oxidative stress, and ferroptosis in HK-2 cells, effects that were reversed by the ferroptosis inducer erastin (p < 0.01). Mechanistically, NLRP3 deficiency was associated with upregulated GPX4 expression and downregulated ACSL4 and COX2 expression. Collectively, these results indicate that inhibition of the NLRP3 inflammasome mitigates DKD progression by suppressing ferroptosis, underscoring its translational potential as a therapeutic target for this condition. Full article

Background: Diabetic kidney disease is a common and serious complication of type 2 diabetes mellitus (T2DM) and represents a major contributor to chronic kidney disease (CKD) globally. While sodium-glucose cotransporter-2 (SGLT2) inhibitors have demonstrated significant renoprotective effects, the potential advantages of combining these agents with micronutrients such as zinc (Zn), known for its antioxidant, anti-inflammatory, and metabolic regulatory properties, have not been fully investigated. This study aimed to assess the effects of dapagliflozin (DAPA) and empagliflozin (EMPA), administered either alone or alongside Zn, in an experimental diabetes model. Methods: T2DM was induced in Sprague-Dawley rats through a high-fat diet (HFD) followed by a low dose of streptozotocin (STZ). Seven experimental groups were established: a control group, an untreated diabetic group, and treatment groups receiving DAPA, EMPA, or their combinations with Zn. Metabolic parameters, renal function, and histopathological alterations were assessed, while immunohistochemistry was used to evaluate the expression of inflammatory and fibrotic markers. Results: Diabetic rats exhibited sustained hyperglycemia, metabolic imbalance, and significant renal damage, accompanied by elevated levels of inflammatory and fibrotic markers. Treatment with SGLT2 inhibitors improved metabolic status, mitigated kidney injury, and reduced inflammatory marker expression. Zn association further potentiated these effects, with the most pronounced benefits observed when combined with EMPA. Conclusions: These findings suggest that SGLT2 inhibitors exert strong renoprotective effects in experimental diabetic nephropathy. Zn supplementation may amplify these benefits through its antioxidant and anti-inflammatory actions. The combination of EMPA and Zn demonstrated the greatest protective effect, highlighting the potential of multi-target therapeutic strategies in diabetic kidney disease. Full article

Background and hypothesis: Sodium–glucose cotransporter 2 inhibitors (SGLT2i) provide consistent cardiorenal benefits; however, tissue-level mechanisms remain insufficiently characterized. We investigated whether SGLT2i were associated with longitudinal remodeling of organ-specific adipose depots in patients with chronic kidney disease (CKD). Methods: In this observational study cohort (ADIPO-CKD; NCT07309094), adults with CKD stages 1–4 underwent clinical, biochemical and ultrasound imaging assessment at baseline (T0) and 8-month follow-up (T8). Thus, epicardial (EAT) and perirenal adipose tissue (PRAT) thickness were measured. Changes over time between patients under SGLT2i treatment and those without (Non-SGLT2i) were assessed using repeated-measures ANOVA and multivariable linear regression models adjusted for age, sex, baseline estimated glomerular filtration rate (eGFR), diabetes status, concomitant glucagon-like peptide 1 (GLP-1) receptor agonist therapy, body mass index (BMI) and visceral fat area (VFA) changes. Results: Among 189 CKD patients (50 SGLT2i and 139 non-SGLT2i), SGLT2i therapy was associated with significant reductions in PRAT (1.28 ± 0.70 to 0.91 ± 0.61 cm; ΔPRAT −0.37 cm; p < 0.002) and EAT (0.57 ± 0.27 to 0.36 ± 0.14 cm; ΔEAT −0.21 cm; p < 0.012), whereas no significant changes were observed in the Non-SGLT2i group. In multivariable models, SGLT2i exposure remained independently associated with ΔPRAT (β = 0.447; 95% CI 0.211–0.682; p < 0.001; R² = 0.371) and ΔEAT (β = 0.061; 95% CI 0.009–0.113; p < 0.021; R² = 0.053), including adjustment for changes in BMI and VFA. These findings were accompanied by trends toward improvement in renal function and systemic inflammation biomarkers in the SGLT2i group, although these changes did not reach statistical significance. In a secondary analysis, dapagliflozin was significantly associated with PRAT reduction, whereas a significant association was found between empagliflozin and EAT decrease. Conclusions: In CKD stages 1–4, SGLT2i use was independently associated with reductions in EAT and PRAT. These findings support a potential link between organ-specific adipose tissue and cardiorenal disease; however, given the observational design, these results should be interpreted as associative and hypothesis-generating. Dedicated mechanistic and adequately powered studies are warranted to determine their clinical relevance. Full article