Search Results (728)

Background/Objectives: Frailty is a validated predictor of waitlist mortality and perioperative risk in liver transplant candidates, but its association with early post-transplant outcomes in large real-world cohorts remains incompletely characterized. This study evaluated the association between administratively defined pre-transplant frailty and early clinical outcomes following liver transplantation. Methods: We conducted a retrospective cohort study using the TriNetX US Collaborative Research Network. Adults undergoing first-time isolated liver transplantation through February 2026 were included. Frailty was identified using ICD-10-CM codes for frailty, sarcopenia, cachexia, weakness, abnormal gait/mobility, or reduced mobility documented within 12 months before transplantation; patients coded only for nonspecific weakness were excluded from the frailty cohort. Patients underwent 1:1 propensity score matching using 18 baseline covariates, including demographics, comorbidities, laboratory values, albumin, and MELD-Na. The primary outcome was all-cause mortality at 7, 30, and 90 days. Secondary outcomes included acute kidney injury, prolonged mechanical ventilation, vasopressor requirement/hemodynamic instability, renal replacement therapy, ICU and hospital length of stay, and 90-day readmission. Sensitivity analyses used a restrictive ≥ 2-code frailty definition and substituted MELD 3.0 for MELD-Na in the propensity model. Results: Among 4860 eligible recipients, 742 had administratively defined frailty and 4118 did not. After matching, 730 patients remained in each group with well-balanced covariates. Administratively defined frailty was associated with higher mortality at 7, 30, and 90 days, with numerically smaller relative risks at later time points. It was also associated with higher risks of acute kidney injury, prolonged mechanical ventilation, vasopressor requirement/hemodynamic instability, renal replacement therapy, longer ICU and hospital stays, and 90-day readmission. Findings were directionally consistent in both sensitivity analyses. Etiology-stratified analyses were exploratory and showed no statistically significant heterogeneity across liver disease etiologies. Conclusions: In this large propensity-matched multicenter cohort, administratively defined pre-transplant frailty was associated with worse early outcomes after liver transplantation. Because frailty and several outcomes were identified using structured EHR and administrative data, findings should be interpreted as associative and hypothesis-generating. Prospective studies using validated frailty instruments and granular donor, intraoperative, and center-level variables are needed to confirm these findings. Full article

Introduction: SGLT2 inhibitors reduce renal composite endpoints and proteinuria, yet RCTs uniformly show an acute eGFR dip within 2 weeks to 2 months after initiation. However, demographic and clinical predictors of an acute eGFR dip demonstrate considerable heterogeneity across studies. This study aims to identify urinary protein biomarkers of this early eGFR dip and integrate them with routine variables to build a clinically actionable prediction model. Methods and analysis: This three-stage proteomics study includes retrospective discovery, prospective internal validation, and external validation cohorts (total n ≈ 600–700). DIA mass spectrometry will screen for urinary proteins associated with ≥10% eGFR decline at 1 month post-SGLT2i initiation in CKD stages 3–4. Top candidates (FDR < 10%, FC > 1.5, ion intensity > 1 × 10⁴, unique gene families) will be validated by ELISA. A LASSO-logistic regression model will integrate the top three proteins with seven routinely available clinical variables: age, BMI, diabetes status, heart failure, systolic blood pressure, baseline eGFR, and diuretic use. Model performance will be assessed using the C-statistic, NRI, IDI, and calibration metrics. Adaptive stopping rules are pre-specified. Ethics and dissemination: Approved by the Ethics Review Committee at Chinese PLA General Hospital (S2025-859-02, 2025KY126-KS002), all participants will provide written informed consent prior to enrollment, and the study will adhere to the Declaration of Helsinki. Data will be pseudonymized and stored securely according to institutional regulations. Findings will be published in peer-reviewed journals and presented at international nephrology conferences. Trial Registration: Registered Report Identifier: ChiCTR2600119772. Date of registration: 3 March 2026. Full article

Background: Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) represents a group of rare systemic autoimmune disorders marked by inflammation and damage to small- and medium-sized blood vessels. The clinical presentation of AAV is highly variable, ranging from isolated organ involvement to severe, life-threatening multisystem disease, posing significant challenges in diagnosis, treatment, and prognosis. Objective: To demonstrate the clinical heterogeneity and different outcomes in three pediatric cases of ANCA-positive disease and emphasize the importance of integrating clinical findings with laboratory and imaging investigations for accurate diagnosis. Methods: We present three pediatric patients (ages 12–15 years) with ANCA-positive results but distinct clinical presentations, evaluated at the Children’s Emergency Hospital “Louis Turcanu”, Timisoara, between 2020 and 2024. All cases were investigated according to EULAR/PRINTO/PReS criteria for pediatric vasculitis. Results: Case 1 (PR3-ANCA positive) developed severe multi-organ involvement, including granulomatosis with polyangiitis (GPA) with pulmonary hemorrhage, pericarditis, thrombotic events, and renal impairment, requiring intensive immunosuppression with cyclophosphamide, rituximab, and mycophenolate mofetil, ultimately developing chronic kidney disease stage 3a. Case 2 (BPI-ANCA positive) presented with purpuric lesions and painless joint swelling, responding favorably to corticosteroid therapy with subsequent remission. Case 3 (MPO-ANCA) manifested as polyarticular arthritis without other organ involvement and was ultimately diagnosed as seronegative juvenile idiopathic arthritis (JIA), achieving complete remission with adalimumab therapy. Conclusions: This case series highlights the diverse clinical and biological features of ANCA-positive conditions in children, emphasizing that ANCA positivity requires careful clinical correlation as it may indicate true vasculitis requiring aggressive treatment or alternative diagnoses such as JIA with incidental ANCA positivity. Tailored therapeutic strategies based on clinical presentation and continued research are essential to improve patient outcomes. Full article

Objective: Solitary kidney tumors are a challenging scenario necessitating both oncologic efficacy and renal function preservation. Partial nephrectomy (PN), when feasible, remains the gold standard for management. We examine intraoperative techniques and their association with renal function decline in patients with solitary kidneys undergoing PN. Methods: In two high volume academic referral centers, we analyzed patients that underwent PN in a solitary kidney from 2000 to 2023. Patient characteristics, tumor details, and operative details were obtained. Chronic kidney disease (CKD) upstaging from pre- to postoperative was the primary outcome, with multivariable analysis examining the association between intraoperative factors and CKD progression. Results: In total, 104 patients were included, of which 38 (36.5%) experienced CKD upstaging. Mean eGFR decline was 15.4% at median follow-up of 16 months. Cold ischemia was associated with higher odds of CKD upstaging compared to warm ischemia (OR 3.64; 95% CI 1.06–12.52) and no ischemia (4.55; 95% CI 1.09). Notably, cold ischemia cases tended to involve significantly larger, more complex tumors in patients with lower baseline renal function. Ischemia time, parenchyma resection, renal volume change, operative time, and renorrhaphy type were not predictors of CKD upstaging. Conclusions: PN in solitary kidneys remains standard with evidence of excellent renal preservation in this cohort. Worse outcomes were observed with cold ischemia, although this more likely represents underlying tumor complexity with other uncontrollable factors; however, this should be explored further. These findings suggest that renal functional outcomes are likely reasonable in patients with solitary kidneys undergoing PN when appropriate patient selection and sound surgical technique are utilized. 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

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: Failure to rescue deteriorating ward patients before irreversible organ injury remains a leading cause of preventable in-hospital mortality, yet current rapid response team (RRT) research relies predominantly on cross-sectional comparisons at the moment of activation, overlooking the short-horizon physiological changes that precede it. Methods: This retrospective cohort study at a tertiary academic hospital in South Korea included 549 adults (191 ICU-transferred, 358 ward-remaining) with a first RRT activation between September 2023 and August 2025. Generalised estimating equations (GEE) with a time × group interaction modelled differential changes in 12 laboratory variables and the DeepCARS AI-derived risk score between 24 h before activation (T−24 h) and the moment of activation (T0). At T−24 h, physiological profiles were largely similar between groups, indicating that conventional static assessment failed to identify patients destined for ICU transfer. Results: Over the ensuing 24 h, patients subsequently transferred to the ICU showed a steeper decline in SpO₂/FiO₂ (S/F) ratio (383.4 → 167.1 vs. 369.1 → 260.3; B = −0.547, p < 0.001) and steeper increases in lactate (2.91 → 4.02 vs. 2.05 → 2.98 mmol/L; B = 0.154, p = 0.045), creatinine (B = 0.076, p = 0.038), potassium (B = 0.019, p = 0.001), and DeepCARS score (B = 0.073, p = 0.028) compared with patients remaining on the ward. All five variables retained significance under Benjamini–Hochberg false discovery rate correction (q < 0.10). Seven inflammatory and haematological markers showed no differential change. Procalcitonin was excluded from the primary analysis because of very high missingness at the pre-activation time point (approximately 75%). Conclusions: These findings demonstrate that short-horizon deterioration in oxygenation, perfusion, and renal function—rather than any single earlier measurement—distinguishes patients requiring ICU transfer, supporting the development of change-based early warning criteria to enable earlier clinical escalation. Full article

Objective: The existing work was designed to appraise whether Secukinumab diminishes acute kidney injury in a Cisplatin- induced rat model and to explore the potential underlying mechanisms for this protective effect. Methods: In vivo study, rats were distributed haphazardly into five sets (six animals in each group): control, Secukinumab control, Cisplatin (8 mg/kg, a single dose, intraperitoneally (IP)), and two pretreated groups; Secukinumab (10 and 20 mg/kg single subcutaneous (SC) injection) + Cisplatin. Blood samples and kidney tissues were gathered and analyzed histopathologically and biochemically. In vitro investigation, MCF-7 human breast cancer cells were treated with Cisplatin alone with Secukinumab, and cell viability (MTT assay), combination index, and apoptosis-related markers were analyzed. Results: Secukinumab administration lowered serum levels of BUN, creatinine and LDH with marked elevation in renal TAC and a significant reduction in MDA, iNOS, KIM-1 and NGAL compared to Cisplatin. Additionally, Secukinumab pre-treatment markedly suppressed the inflammatory process and enhanced autophagy, reflected by elevated AMPKα1, SIRT1, and Beclin-1, accompanied by reduced P38 MAPK and NF-κB p65 (Phospho-Ser536) levels and expression levels of IL-6 and P62/SQSTM1 in kidney tissues, contrasted with the Cisplatin group. Secukinumab administration effectively protected against kidney injury, and histopathological examinations of the kidneys confirmed these results. On the other hand, in vitro study results revealed that the combination of Cisplatin and Secukinumab had a synergistic cytotoxic effect and an enhancing effect on the apoptotic pathway (increased P53 and BAX and decreased BCL-2). Secukinumab effectively protects against Cisplatin- induced acute kidney injury by decreasing oxidative stress, inflammation, and enhancing autophagy. Additionally, it synergizes with Cisplatin in vitro to promote cancer cell apoptosis, highlighting its dual reno-protective and anticancer potential. Full article

Background/Objectives: To determine the effect of single-dose hemodialysis treatment on the inner ear in patients with normal hearing functions using the Distortion product otoacoustic emissions (DPOAE) test. Methods: A total of twenty-four (24) patients with end-stage renal disease were included in the study. For all patients, the DPOAE test was performed immediately before hemodialysis and 3 h after hemodialysis. Both amplitude and signal-to-noise ratio (SNR) values were compared. Results: Compared to pre-dialysis values, the DPOAE test showed a statistically significant decrease in both amplitude and SNR values at all frequencies (1000, 2000, 4000 and 6000 Hz) in patients’ post-dialysis measurements. Conclusions: A single hemodialysis treatment has been found to have an adverse effect on cochlear function at both low and high frequencies. Full article

Parkinson’s disease (PD) and acute kidney injury (AKI) are two conditions with increasing prevalence and severe systemic complications and consequences. This research examines the combined neuroprotective and nephroprotective properties of three medicinal plants, Mucuna pruriens (Muc), Moringa oleifera (Mor), and Silybum marianum (SM), in a murine model of PD, AKI, and their comorbid state (PD–AKI), highlighting the role of the PI3K/AKT/mTOR and Nrf2/NF-κB signaling pathways. The mice were grouped as PD, AKI, or PD-AKI, and with or without the herbal pre-treatment, along with their respective controls. Motor impairments were assessed using the rotarod and pole climb assays. Biochemical indicators of renal function, oxidative stress markers, and inflammatory cytokines were quantified in kidney and brain tissues. Assessment of Nrf2, NF-κB, PI3K, AKT, and mTOR expression levels was performed using qRT-PCR. The AKI groups had significant renal impairment (4-fold increase in creatinine and 7.5-fold increase in BUN), oxidative stress (~5.5-fold increase), and increased cytokine levels (~1.5-fold increase), with downregulation of the PI3K/AKT/mTOR (~2-fold decrease) and Nrf2 signaling pathways (~1.8-fold decrease), alongside upregulation of NF-κB (~2.5-fold increase). The PD and PD-AKI groups exhibited significant neuroinflammation (~1.5-fold increase) and redox imbalance (~6-fold increase) in brain tissue, accompanied by motor impairments (1.6 to 4.6-fold decrease). Pre-treatment with Muc, Mor, and SM significantly ameliorated renal impairments (3.5-fold decrease in creatinine and ~5-fold decrease in BUN) and neurological deficits. These findings establish Muc, Mor, and SM extracts as potent, multi-target interventions capable of disrupting the feed–forward cycle of neuro-renal damage. Full article

Background and Objectives: The presence of comorbidities in both the pre- and post-diagnostic periods is a critical consideration in the diagnosis and management of patients with cancer. This study aimed to investigate the prevalence and burden of pulmonary and extrapulmonary comorbidities in patients diagnosed with lung cancer (LC) and malignant pleural mesothelioma (MPM). Materials and Methods: The data were obtained from official patient records of the Turkish Ministry of Health. Patients diagnosed with either lung cancer (LC) or malignant pleural mesothelioma (MPM) between 2015 and 2018 were included in the study. Comorbidities were classified as pulmonary or extrapulmonary. Results: A total of 74,835 patients with LC and 1678 patients with MPM were included. The burden of comorbid conditions increased significantly in the post-diagnostic period in both males and females across both cancer types. When the two cancer groups were compared with respect to diagnostic periods, comorbidities such as hypertension (HT), phlebitis/venous thrombosis/thrombophlebitis, pulmonary embolism, pneumothorax, and pleural effusion were significantly more prevalent in the MPM group (p < 0.05). Compared with the pre-diagnostic period, the comorbidity risk in LC was highest for pulmonary embolism, ARF, and pneumonia in the post-diagnostic period, whereas renal failure was the most frequent comorbidity in the MPM group (p < 0.001 and p = 0.024). When comparing changes in comorbidity burden between sexes in the lung cancer group, male patients had higher frequencies of pulmonary embolism, pneumonia, pneumothorax, and coronary artery disease than females. In contrast, in the female lung cancer group, the prevalence of chronic renal failure was higher than in males (OR = 2.14 vs. 2.00), whereas acute renal failure was more prominent in the male patient group (OR = 2.64 vs. 1.94). In gender-based comparison of comorbid conditions among patients with MPM, the risk of renal failure was higher in females than in males (CRF and ARF respectively: OR = 2.63 vs. 2.16 and OR = 6.80 vs. 5.44). Additionally, increased rates of COPD were observed in male patients within this group (OR = 1.93 vs. 1.81). Conclusions: Patients with LC and MPM are burdened not only by their primary malignancies but also by a wide spectrum of comorbidities, particularly in the post-diagnostic period. Comprehensive knowledge of comorbid conditions is essential for clinicians to guide clinical decision-making, anticipate disease progression, and optimize treatment strategies, thereby informing national healthcare policies. Future studies incorporating matched control groups or longitudinal designs with standardized surveillance protocols may help conduct better research. Full article

Diabetes complications may increase frailty rates among the elderly, leading to falls, immobility, dependency, hospitalizations, and death. The study aimed to assess any association between frailty status and glycaemic control among older adults with type 2 diabetes mellitus at Kenyatta National Hospital, Kenya. We conducted a cross-sectional study of 430 older individuals aged 60+ years with type 2 diabetes at a specialized diabetes clinic using a modified FRAIL scale. Mean age was 69.1 years; 65.7% were female and 76.2% completed primary school. Frailty prevalence was 3.8%, pre-frailty constituted 24.3%, and robust/non-frail comprised 71.9%. It was associated with age, social status, health knowledge, duration of DM, blood pressure, body mass index, high-density lipoprotein-C, and renal failure. Mean fasting plasma glucose (FPG) was 8.7 mmol/L, with 60% having FPG > 7 mmol/L; mean glycated haemoglobin (HbA1C) was 8.0%, with 41% having HbA1C > 8%. Glycaemic control was correlated with number of medications, blood pressure, and lipidaemia, but not age, sex, or social status. No correlation was found between frailty and glycaemic control: frailty versus FPG (r = 0.038, p = 0.459; χ² = 0.699, p = 0.705) and HbA1C (r = −0.009, p = 0.877; χ² = 0.046, p = 0.977). Low frailty prevalence was noted, with no association to glycaemic control. Our findings provide evidence for conducting frailty assessments in chronic disease care. Full article

Background/Objectives: Candidates with cardiometabolic risk are considered for living kidney donation more frequently because of the global organ shortage. The 2017 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines introduced individualized risk assessment based on composite donor profiles rather than categorical exclusion, but the long-term implications of accepting donors with potential risk factors require careful evaluation. This review synthesizes current evidence on outcomes of living kidney donors with obesity, prediabetes, hypertension, and smoking. Methods: A literature search was conducted in PubMed/MEDLINE for studies published between 1 January 2000 and 28 February 2026, including cohort studies, registry analyses, meta-analyses, and clinical guidelines evaluating living kidney donors with obesity, smoking, prediabetes, or hypertension. Priority was given to large cohorts with long-term follow-up. Over 70 publications were included in the final synthesis. Findings were synthesized narratively by risk factors and outcomes. Results: Obesity was associated with an 86% increased end-stage kidney disease (ESKD) risk and 32% increased 20-year mortality. Central adiposity measures outperformed body mass index (BMI) for predicting estimated glomerular filtration rate (eGFR) decline. Post-donation weight gain increased the risk for developing hypertension and diabetes. Smoking conferred a 7.5-fold chronic kidney disease (CKD) risk, with impaired compensatory renal adaptation after donation. Prediabetic donors showed comparable outcomes to normoglycemic donors, with 57.8% reverting to normoglycemia at 10 years. Pre-donation hypertension increased 15-year ESKD risk 3-fold, but absolute risk remained low. At 15 years post-donation, over 50% of the donors developed hypertension. Glucagon-like peptide-1 (GLP-1) receptor agonists reduce diabetes progression by 73–94% in at-risk populations, but prospective studies in donors are lacking. Conclusions: Each risk factor carries quantifiable risks for individualized stratification. These risk factors usually coexist and interact. Refinement of risk prediction models, strategies for metabolic optimization and prospective evaluation of emerging pharmacologic therapies are key priorities. Full article

Background: Fibroblast growth factor-23 (FGF23) is a key regulator of phosphate homeostasis and an emerging biomarker in cardiovascular disease. Emerging data suggest that FGF23 may also contribute to the pathophysiology of myocardial infarction (MI), but existing studies have largely focused on non-acute stages. To address this gap, we investigated early FGF23 regulation by characterizing serum concentration kinetics over the first 24 h following MI, using both a clinical MI model (TASH) and a cohort of patients with ST-elevation myocardial infarction (STEMI). Methods: Circulating FGF23 concentrations (cFGF23; RU/mL) were determined by C-terminal ELISA in patients with preserved renal function (eGFR > 30 mL/min/1.73 m²). TASH (transcoronary septal ablation) was carried out in patients with hypertrophic obstructive cardiomyopathy (n = 38). Venous serum samples were taken at baseline (pre-TASH) and at 30′, 60′, 2 h, 4 h and 24 h post-TASH. For the STEMI cohort (n = 18), serum was sampled immediately before and 3 h after coronary recanalization. All samples were processed using standardized procedures prior to analysis. Changes over time were assessed using the Friedman test with Bonferroni-corrected pairwise Wilcoxon comparisons. Results: FGF23 concentrations changed significantly over time after TASH (Friedman test, p < 0.000001, Kendall’s W = 0.518). Baseline FGF23 was 28.9 (19.4–71.0) RU/mL and increased significantly at 30′ (68.2 (36.2–178.7) RU/mL, adjusted p < 0.0001 **) after TASH. Concentrations remained elevated at 60′ (54.8 (31.6–118.3) RU/mL; adjusted p = 0.0019 *), returned to baseline at 2 h (30.9 (20–71.2) RU/mL; adjusted p = 1.0 vs. baseline) and decreased significantly below baseline at 4 h (24 (12.13–37.5) RU/mL, adjusted p = 0.0215 *). By 24 h, FGF23 had returned to baseline levels (28.8 (12.8–57.3) RU/mL; adjusted p = 1.0 vs. baseline). Although concentrations were numerically higher than at the 4 h nadir, this recovery did not reach statistical significance (adjusted p = 0.136 vs. 4 h). In STEMI patients, a non-significant decrease was observed from baseline (27 (15.5–35.75) RU/mL) to 3 h after recanalization (15.5 (6.75–34.25) RU/mL; p = 0.074, effect size r = 0.422). In an exploratory normalized analysis, the decline reached significance (p = 0.0241). Conclusions: The triphasic kinetics of circulating FGF23 in TASH patients—characterized by an early rise, transient undershoot, and a recovery toward baseline with a continuing upward trend—are consistent with a dynamic release-and-clearance pattern following myocardial injury. These findings are hypothesis-generating and warrant further investigation in larger cohorts with additional biomarkers to elucidate the source, regulation, and potential functional significance of FGF23 in the acute phase of myocardial infarction. Full article