Search Results (614)

Chronic kidney disease (CKD), especially diabetic kidney disease (DKD), is characterized not only by progressive loss of renal function but also by profound metabolic disturbances, including insulin resistance (IR). Emerging evidence implicates gut-derived uremic toxins as mediators linking intestinal dysbiosis to metabolic and renal injury. Several microbial metabolites, for example, indoxyl sulfate, p-cresyl sulfate, and trimethylamine-N-oxide, are known to accumulate in CKD due to decreased renal excretion and altered tubular secretion. In vitro and in vivo experiments indicate that these gut-derived nephrotoxins impair insulin signaling pathways in cells. This results in increased production of reactive oxygen species, activation of stress kinases, higher levels of inflammatory cytokines, and inhibitory serine phosphorylation of insulin receptor substrates. Consequently, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling is impaired, reducing cellular glucose uptake. At the same time, these toxins induce endothelial dysfunction and mitochondrial damage, not only causing systemic IR but also contributing to the progression of kidney disease. Observational data link higher plasma toxin levels with components of IR, rapid loss of renal function as measured by estimated glomerular filtration rate, and a high risk of cardiovascular events in CKD patients. Although causality in humans remains unproven, interventions targeting the microbiota, toxin binding, and oxidative stress pathways show promise. We propose an integrated gut–kidney–metabolic framework in which dysbiosis-driven toxin production may amplify IR and DKD progression. Full article

Background and Objectives: Appropriate antimicrobial dosing according to kidney function is essential to ensure therapeutic efficacy while minimizing toxicity and antimicrobial resistance. Despite established dosing guidelines and electronic prescribing systems, errors in renal dose adjustment of antimicrobials, particularly in the setting of acute kidney injury, remain common among hospitalized patients. Materials and Methods: A point-prevalence study was conducted on 31 October 2024 at a tertiary-care hospital in Greece to evaluate the appropriateness of antimicrobial dosing in relation to renal function. Patient characteristics, renal parameters, and antimicrobial prescriptions were extracted from electronic medical records. Glomerular filtration rate (GFR) was estimated using the MDRD formula. Comparative analyses were performed between correctly and incorrectly dosed cases, and between overdosing and underdosing episodes. Results: A total of 235 hospitalized patients were evaluated (mean age 64.8 ± 18.6 years; 43.4% female). Overall, 15.7% (37/235) received at least one antimicrobial dose inappropriate for their renal function. Among 37 patients where dosing errors were identified, overdosing was noted in 23 (62.2%), underdosing in 16 (43.2%), adding up to 39 prescriptions, while in 2 patients (5.4%), both mistakes were noted in different prescribed antimicrobials. Drug-specific error rates varied considerably: ceftazidime and cefuroxime showed the highest rates of inappropriate dosing (40% each), followed by colistin (33.3%) and acyclovir (33.3%). Piperacillin/tazobactam, the most frequently prescribed agent (n = 50), had a 14% error rate, mainly due to underdosing (10%). Patients with dosing errors were significantly older (71.5 vs. 64.1 years, p = 0.0220) and had worse renal function, including higher serum creatinine (1.68 vs. 1.19 mg/dL, p = 0.0174), lower GFR (58.5 vs. 75.9 mL/min/1.73 m², p = 0.0009), and more frequent dialysis (13.5% vs. 4.3%, p = 0.0422). They also received a higher median number of antimicrobials (2 vs. 1, p = 0.0185). Conclusions: Inappropriate antimicrobial dosing based on kidney function remains common in hospitalized patients, particularly among older individuals and those with impaired renal function or polypharmacy. Targeted antimicrobial stewardship strategies focusing on renal dose adjustment and agents that are more frequently dosed inappropriately, such as colistin, acyclovir, cefuroxime, and ceftazidime, as well as agents that are frequently prescribed despite a relatively lower rate of inappropriate dose, such as piperacillin/tazobactam, are needed to enhance prescribing safety and optimize therapeutic outcomes. Full article

Background and Objectives: Outcomes after trauma are traditionally attributed to injury severity and acute physiologic derangement. However, host vulnerability at presentation—reflecting underlying physiologic and nutritional status—may also be associated with bleeding severity and transfusion requirements following acute injury. Whether such vulnerability contributes additional risk information beyond established factors remains incompletely understood. Materials and Methods: We conducted a retrospective cohort study of adult trauma patients using a single-center trauma registry. Host vulnerability was assessed using a composite score (CE; range 0–3) based on admission hypoalbuminemia (<3.5 g/dL), anemia (hemoglobin < 11 g/dL), and reduced renal function (estimated glomerular filtration rate < 60 mL/min/1.73 m²). Primary outcomes were any blood transfusion and massive transfusion, defined as transfusion of ≥10 units of packed red blood cells within 24 h of admission. Associations between CE score and transfusion outcomes were evaluated using univariable and multivariable logistic regression models adjusted for age, Injury Severity Score (ISS), admission lactate level, and systolic blood pressure (SBP). Results: Among 4105 trauma patients, transfusion requirements increased progressively with higher CE scores. Rates of any transfusion rose from 21.7% in patients with CE 0 to 78.6% in those with CE 3, while massive transfusion increased from 1.9% to 23.1% across the same categories. In multivariable analyses, each 1-point increase in CE score was independently associated with higher odds of any transfusion (adjusted odds ratio [aOR] 3.21, 95% confidence interval [CI] 2.80–3.68) and massive transfusion (aOR 1.73, 95% CI 1.45–2.07). Conclusions: A composite score reflecting host vulnerability at presentation was associated with bleeding severity and transfusion requirements after trauma, beyond injury severity and acute physiologic factors. These findings suggest that simple laboratory-based markers may provide additional information for early risk stratification of hemorrhagic outcomes after trauma. Full article

Background: Diabetic nephropathy (DN), also referred to as diabetic kidney disease, represents one of the most common microvascular complications of type 2 diabetes mellitus (T2DM) and remains a leading cause of end-stage renal disease worldwide. Conventional clinical markers, including albuminuria and estimated glomerular filtration rate (eGFR), are widely used for diagnosis and staging but may have limited sensitivity for detecting early renal injury and predicting disease progression. In recent years, circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers that reflect underlying molecular mechanisms of diabetic nephropathy and may complement traditional clinical indicators. Objective: The present study aimed to evaluate serum and urinary levels of hsa-miRNA-770-5p across different stages of diabetic nephropathy and to assess its potential diagnostic value in relation to established indicators of renal function. Methods: A total of 257 participants were included and divided into four groups: healthy controls, patients with T2DM without nephropathy, patients with T2DM and DN in CKD stages I–II, and patients with DN undergoing maintenance hemodialysis (MHD). Serum and urinary levels of miRNA-770-5p were measured using quantitative real-time polymerase chain reaction (qPCR) and analyzed using the 2^−ΔΔCt method. Statistical analyses included comparisons between groups using ANOVA, correlation analyses with renal function parameters such as eGFR and proteinuria/albuminuria, and receiver operating characteristic (ROC) curve analysis to evaluate diagnostic performance. Results: Serum levels of miRNA-770-5p were significantly elevated in patients with DN and in patients undergoing maintenance hemodialysis compared with healthy controls and patients with T2DM without nephropathy. In contrast, urinary levels of miRNA-770-5p were markedly reduced in patients with DN. Serum levels in patients with T2DM without nephropathy were slightly lower than those observed in healthy controls. Significant correlations were identified between miRNA-770-5p levels and renal function parameters, including eGFR and proteinuria/albuminuria, supporting the biological relevance of this microRNA in renal injury. ROC curve analysis demonstrated good discriminatory ability for differentiating DN from T2DM without nephropathy (serum AUC = 0.82; urine AUC = 0.79). Conclusions: hsa-miRNA-770-5p demonstrates distinct and opposite patterns in serum and urine that correlate with the severity of diabetic nephropathy. The complementary changes observed in circulating and urinary levels support the potential of miRNA-770-5p as a non-invasive biomarker that may complement conventional clinical markers and provide additional insight into the molecular mechanisms involved in the development and progression of diabetic nephropathy. Full article

Background: The evaluation of renal function in neonates is challenging due to maternal creatinine transfer, reduced muscle mass, and non-steady-state physiology. Cystatin C emerged as a promising biomarker for assessing neonatal glomerular filtration rate. This review summarizes evidence from studies evaluating serum and urine cystatin C in healthy neonates and high-risk groups, including preterm newborns, neonates with acute kidney injury, and those with congenital kidney and urinary tract defects. Methods: Twenty studies were included and qualitatively synthesized following PRISMA guidelines. Results: In the included studies, serum cystatin C exhibited consistent postnatal patterns independent of maternal influence and showed a strong correlation with gestational age and renal development. Cystatin C enabled earlier detection of renal dysfunction compared to serum creatinine, especially in preterm infants and critically ill neonates. In babies with congenital renal abnormalities, cystatin C levels were associated with disease severity and clinical outcomes, while the cystatin C-based estimated glomerular filtration rate surpassed creatinine-based estimations. Urinary cystatin C correlated with tubular damage and increased risk of chronic kidney disease during follow-up. Conclusions: Cystatin C is a reliable biomarker for evaluating neonatal renal function, although further standardization and validation are required for clinical implementation. Full article

Objectives: The impact of renal ischemia during partial nephrectomy (PN) on postoperative renal function remains controversial. On-clamp PN provides improved surgical exposure and haemostasis but induces warm ischemia, which may impair renal function. Off-clamp PN avoids ischemia-related injury and may better preserve renal function, although concerns persist regarding blood loss and oncological safety. We systematically compared perioperative and functional outcomes, as well as surgical margin status between on-clamp and off-clamp PN. Methods: We performed a systematic search of PubMed, Embase, Cochrane, Web of Science, and Scopus to identify randomized controlled trials (RCTs) and observational studies comparing on-clamp versus off-clamp PN with no publication time limitations. Outcomes included estimated glomerular filtration rate (eGFR), percentage eGFR change, estimated blood loss (EBL), transfusion rates, positive surgical margins (PSMs), operative time, and complications. Results: Thirty-nine studies (four RCTs) including 10,154 patients were analysed. Off-clamp PN was associated with a smaller decline in eGFR (mean difference [MD] −4 mL/min/1.73 m², 95% CI −5.7 to −2.8) and lower percentage eGFR loss (MD −1.7%, 95% CI −2.8 to −0.7). On-clamp PN was associated with lower EBL (MD −48 mL, 95% CI −72 to −25). Transfusion rates favored on-clamp PN but were not statistically significant (OR 0.7, 95% CI 0.5–1.0). On-clamp PN was associated with a higher risk of PSM (OR 1.3, 95% CI 1.0–1.7) and postoperative complications (OR 1.3, 95% CI 1.1–1.6). Between-study heterogeneity and predominance of observational data were key limitations. Conclusions: Off-clamp PN provides superior renal functional preservation and lower risks of PSMs and complications, at the cost of increased blood loss. These findings support individualized surgical decision-making based on patient and tumor characteristics. What does the study add?: This study provides an extensive and detailed comparison of off-clamp versus on-clamp partial nephrectomy, encompassing more than 10,000 patients from 39 studies. By integrating the available evidence up to late 2024, it delivers comprehensive estimates of the renal functional benefits associated with ischemia-free surgery. Our findings delineate the trade-offs between renal preservation, blood loss, and surgical margin status, thereby informing individualised decision-making in nephron-sparing surgery and refining current understanding of when ischemia avoidance is most clinically advantageous. Patient summary: Our study suggests that performing partial nephrectomy without temporarily clamping the kidney blood vessels may better preserve kidney function and reduce cancer-related surgical risks, but can lead to increased blood loss during surgery. These findings indicate that the choice of surgical technique should be individualised, taking into account tumour features and patient-specific factors. Full article

Renal involvement in β-thalassemia minor (β-TMin) has been described mainly in case reports and small observational studies, and its clinical significance remains incompletely characterized. Using real-world data from routinely collected electronic medical records, we performed a retrospective cohort study including 1516 adult patients with β-TMin insured by Clalit Healthcare Services to explore renal abnormalities identified during routine clinical care. Urine testing for hematuria, microalbuminuria, and proteinuria was not performed systematically but was ordered at clinicians’ discretion, resulting in evaluation of a clinically selected subset of patients. Among those tested, hematuria, microalbuminuria, and proteinuria were commonly documented, often in the absence of hypertension, diabetes mellitus, congestive heart failure, or impaired kidney function, consistent with largely subclinical renal involvement. Patients who underwent urine testing were older and had more comorbidities than untested patients, indicating potential selection bias. Correlation analyses showed weak associations between hematological and renal parameters, while ferritin levels correlated modestly with selected proteinuria measures. Due to the retrospective design and non-systematic urine assessment, population-level prevalence and clinical impact cannot be determined. Therefore, prospective studies with standardized renal evaluations are needed to better characterize the frequency, mechanisms, and clinical relevance of renal abnormalities in β-TMin. Full article

Background and Objectives: Renal transplantation is the optimal treatment for end-stage renal disease, yet long-term allograft survival remains threatened by immune-mediated injury and chronic nephropathy. Conventional monitoring using serum creatinine and protocol biopsy suffers from limited sensitivity for early, subclinical injury. Liquid biopsy-based biomarkers offer a non-invasive alternative. Materials and Methods: We conducted a systematic narrative review of studies published between January 2010 and December 2024, identified through PubMed, Scopus, and Web of Science. Results: Extracellular vesicles carry injury-specific molecular cargo reflecting the biological state of tubular, glomerular, and endothelial cells; urinary EV CXCL9 protein and exosomal CD3ε mRNA have demonstrated AUC values of 0.81–0.88 for the detection of T-cell-mediated rejection. Donor-derived cell-free DNA quantifies global graft cell death; the FDA-cleared AlloSure assay achieves an AUC of 0.74 and NPV of 84% at the validated ≥1.0% threshold established in the DART trial. Donor-specific antibodies—particularly complement-fixing C1q-positive DSAs—confer markedly inferior 5-year graft survival compared with DSA-negative recipients (54% versus 93%). Multi-biomarker panels integrating all three modalities yield AUCs of 0.88–0.94 and NPVs of 91–95%. Conclusions: The integration of EV, ddcfDNA, and DSA monitoring into a unified surveillance framework offers a clinically meaningful advance over creatinine-based monitoring. Prospective randomized trials confirming improvement in long-term allograft survival will be the critical next step. Full article

Background/Objectives: The renal resistive index (RRI) has emerged as an early marker of renal vascular resistance. The purpose of this study was to investigate the association between RRI on intensive care unit (ICU) admission and the development of acute kidney injury (AKI) in a general ICU population, and to assess its predictive accuracy. Methods: This prospective observational study was conducted in a multidisciplinary ICU. Consecutive mechanically ventilated adults were enrolled; RRI was measured within 24 h of admission after hemodynamic stabilization. AKI was defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria within seven days. Multivariable regression, receiver operating characteristic (ROC), reclassification, and mediation analyses were performed. Results: A total of 181 patients were included. AKI occurred in 36%. Median RRI was 0.73 (0.65–0.80). RRI correlated with age, acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores, lactate, and glomerular filtration rate (GFR) (all p < 0.001). In multivariable analysis, RRI was the only independent predictor of AKI (OR 2.86 per 0.05 increase, 95% CI 1.64–4.98, p = 0.001). It was also associated with an increased likelihood of presenting with a more severe AKI stage. RRI showed high discriminative ability (AUC = 0.89, 95% CI 0.84–0.94); the optimal cut-off was 0.77 (sensitivity 0.83, specificity 0.82). Adding RRI to a clinical model improved prediction (ΔAUC p = 0.049; net reclassification index (NRI) = 0.52, p < 0.001). Mediation analyses showed that RRI significantly mediated the effects of hypertension and low baseline GFR on AKI risk. Subgroup analyses confirmed consistent predictive performance across age, lactate, and sepsis categories. Conclusions: RRI is an independent early predictor of AKI and its severity, as well as a mediator of both hypertension and low GFR, regarding their effect on AKI development in ICU patients. RRI could serve as an early bedside marker of renal perfusion impairment in critically ill patients, guiding strategies aimed at reducing the risk of AKI. Full article

Methotrexate (MTX) is a widely used chemotherapeutic and immunosuppressive agent, but its clinical utility is limited by oxidative stress-mediated renal toxicity. This study evaluated the nephroprotective potential of the dietary polyphenolic bioactive molecule piceatannol (PIC) in its crude and liposomal nanoparticle (PIC-LNP) forms against MTX-induced kidney injury in rats. Sixty rats were allocated into six groups and received vehicle, PIC, PIC-LNPs, MTX, or combinations of MTX with PIC or PIC-LNPs. MTX administration induced marked renal dysfunction and oxidative/nitrosative stress, reflected by elevated serum urea, creatinine, and uric acid, together with increased renal ROS, MDA, protein carbonyls, 8-OHdG, and nitric oxide, in parallel with suppression of the Nrf2/HO-1 antioxidant pathway. These disturbances were accompanied by activation of TLR4/NF-κB and MAPK signaling, upregulation of pro-inflammatory cytokines, and a shift toward apoptosis, as evidenced by increased Bax and caspase-3 and reduced Bcl-2 expression. Histological and ultrastructural analyses confirmed extensive glomerular and tubular damage with mitochondrial disruption and cytoplasmic vacuolations. PIC treatment attenuated these MTX-induced alterations, whereas the liposomal formulation conferred superior protection. PIC-LNPs restored Nrf2/HO-1 signaling, enhanced endogenous antioxidant defenses, reduced oxidative/nitrosative and inflammatory responses, and normalized apoptotic markers, accompanied by substantial preservation of renal architecture and cellular integrity. Immunohistochemistry demonstrated strong Nrf2 expression with minimal NF-κB activation in the PIC-LNP group. Collectively, these findings highlight liposomal piceatannol as a promising bioactive-molecule-based strategy for controlling oxidative stress and mitigating chemotherapy-associated oxidative-stress-related renal injury. Full article

Background and Objectives: Early allograft dysfunction (EAD) after liver transplantation (LT) is associated with adverse graft and patient outcomes. However, its effects on kidney outcomes remain unclear. We retrospectively investigated the association between EAD and various kidney events following LT. Materials and Methods: We included 92 LT recipients. EAD was defined by the presence of ≥1 of the following: total bilirubin level ≥ 10 mg/dL or international normalized ratio ≥ 1.6 on postoperative day 7, or aspartate aminotransferase or alanine aminotransferase level > 2000 U/L within the first 7 days post-LT. Kidney outcomes included acute kidney injury (AKI), acute kidney disease (AKD), kidney replacement therapy (KRT) performance, and changes in estimated glomerular filtration rate (eGFR). Results: AKI incidence was comparable between the non-EAD and EAD groups; however, stage 3 AKI incidence was higher in the EAD group (65.0% vs. 22.2%; p = 0.001). AKD occurred more frequently in the EAD group (75.0% vs. 30.6%, p = 0.001). KRT was required more frequently within 7 days of LT in the EAD group (70.0%) than in the non-EAD group (15.3%) (p < 0.001). Multivariate analysis identified EAD as an independent predictor of KRT requirement (p < 0.001). EAD was associated with prolonged (≥7 days) KRT requirement (p = 0.025). In the receiver operating characteristic curves, all EAD components were associated with KRT requirement following LT. The baseline and 3-month eGFR levels were comparable; however, a trend toward a steeper decline was noted in eGFR in the EAD group than that in the non-EAD group (p = 0.090). The burden of hospitalization and calcineurin inhibitor exposure were similar between the groups. Conclusions: EAD appears to be independently associated with adverse kidney outcomes following LT. Preventive strategies targeting EAD are required to improve post-transplant prognosis and mitigate kidney-related complications. Full article

Drug-induced kidney injury remains a major clinical challenge associated with diverse therapeutic agents and is an important cause of acute kidney injury, chronic renal dysfunction, and treatment-related morbidity. Growing evidence indicates that nephrotoxicity caused by anticancer, immunosuppressive, and anti-infective drugs is strongly driven by oxidative stress and redox homeostasis disruption. Excessive production of reactive oxygen species (ROS) in renal tubular cells overwhelms endogenous antioxidant defenses and triggers mitochondrial dysfunction, inflammatory signaling, and activation of stress-responsive pathways that culminate in tubular injury and renal functional decline. These processes promote apoptosis, necrosis, microvascular injury, and a reduction in the glomerular filtration rate, while dysregulation of redox-sensitive pathways involved in cell survival and repair further heightens renal vulnerability. This review summarizes current mechanistic insights into oxidative stress-mediated pathways of drug-induced nephrotoxicity, with emphasis on their translational relevance. In addition, it discusses emerging biomarkers for early detection and highlights recent advances in antioxidant-based and redox-modulating strategies that may help prevent renal injury and preserve kidney function. Full article

Podocyte injury is an early hallmark of chronic kidney disease (CKD) and can be influenced by SGLT2 inhibitors (SGLT2i). Early effects of SGLT2i include transient estimated glomerular filtration rate (eGFR) dip and reduced proteinuria; however, the latter may be subtle in patients with normal or moderately increased albuminuria. In such cases, urinary podocyte-derived biomarkers may provide sensitive early indicators of SGLT2i effect. This study prospectively assessed short-term changes in urinary podocyte biomarkers (nephrin, podocin, podocalyxin) following SGLT2i initiation in diabetic and non-diabetic CKD patients. Our cohort had a low urinary albumin to creatinine ratio (UACR) of 19.09 mg/g (6.28; 164.93) and preserved eGFR 45 mL/min/1.73 m² (36.85; 53.15). At baseline, podocyte biomarkers were mutually correlated, whereas only podocalyxin was associated with UACR. Baseline podocalyxin independently predicted transient eGFR dip and UACR reduction. Early decreases in both podocin and podocalyxin were associated with eGFR decline and lower UACR at 3 months. ROC analyses identified cutoff values for all three biomarkers that predicted short-term eGFR decline, with baseline podocalyxin demonstrating the highest discriminative accuracy. These findings support pleiotropic nephroprotective effects of SGLT2 inhibitors and identify urinary podocyte biomarkers—particularly podocalyxin, and to a lesser extent podocin—as a sensitive indicator of early renal response. Full article

Background and Objectives: Diabetes mellitus (DM) is a highly prevalent comorbidity among critically ill patients and may significantly influence intensive care unit (ICU) outcomes through metabolic, immune, and cardiovascular mechanisms. This study aimed to evaluate the impact of DM on clinical profile, comorbidities, complications, need for intensive support, and mortality in adult ICU patients. Materials and Methods: A retrospective observational study was conducted between January and December 2024 in a tertiary ICU, including 1344 adult patients. Among them, 435 (32.37%) had DM. Demographic data, admission diagnoses, laboratory parameters, comorbidities, complications, therapeutic interventions, and outcomes were analyzed. Comparative statistical analysis and multivariate logistic regression were performed to identify independent predictors of ICU mortality. Results: Patients with DM were significantly older than patients without diabetes mellitus (non-DM group) (69.62 ± 10.26 vs. 67.16 ± 14.26 years, p < 0.001) and more frequently female (57%, p = 0.0002). At admission, they presented higher glycemia (204.7 vs. 134.0 mg/dL, p < 0.00001), reduced glomerular filtration rate (47.2 vs. 59.5 mL/min/1.73 m², p < 0.00001), and more pronounced lymphocytopenia (p = 0.025). Cardiovascular and renal comorbidities were significantly more prevalent in DM, including hypertension (76.3%), heart failure (32.4%), and chronic kidney disease (33.1%) (all p < 0.01). DM was associated with increased odds of sepsis (OR 1.56), acute kidney injury (OR 1.51), and obesity (OR 2.57). ICU mortality was significantly higher in patients with DM (54.9% vs. 46.3%, p = 0.004; RR 1.19). Independent predictors of death included mechanical ventilation (OR 36.48), inotropic therapy (OR 4.74), hemodialysis (OR 2.57), elevated lactate, neutrophilia, and reduced glomerular filtration rate (GFR). Conclusions: DM was associated with increased ICU mortality and a higher burden of cardio-renal comorbidities and complications; however, mortality in the multivariate model was primarily driven by markers of organ dysfunction and the need for advanced supportive therapies. Early risk stratification and individualized management strategies are essential to improve outcomes in critically ill patients with diabetes. Full article

The high concentration of the inflammatory cytokine IL-36 in the serum of patients with type 2 diabetes mellitus (T2DM), along with the reduced renal damage observed in IL-36R knockout mice following ischemia–reperfusion-induced acute kidney injury, suggests a significant association between IL-36 activity and diabetic complications such as diabetic nephropathy (DN). It is also known that minor structural alterations in glomerular tissues can lead to changes in blood vessel pressure, potentially contributing to the development of DN, with inflammation acting as a triggering factor. However, further studies are needed to confirm this relationship. In this study, we observed that mesangial (MES-SV40) cells cultured under high-glucose conditions produced IL-36α in a dose-dependent manner. This cytokine production was also detected in mesangial cells from the glomerular tissues of mice with a high-calorie diet-induced T2DM, whereas healthy mice did not show such expression. In addition, we observed that mouse endothelial cells (SVECs) showed increased tubule formation in co-culture with MES-SV40 cells that had been previously exposed to 30 mmol/L glucose, as well as with the supernatant from these cells. IL-36R expression was confirmed in endothelial cells, as well as the angiogenic effect of IL-36α. Given that elevated VEGF levels have been reported in patients with DN by other authors, our results suggest that IL-36 produced by mesangial cells under high-glucose conditions may promote angiogenesis in glomerular tissues, potentially initiating the development of diabetic nephropathy. Full article