Search Results (1,752)

Background: Renal injury is a critical health issue in pet dogs, often exacerbated by drug-induced nephrotoxicity such as gentamicin (GM). This study investigated the protective effects of ergosterol (Erg), a natural compound from edible mushrooms, against GM-induced damage in Madin–Darby canine kidney (MDCK) cells. Methods: MDCK cells were treated with GM (0.5–3 mmol/L) for 12 h to establish injury. Erg (1 to 32 μg/mL) was pretreated for 12 h before GM exposure (2 mmol/L). Cell viability, nitric oxide (NO), lactate dehydrogenase (LDH), oxidative stress markers (SOD, GSH, CAT, MDA), inflammatory cytokines (IL-1β, IL-6, TNF-α), renal function indicators (Scr, BUN), and autophagy/apoptosis-related proteins (ATG5, Beclin1, P62, BAX, BCL-2) were assessed via CCK-8, ELISA, fluorescence staining, and Western blot. Statistical significance (p < 0.05) was determined by ANOVA and LSD post hoc tests. Results: GM (2 mmol/L) significantly reduced cell viability (p < 0.01) and elevated NO and LDH levels (p < 0.01). Erg pretreatment (4–8 μg/mL) restored cell viability (p < 0.01), suppressed NO (p < 0.01) and LDH release (p < 0.01), and enhanced antioxidant enzyme activities (SOD, GSH, CAT; p < 0.01). Erg attenuated GM-induced reactive oxygen species (ROS) overproduction (p < 0.01) and decreased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α; p < 0.01). Renal markers Scr and BUN were reduced (p < 0.01). Mechanistically, Erg upregulated autophagy proteins ATG5 and Beclin1 (p < 0.01), reduced P62 accumulation (p < 0.01), and lowered the BAX/BCL-2 ratio (p < 0.01). Conclusions: Erg protects MDCK cells from GM-induced nephrotoxicity by restoring autophagy flux, suppressing mitochondrial apoptosis, and mitigating oxidative stress and inflammation. These findings highlight Erg’s potential as a natural therapeutic agent for canine renal injury. Further in vivo studies are needed to validate its clinical efficacy. Full article

Indoxyl sulfate (IS), which is a protein-bound uremic toxin, is involved in vascular dysfunction and cardiovascular risk in subjects with chronic kidney disease (CKD). However, its role in peripheral arterial stiffness (PAS) remains unclear. This cross-sectional study evaluated the relationship between IS and PAS in patients diagnosed with CKD stages 3 through 5 who are not undergoing dialysis. Patients with CKD from a single center were enrolled. High-performance liquid chromatography analyzed the serum IS levels. PAS was evaluated using brachial–ankle pulse wave velocity (baPWV). IS was independently associated with PAS (odds ratio [OR]: 1.389 for 1 μg/mL increase in IS, 95% confidence interval [CI]: 1.086–1.775, p = 0.009) in a multivariable analysis after adjustment for age, hypertension, diabetes mellitus, blood pressure, lipid profiles, renal function, albumin, and proteinuria. Moreover, the mean baPWV (p = 0.010), left baPWV (p = 0.009), and right baPWV (p = 0.015) levels significantly correlated with the log-transformed IS (log-IS) levels. The area under the receiver operating characteristic curve for serum IS as a predictor of PAS was determined to be 0.667 (95% CI: 0.580−0.754; p = 0.0002). IS was associated with PAS in non-dialysis CKD stages 3–5, suggesting that IS may be a possible vascular risk marker. Future studies should address the nature of the relationship between IS and vascular dysfunction and assess therapeutic strategies to reduce IS. Full article

Chronic kidney disease (CKD) is a global health burden that affects close to one billion individuals. As many healthcare systems struggle to accommodate existing patients, CKD incidence and related costs are projected to continue rising. Based on a systematic search, this narrative review offers an in-depth assessment of advances in CKD pharmacotherapy published between 2020 and 2025, with a specific emphasis on drug combinations. Various treatment approaches for CKD exist, many of them targeting different mechanisms. Therefore, combining multiple medications could provide patients with better outcomes, though this comes with the risk of increased adverse effects and unnecessary costs. Alternatively, using biomarkers presents an opportunity to ascertain the most appropriate treatments specifically tailored to an individual’s molecular profile, thus personalizing CKD management. The second part of this review presents the current state-of-the-art methods to guide CKD therapy based on markers predicting treatment response. Collectively, this review presents possible pathways toward more effective CKD treatment. Full article

Background/Objectives: The present study aimed to evaluate the nephroprotective role of Khellin (Khe) against cisplatin (CDDP)-mediated nephrotoxicity in rats. Methods: We assessed oxidative stress markers (MDA, CAT, SOD, GPx, and iNOs), inflammatory markers (TNFα, IL6, IL10, and MCP1), apoptotic markers (Bax and Bcl2), and the renal damage marker (Kim1). Network pharmacology and molecular docking studies were performed. In vitro, Khe effects were tested on normal kidney cells (Vero) and liver cancer cells (HepG2) treated with CDDP. Results: Network pharmacology and docking suggested Khe’s activity primarily affects oxidative stress and inflammatory pathways, notably through MAPK14 and PI3K downregulation. In vitro, Khe reduced CDDP’s cytotoxicity in Vero cells while maintaining anti-proliferative effects on HepG2 cells. In vivo, CDDP significantly increased serum creatinine, urea, Kim1, oxidative stress markers (MDA and iNOS), and inflammatory markers (TNFα, IL6, and MCP1) while decreasing antioxidant markers (SOD, GPx, CAT, and SOD3) and anti-inflammatory cytokine (IL10) levels. Khe treatment dose-dependently attenuated these changes, with the 100 mg/kg dose showing the most significant renoprotection. Histopathological analysis confirmed improved renal tissue integrity in Khe-treated groups. Conclusions: This study demonstrates that Khe exerts significant nephroprotective effects against CDDP-induced nephrotoxicity by mitigating oxidative stress, inflammation, and apoptosis while improving renal function and structure. These findings suggest Khe as a promising therapeutic candidate for preventing CDDP-related kidney injury. Full article

Background/Objectives: Previous studies have shown that unformulated extracts of Passiflora ligularis leaves exhibit promising antidiabetic activity. This research aimed to demonstrate that formulating the extract into a self-emulsifying drug delivery system (PLE-SEDDS) enhanced its antidiabetic activity in a high-fat-diet/streptozotocin-induced diabetic mouse model. Methods: Blood glucose levels (BGLs) of diabetic mice were monitored during 21 days of oral administration of P. ligularis extract (PLE) and PLE-SEDDS. Control groups included metformin (positive control), vehicle, and SEDDS vehicle (negative controls). The animals underwent an oral glucose tolerance test (OGTT). The oxidative stress markers superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation quantified by malondialdehyde (MDA) levels were measured in the kidney, liver, and pancreas, complemented with histopathological analysis. Additionally, plasma lipid profile parameters were evaluated. Results: The PLE-SEDDS formulation demonstrated superior efficacy compared to the PLE extract in improving antidiabetic outcomes. Animals treated with PLE-SEDDS exhibited a minimal increase in blood glucose levels (11.5%) during the OGTT, compared to 27.4% with PLE and over 77% in the vehicle groups. PLE-SEDDS also showed greater enhancement of SOD and CAT activity, along with a more pronounced reduction in MDA levels, indicating stronger protection against oxidative stress. Histological analysis revealed significant preservation of pancreatic islets, and lipid profile analysis showed greater reductions in triglycerides, cholesterol, and LDL-C, alongside increased HDL-C levels. Conclusions: Altogether, these findings suggest that PLE-SEDDS exhibits superior antihyperglycemic, hypolipidemic, and antioxidant effects compared to the unformulated extract, making this novel formulation a promising option for treating type 2 diabetes mellitus. Full article

Foods such as Curcuma longa L. and propolis can attenuate inflammation in patients with chronic kidney disease (CKD) undergoing hemodialysis (HD). This study aimed to evaluate the effects of microcapsules loaded with Curcuma longa L. and propolis on inflammatory markers and uremic toxins in patients undergoing HD. In this randomized, double-blind clinical trial, 40 patients were divided into two groups: an intervention group (137 mg/day of Curcuma and 500 mg/day of green propolis) in the form of microcapsules, and a placebo group, both administered for 8 weeks. Cytokines were analyzed using a multiplex assay (Bio-Plex Magpix^®). Malondialdehyde was evaluated as a marker of lipid peroxidation. Uremic toxins were analyzed by reversed-phase high-performance liquid chromatography. Demographic and clinical data were obtained from medical records. A total of 38 patients completed the study: 18 were in the intervention group (49 ± 16.2 years; 8 men) and 20 were in the control group (49 ± 18.7 years; 10 men). There was a reduction in levels of C-reactive protein (p = 0.026) and MIP-1 (p = 0.019) in the intervention group. No change in uremic toxins was observed. In conclusion, the intervention with microcapsules containing Curcuma longa L. and green propolis showed potential anti-inflammatory effects in patients with CKD undergoing HD. These findings warrant investigation in larger, long-term trials. Full article

Dogs with acute congestive heart failure (CHF) can develop acute kidney injury (AKI); the prevalence of this condition has not been defined. This study aimed to assess the occurrence of AKI (increase in serum creatinine (sCr) ≥ 0.3 mg/dL) within 48 h from admission in dogs with myxomatous mitral valve disease (MMVD) with acute CHF, and the role of urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a predictive marker of AKI. This was a multicentric, prospective observational study. Thirty dogs were included. The types and dosages of the diuretics administered, as well as the serum and urinary chemistry, including uNGAL and uNGAL, to the urinary creatinine ratio (uNGALC), were determined at admission (T0) and after 24 (T24) and 48 (T48) hours of hospitalization. Nineteen dogs developed AKI. We found no statistically significant differences in sCr, uNGAL, uNGALC, diuretic dosage, or hours of hospitalization between dogs that developed AKI and those that did not. The urinary NGAL and uNGALC values were not statistically significantly different at any time point, while the sCr was higher at T24 and T48 than T0. Our findings suggest that AKI in MMVD dogs with CHF is primarily functional, driven by effective decongestion rather than severe tubular damage, with the benefits of decongestion outweighing transient increases in sCr. Full article

Objective: Study the mechanism of ginsenoside Rg₁ in ameliorating hyperuricemia (HUA) induced by high-purine diet. Methods: Rats were randomly divided into groups, and the HUA model was established by administering a high-purine diet containing potassium oxonate combined with yeast. After the experiment, blood was collected via cardiac puncture, and the organ indices of the rats were calculated. Serum biochemical markers including aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), total cholesterol (TC), xanthine oxidase (XOD), creatinine (CREA), uric acid (UA), and blood urea nitrogen (BUN) were measured. Histopathological sections of the kidney and intestine were prepared. Western blot was used to assess the expression levels of intestinal occludin and zonula occludens-1 barrier proteins and key proteins in IL-17/NF-κB inflammatory pathways. After the experiment, fecal samples were collected from the rats. The gut microbiota of HUA-induced rats was analyzed via 16S rRNA sequencing, and the levels of short-chain fatty acids in the fecal samples were quantified using gas chromatography–mass spectrometry. Results: Ginsenoside Rg₁ significantly increased body weight and organ indexes as well as reduced serum levels of BUN, CREA, ALT, AST, XOD, and UA. Pathologic analysis showed that ginsenoside Rg₁ improved renal cell injury, glomerulosclerosis, and renal interstitial fibrosis while restoring intestinal barrier function. Ginsenoside Rg₁ down-regulated the expression of inflammatory proteins and up-regulated the levels of intestinal barrier proteins. The results of 16S rRNA sequencing showed that ginsenoside Rg₁ significantly increased the diversity index of gut microbiota and enhanced the number of beneficial bacteria in HUA rats. Short-chain fatty acids analysis demonstrated that ginsenoside Rg₁ markedly elevated the levels of acetate, propionate, butyrate, and valerate in HUA rats. Conclusions: Ginsenoside Rg₁ ameliorates and treats HUA by improving the composition of intestinal flora and inhibiting the IL-17/NF-κB signaling pathway to reduce inflammatory factors in the intestinal tract in HUA rats. Full article

Aims: This study aimed to evaluate whether the pan-immune inflammation value (PIV) has prognostic value for major adverse cardiac events (MACEs), including stroke, rehospitalization, and in-hospital and one-year all-cause mortality, in patients with aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). Methods: A total of 152 patients undergoing TAVI were retrospectively analyzed and stratified into two groups based on a PIV cutoff value of 488. Baseline clinical, laboratory, echocardiographic, and procedural characteristics were compared. Clinical outcomes, including mortality, cerebrovascular events, and bleeding complications, were assessed. Multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were performed to identify independent mortality predictors and evaluate the predictive performance of PIV. Results: Among the 152 patients (mean age 77 ± 7 years; 59.9% female), 52 (34.2%) had a PIV ≥ 488. These patients had significantly higher rates of diabetes mellitus (62% vs. 38%, p = 0.006), chronic kidney disease (31% vs. 12%, p = 0.005), and chronic obstructive lung disease (31% vs. 15%, p = 0.022), along with higher STS scores (16.3 vs. 11.7, p = 0.003). Inflammatory markers were elevated, and lymphocyte and hemoglobin levels were reduced in the high PIV group (p < 0.001). Patients with PIV ≥ 488 experienced significantly higher one-year mortality (58% vs. 4%, p < 0.001), in-hospital mortality (21% vs. 2%, p < 0.001), rehospitalization (29% vs. 4%, p < 0.001), ischemic cerebrovascular events (12% vs. 4%, p < 0.001), and major bleeding (10% vs. 2%, p = 0.034). Multivariable analysis identified age (OR: 1.108; 95% CI: 1.010–1.217; p = 0.031) and PIV (OR: 1.006; 95% CI: 1.003–1.008; p < 0.001) as independent mortality predictors. The PIV showed a strong predictive performance (AUC: 0.90, p < 0.001), with 88% sensitivity and 81% specificity. Kaplan–Meier analysis showed significantly lower survival in the high PIV group (p < 0.001). Conclusions: A high preprocedural PIV is an independent predictor of MACEs, in-hospital, and one-year mortality in AS patients undergoing TAVI. Full article

Background and Objectives: Chronic kidney disease (CKD) is an increasingly significant global public health issue, with cardiovascular disease being the leading cause of mortality. Endothelial dysfunction plays a critical role, but diagnostic tools have certain limitations. Endocan, a soluble proteoglycan, emerged as a promising endothelial dysfunction marker and potential major adverse cardiovascular event (MACE) predictor in haemodialysis (HD) patients. Materials and Methods: In this single-centre, observational, prospective study, non-diabetic HD patients without prior MACEs were monitored. A total of 75 participants met the inclusion criteria. We measured serum endocan, standard biochemical and anthropometric parameters, and parameters of peripheral and central haemodynamics before and after HD in all participants. Results: Patients with higher endocan were older, had elevated CRP and reduced albumin concentrations, and often had a tunnelled central venous catheter (TCVC) for vascular access. Higher serum endocan levels were independently associated with an increased risk of MACEs (aHR = 4.09, 95%-CI: 1.72–9.74), MACE-related mortality (aHR = 2.64, 95%-CI: 1.23–5.66), and all-cause mortality (aHR = 1.86, 95%-CI: 1.07–3.23), both before and after adjusting for predefined confounders, with the highest endocan tercile exhibiting the shortest event-free survival. Conclusions: Endocan is a valuable marker of inflammation and endothelial dysfunction in non-diabetic HD patients. Its elevated concentration indicates an increased cardiovascular risk and more frequent MACEs. Future multicentre studies with repeated endocan assessments should validate its prognostic and diagnostic utility, particularly in long-term patient follow-up. Full article

Background: The aim of this study was to compare the levels of Neuropilin-1 (NRP-1) in maternal plasma and fetal cord blood plasma between pregnancies complicated by preeclampsia (PE) and those in normotensive pregnant women. Materials and Methods: This prospectively designed study included 53 pregnant women aged 18 years or older and at least 20 weeks into gestation, who were admitted to the Maternity Department of Izmir Katip Çelebi University Atatürk Training and Research Hospital. The patient group consisted of 28 pregnant women who met the diagnostic criteria for PE, while the control group included 25 normotensive pregnant women. The diagnosis of PE was established based on the 2020 diagnostic criteria of the American College of Obstetricians and Gynecologists (ACOG). After detailed anamnesis, blood samples were collected immediately after delivery in EDTA tubes to assess serum NRP-1 levels. These samples included maternal blood, fetal cord blood, and additional tests such as CBC, liver and kidney function tests, serum electrolytes, spot urinalysis, prothrombin time (PT), and activated partial thromboplastin time (APTT). Results: There was a statistically significant difference between the two groups in terms of gestational week, presence of comorbidities, hypertension (HT), diabetes mellitus (DM), history of PE, and protein detected in spot urine examinations. Pregnant women in the PE group had significantly higher rates of comorbidities, HT, and DM compared to the control group (p < 0.001, 0.002, and 0.007, respectively). No statistically significant differences were observed between the two groups regarding hemoglobin, platelet count, aspartate aminotransferase (AST), alanine aminotransferase (ALT), or fetal cord plasma NRP-1 levels (p: 0.736, 0.831, 0.561, and 0.734, respectively). However, a statistically significant difference was found in maternal plasma NRP-1 levels (p: 0.02), which were lower in the control group compared to the PE group (median: 473.3 pg/mL vs. 587.7 pg/mL, respectively). The optimal cut-off value for maternal plasma NRP-1 to predict PE, with the best sensitivity and specificity, was determined to be 358.4 pg/mL. Among the study participants, 40 pregnant women had maternal plasma NRP-1 levels above the cut-off value, while 13 had levels below it. PE occurred significantly more frequently in the high NRP-1 group than in the low group. When demographic and clinical characteristics were analyzed, a statistically significant but weak positive correlation was found between body mass index (BMI) and maternal plasma NRP-1 levels (p: 0.02, Rho: 0.304). No strong or statistically significant relationships were identified with other variables. There was no significant difference in fetal cord plasma NRP-1 levels between the PE group and the normotensive group. In contrast, maternal plasma NRP-1 levels were significantly higher in the PE group. The cut-off value for maternal plasma NRP-1, providing optimal sensitivity and specificity for predicting PE, remained 358.4 pg/mL. Conclusions: While further studies involving larger cohorts of pregnant women from diverse racial backgrounds and various hospitals are needed to better understand the relationship between NRP-1 and PE, maternal NRP-1 concentration shows promise as a diagnostic marker. Full article

Background: Acute kidney injury (AKI), characterized by high morbidity and mortality, is primarily caused by renal ischemia–reperfusion injury (RIRI). Ferroptosis plays a key role in RIRI, yet its underlying mechanisms remain unclear. The drug pair of Astragali Radix–Ligustri Lucidi Fructus (DAL) shows promise in renal diseases, but its protective effects against RIRI and associated molecular pathways via ferroptosis inhibition are unknown. This study aimed to investigate DAL’s therapeutic effects on RIRI and its mechanisms. Methods: A mouse model of bilateral renal ischemia–reperfusion was established. Renal function (serum creatinine, Scr; blood urea nitrogen, BUN), inflammatory cytokines (TNF-α, IFN-γ, IL-6), ferroptosis markers (GPX4, MDA, GSH, tissue iron), and pathological damage were evaluated. Transcriptomic sequencing and electron microscopy analyzed gene pathways and mitochondrial structure. In HK-2 cells, oxygen–glucose deprivation/reoxygenation (OGD/R) and RSL3-induced ferroptosis models were used to assess DAL-containing serum effects via cell viability, GPX4 expression, and mitochondrial morphology. LC-MS analyzed DAL’s chemical components, and network pharmacology predicted ferroptosis-related targets. Results: DAL significantly reduced Scr/BUN levels, alleviated tubular injury, fibrosis, and apoptosis, and downregulated inflammatory cytokines and damage markers. It inhibited ferroptosis by upregulating GPX4, decreasing MDA/tissue iron, and increasing GSH. Transcriptomics revealed enrichment in lipid metabolism pathways. DAL restored the mitochondrial cristae structure; DAL-containing serum improved cell viability, blocked RSL3-induced GPX4 downregulation, and mitigated mitochondrial dysfunction. Network pharmacology identified DAL’s potential active components and targets. Molecular docking validated binding affinity and interaction patterns of active components with targets. Conclusions: DAL protects against RIRI by upregulating GPX4, preserving the mitochondrial structure, and inhibiting ferroptosis, highlighting its therapeutic potential for AKI prevention and treatment. Full article

Background: Thrombophilia is a prothrombotic disorder that can affect pregnancy outcomes, potentially leading to maternal complications, fetal growth restriction, and adverse perinatal events. However, the precise relationship between thrombophilia and these outcomes remains under investigation, and the impact of hematological, renal, hepatic, and coagulation alterations in thrombophilic pregnancies is not yet fully understood. This study aims to examine the maternal and neonatal consequences of thrombophilia by analyzing key laboratory parameters and perinatal outcomes in affected pregnancies. Methods: A retrospective observational study was conducted on 251 pregnant women, divided into thrombophilic (n = 226) and non-thrombophilic (n = 25) groups. Data on maternal demographics, laboratory parameters (hematological, metabolic, renal, hepatic, and coagulation markers), obstetric outcomes, and neonatal characteristics were extracted from medical records. Statistical analysis included t-tests, chi-square tests, and Pearson correlation analysis to assess the association between thrombophilia and clinical outcomes. Results: Thrombophilic pregnancies were associated with significantly lower fibrinogen levels (p = 0.036) and decreased INR (p = 0.006), suggesting a hypercoagulable state. Renal function was affected, as evidenced by elevated urea (p = 0.012) and creatinine (p = 0.009), indicating a predisposition to kidney dysfunction. Neonates from thrombophilic pregnancies exhibited slightly lower Apgar scores at 1 and 5 min, though the differences were not statistically significant (p = 0.101, p = 0.131). NICU admission rates were comparable between groups (p = 0.317), suggesting that thrombophilia may not be a major determinant of neonatal intensive care needs. However, gestational age and birth weight remained the strongest predictors of neonatal vitality (p < 0.001), while coagulation abnormalities and renal dysfunction correlated with poorer perinatal outcomes. Conclusions: Thrombophilia is associated with altered coagulation profiles, renal dysfunction, and potential risks for maternal complications. While neonatal outcomes were not significantly different, the observed trends suggest the need for enhanced monitoring in thrombophilic pregnancies. Early intervention, thromboprophylaxis, and individualized management strategies may improve maternal and neonatal prognosis. Further research is needed to refine preventive strategies and optimize therapeutic approaches in high-risk pregnancies. Full article

Background/Objectives: In the context of acute heart failure, proenkephalin A (penKid) has emerged as a prognostic marker for acute kidney injury (AKI), whereas bioactive adrenomedullin (bio-ADM) has been identified as a significant biomarker linked to shock and organ dysfunction. This raises the question of whether they can serve as predictors of postoperative complications in patients receiving left ventricular assist devices (LVADs). Methods: This observational study prospectively enrolled patients who had received LVAD implantation. Routine laboratory values as well as plasma levels of penKid and bio-ADM were assessed at four time intervals, spanning from preinduction of anesthesia to 48 h post surgery. Clinical data, the HeartMate 3-risk-score (HM3RS), HeartMateII-risk-score (HMRS), Michigan-right-heart-failure risk score (MRHFS), Euromacs-RHFS (EURORHFS), and kidney failure risk score (KFR) were calculated. Multivariate logistic regression and receiver operating characteristic (ROC) analysis were performed. We entered the biomarkers with the established risk scores into the models. Results: In 20 patients who had undergone LVAD implantation, preoperative penKid level was a predictor of postoperative AKI (OR: 1.05, 95%-CI: 1.0–1.09; p = 0.049) and 30-day mortality (OR: 1.01, 95%-CI: 1.0–1.02; p = 0.033). Bio-ADM was the only predictor of postoperative right heart failure (RHF) (OR: 1.11, 95%-CI: 1.01–1.23; p = 0.034) and rehospitalization (OR: 1.06, 95%-CI: 1.0–1.13; p = 0.047). In the ROC analysis, bio-ADM, as a predictor of post-LVAD RHF, had an area under the curve (AUC) of 0.88. When bio-ADM was added to the accepted clinical scores for post-LVAD RHF prediction (CRITT-score, MRHFS, and EURORHFS), the AUC reached 0.98. The AUC for preoperative penKid, as a predictor of postoperative AKI, was 0.95, and after adding its predictive value to the KFR score, the AUC reached 0.97. Conclusions: In the present study, the biomarkers penKid and bio-ADM predicted clinically significant patient outcomes after LVAD implantation such as AKI, RHF, and 30-day mortality. Adding biomarkers to well-established risk scores improved the AUC for prediction of postoperative complications. Full article

Background/Objectives: Diabetic kidney disease (DKD) is a common diabetic complication, driven by a multifactorial pathogenesis that includes various genetic components. However, the precise causative genes and their underlying biological pathways remain poorly understood. Methods: We performed a cross-tissue transcriptome-wide association study (TWAS) of DKD using expression quantitative trait loci (eQTL) data from 49 tissues in the Genotype—Tissue Expression (GTEx) version 8 (v8) resource. Five complementary analytical frameworks—sparse canonical correlation analysis (sCCA), functional summary-based imputation (FUSION), fine-mapping of causal gene sets (FOCUS), summary-data-based Mendelian randomization (SMR), and multi-marker analysis of genomic annotation (MAGMA)—were integrated to nominate candidate genes. Causal inference was refined using Mendelian randomization (MR), and biological significance was evaluated through pathway enrichment, protein interaction networks, and druggability profiling. Results: We identified 23 candidate genes associated with DKD risk, of which 13 were supported by MR analysis. Among these, 10 represent previously unreported susceptibility genes. Notably, four genes—HLA-DRB1, HLA-DRB5, NOTCH4, and CYP21A2—encode potentially druggable proteins, with HLA-DRB5 and CYP21A2 both qualifying as novel susceptibility genes and therapeutic targets. These genes converge on immune modulation, steroid biosynthesis, DNA repair, and transcriptional regulation—processes central to DKD pathogenesis. Conclusions: Our study represents the first systematic cross-tissue TWAS of DKD, revealing a prioritized set of genetically and functionally supported susceptibility genes. The identification of druggable targets among these genes provides critical insight into the mechanistic underpinnings of DKD and highlights their potential for future therapeutic development. These findings enhance our understanding of DKD pathophysiology and offer a foundation for precision medicine strategies in nephrology. Full article