Kidney360最新文献

{"title":"Activin A Antagonism with Follistatin Reduces Kidney Fibrosis, Injury, and Cellular Senescence-Associated Inflammation in Murine Diabetic Kidney Disease.","authors":"Xiaohui Bian, Zachary K Snow, Caroline J Zinn, Cody C Gowan, Sabena M Conley, Anastasia L Bratulin, Khaled M Elhusseiny, Jordan Miller, Tamar Tchkonia, James L Kirkland, Lilach O Lerman, LaTonya J Hickson","doi":"10.34067/KID.0000000776","DOIUrl":"https://doi.org/10.34067/KID.0000000776","url":null,"abstract":"<p><strong>Background: </strong>Circulating activin A, an inflammatory mediator implicated in profibrotic kidney injury and cellular senescence-induced adipose tissue dysfunction, is increased in human diabetic kidney disease (DKD) and directly correlates with kidney dysfunction. We tested the hypothesis that activin A increases kidney injury, senescent cell abundance, and macrophage infiltration in DKD and antagonism through follistatin therapy diminishes these effects.</p><p><strong>Methods: </strong>An accelerated nephropathy type 2 diabetes (db/db) mouse model was generated by implantation of angiotensin II-loaded osmotic minipumps resulting in increased albuminuria and glomerular and tubular injury. Kidney repair effects of follistatin (5µg intraperitoneal; two doses) were assessed through markers of kidney injury, fibrosis, inflammation, cellular senescence, and macrophage infiltration. In vitro studies examined anti-activin effects of follistatin on high glucose-exposed human monocytes, renal fibroblasts, and renal tubule epithelial cells.</p><p><strong>Results: </strong>Activin A antagonism with follistatin reduced senescence (p19), pro-inflammatory (including senescence-associated secretory phenotype), and pro-fibrotic markers including activin A. Follistatin improved kidney morphology, restored podocyte markers (nephrin and Wilms tumor-1) and reduced kidney injury biomarkers, albuminuria and kidney fibrosis. Follistatin decreased kidney macrophage and leukocyte infiltration and AIM2 inflammasome activation. Follistatin appeared to suppress inflammation through the toll-like receptor-4 (TLR4)/nuclear factor-κB (NF-κB) pathway in vivo further supported in human macrophages in vitro. Additionally, follistatin reduced hyperglycemia-induced renal fibroblast activation and renal tubule epithelial cell senescence in vitro.</p><p><strong>Conclusion: </strong>Activin A is a mediator of kidney injury through macrophage-associated inflammation in murine DKD. Follistatin acts through senomorphic activities which inhibit profibrotic, proinflammatory, and pro-senescence signaling by activin A. Hence, anti-activin targeting may aid in development of a promising, novel therapeutic for DKD.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Relationship Between Rate of Hypernatremia Correction and Outcomes in Hospitalized Patients.","authors":"Gabriela Chacon-Palma, J Pedro Teixeira, Igor Litvinovich, Cristian G Bologa, Maria-Eleni Roumelioti, MingAn Yang, Mark L Unruh","doi":"10.34067/KID.0000000785","DOIUrl":"https://doi.org/10.34067/KID.0000000785","url":null,"abstract":"<p><strong>Background: </strong>Current recommendations for limiting hypernatremia correction rates to avoid cerebral edema in adults are supported by limited evidence. We explored the associations between rate of hypernatremia correction in hospitalized adults, in-hospital mortality, and discharge disposition.</p><p><strong>Methods: </strong>Using a large, multicenter database, we analyzed 37,913 hospitalized adults with hypernatremia on admission. For the primary analysis, hypernatremia correction rates were categorized as slow (≤0.50 mEq/L/hour) or fast (>0.50 mEq/L/hour). Propensity score (PS) weighting and PS stratification were employed to adjust for confounders. In secondary analyses, results were stratified by initial sodium concentration, age, and initial estimated glomerular filtration rate. In a sensitivity analysis, correction rates were categorized as <0.40 mEq/L/hour, 0.40-0.60 mEq/L/hour, or >0.60 mEq/L/hour.</p><p><strong>Results: </strong>Most (89%) patients experienced slow hypernatremia correction. In PS-weighted analyses, slow correction was associated with overall lower in-hospital mortality (adjusted odds ratio [aOR] 0.63, 95% confidence interval [CI] 0.59-0.67) but higher odds of discharge to hospice (aOR 1.57, 95% CI 1.38-1.78) or nursing facilities (aOR 1.60, 95% CI 1.52-1.69) than fast (reference) correction rates. After stratification by initial hypernatremia severity, age, and kidney function at admission, the associations between slow versus fast correction, in-hospital mortality, and discharge disposition were largely preserved without clear signals of effect modification by subgroup. When categorizing hypernatremia correction rates into three groups, <0.40 mEq/L/hour versus >0.60 mEq/L/hour (analogous to slow versus fast, respectively) continued to be independently associated with lower in-hospital mortality but higher rates of discharge to nursing facilities or hospice.</p><p><strong>Conclusions: </strong>In this analysis, the rate of hypernatremia correction was independently associated with opposing effects on survival and a favorable discharge disposition. Our findings suggest that balancing the risks and benefits of different dysnatremia correction rates should consider not only mortality but also patient-centered outcomes such as discharge disposition.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143736023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes by Dialysis Modality in a Safety-Net Population: A 10-Year Retrospective Cohort Study.","authors":"Jiten Patel, Anisha P Ganguly, Huzair Ali, Jaspreet Sian, Jillian Smartt, Michael Harms, Ramesh Saxena, Kavita P Bhavan","doi":"10.34067/KID.0000000745","DOIUrl":"https://doi.org/10.34067/KID.0000000745","url":null,"abstract":"<p><strong>Background: </strong>In-center hemodialysis (HD) is delivered by dialysis providers, while peritoneal dialysis (PD) involves active patient engagement through self-care. This self-care process may be associated with potential collateral health benefits that can positively impact clinical and patient-centered outcomes. Kidney transplantation (KT) is the primary goal among kidney failure (KF) patients. Several studies have shown that PD patients are more likely to receive KT than HD patients; however, baseline socioeconomic differences may confound differences in receipt of KT. Furthermore, differences in KT among low-income dialysis recipients remain uncharacterized. In this retrospective study, we compared transplant evaluation and listing status among propensity-matched incident HD and PD patients within a large safety-net health system.</p><p><strong>Methods: </strong>150 adult PD patients who initiated at Parkland Health from January 2012 to December 2022 were propensity-matched 1:1 with HD patients based on age, race/ethnicity, language, and co-morbidities. The primary outcome was the proportion of patients evaluated for transplantation. Secondary outcomes included the proportion of patients listed for transplantation, reasons for not listing, proportion transplanted, time to transplant, hospitalization rates, and mortality.</p><p><strong>Results: </strong>Propensity score-matched HD and PD patients had similar age, distribution of gender, race/ethnicity, language preference, co-morbidities, education, and insurance. Among patients initiated on PD, 129 (86.0%) were evaluated for KT, compared to 105 (70.0%) patients on HD (p=0.001). Furthermore, a significantly higher proportion of PD patients than HD patients were ultimately listed for transplantation (51.3% vs. 31.3%, p<0.001). Moreover, 26 (17.3%) HD patients and 33 (22.0%) PD patients underwent KT (p=0.309). The difference in kidney transplant among the two groups was not significant.</p><p><strong>Conclusions: </strong>In this observational study of dialysis patients in a safety-net health system, we observed that more patients on PD were evaluated for transplant than those on HD, leading to higher KT listings of PD patients. These findings suggest that equitable implementation of PD can improve KT evaluation, even among underserved populations.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143719995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tubule-Specific Compensatory Responses to Cpt1a Deletion in Aged Mice.","authors":"Steven D Funk, Justin T Kern, Olga M Viquez, Elizabeth Sulvaran-Guel, Jeffrey R Koenitzer, Kyle C Feola, Jacob S Blum, Roy Zent, Benjamin D Humphreys, Sarah C Huen, Leslie S Gewin","doi":"10.34067/KID.0000000746","DOIUrl":"https://doi.org/10.34067/KID.0000000746","url":null,"abstract":"<p><strong>Background: </strong>Fatty acid oxidation (FAO) is the preferred energy pathway in the proximal tubule (PT), and carnitine palmitoyltransferase 1A (CPT1A) is the rate-limiting enzyme of mitochondrial FAO. CPT1A expression and FAO decrease after renal injury. Our recent work demonstrated that genetic deletion of tubular Cpt1a did not significantly worsen the response to injury or aging and did not completely block FAO, suggesting compensatory metabolic pathways1. Additionally, CPT1A was most highly expressed in distal convoluted tubules (DCT), a segment not known for FAO. Therefore, we used single nuclear RNA sequencing to explore a cell-specific responses to aging with high fat diet (HFD-aging), to define compensatory metabolic pathways in PT segments lacking Cpt1a, and to determine the role of Cpt1a in the DCT.</p><p><strong>Methods: </strong>Cpt1a floxed (Cpt1afl/fl) and tubule-specific conditional Cpt1a knockout (Cpt1aCKO) mice were aged for 2 years with HFD. Single nuclear RNA-sequencing was performed on these HFD-aged mice plus young controls.</p><p><strong>Results: </strong>HFD-aged mice had increased fibrosis, inflammation, and more injured PT cells than young mice. Whereas PT segments from HFD-aged mice had significant transcriptional changes in metabolism-related pathways, the DCT had more changes in inflammation-related pathways. Compared with floxed mice, HFD-aged Cpt1aCKO mice had increased lipid deposition and increased inflammation but no significant differences in fibrosis or renal function. PT segments from HFD-aged Cpt1aCKO mice had significantly upregulated Hmgcs2, a promoter of ketogenesis and fatty acid oxidation, and upregulated genes in peroxisomal fatty acid oxidation and omega-fatty acid oxidation (CYP4A family) pathways. DCT from HFD-aged Cpt1aCKO mice had decreased expression of DCT-specific markers of cell differentiation.</p><p><strong>Conclusions: </strong>The upregulated Hmgcs2, peroxisomal fatty acid oxidation genes, and CYP4A genes may compensate for impaired mitochondrial metabolism of long chain fatty acids in PT cells lacking Cpt1a. Our data suggest that CPT1A may be important in maintenance of cell differentiation for DCT.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Inside-Out Overview of the IOTA Model: Bridging the Gap Between Stakeholders, Providers, Patients, and Donors.","authors":"Karim M Soliman, Prince M Anand, Amy Perry, Wisit Cheungpasitporn, Ahmed Daoud, Ahmed I Kamal, Tibor Fulop, Derek DuBay","doi":"10.34067/KID.0000000780","DOIUrl":"https://doi.org/10.34067/KID.0000000780","url":null,"abstract":"","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Continuing Versus Withholding SGLT2 inhibitors on Incidence of Contrast Associated Acute Kidney Injury in Patients Undergoing Coronary Angiography: A Randomized Controlled Trial (BELIEVE Trial).","authors":"Theera Phatikraisri, Massupa Krisem, Thamarath Chantadansuwan, Pichaya Tantiyavarong, Pisit Hutayanon, Nattachai Srisawat, Peerapat Thanapongsatorn","doi":"10.34067/KID.0000000781","DOIUrl":"https://doi.org/10.34067/KID.0000000781","url":null,"abstract":"<p><strong>Background: </strong>Sodium-glucose co-transporter 2 (SGLT2) inhibitors are increasingly recognized as first-line treatments for type 2 diabetes mellitus, chronic kidney disease, and heart failure. However, peri-procedural management of SGLT2 inhibitors in patients undergoing elective coronary angiography (CAG) remains unclear. This study aimed to evaluate the effects of continuing versus withholding SGLT2 inhibitors on the incidence of contrast-associated acute kidney injury (CA-AKI) in patients undergoing elective CAG.</p><p><strong>Methods: </strong>In this prospective, multicenter, open-label randomized controlled trial, patients who had been using SGLT2 inhibitors for at least three months were randomly assigned to either continue (n = 102) or withhold (n = 98) their SGLT2 inhibitors during the peri-procedural period. In the continuing group, patients maintained their SGLT2 inhibitor regimen uninterrupted, while in the withholding group, patients discontinued SGLT2 inhibitors 72 hours before CAG and resumed them post-procedure. The primary outcome was the incidence of CA-AKI, defined according to the KDIGO criteria. Secondary outcomes included changes in renal function, adverse events during hospitalization, and 90-day clinical outcomes.</p><p><strong>Results: </strong>The incidence of CA-AKI was comparable between the two groups, occurring in 3.92% (4/102) of patients in the continuing group and 3.06% (3/98) in the withholding group (risk difference: 0.86%; 95% CI: -4.22% to 5.94%; p = 0.74). The change in serum creatinine at 48 hours post-CAG was significantly lower in the continuing group (-0.06 ± 0.15 mg/dL) than in the withholding group (-0.02 ± 0.16 mg/dL), with a mean difference of -0.05 mg/dL (95% CI: -0.09 to -0.004; p = 0.047). One patient in the continuing group developed diabetic ketoacidosis, and no other significant safety concerns were observed.</p><p><strong>Conclusions: </strong>Among low-risk patients undergoing coronary angiography, contrast-associated AKI was rare, and withholding or continuing SGLT2 inhibitors had no meaningful impact on AKI risk or renal function. Routine discontinuation in this setting may not be necessary.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neighborhood Disadvantage and Inequities in Access to Preemptive and Living Kidney Transplantation.","authors":"Brandon M Fairless, Oluwatunmise Fawole, Duc T Nguyen, Ankona Banerjee, Kenneth J Nobleza, Abiodun Oluyomi, Omar Rosales, Jayna M Dave, Elizabeth A Onugha","doi":"10.34067/KID.0000000724","DOIUrl":"https://doi.org/10.34067/KID.0000000724","url":null,"abstract":"<p><strong>Background: </strong>Living donor kidney transplant (LDKT) generally results in better outcomes than deceased donor kidney transplant (DDKT). Pre-emptive kidney transplant (KT) allows patients to bypass undergoing maintenance dialysis, and is associated with improved patient and graft survival. Studies in the US pediatric population have shown racial-ethnic disparities in kidney transplant listing and the type of transplant received, but have yet to assess the association between neighborhood disadvantage and transplant type (LDKT vs DDKT), access to pre-emptive KT, or waitlisting.</p><p><strong>Methods: </strong>To utilize geocoded data to quantify neighborhood disadvantage and analyze its impact on access to pediatric KT. Design/Methods: Single-center retrospective chart review of all pediatric kidney transplant recipients at Texas Children's Hospital from 2000 to 2022. Multi-organ transplantation, patients >18 years, and re-transplantation were excluded. Transplant type, listing date, and patient address were obtained from UNET transplant registry. Neighborhood-level disadvantage was categorized using the Area Deprivation Index (ADI) score. ADI scores were calculated based on patient address and transplant year, and then stratified into US-based quartiles (Q1=least disadvantaged, Q4=most disadvantaged). Differences in characteristics between groups were determined by the chi-square or Fisher's exact tests for categorical variables and Kruskal Wallis test for continuous variables.</p><p><strong>Results: </strong>There was a significant trend favoring DDKT as ADI quartile increased (Q1=59.1%, Q4=83.5%, p=0.001). Concurrently there was a significant decline in pre-emptive KT rates as ADI quartile increased (Q1=34.1%, Q4=10%, p=0.001). No pre-emptive KT or LDKT occurred for African-American patients in the most disadvantaged neighborhoods (Q3-4). There was no difference in the time from dialysis to transplant across ADI quartiles.</p><p><strong>Conclusion: </strong>These findings suggest that pediatric KT recipients from disadvantaged households were less likely to receive a pre-emptive KT or a LDKT. Utilizing geocoded data can provide an objective assessment of patients' neighborhood disadvantage that supplements subjective pre-transplant screening tools.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiologic Solutions are Superior to Normal Saline in Critically Ill Patients: Commentary.","authors":"Sarah F Sanghavi","doi":"10.34067/KID.0000000779","DOIUrl":"https://doi.org/10.34067/KID.0000000779","url":null,"abstract":"","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiologic Solutions are Superior to Normal Saline in Critically Ill Patients: CON.","authors":"Andrew Z Fenves, Andrew S Allegretti","doi":"10.34067/KID.0000000607","DOIUrl":"https://doi.org/10.34067/KID.0000000607","url":null,"abstract":"","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Physiologic Solutions are Superior to Normal Saline in Critically Ill Patients: PRO.","authors":"Luis A Juncos, Michael Connor","doi":"10.34067/KID.0000000629","DOIUrl":"10.34067/KID.0000000629","url":null,"abstract":"","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}