Abstract Hyperkalemia (serum potassium >5.0 mEq/l) is a significant complication in patients with heart failure, chronic kidney disease, and diabetes mellitus, particularly when treated with renin-angiotensin-aldosterone system inhibitors (RAASi). Both hyperkalemia and RAASi interruption are associated with increased cardiovascular events, hospitalizations, and mortality. This expert opinion document, developed between January and December 2024 through a systematic process, aims to establish guidance for hyperkalemia treatment in Indonesian patients with cardiorenal diseases receiving RAASi therapy, addressing the unique challenges within the Indonesian healthcare context. A comprehensive literature review of international guidelines and regional studies was conducted by a panel of 11 expert specialists (3 cardiologists, 6 internist-nephrologists, and 2 internist-cardiologists), who evaluated 29 statements covering diagnosis, monitoring, prevention, and treatment of hyperkalemia. Of the 29 statements, 26 reached consensus: 17 statements achieved very high agreement (≥90%) and 9 attained high agreement (≥67% – <90%). The agreed statements covered key areas, including potassium monitoring frequency, RAASi dose optimization strategies, dietary modifications, and treatment thresholds. Three statements regarding alternative therapeutic approaches did not receive agreement (<67%) due to limited local availability and cost considerations. Key recommendations include structured monitoring protocols for high-risk patients, strategies for RAASi dose optimization while managing hyperkalemia risk, and specific interventions adapted to local resources. This document provides a practical approach for managing hyperkalemia in Indonesian patients with cardiorenal diseases while maintaining optimal RAASi therapy, considering local Indonesian healthcare resources and constraints.
Hyperkalemia ; Cardio-Renal Syndrome ; Renin-Angiotensin System ; Indonesia

Angiomyolipoma with epithelial cysts (AMLEC) is a rare subtype of angiomyolipoma that may closely mimic both malignant and benign neoplasms. We report a case of AMLEC in an 18-year-old female presenting with acute flank pain and radiologic suspicion for malignancy. This case highlights the diagnostic challenges posed by AMLEC, emphasizes its characteristic histopathologic and immunohistochemical features, and reviews current concepts regarding its pathogenesis. This case represents the first documented case of AMLEC in the Philippines.

Introduction: X-linked hypophosphatemia (XLH) is a rare genetic disorder caused by PHEX mutations, characterized by chronic hypophosphatemia and renal phosphate wasting, resulting in skeletal, dental, and extra-skeletal complications. To date, no data from Malaysia are currently available on clinical characteristics or health-related quality of life (HRQoL) in paediatric patients. Methodology: This cross-sectional study evaluated HRQoL among children and adolescents with XLH, using validated PROMIS (PatientReported Outcomes Measurement Information System) instruments, sociodemographic and clinical factors associated with HRQoL. This includes children and adolescents with confirmed XLH followed up at Universiti Malaya Medical Centre (UMMC) between November 2024 and March 2025. Results: Seventeen patients were analyzed (76.5% female and 23.5% male). The mean age at symptom onset was 2.82 ± 2.42 years, with a mean age at diagnosis of 5.21 ± 3.29 years. All patients continued to have musculoskeletal complications, including short stature (76.5%), bowing of legs (76.5%), bone/joint pain (47.1%), muscle pain (47.1%), and dental complications (52.9%). Serum alkaline phosphatase improved significantly (p = 0.011); persistent hypophosphatemia and ongoing musculoskeletal manifestations indicated suboptimal disease control. Elevated parathyroid hormone levels and an increase in urine calciumto-creatinine ratio (p = 0.020) lead to secondary hyperparathyroidism and nephrocalcinosis. Adherence to conventional therapy was poor. Non-adherence was associated with worse pain outcomes (higher pain interference [p = 0.037] and greater pain intensity [p = 0.025]). PROMIS scores revealed severely impaired mobility (mean T-score 31.31 ± 12.17), increased fatigue (mean T-score 54.22 ± 7.60), and high pain interference (mean T-score 63.11 ± 9.50). Larger household size was also strongly associated with higher pain intensity (p = 0.004). Conclusion Malaysian children and adolescents with XLH continue to have significantly poor HRQoL, particularly in mobility, fatigue, and pain. These findings highlight the need for access to targeted therapies, such as burosumab, to improve long-term outcomes and QOL in XLH patients.
Adolescent ; Child ; Familial Hypophosphatemic Rickets ; Malaysia ; Quality of Life

OBJECTIVES: Renal cell carcinoma (RCC) is a malignant renal tumor that poses a significant threat to patient health. Accurate preoperative pathological grading plays a crucial role in determining the appropriate treatment for this disease. Currently, deep learning technology has become an important method for pathological grading of RCC. However, existing methods primarily rely on single-phase computed tomography (CT) imaging for analysis and prediction, which has limitations such as missing small lesions, one-sided evaluation, and local focusing issues. Therefore, this study proposes a multi-modal deep learning algorithm that integrates multi-phase enhanced CT images with clinical variable data, aiming to provide a basis for predicting the pathological grading of RCC. METHODS: First, the algorithm took four-phase enhanced CT images from the plain scan, arterial phase, venous phase, and delayed phase, along with clinical variables, as inputs. Then, an embedding encoding module was used to extract heterogeneous information from the clinical variables, and a 3-dimensional (3D) ResNet50 model was employed to capture spatial information from the multi-phase enhanced CT image data. Finally, a Fusion module deeply integrated the feature information from clinical variables and each phase's CT image features, further utilizing a cross-self-attention mechanism to achieve multi-phase feature fusion. This approach comprehensively captures the deep semantic information from the patient data, fully leveraging the complementary advantages of multi-modal and multi-phase data. To validate the effectiveness of the proposed method, a total of 1 229 RCC patients were approved by ethics review were included to train the model. RESULTS: Experimental results demonstrated superior performance compared to traditional radiomics and state-of-the-art deep learning methods, achieving an accuracy of 83.87%, a recall rate of 95.04%, and an F1-score of 82.23%. CONCLUSIONS The proposed algorithm exhibits strong stability and sensitivity, significantly enhancing the predictive performance of RCC pathological grading. It offers a novel approach for accurate RCC diagnosis and personalized treatment planning.
Humans ; Carcinoma, Renal Cell/pathology* ; Deep Learning ; Kidney Neoplasms/diagnostic imaging* ; Tomography, X-Ray Computed/methods* ; Algorithms ; Neoplasm Grading ; Male ; Female ; Middle Aged

OBJECTIVES: To analyze the association of CHMP2B expression level of with clinicopathological characteristics and prognosis of clear cell renal cell carcinoma (CRCC) and the possible role of CHMP2B in tumorigenesis and progression of CRCC. METHODS: RNAseq data of CRCC were downloaded from the TCGA database for analysis of CHMP2B expression levels in tumor and adjacent tissues and their correlation with clinicopathological characteristics of the patients. Survival outcomes of the patients with high and low CHMP2B expressions were analyzed using the Kaplan-Meier model, and the COX risk regression model was used for identifying the prognostic factors of the patients. The correlation between CHMP2B expression and immune infiltration, its co-expressed genes, and the effect of CHMP2B gene mutations on immunotherapy responses, and its immunohistochemical expression in CRCC and normal tissues were analyzed. Clinical samples of CRCC were collected to examine CHMP2B expressions using RT-PCR, and cell experiment was carried out to test the effect of CHMP2B overexpression on biological behaviors of CRCC cells. RESULTS: CHMP2B was significantly under-expressed in renal cancer tissues, and its overexpression obviously inhibited the proliferation of CRCC cells in vitro. CHMP2B expression level was significantly correlated with age, gender, lymph node metastasis, and tumor stage, and the patients with low CHMP2B expression had poor survival outcomes. Enrichment and co-expression gene analyses suggested that CHMP2B was mainly involved in viral outgrowth, necrotic apoptosis, endocytosis, and immune-regulatory processes in kidney cancer. CONCLUSIONS CHMP2B is lowly expressed in renal cancer tissues to affect tumor progression and tumor immune processes, and may serve as a prognostic biomarker and therapeutic target for CRCC.
Humans ; Carcinoma, Renal Cell/metabolism* ; Kidney Neoplasms/metabolism* ; Cell Proliferation ; Prognosis ; Cell Line, Tumor ; Male ; Female ; Gene Expression Regulation, Neoplastic

OBJECTIVES: To identify potential molecular targets of quercetin in the treatment of clear cell renal carcinoma (ccRCC). METHODS: The therapeutic targets of quercetin were screened from multiple databases by network pharmacology analysis, and the targets significantly correlated with ccRCC were screened from 4907 plasma proteins using a Mendelian randomization method. The drug-disease network model was constructed to screen the potential key targets. The functions of these targets were evaluated via bioinformatics analysis, and the screened targets were verified in cultured ccRCC cells. RESULTS: Network pharmacology analysis combined with Mendelian randomization identified TP53 (OR=3.325, 95% CI: 1.805-6.124, P=0.0001), ARF4 (OR=0.173, 95% CI: 0.065-0.456, P=0.0003), and DPP4 (OR=0.463, 95% CI: 0.302-0.711, P=0.0004) as the core targets in quercetin treatment of ccRCC. Bioinformatics analysis showed that TP53 was highly expressed in ccRCC, and patients with high TP53 expressions had worse survival outcomes. Molecular docking studies showed that the binding energy between quercetin and TP53 was -5.83 kcal/mol. In cultured 786-O cells, CCK-8 assay and wound healing assay showed that treatment with quercetin significantly inhibited cell proliferation and migration. Quercetin treatment also strongly suppressed the expression of TP53 at both the mRNA and protein levels in 786-O cells as shown by RT-qPCR and Western blotting. CONCLUSIONS TP53 may be the key target of quercetin in the treatment of ccRCC, which sheds light on potential molecular mechanism that mediate the therapeutic effect of quercetin.
Humans ; Quercetin/pharmacology* ; Carcinoma, Renal Cell/genetics* ; Cell Proliferation/drug effects* ; Kidney Neoplasms/genetics* ; Cell Movement/drug effects* ; Tumor Suppressor Protein p53/metabolism* ; Cell Line, Tumor ; Computational Biology

OBJECTIVES: To evaluate the correlation of mean arterial oxygen tension (PaO₂) during the first 24 h following intensive care unit (ICU) admission with mortality in critically ill patients with acute kidney injury (AKI) and determine the optimal PaO₂ threshold for devising oxygen therapy strategies for these patients. METHODS: We collected the clinical data of ICU patients with AKI from the MIMIC-IV database. Based on the optimal first 24-h PaO₂ threshold determined by receiver operating characteristic (ROC) curve analysis and the Youden index maximization principle, we classified the patients into hyperoxia group (with PaO₂ ≥137.029 mmHg) and hypoxemia group (PaO₂<137.029 mm Hg). Multivariable logistic regression and propensity score matching were used to evaluate the correlation of first 24-h PaO₂ levels with in-hospital mortality of the patients. RESULTS: Among the 18 335 patients, 46.7% were in the hyperoxia group, who had an overall mortality rate of 16.9%. The optimal PaO₂ threshold (137.029 mm Hg) had a sensitivity of 78.3%, a specificity of 63.7%, and an AUC of 0.76 (95% CI: 0.74=0.78). Hyperoxia within the first 24 h after ICU admission was associated with a significantly lower in-hospital mortality (OR=0.78) and 90-day mortality (OR=0.77), particularly in stage 1 AKI patients. A non-linear relationship was identified between PaO₂ and mortality of the patients (P<0.001). Kaplan-Meier survival curves indicated a significantly increased 90-day survival rate in the patients in hyperoxia group (P<0.001), who also had shorter durations of mechanical ventilation, less vasopressor use, and shorter lengths of hospital/ICU stay. CONCLUSIONS Maintenance of a PaO₂ level ≥137.029 mmHg within 24 h after ICU admission may improve clinical outcomes of critically ill AKI patients, which underscores the importance of targeted oxygen delivery in ICU care.
Humans ; Acute Kidney Injury/blood* ; Male ; Female ; Middle Aged ; Intensive Care Units ; Aged ; Oxygen/blood* ; Hospital Mortality ; Partial Pressure ; Adult ; Databases, Factual

OBJECTIVES: To investigate the association of serum albumin level after human albumin infusion with 28-day mortality in critically ill patients with acute kidney injury (AKI) and its impact on 90-day outcomes of the patients. METHODS: We conducted a retrospective cohort study based on the MIMIC IV database (2008-2019), including 5918 AKI patients treated with albumin in the ICU. Based on serum albumin levels within 72 h after albumin infusion, the patients were divided into low (<30 g/L), medium (30-35 g/L), and high albumin (>35 g/L) groups. Restricted cubic spline regression and multivariate logistic regression were used to analyze the association of albumin levels with patient mortality, and the results were verified in a external validation cohort consisting of 110 sepsis-induced AKI patients treated in Nanfang Hospital between 2017 and 2022 using survival analysis and multivariate adjustment. RESULTS: In the MIMIC training cohort, multivariate logistic regression showed no significant differences in 28-day mortality of the patients with different albumin levels (P>0.05). However, restricted cubic spline analysis indicated a non-linear dose-response relationship between albumin levels and 28-day mortality (threshold effect: risk increased when albumin levels >3.6 g/dL). Secondary endpoint analysis revealed that the patients with high albumin levels had a shorter duration of mechanical ventilation (P<0.001) but a longer ICU stay (P<0.001). In the validation cohort, albumin levels ≥30 g/L were significantly associated with a reduced 28-day mortality rate (P<0.05). CONCLUSIONS The association between increased serum albumin levels following albumin infusion and 28-day mortality of critically ill patients with AKI exhibits a cohort dependency and can be influenced by multiple factors including disease type and severity, infusion strategies, and statistical methods.
Humans ; Acute Kidney Injury/therapy* ; Critical Illness/mortality* ; Retrospective Studies ; Serum Albumin/analysis* ; Male ; Female ; Intensive Care Units ; Middle Aged ; Logistic Models ; Aged

OBJECTIVES: To investigate the characteristics of immune cell infiltration in tumor samples from Chinese patients with clear cell renal cell carcinoma (ccRCC) and the correlation of immune cell infiltration with tumor stage and response to immunotherapy. METHODS: Tumor samples and clinicopathological data were collected from 154 ccRCC patients treated in Nanfang Hospital, Southern Medical University from October, 2020 to October, 2023. The immune cell types infiltrating the tumor tissues were identified using immunohistochemistry and immunofluorescence staining, and their correlations with the patients' clinicopathological characteristics were analyzed. Patient-derived tumor tissue fragment models (PDTF) models, constructed using tumor tissues from 22 patients, were treated with PD-1 monoclonal antibody, and T cell activation was detected using flow cytometry to assess the patients' responses to immunotherapy. RESULTS: In Chinese ccRCC patients included in this study, CD8⁺ T cells, CD4⁺ T cells, and CD3⁺ T cells were the most abundant in the tumor tissues. Higher infiltration levels of CD3⁺ T cells (P=0.004), PD-1⁺ T cells (P=0.020), CD68⁺ T cells (P=0.049), CD79⁺ T cells (P=0.049), and Tryptase⁺ cells (P=0.049) were all positively correlated with a larger tumor size (≥5 cm). A higher infiltration level of CD4⁺ T cells was associated with a lower tumor stage. Patients with higher International Society of Urological Pathology (ISUP) grades had higher infiltration levels of CD3⁺ T cells (P=0.023), CD8⁺ T cells (P=0.045), PD-1⁺ T cells (P=0.014), CD20⁺ B cells (P=0.020) and CD79⁺ B cells (P=0.049), and lower levels of Tryptase⁺ cells (P=0.001). Patients with abundant infiltrating immune cells tended to have better responses to immunotherapy. CONCLUSIONS The infiltrating immune cells are heterogeneous in Chinese ccRCC patients, and immune cell infiltration characteristics are closely correlated with clinicopathological parameters of the patients.
Humans ; Carcinoma, Renal Cell/pathology* ; Kidney Neoplasms/pathology* ; Immunotherapy ; Male ; Lymphocytes, Tumor-Infiltrating/immunology* ; Female ; Middle Aged ; CD8-Positive T-Lymphocytes/immunology* ; Aged ; T-Lymphocytes/immunology* ; Programmed Cell Death 1 Receptor/immunology* ; Adult ; CD4-Positive T-Lymphocytes/immunology* ; Neoplasm Staging

OBJECTIVES: To investigate the role of ferroptosis in diquat-induced acute kidney injury (AKI) and its molecular mechanisms. METHODS: Transgenic zebrafish models with Tg (Eco.Tshb:EGFP) labeling of the renal tubules and Tg (lyz:dsRed2) labeling of the neutrophils were both divided into control group, gentamicin (positive control) group, diquat poisoning group, ferroptosis inhibitor group. The indicators of kidney injury, inflammatory response, and ferroptosis were examined in the zebrafish, and the changes in expressions of voltage-dependent anion-selective channel protein 1 (VDAC1) and mitochondrial ferritin (FTMT) were detected using Western blotting. RESULTS: AKI induced by diquat exhibited a significant dose-effect relationship, and the severity of injury was proportional to the exposure concentration. Diquat also caused marked oxidative stress and inflammatory responses in the zebrafish models. Rhodamine metabolism assay and HE staining revealed significantly declined glomerular filtration function of the zebrafish as diquat exposure concentration increased. Immunofluorescence staining highlighted significant changes in the expressions of ferroptosis markers GPX4 and FTH1 in zebrafish renal tissues following diquat exposure. In diquat-exposed zebrafish, treatment with ferrostatin-1, a ferroptosis inhibitor, obviously upregulated GPX4 and downregulated FTH1 expressions and improved the metabolic rate of glucan labeled with rhodamine B. Diquat exposure significantly upregulated the expression of VDAC1 and FTMT in zebrafish, and the application of ferrostatin-1 and VBIT-12 (a VDAC1 inhibitor) both caused pronounced downregulation of FTMT expression. CONCLUSIONS Ferroptosis is a critical mechanism underlying diquat-induced AKI, in which VDAC1 and FTMT play important regulatory roles, suggesting their potential as therapeutic target for AKI caused by diquat.
Animals ; Zebrafish ; Ferroptosis/drug effects* ; Acute Kidney Injury/chemically induced* ; Diquat/toxicity* ; Animals, Genetically Modified ; Voltage-Dependent Anion Channel 1/metabolism* ; Ferritins/metabolism* ; Oxidative Stress