Search Results (560)

Hepatorenal syndrome (HRS) is a high-mortality, potentially reversible form of kidney failure that arises from a tight hemodynamic–inflammatory coupling in cirrhosis. Contemporary redefinitions prioritize creatinine kinetics over static thresholds and recognize non-acute kidney injury (AKI) functional phenotypes, enabling earlier recognition but heightening the need for precise etiologic triage. This narrative synthesis integrates current concepts across pathophysiology, diagnosis and management. Portal hypertension, bacterial translocation and inflammatory mediators amplify splanchnic vasodilation and effective arterial underfilling. Compensatory neurohumoral activation precipitates renal vasoconstriction, intrarenal microcirculatory dysfunction and sodium–water retention. The pivotal diagnostic fork remains HRS–AKI versus acute tubular necrosis. A pragmatic, tiered strategy, structured volume assessment, filtration markers and a parsimonious tubular-injury panel offer actionable discrimination, whereas fractional excretion indices serve as adjuncts only. Initial therapy should be bundled and time-sensitive: remove nephrotoxins, treat infection and initiate albumin plus a vasoconstrictor. The transplant strategy should default to isolated liver transplantation unless end-stage renal disease is established. Future priorities include validated biomarker cut-offs, ultrasound-guided volume algorithms and pathway-based trials to reduce diagnostic delay and improve survival. Full article

Background: Primary graft dysfunction (PGD) is the leading cause of early mortality after lung transplantation. Albumin is commonly used during lung transplantation to maintain intravascular volume while minimizing total intravenous fluid administration, given the established association between larger intravenous fluid and PGD. However, the direct impact of albumin on PGD remains unclear. Methods: We conducted a single-center retrospective cohort study of lung transplant recipients between 2018 and 2023. We calculated the corrected albumin proportion (cAP), representing the ratio of albumin to total intravenous fluid administered. We analyzed associations between cAP and PGD at 24, 48, and 72 h, as well as secondary outcomes including total fluid administration, 30-day acute kidney injury, mortality, and ICU length of stay. Results: A total of 190 patients were included in this study. A higher cAP was associated with lower total intravenous fluid administration (r = −0.15, p = 0.03), whereas a higher total intravenous fluid administration was associated with higher PGD at 72 h (OR 1.02, 95% CI 1.00–1.03, p = 0.04). However, cAP was not independently associated with PGD or other short-term outcomes. Conclusions: Intraoperative albumin use modestly reduced total intravenous fluid administration but was not independently associated with significant reductions in PGD or improvements in other short-term outcomes. Full article

Permethrin (PERM) is a synthetic pyrethroid insecticide initially regarded as low risk. However, evidence now indicates that misuse and prolonged exposure can damage multiple physiological systems by disrupting enzymatic functions in subcellular structures. In this study, male Wistar rats were administered PERM (75, 150, or 300 mg/kg/day) for 15 days to assess its effect on hematological and biochemical parameters, including oxidative stress markers in the liver, kidney, and heart. Subacute PERM administration induced significant, dose-dependent toxicological alterations in exposed animals. Hematological analysis revealed impaired hematopoiesis, characterized by increased erythrocytes and platelets alongside decreased hemoglobin, hematocrit, mean corpuscular volume, and red cell distribution width. Biochemical analysis revealed elevated liver enzymes and bilirubin, along with reduced albumin levels, indicating hepatic alterations associated with PERM. The assessment of oxidative stress revealed tissue-specific responses following PERM exposure. While GPx, CAT, and SOD levels remained unchanged, GR activity increased in the heart, and GST activity increased in the liver. Additionally, a substantial decrease in MDA was observed in both the liver and heart. These collective alterations found in PERM-subacute exposed rats suggest the potential for cellular damage with the possible development of chronic pathologies, warranting further investigation. Full article

We compared oxidative markers and their links to inflammation in diabetic nephropathy and hemodialysis to identify independent determinants. We studied 180 adults, 90 patients with type 2 diabetes and diabetic nephropathy and 90 patients on hemodialysis. We measured serum advanced oxidation protein products (AOPP) and thiobarbituric acid reactive substances (TBARS) by enzyme-linked immunosorbent assay (ELISA). Partial correlations were adjusted for age, sex, and albumin with false discovery rate (FDR) control. Principal component analysis (PCA) summarized inflammatory indices and linear models tested predictors of AOPP and TBARS. Oxidative damage was higher in hemodialysis, with AOPP median 25.80 versus 5.06 and TBARS 8.49 versus 1.89, p less than 0.0001. C reactive protein (CRP) and mean corpuscular volume-to-lymphocyte ratio (MCVL) were higher in patients ongoing hemodialysis; systemic immune-inflammation index (SII) was higher in diabetic nephropathy. PCA yielded a dominant inflammation axis in both cohorts, 74.73 percent in hemodialysis and 85.20 percent in diabetic nephropathy. In regression, creatinine (β = 2.47, p = 0.026) predicted AOPP in hemodialysis. Dialysis vintage inversely predicted TBARS, β = −0.2305, p = 0.0209. In diabetic nephropathy, the PCA inflammation score predicted AOPP, β = 1.134, p = 0.0003. Protein oxidation tracked systemic inflammation in diabetic nephropathy, but not in hemodialysis. AOPP outperformed TBARS as an inflammatory partner and a practical monitoring candidate in diabetic kidney disease. Prospective studies should test for prognostic value and therapy sensitivity. Full article

Background/Objectives: Systemic sclerosis-associated interstitial lung disease (SSc-ILD) and chronic obstructive pulmonary disease (COPD) are linked to multi-organ vulnerability involving the lungs, heart, and kidneys. This study aimed to compare the annual changes in pulmonary, cardiac, and renal parameters in patients with SSc-ILD and COPD across three consecutive years, using both individual biomarkers and integrated composite profiles. Methods: This observational longitudinal study included repeated assessments in 2023, 2024, and 2025. Functional, laboratory, and imaging parameters were collected: 6-min walk test (6MWT), SpO₂ (pre-/post-exercise), spirometry/CT lung volumes, gas exchange (pO₂/pCO₂/lactate), echocardiography [left ventricular ejection fraction (LVEF), estimated systolic pulmonary artery pressure (sPAP)], cardiac biomarkers (NT-proBNP, MR-proANP, hsTnT), renal markers [eGFR, creatinine, albuminuria, albumin-to-creatinine ratio (ACR)], heart rate variability (HRV), and renal CT densitometry. All markers were standardized (z-scores, higher values = worse). Subprofiles were generated and aggregated into three integrated profiles (cardiac, renal, pulmonary). Within-group dynamics were analyzed using the Wilcoxon signed-rank test (year-to-year deltas), between-group comparisons with the Mann–Whitney U test, effect sizes via Cliff’s delta, and multiple testing correction with the Benjamini–Hochberg false discovery rate (FDR). Results: Exercise tolerance declined in both groups: by 2025, 6MWT distance decreased by −10 m in SSc-ILD (p = 0.006; q = 0.010) and −20 m in COPD (p = 0.002; q = 0.004); post-exercise SpO₂ fell in both cohorts (both p < 0.001; q < 0.001). MR-proANP remained consistently higher in SSc-ILD across all years (p ≤ 0.005; q ≤ 0.028). sPAP increased in both groups, reaching higher values in COPD by 2025 (p = 0.007; q = 0.033). NT-proBNP and hsTnT increased over time, while eGFR declined, and ACR rose in both cohorts (both p < 0.001; q < 0.001). HRV (HF/total power) decreased by 2025. Composite profiles showed: in 2023, the cardiac profile was worse in SSc-ILD (δ ≈ 0.27; p = 0.011; q = 0.048), but differences diminished by 2025; the renal profile was initially worse in SSc-ILD but later shifted unfavorably in COPD; the pulmonary profile showed no consistent between-group differences. Conclusions: Over three years, patients with SSc-ILD and COPD exhibited concordant deterioration in pulmonary, cardiac, and renal function. Distinct leading markers emerged: desaturation during exercise and neurohormonal activation (MR-proANP) in SSc-ILD, versus reduced 6MWT and higher sPAP in COPD. These findings support the need for integrated monitoring of the cardio–pulmo–renal continuum. Limitations include the observational design, multiple comparisons, and absence of advanced repeated-measures modeling. Full article

Through the mineralocorticoid receptor, aldosterone controls extracellular volume and arterial blood pressure by stimulating Na⁺ absorption and K⁺ secretion in epithelial cells of the kidney, colon, and several glands. Hyperaldosteronism promotes fibrosis and inflammation in epithelial and non-epithelial tissues, thereby favoring loss of kidney and heart function. Mineralocorticoid receptor blockade therefore gains relevance especially in renal and cardiac disease. Kidney-derived Klotho is a powerful anti-aging protein with anti-fibrosis and anti-inflammatory effects providing cardio- and nephroprotection. We wondered whether Klotho expression and production is influenced by mineralocorticoid receptor agonists and antagonists. Using four renal cell lines, Madin-Darby canine kidney (MDCK), normal rat kidney, subtype 52E (NRK-52E), human kidney 2 (HK2) cells, and primary renal proximal tubule epithelial cells (RPTECs), and the four most frequently prescribed mineralocorticoid receptor blockers, spironolactone, eplerenone, finerenone, and esaxerenone, we assessed Klotho gene expression by qRT-PCR and Klotho protein by Western blotting. Aldosterone and eplerenone did not significantly affect Klotho expression in either cell line. Spironolactone enhanced Klotho expression in MDCK and NRK-52E cells and downregulated Klotho in HK2 cells and RPTECs. Novel non-steroidal mineralocorticoid receptor antagonist finerenone downregulated Klotho expression in MDCK, NRK-52E, and low-dose finerenone in HK2 cells. To conclude, common mineralocorticoid receptor antagonists are characterized by highly diverse effects on Klotho in four renal cell lines. Further studies are needed to define the role of mineralocorticoid receptor blockade for Klotho production. Full article

Background: Prostate cancer is the most frequent malignancy in men, with an incidence of 21% of all diagnosed tumors in this population in Spain. Between 10 and 20% of patients with prostate cancer develop castration-resistant prostate cancer (CRPC). Abiraterone is widely used in CRPC and metastatic prostate cancer, but data on its renal safety are limited. Methods: We performed a single-center, retrospective observational study including patients with advanced prostate cancer who initiated abiraterone between January 2013 and July 2024 at Hospital Clínico San Carlos (Madrid, Spain). Patients were followed until December 2024. Renal events were defined as acute kidney injury (AKI), electrolyte imbalance, new onset or worsening hypertension (HTN), and/or volume overload. Risk factors and associations with mortality were analyzed using multivariate models. Results: Seventy-nine patients were included (mean age 76 ± 9.5 years; 70.9% CRPC; 89.9% metastatic disease). Median follow-up was 17 months. Renal events occurred in 63.3% of patients. Independent risk factors were metastatic disease (OR 13.335; 95% CI 1.418–124.444; p < 0.0235) and HTN (OR 3.336; 95% CI 1.091–10.206; p < 0.0347). Electrolyte imbalance occurred in 36.7% of patients. AKI developed in 30.4% of patients, of whom 50% progressed to chronic kidney disease. New/worsening HTN occurred in 25.5%, and volume overload occurred in 16.5%. Abiraterone discontinuation due to renal events was rare (4%). At the end of follow-up, 18.9% of patients had died. In a multivariate Cox analysis, AKI was identified as an independent predictor of mortality [HR 3.044 (95% CI 1.001–9.260); p = 0.05]. Conclusions: Renal events are common in patients treated with abiraterone, especially in those with metastatic disease and hypertension. AKI independently predicted mortality. Close monitoring of renal function and blood pressure is essential in this population. Full article

Objectives: To evaluate perioperative outcomes, renal function preservation, and short-term oncologic results of off-clamp, sutureless, or selectively sutured robotic-assisted partial nephrectomy (RAPN) in patients with renal tumors treated at multiple high-volume centers. Methods: This multicenter retrospective study included 250 patients who underwent off-clamp, sutureless/selectively sutured RAPN between January 2018 and December 2024. Patients with solitary kidneys, tumors > 7 cm, or prior renal surgery were excluded. All procedures were performed without renal artery clamping, using hemostatic agents and selective suturing when necessary. Perioperative, functional, and oncologic outcomes were compared with 313 patients who underwent standard RAPN with parenchymal suturing. Results: The median operative time was 110 min (IQR 100–140), and the median estimated blood loss was 180 mL (IQR 100–250). The overall complication rate was 8.4%, predominantly Clavien–Dindo grade I–II, with no conversions to open surgery. The median decline in estimated glomerular filtration rate (eGFR) at three months was 5.5% (IQR 3.5–8.9; p = 0.56), and no cases of acute kidney injury were recorded. The positive surgical margin rate was 3.7%, and no tumor recurrences were observed during the 12-month follow-up period. Conclusions: Off-clamp, sutureless or selectively sutured robotic-assisted partial nephrectomy (RAPN) was not associated with increased perioperative risk, renal functional decline, or compromised short-term oncologic control compared with conventional sutured RAPN. These findings indicate that the technique is feasible and safe in appropriately selected patients, although prospective studies with longer follow-up are needed to confirm long-term outcomes and refine patient selection criteria. Full article

Novel antidiabetic drugs introduced in the last decade have not only revolutionized the treatment of type 2 diabetes mellitus but have also changed our cardiovascular risk reduction strategy. Glucagon-like peptide-1 (GLP-1) receptor agonists reduce the risk of atherosclerotic diseases primarily through their complex anti-atherosclerotic effect due to their endothelial function-improving, anti-inflammatory, anti-thrombotic, and plaque-stabilizing effects. Sodium–glucose cotransporter 2 (SGLT2) inhibitors, on the other hand, have a favorable cardiovascular effect, mainly by increasing sodium excretion, reducing plasma volume, enhancing the use of ketone bodies as metabolic substrates in heart and kidney tissues, and reducing oxidative stress and uric acid serum levels. However, when using these two groups of drugs, important questions arise. What criteria should be used to decide on the administration of one or the other class of drugs? Which group of agents can be used more effectively to reduce our patients’ cardiovascular risk? What are the possible adverse effects? What can be gained by combining the two drugs? Our objective was to provide a current literature-based and comparative summary on the mechanisms of action, cardiovascular-risk-reducing efficacy, and safety profiles of these two drug classes, with an emphasis on identifying key factors influencing everyday clinical decision-making. Full article

Objectives: Evaluate the agreement and interobserver variability between manual segmentation and the ellipsoid formula in estimating single kidney volume (SKV) in patients with autosomal dominant polycystic kidney disease (ADPKD). Methods: In this retrospective study, 130 unenhanced CT scans of ADPKD kidneys were analyzed. Three radiologists (one senior, two juniors) measured SKV using manual segmentation and the ellipsoid formula. Statistical analyses included intraclass correlation coefficient (ICC), Wilcoxon signed-rank test, Bland–Altman analysis, and paired t-tests to compare measurement values and computation times. Results: Both methods showed excellent interobserver agreement (ICC ≥ 0.977). No significant difference was observed in volume estimates between the two techniques (Wilcoxon p = 0.295). Bland–Altman analysis confirmed strong agreement between methods for the senior radiologist. The ellipsoid method was significantly faster for all readers (p < 0.05). Conclusions: The ellipsoid formula is a reliable, time-efficient alternative to manual segmentation for SKV estimation in ADPKD, offering comparable accuracy with reduced resource demands in clinical settings. Full article

In the last twenty years, an increasing volume of research has characterized lipids as dynamic signaling molecules that play essential roles in various physiological and pathological processes, especially concerning chronic diseases such as cardiovascular disorders, diabetes, liver disease, neurodegeneration, cancer, obesity, diabetic and chronic kidney diseases and atherosclerosis. Dysregulation of lipid synthesis and storage, lipolysis, fatty acid oxidation, lipid signaling pathways, and organelle-specific lipid modifications, including mitochondrial phospholipid remodeling and endoplasmic reticulum stress induced by saturated fatty acids, are recognized as contributors to the initiation and progression of this pathogenesis. Concurrently with the increasing comprehension of lipid metabolism, the last decade has seen progress in the understanding of genome control, especially with non-coding RNAs (ncRNAs). MicroRNAs, long non-coding RNAs, and circular RNAs, as ncRNAs, are essential modulators of gene expression at the epigenetic, transcriptional, and post-transcriptional levels that affect a number of lipid metabolism-related processes, such as fatty acid synthesis and oxidation, cholesterol homeostasis, and lipid droplet dynamics. Therapeutically, ncRNAs hold considerable promise owing to their tissue specificity and modularity, with antisense oligonucleotides and CRISPR-based editing currently under preclinical evaluation. In this context, we review recent studies exploring the interplay between ncRNAs and the regulatory networks governing lipid metabolism, and how disruptions in these networks contribute to chronic disease. This emerging paradigm underscores the role of ncRNA–lipid metabolism interactions as central nodes in metabolic and inflammatory pathways, highlighting the need for a holistic approach to therapeutic targeting. Full article

Background: In recent years, indications for liver transplantation have expanded, while the age of transplant recipients has significantly increased due to improvements in perioperative management. As clinical manifestations of posttransplant complications vary and are often nonspecific, the identification of appropriate biomarkers is important for the assessment of graft quality and early recognition of potential complications following liver transplantation. Liver-type FABP (L-FABP) is a small cytoplasmic protein found abundantly in hepatocytes and is involved in the intracellular transport of long-chain fatty acids. Elevated serum levels have been detected in acute and chronic liver failure, kidney failure, and some malignancies. Materials and Methods: We conducted a prospective, single-center study from July 2023 to January 2025, including 29 adult patients who underwent deceased-donor transplantation. Three patients were excluded due to inadequate sample withdrawals. Serum L-FABP was measured preoperatively and on postoperative days 1, 3, 5, 7, and 14. Clinical, surgical, and biochemical data were collected and analyzed using non-parametric statistical tests. Results: L-FABP levels were significantly higher on POD 7 in recipients of grafts from donors ≥ 65 years (p = 0.035), with no corresponding changes in standard liver function markers. While no significant differences in L-FABP levels were found between patients with and without infectious biliary or vascular complications (all p > 0.05), we proved a strong negative correlation between intraoperative blood transfusion volume and L-FABP levels on POD 5 (ρ = −0.677, p < 0.001) and POD 7 (ρ = −0.455, p = 0.025). Conclusions: Our findings suggest that L-FABP holds promise as a biomarker for the early detection of subclinical hepatic graft cellular injury, which is not detected by means of conventional biomarkers for liver function. Full article

Background: Diabetic ketoacidosis (DKA) in patients with kidney failure receiving dialysis presents a formidable clinical challenge. Standard DKA protocols, designed for patients with preserved renal function, often fail in this cohort and can be unsafe when applied without modification. Patients are at risk of iatrogenic fluid overload, dyskalaemia, and hypoglycaemia due to altered insulin kinetics, impaired gluconeogenesis, and the absence of osmotic diuresis. Purpose: This narrative review aims to synthesise current understanding of DKA pathophysiology in dialysis patients, delineate distinct clinical phenotypes, and propose individualised management strategies grounded in physiology-based reasoning, comparative guideline insights, and consensus-supported literature. Methods: We searched PubMed/MEDLINE, Embase, and Google Scholar (January 2004–June 2024) for adult dialysis populations, using terms spanning DKA, kidney failure, insulin kinetics, fluid balance, and cerebral oedema. Reviews, observational cohorts, guidelines, consensus statements, and physiology papers were prioritised; case reports were used selectively for illustration. Evidence was weighted by physiological plausibility and practice relevance. Nephrology-led authors aimed for a pragmatic, safety-first synthesis, seeking and integrating contradictory recommendations. Conclusions: Our findings highlight the critical need for a nuanced approach to fluid management, a tailored insulin strategy that accounts for glucose-insulin decoupling and prolonged insulin half-life, and careful consideration of potassium and acidosis correction. We emphasise the importance of recognising specific volume phenotypes (hypovolaemic, euvolaemic, hypervolaemic) to guide fluid therapy, and advocating the judicious use of variable-rate insulin infusions (‘dry insulin’) to mitigate fluid overload. We also show that service-level factors are critical. Dialysis-specific pathways, interdisciplinary training, and quality improvement metrics can reduce iatrogenic harm. By linking physiology with workflow adaptations, this review provides a physiologically sound, bedside-oriented map for navigating this complex emergency safely and effectively. In doing so, it advances an individualised model of DKA care for dialysis-dependent patients. Full article

Background and Objective: Acute kidney injury (AKI) is a serious condition requiring prompt fluid resuscitation, yet both under- and over-treatment carry risks. Accurate volume assessment is essential, especially in emergency settings. The Inferior Vena Cava Collapsibility Index (IVCCI) is commonly used but has limitations. The Pleth Variability Index (PVI) offers a non-invasive alternative, though its role in AKI remains unclear. To compare the efficacy of the Pleth Variability Index (PVI) and Inferior Vena Cava Collapsibility Index (IVCCI) in assessing fluid responsiveness and predicting in-hospital mortality in patients with acute kidney injury. Materials and Methods: This prospective observational study enrolled 50 adult AKI patients presenting to a tertiary emergency department. All patients received sequential fluid resuscitation with 1000 mL and 2000 mL of isotonic saline. PVI, IVCCI, mean arterial pressure (MAP), peripheral oxygen saturation (SpO₂, perfusion index (PI), and shock index (SI) were recorded at baseline and after each fluid bolus. Changes in these parameters were analyzed to assess their utility in fluid responsiveness. Additionally, the prognostic value of baseline PVI for in-hospital mortality was investigated. Results: PVI demonstrated a significant and dose-responsive decrease following fluid administration, outperforming IVCCI, MAP, PI, SpO₂, and SI in sensitivity (p < 0.001). Baseline PVI values were significantly associated with mortality (AUC: 0.821, p < 0.001), whereas post-resuscitation PVI values showed no prognostic significance. IVCCI and PI showed comparable reliability but were less sensitive to incremental volume changes. Conclusions: PVI is a sensitive, non-invasive marker of fluid responsiveness in non-intubated AKI patients and may also serve as an early prognostic indicator. Its use in emergency departments could support fluid management decisions, but further large-scale, multicenter studies are needed to validate these findings. Full article

Pressure overload in non-treated or resistant hypertension (HTN) increases the risk of heart failure (HF) as well as the occurrence of fatal ventricular arrhythmias and stroke-provoking atrial fibrillation (AF), while perturbed connexin-43 (Cx43) and Cx40 might be involved. In addition, kidney dysfunction may facilitate hemodynamic volume overload and congestive HF. We investigated the impact of volume overload on Cx43 and Cx40 in right and left heart atria of hypertensive pressure overloaded Ren-2 transgenic (TGR) strain and normotensive Hannover Sprague Dawley (HSD) rats, as well as the efficacy of renin–angiotensin blockade with trandolapril and losartan. Key novel findings revealed lower levels of Cx43 and Cx40 proteins in left as well as right heart atria in pressure overloaded hypertensive rats compared to normotensive rats. There was a significant decrease in Cx43 and Cx40 proteins due to volume overload in both atria of normotensive as well as hypertensive rats. Treatment with trandolapril increased Cx43 and Cx40 levels in right and left heart atria of normotensive as well as hypertensive volume overloaded rats. While losartan increased Cx43 and did not affect Cx40 in left and right heart atria of volume overloaded rats. Findings of this study point out that right heart atria of normotensive as well as hypertensive rats are more susceptible to volume overload comparing to the left heart atria. Trandolapril attenuated pro-arrhythmic downregulation of Cx43 and Cx40 in atria of volume overloaded normotensive as well as hypertensive rats. This fact as well as examining AF inducibility requires further investigation. Full article