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Kidney Research and Clinical Practice May 2024Transferrin saturation (TSAT) has been used as an indicator of iron deficiency. However, there is no consensus regarding its optimal range for patient with chronic...
The association between transferrin saturation and all-cause mortality in chronic kidney disease: findings from Korean Cohort Study for Outcome in Patients with Chronic Kidney Disease.
BACKGROUND
Transferrin saturation (TSAT) has been used as an indicator of iron deficiency. However, there is no consensus regarding its optimal range for patient with chronic kidney disease (CKD). We aimed to analyze the effect of TSAT on the prognosis of patients with non-dialysis CKD (NDCKD).
METHODS
From 2011 to 2016, 2157 NDCKD patients with baseline TSAT measurements were followed for 10 years. Patients were divided into three groups based on baseline TSAT values: <25%, ≥25% and <45%, and ≥45%. All-cause mortality and 4-point major adverse cardiovascular events (MACE) were analyzed using multivariable Cox regression analysis. Other iron biomarkers and mortality were also analyzed.
RESULTS
During a mean follow-up of 7.1 ± 2.9 years, 182 of a total of 2,157 patients (8.4%) died. Compared with the TSAT ≥25% and <45% group, the TSAT <25% group showed significantly increased all-cause mortality (hazard ratio [HR], 1.44; 95% confidence interval (CI), 1.02-2.03; p = 0.04). The occurrence of 4-point MACE was significantly increased in univariable analysis in the TSAT <25% group (HR, 1.48; 95% CI, 1.02-2.15; p = 0.04), but it was not significant in the multivariable analysis (HR, 1.38; 95% CI, 0.89-2.15; p = 0.15). Tertile comparisons of the iron-to-log-ferritin ratio showed increased mortality in the first tertile group.
CONCLUSION
TSAT <25% is an independent risk factor for all-cause mortality in patients with NDCKD and care should be taken to prevent TSAT values of <25%. Other indicators, such as serum iron and iron-to-log-ferritin ratio, may also be used to assess iron deficiency.
PubMed: 38934042
DOI: 10.23876/j.krcp.23.278 -
Kidney Research and Clinical Practice Jun 2024Traditional acute kidney injury (AKI) classifications, which are centered around semi-anatomical lines, can no longer capture the complexity of AKI. By employing...
Traditional acute kidney injury (AKI) classifications, which are centered around semi-anatomical lines, can no longer capture the complexity of AKI. By employing strategies to identify predictive and prognostic enrichment targets, experts could gain a deeper comprehension of AKI's pathophysiology, allowing for the development of treatment-specific targets and enhancing individualized care. Subphenotyping, which is enriched with AKI biomarkers, holds insights into distinct risk profiles and tailored treatment strategies that redefine AKI and contribute to improved clinical management. The utilization of biomarkers such as N-acetyl-β-D-glucosaminidase, tissue inhibitor of metalloprotease-2•insulin-like growth factor-binding protein 7, kidney injury molecule-1, and liver fatty acid-binding protein garnered significant attention as a means to predict subclinical AKI. Novel biomarkers offer promise in predicting persistent AKI, with urinary motif chemokine ligand 14 displaying significant sensitivity and specificity. Furthermore, they serve as predictive markers for weaning patients from acute dialysis and offer valuable insights into distinct AKI subgroups. The proposed management of AKI, which is encapsulated in a structured flowchart, bridges the gap between research and clinical practice. It streamlines the utilization of biomarkers and subphenotyping, promising a future in which AKI is swiftly identified and managed with unprecedented precision. Incorporating kidney biomarkers into strategies for early AKI detection and the initiation of AKI care bundles has proven to be more effective than using care bundles without these novel biomarkers. This comprehensive approach represents a significant stride toward precision medicine, enabling the identification of high-risk subphenotypes in patients with AKI.
PubMed: 38934040
DOI: 10.23876/j.krcp.23.284 -
Kidney Research and Clinical Practice Jun 2024Acute kidney disease (AKD) is a critical transitional period between acute kidney injury and chronic kidney disease. The incidence of AKD following acute kidney injury...
Acute kidney disease (AKD) is a critical transitional period between acute kidney injury and chronic kidney disease. The incidence of AKD following acute kidney injury is approximately 33.6%, and it can occur without identifiable preceding acute kidney injury. The development of AKD is associated with increased risks of chronic kidney disease, dialysis, and mortality. Biomarkers and subphenotypes are promising tools to predict prognosis in AKD. The complex clinical situations in patients with AKD necessitate a comprehensive and structured approach, termed "KAMPS" (kidney function check, advocacy, medications, pressure, sick day protocols). We introduce "MAND-MASS," an acronym devised to summarize the reconciliation of medications during episodes of acute illness, as a critical component of the sick day protocols at AKD. A multidisciplinary team care, consisting of nephrologists, pharmacists, dietitians, health educators, and nurses, is an optimal model to achieve the care bundle in KAMPS. Although the evidence for patients with AKD is still lacking, several potential pharmacological agents may improve outcomes, including but not limited to angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, sodium-glucose cotransporter 2 inhibitors, and glucagon-like peptide 1 receptor agonists. In conclusion, accurate prognosis prediction and effective treatment for AKD are critical yet unmet clinical needs. Future studies are urgently needed to improve patient care in this complex and rapidly evolving field.
PubMed: 38934037
DOI: 10.23876/j.krcp.23.289 -
Kidney Research and Clinical Practice Jun 2024The reliability of presepsin as a biomarker of sepsis may be reduced in patients with acute kidney injury (AKI) requiring continuous kidney replacement therapy (CKRT)....
BACKGROUND
The reliability of presepsin as a biomarker of sepsis may be reduced in patients with acute kidney injury (AKI) requiring continuous kidney replacement therapy (CKRT). This study analyzed the utility of plasma presepsin values in predicting mortality in patients with AKI requiring CKRT, particularly those with sepsis-associated AKI.
METHODS
This single-center retrospective study included 57 patients who underwent CKRT, with plasma presepsin measurements, from April 2022 to March 2023; 35 had sepsis-associated AKI. The predictive values of plasma presepsin, as well as Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment (SOFA) scores, for 28-day mortality were analyzed using receiver operating characteristic curves. Multivariate Cox regression analysis was performed to identify risk factors for 28-day mortality in the sepsis-associated AKI subgroup.
RESULTS
Overall, plasma presepsin showed a lower area under the curve value (0.636; 95% confidence interval [CI], 0.491-0.781) than the APACHE II (0.663; 95% CI, 0.521-0.804) and SOFA (0.731; 95% CI, 0.599-0.863) scores did. However, in sepsis-associated AKI, the area under the curve increased to 0.799 (95% CI, 0.653-0.946), which was higher than that of the APACHE II (0.651; 95% CI, 0.450-0.826) and SOFA (0.697; 95% CI, 0.519-0.875) scores. In the multivariate Cox regression analysis, a high presepsin level was an independent risk factor for 28-day mortality in sepsis-associated AKI (hazard ratio, 3.437; p = 0.03).
CONCLUSION
Presepsin is a potential prognostic marker in patients with sepsis-associated AKI injury requiring CKRT.
PubMed: 38934036
DOI: 10.23876/j.krcp.23.301 -
Kidney Research and Clinical Practice Jun 2024Identifying risk factors and improving prognostication for mortality among patients with sepsis-associated acute kidney injury (AKI) undergoing continuous kidney...
Association between systemic inflammation biomarkers and mortality in patients with sepsis-associated acute kidney injury receiving intensive care and continuous kidney replacement therapy: results from the RENERGY (REsearches for NEphRology and epidemioloGY) study.
BACKGROUND
Identifying risk factors and improving prognostication for mortality among patients with sepsis-associated acute kidney injury (AKI) undergoing continuous kidney replacement therapy (CKRT) is important in improving the adverse prognosis of this patient population. This study aimed to compare the prognostic value of existing systemic inflammation biomarkers and determine the optimal systemic inflammation biomarker in patients with sepsis-associated AKI receiving CKRT.
METHODS
This multi-center, retrospective, observational cohort study included 1,500 patients with sepsis-associated AKI treated with intensive care and CKRT. The main predictor was a panel of 13 different systemic inflammation biomarkers. The primary outcome was 28-day mortality after CKRT initiation. Secondary outcomes included 90-day mortality after CKRT initiation, CKRT duration, kidney replacement therapy dependence at discharge, and lengths of intensive care unit (ICU) and hospital stays.
RESULTS
When added to the widely accepted Acute Physiology and Chronic Health Evaluation II score, platelet-to-albumin ratio (PAR) and neutrophil-platelet score (NPS) had the highest improvements in prognostication of 28-day mortality, where the corresponding increases in C-statistic were 0.01 (95% confidence interval [CI], 0.00-0.02) and 0.02 (95% CI, 0.01-0.03). Similar findings were observed for 90-day mortality. The 28- and 90-day mortality rates were significantly lower for the higher PAR and NPS quartiles. These associations remained significant even after adjustment for potential confounding variables in multivariable Cox proportional hazards models.
CONCLUSION
Of the available systemic inflammation biomarkers, the addition of PAR or NPS to conventional ICU prediction models improved the prognostication of patients with sepsis-associated AKI receiving intensive care and CKRT.
PubMed: 38934032
DOI: 10.23876/j.krcp.23.321 -
Kidney Research and Clinical Practice Jun 2024Acute kidney injury (AKI) is a significant challenge in healthcare, imposing a significant social burden. While there are considerable researches dedicated to AKI and...
BACKGROUND
Acute kidney injury (AKI) is a significant challenge in healthcare, imposing a significant social burden. While there are considerable researches dedicated to AKI and the recovery of AKI patients, a crucial factor in their prognosis, is often overlooked. Thus, our study aims to address this issue through the development of a machine learning-based approach to predict restoration of kidney function in patients with AKI.
METHODS
Our study encompassed data from 350,345 cases, derived from two hospitals. AKI was classified in accordance with the Kidney Disease: Improving Global Outcomes. Criteria for recovery were established as either a 33% decrease in serum creatinine levels at AKI onset or reduction to values lower than the baseline, which was initially employed for the diagnosis of AKI. We employed various machine learning models, selecting 43 pertinent features for analysis.
RESULTS
Our analysis contained 7,041 and 2,929 patients' data from internal cohort and external cohort respectively. The Categorical Boosting model demonstrated significant predictive accuracy, as evidenced by an internal area under the receiver operating characteristic curve (AUROC) of 0.7860, and an external AUROC score of 0.7316, thereby confirming its robustness in predictive performance. SHapley Additive exPlanations values were employed to explain key factors impacting recovery of renal function in AKI patients, highlighting factors such as elevated urine specific gravity, body temperature, and phosphorus levels.
CONCLUSION
This study presented a novel machine learning framework for predicting renal function recovery in patients with AKI, offering a deeper understanding of the key variables affecting recovery. The clinical applicability of the model was assessed across distinct hospital settings, which revealed variations in its efficacy. Although the model exhibited favorable outcomes, the necessity for further enhancements and the incorporation of more diverse datasets is imperative for its application in real-world scenarios.
PubMed: 38934029
DOI: 10.23876/j.krcp.23.330 -
Heliyon Jun 2024Residual mitral regurgitation (MR) is frequent after transcatheter edge-to-edge repair (TEER). There is controversy regarding the clinical impact of residual MR and its...
Association between echocardiographic velocity time integral ratio of mitral valve and left ventricular outflow tract and clinical outcomes post transcatheter edge-to-edge mitral valve repair.
BACKGROUND
Residual mitral regurgitation (MR) is frequent after transcatheter edge-to-edge repair (TEER). There is controversy regarding the clinical impact of residual MR and its quantitative assessment by transthoracic echocardiography (TTE), which is often challenging with multiple eccentric jets and artifact from the clip. The utility of the velocity time integral (VTI) ratio between the mitral valve (MV) and left ventricular outflow tract (LVOT), (VTI), a simple Doppler measurement that increases with MR, has not been assessed post TEER.
METHODS
Baseline characteristics, clinical outcomes, and TTE data from patients who underwent TEER between 2014 and 2021 across three academic centers were retrospectively analyzed. Post-procedure TTEs were evaluated for VTI in the first three months after TEER. One-year outcomes including all-cause and cardiac mortality, major adverse cardiac events, and MV reintervention were compared between patients with high VTI (≥2.5) and low (<2.5).
RESULTS
In total, 372 patients were included (mean age 78.7 ± 8.8 years, 68 % male, mean pre-TEER ejection fraction of 50.5 ± 14.7 %). Follow up TTEs were performed at a median of 37.5 (IQR 30-48) days post-procedure. Patients with high VTI had significantly higher all-cause mortality (HR 2.10, p = 0.003), cardiac mortality (HR 3.03, p = 0.004) and heart failure admissions (HR 2.28, p < 0.001) at one-year post-procedure. There was no association between raised VTI and subsequent MV reintervention.
CONCLUSION
High VTI has clinically significant prognostic value at one year post TEER. This tool could be used to select patients for consideration of repeat intervention.
PubMed: 38933987
DOI: 10.1016/j.heliyon.2024.e32378 -
Heliyon Jun 2024Identification of novel biomarkers for prediction of disease course and prognosis is needed to reduce morbidity of liver hepatocellular carcinoma (LIHC/HCC) patients....
Identification of novel biomarkers for prediction of disease course and prognosis is needed to reduce morbidity of liver hepatocellular carcinoma (LIHC/HCC) patients. Although dysregulated Periodic tryptophan protein 1 homolog (PWP1/endonuclein) expression has been detected in several tumors, the potential regulatory effect of PWP1 on LIHC remains uncertain. Here we evaluated the expression of PWP1 using multiple online platforms, and demonstrated that PWP1 upregulation was consistently observed in LIHC relative to non-tumor liver tissues and correlated with unfavorable prognosis. Moreover, HCC prognosis was significantly influenced by the methylation status of various CpG sites in the PWP1 gene. Lastly, we provide direct evidence that PWP1 acts as a driver of HCC progression by showing that siRNA-mediated PWP1 silencing significantly suppressed HCC cell proliferation in vitro. These data strongly suggest that PWP1 silencing may be an effective therapeutic strategy to treat LIHC.
PubMed: 38933950
DOI: 10.1016/j.heliyon.2024.e32409 -
Frontiers in Genetics 2024Cervical cancer, a prevalent gynecological malignant tumor, poses a significant threat to women's health and lives. Immune checkpoint inhibitor (ICI) therapy has emerged...
BACKGROUND AND AIMS
Cervical cancer, a prevalent gynecological malignant tumor, poses a significant threat to women's health and lives. Immune checkpoint inhibitor (ICI) therapy has emerged as a promising avenue for treating cervical cancer. For patients with persistent or recurrent metastatic cervical cancer, If the sequence of dead receptor ligand-1 (PD-L1) is positive, ICI show significant clinical efficacy. PD-L1 expression serves as a valuable biomarker for assessing ICI therapeutic efficacy. However, the complex tumor immune microenvironment (TIME), encompassing immune cell composition and tumor-infiltrating lymphocyte (TIL) status, also exerts a profound influence on tumor immunity and prognosis. Given the remarkable strides made by ICI treatments in improving the survival rates of cervical cancer patients, it becomes essential to identify a comprehensive biomarker that integrates various TIME aspects to enhance the effectiveness of ICI treatment. Therefore, the quest for biomarkers linked to multiple facets of TIME in cervical cancer is a vital pursuit.
METHODS
In this study, we have developed an Immune-Associated Gene Prognostic Index (IRGPI) with remarkable prognostic value specifically for cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). The Cancer Genome Atlas CESC dataset ( = 305) was meticulously analyzed to pinpoint key immune-related genes via weighted gene co-expression network analysis and differential gene expression assays. Subsequently, we employed Cox regression analysis to construct the IRGPI. Furthermore, the composition of immune cells and TIL status were examined using CIBERSORT and TIDE. Tumor expression of Epigen, LCN10, and P73 were determined with immunohistochemistry.
RESULTS
The resulting IRGPI, composed of EPGN, LCN10, and TP73 genes, displayed a strong negative correlation with patient survival. The discovery was validated with a patient cohort from our hospital. The IRGPI not only predicts the composition of immune cell subtypes such as Macrophages M1, NK cells, Mast cells, Plasma cells, Neutrophils, Dendritic cells, T cells CD8, and T cells CD4 within CESC, but also indicates TIL exclusion, dysfunction, and PD-1 and PD-L1 expression. Therefore, the IRGPI emerges as a promising biomarker not only for prognostic assessment but also for characterizing multiple immune features in CESC. Additionally, our results underscored the significant associations between the IRGPI and immune cell composition, TIL exclusion, and dysfunction, along with PD-1 and PD-L1 expression in the TIME.
CONCLUSION
Consequently, the IRGPI stands out as a biomarker intimately connected to both the survival and TIME status of CESC patients, offering potential insights into immunotherapy strategies for CESC.
PubMed: 38933923
DOI: 10.3389/fgene.2024.1340569 -
Frontiers in Endocrinology 2024Radiofrequency ablation (RFA) is an emerging non-surgical treatment for benign thyroid nodules (BTN). Despite its proven safety profile, data on the learning curve (LC)...
OBJECTIVE
Radiofrequency ablation (RFA) is an emerging non-surgical treatment for benign thyroid nodules (BTN). Despite its proven safety profile, data on the learning curve (LC) required to achieve proficiency are still lacking.
MATERIALS AND METHODS
The first 179 RFA procedures performed by a single operator in patients with non-functioning BTN were retrospectively analyzed. Six-month nodule volume reduction rate (VRR) ≥ 50% was regarded as reflection of proficiency. Multiple linear regression analysis has been performed to determine the relationship between the VRR and clinical variables. Cumulative sum (CUSUM) charts were plotted to assess LCs for all consecutive procedures and in relation to basal nodule size. In details, Group 1 (G1): 57 patients with small nodules (<10 ml); Group 2 (G2): 87 patients with intermediate nodules (10 - 25 ml); Group 3 (G3): 35 patients with large size (> 25 ml).
RESULTS
LC of all 179 procedures showed 3 phases: initial learning (1-39 procedures); consolidation (40-145 procedures); and experienced period (146-179 procedures). For G1 and G2 proficiency is achieved starting from the 10th procedure within the group (or 37th considering consecutively all procedures) and from the 59th procedure within the group (or 116th considering consecutively all procedures), respectively. LC of G3 did not detect operator proficiency.
CONCLUSION
Specific LCs exist concerning the basal size of the nodule treated with RFA. In nodules with baseline volume > 25 ml suboptimal VRR has to be expected. Previously achieved experience on small-intermediate nodules does not seem to provide advantages in terms of higher VRR in the treatment of large nodules. Other potential and non-modifiable factors likely play a key role in the final volume reduction independently from the increased skill of the operator.
Topics: Humans; Thyroid Nodule; Female; Male; Radiofrequency Ablation; Retrospective Studies; Middle Aged; Adult; Learning Curve; Clinical Competence; Aged; Treatment Outcome
PubMed: 38933827
DOI: 10.3389/fendo.2024.1399912