Kidney Research and Clinical Practice最新文献

{"title":"Incretin-based therapies in diabetic kidney disease: toward integrated cardio-kidney-metabolic disease modification.","authors":"Yaeni Kim, Eun Young Lee","doi":"10.23876/j.krcp.26.272","DOIUrl":"https://doi.org/10.23876/j.krcp.26.272","url":null,"abstract":"<p><p>Obesity and type 2 diabetes (T2D) are dominant drivers of chronic kidney disease (CKD) within the cardio-kidney-metabolic (CKM) syndrome. Despite advances with renin-angiotensin system inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors, substantial residual cardiovascular and renal risk persists, highlighting the need for therapies targeting upstream metabolic dysfunction. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) have emerged as key modulators of CKM disease through integrated metabolic, vascular, and anti-inflammatory mechanisms. Cardiovascular outcome trials first established their cardioprotective effects, while the FLOW trial definitively demonstrated kidney protection, showing a 24% reduction in major kidney outcomes in patients with T2D and CKD. Mechanistic insights from translational studies further suggest that GLP-1 receptor activation promotes metabolic decongestion, improves intrarenal hemodynamics, and attenuates inflammatory and fibrotic pathways. Beyond selective GLP-1 receptor agonism, dual (glucose-dependent insulinotropic polypeptide [GIP]/GLP-1) and triple (GIP/GLP-1/glucagon) incretin agonists, including tirzepatide and retatrutide, extend this paradigm by delivering greater weight reduction and systemic metabolic reprogramming, with emerging signals for cardiovascular and renal benefit. Contemporary CKD management is shifting toward a phenotype-driven, layered therapeutic strategy in which SGLT2 inhibitors provide foundational kidney protection and incretin-based therapies are integrated to address residual metabolic and cardiovascular risk. In this evolving CKM framework, incretin-based therapies represent a central component of multi-mechanistic disease modification, extending beyond glycemic control to coordinated protection across the heart, kidney, and metabolic systems.</p>","PeriodicalId":17716,"journal":{"name":"Kidney Research and Clinical Practice","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of exercise as an adjunctive therapy in patients on maintenance hemodiafiltration: clinical benefits and implications.","authors":"Moo Jun Kim, Hyo-Wook Gil","doi":"10.23876/j.krcp.26.038","DOIUrl":"10.23876/j.krcp.26.038","url":null,"abstract":"","PeriodicalId":17716,"journal":{"name":"Kidney Research and Clinical Practice","volume":" ","pages":"647-649"},"PeriodicalIF":3.5,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147868676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the immuno-inflammatory endotype of sepsis-associated acute kidney injury: a machine learning-based approach.","authors":"Jin Zhang, Pengchao Tian, Jingyi Wang, Wenxiong Li, Na Cui","doi":"10.23876/j.krcp.26.112","DOIUrl":"https://doi.org/10.23876/j.krcp.26.112","url":null,"abstract":"<p><strong>Background: </strong>Sepsis-associated acute kidney injury (SA-AKI) is a frequent and high-mortality complication in critically ill patients. Current diagnostic criteria rely on functional markers that often lag behind the onset of renal injury. While immune dysregulation is central to SA-AKI pathogenesis, few prediction models systematically integrate multidimensional immune phenotypes.</p><p><strong>Methods: </strong>The present analysis was based on a multicenter prospective cohort study involving 1,551 septic patients. The study was carried out across five tertiary hospitals in Beijing. Clinical data and immuno-inflammatory biomarkers (including humoral, complement, and T lymphocyte subsets) were collected within 24 hours of sepsis diagnosis. An Extreme Gradient Boosting (XGBoost) model was then developed to predict SA-AKI.</p><p><strong>Results: </strong>New-onset SA-AKI occurred in 44.8% of the cohort and was associated with increased mortality. We identified a distinct high-risk immuno-inflammatory endotype characterized by elevated immunoglobulin A and procalcitonin (PCT), consumptive complement component 3 depletion, and a \"complex and divergent cellular immune pattern\"-manifested as depleted naïve CD4+ T cells coexisting with expanded CD28+CD4+ T cells. Integrating these immune features with routine clinical variables (Acute Physiology and Chronic Health Evaluation II (APACHE II), the Sequential Organ Failure Assessment [SOFA], PCT, prothrombin time [PT], sex) yielded an XGBoost-based clinical-immune model with superior discrimination (area under the curve [AUC], 0.914), significantly outperforming the clinical model (AUC, 0.788). Decision curve analysis further confirmed greater net clinical benefit for the integrated model.</p><p><strong>Conclusion: </strong>Immune dysregulation plays an important role in developing AKI in sepsis patients. Immune biomarkers could significantly improve early identification of high SA-AKI risk patients.</p>","PeriodicalId":17716,"journal":{"name":"Kidney Research and Clinical Practice","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FOXO4 enhances high glucose-induced HK-2 cell damage and inflammation by targeting TFPI2 in diabetic nephropathy.","authors":"Liqin Mu, Yu Zhao, Yang Li, Wei Gao, Jing Wang","doi":"10.23876/j.krcp.25.389","DOIUrl":"https://doi.org/10.23876/j.krcp.25.389","url":null,"abstract":"<p><strong>Background: </strong>Diabetic nephropathy (DN) represents the leading cause of end-stage renal disease; however, its molecular mechanisms remain incompletely understood. This study aims to elucidate the specific roles and regulatory mechanisms of Tissue factor pathway inhibitor 2 (TFPI2) and forkhead box O4 (FOXO4) in DN.</p><p><strong>Methods: </strong>Differentially expressed genes were identified from the GSE30529 dataset. TFPI2 expression in renal tubules was predicted using the kidney interactive transcriptomics database. Gene expression was examined using reverse transcription-polymerase chain reaction and western blot assay. Functional outcomes were examined using cell counting kit 8, 5‑ethynyl2'‑deoxyuridine, flow cytometry, TUNEL assays, and corresponding commercial assay kits. The relationship between TFPI2 and FOXO4 was analyzed by GeneCards and JASPAR websites, and dual luciferase reporter and chromatin immunoprecipitation assays. DN model mice were constructed to analyze the role of TFPI2 in vivo.</p><p><strong>Results: </strong>TFPI2 was significantly increased in DN patients and high glucose (HG)-stimulated HK-2 cells. TFPI2 down-regulation mitigated HG-induced HK-2 cell damage, inflammation, and oxidative stress. Mechanistically, FOXO4 targeted and promoted the transcription of TFPI2. FOXO4 down-regulation alleviated HG-induced HK-2 cell injury by targeting TFPI2. In vivo, TFPI2 knockdown inhibited damage and inflammation.</p><p><strong>Conclusion: </strong>FOXO4 promotes HG-induced HK-2 cell damage and inflammation via regulating TFPI2 in vitro. Furthermore, TFPI2 knockdown alone alleviates renal injury and inflammation in vivo.</p>","PeriodicalId":17716,"journal":{"name":"Kidney Research and Clinical Practice","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148794979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond current standards: combination therapy and emerging targets in diabetic kidney disease.","authors":"Jiwon Lee, Mi-Yeon Yu","doi":"10.23876/j.krcp.26.234","DOIUrl":"https://doi.org/10.23876/j.krcp.26.234","url":null,"abstract":"<p><p>Diabetic kidney disease continues to be a major contributor to kidney failure and is strongly associated with adverse cardiovascular outcomes. Even with routine use of renin-angiotensin system blockade, many patients show ongoing disease progression, indicating that current treatment alone is often insufficient. Treatment approaches are increasingly focused on combining agents that act through different biological pathways. Among these, sodium-glucose cotransporter 2 inhibitors have taken a central role, supported by consistent evidence for kidney and cardiovascular protection. Their use alongside nonsteroidal mineralocorticoid receptor antagonists, particularly finerenone, has further strengthened this strategy. Glucagon-like peptide-1 receptor agonists are also being incorporated into clinical practice, largely because of their metabolic and vascular effects, although direct evidence for additional kidney benefit remains limited. Interest has also grown in therapies that target pathways not fully addressed by existing drugs. Aldosterone synthase inhibitors reduce aldosterone production at its source, whereas endothelin receptor antagonists act on mechanisms linked to persistent albuminuria and progressive fibrosis. These approaches may help address residual risk in diabetic kidney disease, particularly in patients with persistent albuminuria despite optimized therapy. Data supporting multidrug or triple therapy remain limited. Nonetheless, current evidence suggests that earlier use of combination therapy may offer advantages. Further research is needed to determine how best to integrate these treatments and to confirm their long-term effects on kidney and cardiovascular outcomes.</p>","PeriodicalId":17716,"journal":{"name":"Kidney Research and Clinical Practice","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning-assisted prediction of 5-year mortality in chronic kidney disease: the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD).","authors":"Sang Heon Suh, Hong Sang Choi, Chang Seong Kim, Sangjun Lee, Eun Hui Bae, Seong Kwon Ma, Sue K Park, Kook-Hwan Oh, Soo Wan Kim","doi":"10.23876/j.krcp.25.471","DOIUrl":"https://doi.org/10.23876/j.krcp.25.471","url":null,"abstract":"<p><strong>Background: </strong>Mortality prediction models for patients with non-dialysis chronic kidney disease (CKD) remain limited despite their clinical importance. While machine learning (ML) offers the potential to improve prediction accuracy, its \"black-box\" nature has hindered clinical adoption. This study aimed to develop and validate an interpretable ML model for predicting 5-year all-cause mortality in patients with non-dialysis CKD and to deploy it as a user-friendly web-based risk stratification tool.</p><p><strong>Methods: </strong>We analyzed 1,858 patients (94 deaths) from a prospective cohort of non-dialysis CKD patients. Several ML algorithms including CatBoost were trained and compared with conventional logistic regression. SHapley Additive exPlanations (SHAP) analysis was employed to identify key prognostic features and ensure model interpretability. The final simplified model was externally validated in an independent cohort of 348 CKD patients.</p><p><strong>Results: </strong>The CatBoost model demonstrated superior performance (area under the curve [AUC], 0.813; 95% confidence interval [CI], 0.737-0.888; p = 0.04) compared to logistic regression (AUC, 0.747; 95% CI, 0.655-0.840). A simplified model using only the top-5 SHAP-ranked features-age, estimated glomerular filtration rate, serum albumin, spot urine protein-to-creatinine ratio, and serum total calcium-maintained robust predictive accuracy in the external validation cohort (AUC, 0.795). Notably, SHAP visualization revealed a U-shaped relationship for serum calcium, identifying hypocalcemia as a significant and under-recognized mortality risk factor.</p><p><strong>Conclusion: </strong>The CatBoost-based ML model accurately predicts 5-year mortality in non-dialysis CKD patients using five readily available clinical parameters. We expect that the clinical implementation of this model may offer a practical method for early risk stratification and personalized management.</p>","PeriodicalId":17716,"journal":{"name":"Kidney Research and Clinical Practice","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new era in diabetic kidney disease therapy: toward remission and survival.","authors":"Eun Young Lee","doi":"10.23876/j.krcp.26.213","DOIUrl":"https://doi.org/10.23876/j.krcp.26.213","url":null,"abstract":"","PeriodicalId":17716,"journal":{"name":"Kidney Research and Clinical Practice","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148685148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rationale and design of the EXCELSIOR-CKD trial: intensive blood pressure and lipid control in advanced chronic kidney disease.","authors":"Yaerim Kim, Jwa-Kyung Kim, Gang-Jee Ko, Jeong-Hoon Lim, Jung-Ho Shin, Jee Young Lee, Chan-Young Jung, Byung Ha Chung, Hoon Suk Park, Sung Gyun Kim, Yong Chul Kim, Dong Ki Kim, Sejoong Kim, Tae Ik Chang, Sun-Hee Park, Seung Hyeok Han","doi":"10.23876/j.krcp.26.086","DOIUrl":"https://doi.org/10.23876/j.krcp.26.086","url":null,"abstract":"<p><strong>Background: </strong>Although blood pressure and lipid control are key in advanced chronic kidney disease (CKD), the optimal targets for systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) remain unclear because patients with estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 were often excluded or underrepresented in prior trials. This study aims to compare the clinical outcomes of intensive versus standard control strategies for SBP and LDL-C in patients with advanced CKD.</p><p><strong>Methods: </strong>This multicenter, open-label, randomized controlled trial with a 2 × 2 factorial design is being conducted across 13 centers in Korea. Adults aged ≥19 years with eGFR ≥15 and <45 mL/min/1.73 m2 , SBP ≥130 mmHg, and LDL-C ≥100 mg/dL are eligible. Participants will be randomized according to intensive or standard targets for SBP (<120 mmHg vs. <140 mmHg) and LDL-C (<70 mg/dL vs. <100 mg/dL). The effects of blood pressure and lipid interventions will be evaluated independently, sharing the same primary endpoint: time to the first composite kidney outcome, including ≥40% sustained decline in eGFR, initiation of kidney replacement therapy, sustained eGFR <10 mL/min/1.73 m2 , or kidney death. Secondary endpoints will include eGFR slope and major adverse cardiovascular events. Participants will be followed up for 3 years, with an additional 3 years for the observational phase.</p><p><strong>Results: </strong>This report describes the rationale and design; trial results are pending.</p><p><strong>Conclusion: </strong>As the first randomized trial to determine whether intensive SBP and LDL-C lowering improve kidney outcomes in advanced CKD, this study could help define optimal targets and inform future guideline recommendations.</p>","PeriodicalId":17716,"journal":{"name":"Kidney Research and Clinical Practice","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670062","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic stratification in a diabetic kidney disease trial using plasma concentrations of soluble tumor necrosis factor receptor 1.","authors":"Vladimir Petrovic, Vladislav A Malkov, Andrew N Billin, Uptal D Patel, Pablo E Pergola, Glenn M Chertow, Jan Skupien, Andrzej S Krolewski","doi":"10.23876/j.krcp.25.198","DOIUrl":"https://doi.org/10.23876/j.krcp.25.198","url":null,"abstract":"<p><strong>Background: </strong>Concentration of circulating soluble tumor necrosis factor receptor 1 is associated with faster progression in patients with diabetic kidney disease based on data obtained from large longitudinal cohort studies. A cutpoint of 4.3 ng/mL baseline plasma concentration was identified to stratify patients and predict clinical outcome. We set out to test the prognostic utility of this cutpoint in a randomized clinical trial.</p><p><strong>Methods: </strong>Soluble tumor necrosis factor receptor 1 concentration was measured across plasma samples from Joslin cohort and selonsertib trial cohort. Estimated glomerular filtration rate slope was calculated using a patient-specific linear regression model based on serum creatinine concentration and compared between the cohorts. Kidney-related events were plotted using Kaplan-Meier estimates for both cohorts.</p><p><strong>Results: </strong>Participants from both the clinical study cohort and the observational cohort showed an inverse relationship between baseline plasma concentrations of tumor necrosis factor receptor 1 and estimated glomerular filtration rate. When stratified based on baseline soluble tumor necrosis factor receptor 1 cutpoint, higher probability of experiencing a clinical event was found in patients with levels of soluble tumor necrosis factor receptor 1 exceeding 4.3 ng/mL in either of the cohorts.</p><p><strong>Conclusion: </strong>We demonstrated the prognostic utility of plasma concentrations of circulating soluble tumor necrosis factor receptor 1 in identifying individuals with diabetic kidney disease at an elevated risk of progressive kidney function decline in a randomized clinical study setting. This data supports previous findings from large observational cohorts and supports the use of this marker as a reliable predictor of disease outcome.</p>","PeriodicalId":17716,"journal":{"name":"Kidney Research and Clinical Practice","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unlocking potassium secretion: the roles of aldosterone, ROMK, and WNK kinases in kidney potassium handling.","authors":"Biff F Palmer","doi":"10.23876/j.krcp.26.254","DOIUrl":"https://doi.org/10.23876/j.krcp.26.254","url":null,"abstract":"<p><p>The normal human kidney possesses a prodigious capacity to excrete dietary potassium (K+). This evolutionary adaptation is rooted in the high-K+ diets of prehistoric hominids, which are estimated to have reached 15,000 mg/day. Despite the progressive reduction in dietary K+ since the advent of agriculture, the modern distal nephron remains an exquisite K+ sensor. This review elucidates the molecular mechanisms governing kidney K+ handling, tracing the pathway from early enteric sensing to the structural reorganization of WNK (with-no-lysine [K+] kinase), and detailing how the interplay between aldosterone and angiotensin II ultimately resolves the aldosterone paradox in the distal nephron.</p>","PeriodicalId":17716,"journal":{"name":"Kidney Research and Clinical Practice","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}