Search Results (977)

Background/Objectives: Atrasentan is a selective endothelin A receptor antagonist (SERA) developed as a potential therapy for chronic renal diseases, including diabetic nephropathy and immunoglobulin A nephropathy. Despite this potential, understanding its metabolic bioactivation is essential for assessing the risks of drug-induced liver injury (DILI). However, the metabolic profile of atrasentan remains poorly characterized, and the mechanisms underlying its potential hepatotoxicity remain underexplored. Therefore, this study aims to investigate the metabolic pathways of atrasentan in human liver microsomes (HLMs) in the presence of nicotinamide adenine dinucleotide phosphate (NADP⁺), uridine diphosphate glucuronic acid (UDPGA), or glutathione (GSH). Methods: A liquid chromatography–high resolution mass spectrometry (LC-HRMS) coupled with a feature-based molecular networking approach was used to characterize metabolites. Characterization of the major metabolites was achieved through cytochrome P450 (P450) phenotyping with human recombinant P450 isoforms. Results: A total of eighteen metabolites were characterized through phase I and II metabolic reactions, including demethylenation, N-dealkylation, O-demethylation, hydroxylation, dehydrogenation, and glucuronidation. Atrasentan acyl glucuronide (M8) was confirmed as the predominant metabolite, and we also putatively annotated a catechol intermediate (M5) and its corresponding GSH conjugate (M15). Characterizing the GSH conjugate (M15) indicates that catechol intermediate (M5) can be further oxidized to a reactive ortho-quinone intermediate, which is subsequently trapped by GSH, suggesting the potential for a bioactivation mechanism. Reaction phenotyping demonstrated that the formation of M5 is catalyzed almost exclusively by the CYP3A subfamily. However, its direct translation to in vivo oxidative stress or covalent protein binding requires further studies. Conclusions: These findings demonstrate that feature-based molecular networking is a valuable strategy for metabolite characterization, underscoring the urgent need for further in vivo metabolism studies to definitively assess hepatotoxic risks associated with these reactive metabolites. Full article

Renal venous thrombosis (RVT) is a location of unusual-site venous thromboembolism. RVT occurs more commonly in males, and shows a bimodal age distribution, with a neonatal and adult peak. Abdominal malignancies and nephrotic syndrome are prominent risk factors in adults, whereas hypotension, birth asphyxia, sepsis, umbilical venous catheters and prematurity are the predominant causes in children. The most common symptoms of RVT include abdominal pain and macroscopic haematuria. A palpable abdominal mass is often observed in neonates, while antenatal RVT may present with signs of foetal distress. Bilateral RVT can lead to acute renal failure. Anticoagulation is the cornerstone of treatment, traditionally with unfractionated heparin, low molecular weight heparin and vitamin K antagonists, although recent evidence is emerging on the use of the direct oral anticoagulants in selected RVT patients. Endovascular procedures (e.g., local thrombolysis or mechanical thrombectomy) are usually reserved for more severe cases, such as bilateral acute RVT causing kidney dysfunction. Outcome data show variability in mortality rates, with some adult cohorts reporting high mortality linked to underlying malignancies and other comorbidities. In paediatric cohorts, mortality is low, but RVT can lead to long-term complications, including kidney atrophy, kidney dysfunction and hypertension. This narrative review aims to synthesise the current evidence on RVT, with a particular focus on anticoagulant prophylaxis and treatment, and clinical outcomes in adult and paediatric populations. Full article

Introduction: Cryoablation is an established nephron-sparing option for small renal masses, particularly in patients unsuitable for surgery. However, definitive histopathological assessment post-ablation is limited due to the in situ nature of treatment. This report details a case of delayed partial nephrectomy after cryoablation, enabling comprehensive histopathological evaluation of long-term treatment effects. Case presentation: A 50-year-old man with uncontrolled hypertension, diabetes, and triple-vessel coronary disease presented with a 2.5 cm right renal mass. Cardiovascular instability deferred initial surgery. Following coronary intervention requiring anticoagulation, percutaneous cryoablation was performed using CT-guided 3D reconstruction for precise probe placement and ice-ball confirmation. After 388 days, laparoscopic partial nephrectomy was performed. Histopathology revealed a 1.9 cm clear cell renal cell carcinoma. Approximately one-third of tissue showed post-cryoablation changes. Three distinct zones were identified: viable carcinoma, coagulative necrosis with preserved glomerular outlines, and viable parenchyma. Serial follow-up over 2 years showed transient creatinine elevation normalizing by 3 months, with no recurrence or metastasis. Conclusions: This case provides rare whole-lesion histopathological assessment after renal cryoablation, illustrating heterogeneous long-term tissue response and supporting cryoablation as a disease-control or bridging strategy in medically high-risk patients. Full article

Background: Nutritional therapy is central in the management of chronic kidney disease (CKD) and cancer, yet these conditions impose partially conflicting requirements. The 2024 KDIGO guideline recommends a controlled protein intake (~0.8 g/kg/day) to reduce metabolic burden in non-dialysis CKD patients, whereas the ESPEN (European Society for Clinical Nutrition and Metabolism) guidelines support higher protein intake (≥1.0–1.5 g/kg/day) to prevent cancer-related malnutrition. Evidence guiding patients affected by both conditions is limited. We evaluated the effects of a Mediterranean-like controlled protein diet in onconephrological patients compared with CKD controls. Methods: In this retrospective study, 358 CKD patients (183 onconephrological, 175 controls) were followed at a tertiary center (2017–2024). Patients received a protein-controlled diet (0.6–1.0 g/kg/day) tailored to comorbidities and nutritional status. Nutritional assessment included bioelectrical impedance analysis and anthropometry. Renal function was evaluated using creatinine and cystatin C, and measured GFR by iohexol clearance at baseline and 12 months. Results: Baseline body composition was comparable between groups. After intervention, serum urea significantly decreased in both groups, without a decline in measured or estimated GFR. Fat mass and central adiposity indices were reduced, while lean mass and phase angle remained stable. No evidence of protein–energy wasting or catabolic activation emerged. Longitudinal analyses showed no significant time × cancer interaction for renal function or most bioimpedance-derived body composition parameters. However, at extended follow-up, arm circumference and tricipital skinfold thickness showed significant time × cancer interactions, suggesting different longer-term peripheral anthropometric trajectories according to cancer status. Conclusions: In this retrospective real-world cohort, structured nephro-nutritional management with an individualized Mediterranean-like controlled protein prescription was associated with preserved renal function and no evidence of overt nutritional deterioration in onconephrological patients. These findings support the feasibility and apparent safety of this approach in selected patients, while highlighting the need for prospective studies with objective dietary adherence assessment and longer-term evaluation of cancer-related anthropometric trajectories. Full article

Background: Septic Charcot neuroarthropathy is a limb- and life-threatening condition characterized by the coexistence of neuropathic joint destruction and infection. In patients with severe systemic compromise, major amputation is often considered inevitable. Case Presentation: A 47-year-old man with untreated diabetes mellitus presented with progressive painless swelling of the left foot. He had morbid obesity (120 kg, 165 cm; body mass index 44.1 kg/m²), severe hypoalbuminemia, and chronic kidney disease associated with nephrotic syndrome. Laboratory tests showed marked inflammation and poor glycemic control, and blood cultures were positive for methicillin-resistant Staphylococcus aureus (MRSA). Radiographs and computed tomography demonstrated destructive changes involving the talonavicular and subtalar joints, consistent with septic Charcot neuroarthropathy involving the midfoot. Because of sepsis, pulmonary edema, and heart failure, below-knee amputation was proposed at the referring hospital. However, limb salvage was attempted using aggressive debridement, continuous local antibiotic perfusion (CLAP; gentamicin 1200 μg/mL) administered for 14 days, and temporary circular external fixation. Serum gentamicin concentrations and renal function were regularly monitored to ensure systemic safety and avoid nephrotoxicity. Results: Repeat irrigation and final debridement were performed 20 days after the index surgery, at which time the external fixator was removed and intraoperative cultures were negative. The patient was discharged 2 months after surgery without evidence of recurrent infection. At 4-year follow-up, no recurrence had occurred, and the patient was able to walk independently. Conclusions: Limb salvage may be feasible even in severely compromised patients with septic Charcot midfoot and MRSA bacteremia when aggressive debridement, CLAP, and temporary external fixation are combined with careful systemic safety monitoring. This case suggests that limb salvage may be considered in selected high-risk patients, although further studies are required. Full article

Background and Clinical Significance: Clear cell renal cell carcinoma (ccRCC) is notorious for its aggressiveness and great propensity to metastasize to virtually any organ, with a dismal five-year survival rate. While metastases from ccRCC typically occur in the lungs, lymph nodes, bones and liver, involvement of atypical locations such as the breast, pituitary gland and stomach is extremely rare. These unusual metastases can masquerade as primary tumours at their respective sites, posing significant diagnostic challenges. Case Presentation: Here, we describe three cases of metastatic ccRCC to unusual anatomical sites following nephrectomy: (1) a patient who presented with a suspicious left-sided breast mass and synchronous liver and lung metastases six months following the initial diagnosis of ccRCC; (2) a patient who presented with diplopia, found to have a pituitary lesion four months after nephrectomy; and (3) a patient with known pre-existing lung metastases who developed upper gastrointestinal bleeding one year post-nephrectomy, in whom oesophagogastroduodenoscopy (OGDS) revealed an 8 mm pedunculated gastric polyp. Histopathological examination following biopsies of these lesions showed compact nests and sheets of malignant cells with clear to eosinophilic cytoplasm and distinct membranes. Immunohistochemically, these malignant cells demonstrated CD10 immunopositivity, and were negative for CK7 and CK20, in keeping with the diagnosis of metastatic ccRCC. Conclusions: This case series illustrates the rare metastatic behaviour of ccRCC with its potential to spread to uncommon sites. Awareness of such presentations is crucial, particularly in patients with a known history of ccRCC, as these lesions may clinically and radiologically mimic primary tumours of the affected sites. Careful evaluation of its histomorphological features and judicious use of immunohistochemical panels, together with clinical and radiological correlations, is the key to arriving at an accurate diagnosis. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder associated with insulin resistance, β-cell dysfunction, and systemic complications. Methods: In this preliminary study, the metabolic effects of BE-FD-1, a water extract of Raphanus sativus L. leaves cultivated under a mineral-fortification protocol, were investigated in a high-fat-diet/streptozotocin (HFD/STZ)-induced diabetic mouse model. Inductively coupled plasma mass spectrometry analysis confirmed the presence of vanadium, chromium, magnesium, zinc, and calcium in radish leaf. Male C57BL/6 mice (n = 5/group) were orally administered BE-FD-1 at 250 or 500 mg/kg once daily for four weeks, with metformin (250 mg/kg) as a positive reference. Results: BE-FD-1 at 500 mg/kg significantly reduced the oral glucose tolerance test area under the curve and fasting blood glucose levels, significantly restored serum insulin levels, and significantly decreased serum ALT, triglyceride, and total cholesterol levels relative to the HFD/STZ control group. Body weight gain and AST showed non-significant decreasing tendencies. Serum creatinine remained within the normal range, providing a preliminary safety signal that should be interpreted with caution given the absence of additional renal biomarkers and histopathological evaluation. Conclusions: These exploratory findings suggest that BE-FD-1 may warrant further investigation as a candidate functional ingredient for T2DM-related metabolic dysfunction; however, larger studies with comprehensive phytochemical characterization, mechanistic validation, and broader safety evaluation are required. Full article

Background: Obesity is increasing worldwide and remains a major contributor to cardiovascular morbidity and mortality. It is strongly associated with hypertension, dyslipidemia, diabetes mellitus, endothelial dysfunction, and chronic inflammation, all of which promote coronary artery disease and acute coronary syndrome (ACS). Despite this well-established risk profile, multiple studies have described an “obesity paradox,” suggesting that obese patients may experience better outcomes after percutaneous coronary intervention (PCI) for ACS than normal-weight individuals. Objective: This narrative review aims to discuss the pathophysiological basis of the obesity paradox and to synthesize contemporary evidence regarding the relationship between body mass index (BMI), major adverse cardiovascular events (MACE), and mortality after PCI in patients presenting with ACS. Results: Contemporary observational cohorts consistently suggest a non-linear relationship between BMI and MACE outcomes after PCI. Overweight and mildly obese patients often demonstrate lower crude mortality and fewer MACE, whereas underweight patients consistently show the poorest prognosis. However, after adjustment for age, left ventricular ejection fraction (LVEF), renal function, frailty, and nutritional status, obesity is less consistently associated with improved outcomes. Overweight status appears to be more reproducibly associated with better prognosis than obesity itself. Conclusions: The obesity paradox is likely driven less by a true protective effect of excess adiposity and more by younger age at presentation, preserved physiological reserve, lower frailty burden, and the limitations of BMI as a marker of cardiovascular risk. Underweight status emerges as the strongest predictor of adverse outcomes. Nutritional assessment and body composition should complement BMI in risk stratification after ACS. Full article

Background: Distinguishing diabetic nephropathy (DN) from non-diabetic kidney disease (NDKD) in patients with diabetes remains clinically challenging, particularly when renal biopsy is not routinely performed. We aimed to identify clinical predictors of biopsy-proven NDKD. Methods: We conducted a retrospective cohort study of patients with type 2 diabetes who underwent native kidney biopsy at a tertiary referral center. Patients were classified as DN alone, mixed DN with NDKD, or pure NDKD. Baseline clinical and laboratory variables were analyzed. Logistic regression models were used to identify factors associated with NDKD. Results: Among 664 patients, 18.7% had DN alone, 27.0% had mixed lesions, and 54.3% had pure NDKD. In multivariable analysis, higher HbA1c, lower body mass index, lower low-density lipoprotein cholesterol, and higher urine albumin-to-creatinine ratio were independently associated with NDKD. For pure NDKD, lower HbA1c, lower serum albumin, lower body mass index, higher IgA levels, and absence of hypertension were significant predictors. Conclusions: NDKD is common among patients with diabetes undergoing biopsy and can be partially predicted using routinely available clinical parameters. These findings may aid in identifying patients who could benefit from timely renal biopsy and individualized management. Full article

Background/Objectives: Although creatine (Cr) supplementation is well established for enhancing strength exercise adaptations, limited evidence exists regarding whether the timing of a single Cr dose relative to exercise acutely influences performance and related physiological and perceptual responses. This study examined whether the timing of a single dose of Cr ingestion relative to a strength exercise session influences acute strength and power performance, cognitive function, perceptual responses, and selected blood biomarkers in physically active men. Methods: In a randomized, placebo-controlled crossover design, 11 physically active men (26.09 ± 4.39 years) completed five experimental conditions: Cr ingested before exercise (CrB), during exercise (CrD), and after exercise (CrF), placebo (PL), and a no-supplement control. Participants ingested 0.1 g·kg⁻¹ body mass of monohydrate Cr or placebo. Each condition included a standardized strength training session, where bench press (BP) and back squat (BSQ) performance was assessed as the total external load lifted (kg) across six sets performed at 80% of 1-RM for each exercise. Countermovement jump (CMJ) performance, Profile of Mood States (POMS), cognitive performance (digit cancelation test), perceived exertion (RPE), perceived recovery scale (PRS), Delayed-Onset Muscle Soreness (DOMS), and blood markers of muscle damage and renal function were assessed after the resistance training session. Data were analyzed using repeated-measures ANOVA or non-parametric equivalents, with post hoc comparisons adjusted for multiple testing. Results: There was a significant main effect of condition for both BP (F = 4.91, ηp² = 0.33, p = 0.035) and BSQ performance (F = 33.22, ηp² = 0.77, p < 0.001), with greater performance under the CrB condition compared with PL and control (p < 0.05). A significant effect of condition was also observed for creatine kinase (χ² (4) = 12.22, p = 0.016) and creatinine concentrations (χ² (4) = 17.75, p = 0.001). Blood creatine kinase concentrations were greater under CrF conditions than control (p = 0.013) and PL (p = 0.041). Moreover, creatinine concentration was lower under the CrB condition compared to CrD (p = 0.033), CrF (p = 0.003), and the control (p = 0.021). No differences were observed for CMJ performance, cognitive performance, POMS, RPE, PRS, DOMS, or the remaining biochemical markers across treatments. Conclusions: Pre-exercise creatine ingestion (without loading phase) was associated with greater acute strength performance compared with other timing conditions. However, the findings are exploratory and have to be confirmed with a higher sample size and robust placebo/control structures. Full article

Objective: This study aimed to investigate the impact of elevated CRP on survival outcomes in small renal masses (SRM). Methods: This was a multi-institutional retrospective analysis of SRM (≤3 cm) managed surgically. The cohort was divided into elevated CRP (≥0.5 mg/dL) vs. non-elevated CRP groups (<0.5). The primary outcome was all-cause mortality (ACM). The secondary outcomes were non-cancer (NCM) and cancer-specific mortality (CSM). Cox-regression analysis was used to elucidate predictive factors for mortality outcomes. Kaplan–Meier Analysis (KMA) was performed to analyze 10-year overall (OS), cancer-specific (CSS) and non-cancer-specific survival (NCS). Results: A total of 1001 patients were analyzed (309 non-elevated CRP/692 elevated CRP; median follow-up 70 months). Elevated CRP was an independent predictor for ACM (HR = 2.60, p < 0.001) NCM (HR = 2.90, p = 0.002), and CSM (HR = 1.20, p = 0.011). KMA comparing elevated vs. non-elevated groups revealed greater 10-year OS (p < 0.001) and NCS (p < 0.001) for non-elevated CRP, but no significant difference in 10-year CSS (p = 0.295). A total of 83 deaths were observed in elevated CRP (71 NCM/12 CSM—all clear-cell histology). The sensitivity/specificity of elevated CRP was 0.87/0.33, 0.75/0.81, and 0.90/0.33 for ACM, CSM, and NCM. By utilizing CRP for a decision-making algorithm prioritizing biopsy in CRP elevation and offering surveillance in benign or indolent histology, surgery may be avoided in 218 patients, in whom there were 38 fatalities, all NCM. Conclusions: Elevated CRP was an independent predictor of survival outcomes in SRM ≤ 3 cm. From a competing mortality standpoint, patients with elevated CRP had significantly worsened NCM compared to CSM. In such patients, upfront oncologic risk stratification through biopsy may be considered, and indolent/low-grade neoplasms should be strongly considered for non-surgical management. Full article

Background/Objectives: Type 2 diabetes is a group of metabolic disorders whose pathophysiological outcome is sustained hyperglycemia. Several medications are available for the treatment. SGLT2 simultaneously inhibits glucose and sodium reabsorption in the renal proximal tubule, resulting in urinary glucose excretion. This study assessed the pharmacokinetic profiles of two empagliflozin 25 mg drug products under fasting conditions in healthy Mexican subjects to establish bioequivalence. Methods: This was a randomized, open-label, two-way crossover, single-dose, prospective study with a 7-day washout period. Eligible subjects were healthy adult Mexican volunteers. The drugs were dosed orally, according to the randomization, after 10 h of fasting and 4 h before breakfast, with 250 mL of 10% glucose solution at room temperature. Serial blood samples were collected before and after dosing. Empagliflozin concentrations were analyzed using high-performance liquid chromatography–tandem mass spectrometry. Results: A total of 32 subjects were enrolled, and 30 completed the study. Pharmacokinetic parameters C_max, t_max, AUC_0–t, AUC _0–∞, and t_½ of empagliflozin for test and reference formulation, expressed as mean ± SD, were 578.28 ± 125.60 ng/mL, 2.72 ± 0.85 h, 4370.88 ± 769.50 ngh/mL, 4423.93 ± 776.02 ngh/mL, 7.62 ± 0.83 h, and 593.99 ± 156.78 ng/mL, 2.86 ± 1.00 h, 4313.24 ± 885.02 ngh/mL, 4368.04 ± 887.75 ngh/mL, and 7.61 ± 0.68 h, respectively. The 90% CI for C_max, AUC_0–t, and AUC _0–∞ were 98.30 [92.72–104.22], 101.72 [98.77–104.77], and 101.64 [98.73–104.63], respectively. Serious adverse events were not observed. Conclusions: Our study demonstrated bioequivalence between the empagliflozin formulations tested in healthy subjects under fasting conditions. Full article

The clinical management of nutrition in acute and chronic diseases requires an integrated understanding of the interactions between energy intake, dietary protein, and amino acids (AAs). Many conditions (including sepsis, major trauma, cancer cachexia, chronic heart failure, chronic obstructive pulmonary disease, renal and liver failure, autoimmune diseases, and aging) share a common pathophysiological feature: the hypercatabolic state (HCS). HCS is characterized by systemic inflammation and neuroendocrine activation that increase basal metabolic rate, induce insulin resistance, and accelerate skeletal muscle proteolysis, leading to negative nitrogen balance, sarcopenia, and cachexia. Under these conditions, skeletal muscle acts as a metabolic reservoir of AAs mobilized to support energy production, gluconeogenesis, immune function, and vital organ metabolism, often at the expense of lean body mass and clinical outcomes. This narrative review examines the distinct and non-overlapping roles of calories, proteins, and AAs in metabolic regulation, with a particular focus on HCS. Calories primarily act as a permissive factor for protein utilization, whereas proteins and especially essential amino acids (EAAs) function not only as substrates for protein synthesis but also as signaling molecules (metabokines) regulating anabolic and catabolic pathways, including mTORC1 and AMPK. Energy provision alone is insufficient to prevent muscle loss when EAA availability is inadequate, while high protein intake without sufficient energy fails to sustain anabolism due to anabolic resistance. Evidence indicates that protein quality and the balanced availability of all EAAs are more critical for lean mass preservation than total caloric intake alone. Strategies based solely on calorie provision or protein quantity are therefore limited, whereas targeted EAA supplementation may partially overcome anabolic resistance in selected hypercatabolic conditions. Overall, this review supports a shift from calorie-centered nutrition toward a signal-based, quality-oriented approach, based on personalized needs, that integrates metabolic status, protein quality, and AA signaling to preserve lean body mass and improve clinical outcomes. Full article

Background: Diabetic nephropathy (DN) is characterized by complex and region-specific metabolic dysregulation that is not captured by conventional biomarkers. However, the spatiotemporal organization of metabolic alterations across renal compartments in type 1 diabetes remains poorly understood. Methods: In this study, spatial metabolomics based on air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was applied to investigate metabolic alterations in kidney tissues from alloxan-induced diabetic rats at 4 and 8 weeks post-induction. Complementary LC–MS/MS metabolite profiling and label-free proteomic analysis were performed to support pathway interpretation. Results: Spatial metabolomics revealed pronounced region- and time-dependent metabolic reprogramming in diabetic kidneys. Early-stage (DN-4w) changes were characterized by elevated glucose and activation of glucose-associated pathways, including the polyol pathway, accompanied by accumulation of acylcarnitines and lipid intermediates, indicating metabolic substrate overload. At later stages (DN-8w), glucose and related metabolites declined, reflecting impaired metabolic capacity and mitochondrial dysfunction. Broad remodeling of lipid metabolism, including glycerophospholipids, fatty acids, and hexosylceramide, was observed, along with dysregulation of amino acid metabolism and redox-related pathways. These alterations exhibited clear regional heterogeneity across renal cortex and medulla, highlighting compartment-specific metabolic vulnerability. Conclusions: This study provides a comprehensive spatial characterization of metabolic perturbations during DN progression, revealing coordinated alterations in glucose utilization, lipid metabolism, and mitochondrial function. The findings demonstrate the value of spatial metabolomics in uncovering region-specific metabolic mechanisms and provide new insights into the pathogenesis of diabetic nephropathy. 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