American journal of physiology. Renal physiology最新文献

{"title":"Adverse functions of neutrophils are regulated by neutrophilic angiotensin-converting enzyme in immune complex-mediated crescentic glomerulonephritis.","authors":"Suguru Saito, Satoshi Kumakura, Zakir Khan, Ellen A Bernstein, S Ananth Karumanchi, Kenneth E Bernstein, Michifumi Yamashita","doi":"10.1152/ajprenal.00378.2024","DOIUrl":"10.1152/ajprenal.00378.2024","url":null,"abstract":"<p><p>Neutrophils play a pathogenic role in immune complex (IC)-mediated crescentic glomerulonephritis (GN). Angiotensin-converting enzyme (ACE) plays a crucial role in regulating blood pressure and inflammation via angiotensin II. We recently reported that ACE-overexpressing neutrophils have the renoprotective role in IC-mediated crescentic GN by the complement C3b-complement receptor1/2 axis. Here, we further investigate the precise mechanism of the adverse, pathogenic, and renoprotective functions of neutrophils in GN. Nephrotoxic serum nephritis (NTN) was induced in the mice with four different conditions and analyzed: <i>1</i>) neutrophil depletion in wild-type (WT) and NeuACE mice that overexpress ACE specifically in neutrophils; <i>2</i>) adoptive transfer of ACE-overexpressing neutrophils into WT mice; <i>3</i>) analysis of ACE's catalytic C and N domains using each domain-knockout (Tg-CKO and Tg-NKO) and WT-ACE transgenic (Tg-ACE) mice; and <i>4</i>) comparison between C3KO and C3KO-NeuACE mice that overexpress ACE in neutrophils but lack of complement C3. The results were as follows: <i>1</i>) WT mice without neutrophils showed ameliorated glomerular injury, whereas neutrophil-depleted NeuACE mice lost the renoprotective effect; <i>2</i>) WT mice with ACE-overexpressing neutrophils exhibited less severe glomerular injury; <i>3</i>) Tg-CKO or Tg-NKO mice showed a partial loss of the renoprotective effects compared with Tg-ACE mice, suggesting both C and N domains are needed for full renoprotection; and <i>4</i>) C3KO-NeuACE mice lost the renoprotective effects. Complement C3 is essential for the renoprotection of overexpressed neutrophilic ACE in NeuACE mice. The present study demonstrated that canonical pathogenic effects of neutrophils were overcome by the noncanonical renoprotection by neutrophils through both C and N domains of ACE and complement C3.<b>NEW & NOTEWORTHY</b> We recently reported that NeuACE mice that overexpress angiotensin-converting enzyme (ACE), specifically in neutrophils, alleviate glomerular injury in immune complex-mediated crescentic glomerulonephritis by the complement C3b-complement receptor 1/2 axis. Here, we showed that catalytically active C and N domains of ACE were needed for full renoprotection, and complement C3 was essential for the renoprotective role of overexpressed neutrophilic ACE. Furthermore, we highlighted the neutrophils' canonical pathogenic and noncanonical renoprotective functions via neutrophilic ACE through complement C3 in glomerulonephritis.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F190-F201"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144318929","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":"Gliflozins in hypertension: basic mechanisms and clinical insights.","authors":"Timo Rieg, Ruisheng Liu, Alexander Staruschenko","doi":"10.1152/ajprenal.00119.2025","DOIUrl":"10.1152/ajprenal.00119.2025","url":null,"abstract":"<p><p>Sodium-glucose cotransport (SGLT) inhibitors, or gliflozins, initially developed for managing type 2 diabetes mellitus, have emerged as promising therapeutic agents for hypertension, offering both cardiovascular and renal protection. Recently, a dual SGLT1/SGLT2 inhibitor was approved for the treatment of heart failure (HF), including preserved and reduced ejection fraction. Clinical trials consistently demonstrate the ability of gliflozins to lower blood pressure (BP) and reduce cardiovascular events, particularly in patients with comorbid conditions such as chronic kidney disease and HF. However, these trials typically include hypertension as a comorbidity rather than as the primary condition, and data specific to patients with hypertension and without diabetes mellitus remain limited. This review highlights recent clinical and basic mechanistic insights into the antihypertensive effects of gliflozins. We discuss their influence on BP regulation, including modulation of renal sodium handling, the renin-angiotensin-aldosterone system, and vascular function. In addition, gliflozins exhibit significant anti-inflammatory and antifibrotic properties, reducing the risk of organ damage associated with chronic hypertension. Their metabolic benefits extend beyond glucose control, contributing to weight loss, and reduced uric acid levels, collectively supporting better cardiovascular outcomes. Accordingly, we also provide a brief overview of these metabolic effects. As ongoing research continues to explore the broader therapeutic applications of gliflozins, these agents may become integral to the management of hypertension, particularly in patients with complex cardiovascular and renal conditions.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F32-F45"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12264825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153035","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kidney organoid models of polycystic kidney disease: challenges and future directions.","authors":"Humayra Afrin, Usama Qamar, Jielu Hao Robichaud, Mohammad Ellabbad, Peter C Harris, Navin Gupta","doi":"10.1152/ajprenal.00116.2025","DOIUrl":"10.1152/ajprenal.00116.2025","url":null,"abstract":"<p><p>Kidney organoids are an increasingly established model of polycystic kidney disease (PKD). Derived from human pluripotent stem cells (hPSCs), organoids may be generated from induced pluripotent stem cells (iPSCs) of patients that bear naturally occurring mutations or from CRISPR mutant hPSCs by virtue of their genetic tractability. PKD is the leading inheritable cause of kidney failure (KF), accounting for ∼5%-10% of the kidney transplant and dialysis needs worldwide. PKD is a disorder of considerable genetic heterogeneity, composed of typical adult-onset autosomal dominant (ADPKD) and fetal-onset autosomal recessive (ARPKD) forms, which share pathomechanisms. Despite advances in our understanding of the genetic and molecular underpinnings of PKD, the limited clinical treatment options have raised concerns regarding the faithfulness of preclinical models. Kidney organoids have emerged as a promising platform to study PKD by mimicking human-specific responses, enabling personalized medicine, and supporting high-throughput screens. Yet, valid criticisms have related to the relative immaturity of kidney organoids for modeling adult-onset forms of PKD, the faithfulness of organoids in modeling the cystic distribution of afflicted patients, and their batch-to-batch variability limiting experimental reproducibility. Here, we summarize a decade of kidney organoid models of PKD, emphasizing their role in advancing translational and therapeutic applications while addressing their limitations and future potential.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F143-F159"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276946","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":"First Author Highlights.","authors":"","doi":"10.1152/ajprenal.2005.329.1.AU","DOIUrl":"https://doi.org/10.1152/ajprenal.2005.329.1.AU","url":null,"abstract":"","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":"329 1","pages":"i-ii"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144755315","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":"Kidney transplant injury associated with brain death is mediated by TNFα, independently of renal innervation.","authors":"Tiago Pinto Coelho, Pauline Erpicum, Margaux Navez, Morgan Vandermeulen, Olivier Detry, Francois Jouret","doi":"10.1152/ajprenal.00109.2025","DOIUrl":"10.1152/ajprenal.00109.2025","url":null,"abstract":"<p><p>Kidney transplant outcomes depend on various factors, including donor type. Brain death (BD) has been associated with significant kidney injury, with long-term sequelae. Deciphering the impact of BD versus circulatory death on kidney pathophysiology may help to prevent kidney transplant injury. We developed three rat models: 6 h of BD [donor after brain death (DBD, <i>n</i> = 10)]; donor after circulatory death (DCD, <i>n</i> = 10) with 20 min of warm ischemia; and 6-h BD with renal denervation before BD (DNRV, <i>n</i> = 6). RNA-Seq was performed on kidney tissue, followed by differential gene expression and pathway enrichment analyses. Circulating cytokines were measured by Luminex/ELISA. Our findings were validated in 10 human preimplantation biopsies matching our rat models (<i>n</i> = 5 DBD; <i>n</i> = 5 DCD). After BD, serum creatinine levels increased from 0.33 [0.31-0.38] to 0.61 [0.59-0.67] mg/dL (<i>P</i> < 0.0001). Compared with DCD, DBD rats exhibited significantly higher levels of IL-6 (26.67 [19.10-32.35] vs. 10.32 [9.76-13.28] ng/mL, <i>P</i> = 0.006) and TNFα (21.98 [16.48-32.60] vs. 9.64 pg/mL [7.96-11.13], <i>P</i> = 0.0012) and lower levels of IL-10 (1.28 [1.11-1.65] vs. 1.79 [1.46-2.18] ng/mL, <i>P</i> = 0.049). Differential expression analysis revealed that DBD kidneys exhibited CD11b-associated inflammation, Caspase-3-mediated apoptosis, and TNFα-driven injury (<i>P</i> = 7.34 × 10^-7; <i>z</i>-score = 2.475), whereas DCD kidneys activated EIF2/NRF2 stress-response pathways. Notably, denervation did not mitigate BD-induced injury. Human biopsies confirmed the positive enrichment of inflammatory pathways (<i>P</i> = 0.01 to 1.18 × 10^-7) in DBD compared with DCD, with 6 out of the top 15 pathways shared across species. Our findings highlight specific mechanisms affecting differently kidneys derived from DBD versus DCD donors, with a potential role of TNFα in BD-associated kidney injury. Kidney denervation before BD does not prevent kidney injury.<b>NEW & NOTEWORTHY</b> Kidney transplantation outcomes are influenced by donor type. Brain death has been associated with significant kidney injury, with long-term sequelae. We established two rat models mimicking human conditions of kidney donation after brain death or circulatory arrest. We identified TNFα as the main driver of BD-induced kidney injury, as validated in human pretransplant biopsies. Notably, kidney denervation before BD failed to prevent TNFα-mediated damage. Targeting TNFα signaling in DBD donors may improve transplant outcomes.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F128-F142"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144217832","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":"Intersecting transcriptomic landscapes of hypertension and kidney function in African American women.","authors":"Malak Abbas, Pamela Martin, Merry L Lindsey, Eric S Bennett, Thomas L Brown, Chike Nzerue, Clintoria R Williams, Amadou Gaye","doi":"10.1152/ajprenal.00067.2025","DOIUrl":"10.1152/ajprenal.00067.2025","url":null,"abstract":"<p><p>Hypertension is a risk factor for chronic kidney disease (CKD) and disproportionately affects African American women, contributing to disparities in kidney health. The biological mechanisms connecting hypertension to reduced kidney function remain poorly understood. This study leverages transcriptomic analyses to uncover shared molecular signatures associated with hypertension and kidney function, focusing on female-specific profiles. The study analyzed whole blood mRNA sequencing data from 344 African American women, divided into discovery (<i>n</i> = 172) and validation (<i>n</i> = 172) datasets, along with 147 African American men. Differential expression (DE) analyses were performed to identify mRNAs associated with hypertension and kidney function [measured as estimated glomerular filtration rate (eGFR)]. Female-specific findings were determined by comparing results between females and males. Pathway enrichment analyses were subsequently conducted to link the identified mRNAs to key biological mechanisms. Comparative analyses revealed unique transcriptomic profiles in females, underscoring the role of sex-specific factors in kidney function. DE analyses identified 95 female-specific genes associated with both hypertension and eGFR. Subsequent pathway enrichment analysis with the 95 genes revealed key pathways related to fibrosis, inflammation, lipid metabolism, and endothelial dysfunction. The list of 95 includes immune system players such as <i>IL32</i> and <i>TNFSF12</i> that amplify inflammation and kidney injury. This study provides novel insights into the transcriptomic mechanisms underlying hypertension and kidney function in African American women. The findings emphasize the importance of addressing sex-specific molecular mechanisms associated with hypertension-related impaired kidney function. Future research should prioritize experimental validation and longitudinal studies to further elucidate these pathways.<b>NEW & NOTEWORTHY</b> African American women experience a disproportionate burden of hypertension and chronic kidney disease, yet their molecular underpinnings remain understudied. This study uniquely integrates transcriptomic data from 344 African American women to uncover 95 female-specific genes jointly associated with hypertension and reduced kidney function. These genes implicate immune activation, cytoskeletal remodeling, and metabolic dysregulation as key contributors to renal decline. By identifying sex-specific molecular pathways, this work advances precision medicine approaches to address kidney health disparities.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F59-F70"},"PeriodicalIF":3.4,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12316382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188626","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiparametric quantitative magnetic resonance imaging of skeletal muscle in CKD.","authors":"Noah Markewitz, Can Wu, Moriel Vandsburger, William Paredes, Sally Duran, Saisha Islam, Brian Noehren, Christopher S Fry, Qi Peng, Matthew K Abramowitz","doi":"10.1152/ajprenal.00254.2024","DOIUrl":"10.1152/ajprenal.00254.2024","url":null,"abstract":"<p><p>Skeletal muscle dysfunction causes functional decline and disability in patients with chronic kidney disease (CKD). Identification of muscle pathology before significant loss of physical function would be a major advance. Multiparametric, quantitative magnetic resonance imaging (qMRI) of seven leg muscle groups (3 thigh and 4 calf) was conducted in patients with CKD stages 4-5 (<i>n</i> = 6), end-stage kidney disease (ESKD, <i>n</i> = 3), and healthy controls (<i>n</i> = 10) using a 3 Tesla MRI scanner. Measurements included T1 relaxation time in the rotating frame (T1ρ) and transverse relaxation time (T2) mapping, Dixon imaging of intramuscular fat content, diffusion tensor imaging (DTI) for muscle structure, and ¹H-MR spectroscopy for intra- and extra-myocellular lipid (IMCL and EMCL, respectively) and physiologically relevant muscle metabolites. T1ρ and T2 times were prolonged and fat fraction (FF) was higher in patients with CKD compared with controls (differences of 4.99 ms (95% CI 1.71-8.27), 6.72 ms (95% CI 3.78-9.66), and 6.67% (95% CI 0.65-12.68), respectively). T1ρ and FF were similarly elevated across muscle groups, whereas T2 differences may have been greater in calf muscles. T1ρ and T2 were lower in patients with ESKD compared with CKD and similar to controls, consistent with prior histologic assessment of muscle fibrosis. No significant differences by CKD status were observed for DTI parameters. Compared with controls, IMCL was higher in patients with CKD, and trimethylamine and creatine concentrations were lower. In sum, multiparametric qMRI of skeletal muscle in patients with CKD noninvasively identified differences in metrics associated with fibrosis, fat infiltration, and metabolic dysregulation.<b>NEW & NOTEWORTHY</b> In this study, we demonstrate that multiparametric, quantitative magnetic resonance imaging (qMRI) can quantify multiple distinct anatomic and pathologic features of skeletal muscle pathology in patients with CKD before significant functional decline. qMRI metrics of fibrosis and fat infiltration were elevated, and muscle metabolite concentrations were reduced, in patients with CKD compared with controls. This noninvasive approach offers a valuable alternative to traditional muscle biopsies for evaluating muscle health in patients with CKD.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F99-F111"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208609/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Logic-based modeling of inflammatory macrophage cross talk with glomerular endothelial cells in diabetic kidney disease.","authors":"Krutika Patidar, Ashlee N Ford Versypt","doi":"10.1152/ajprenal.00362.2024","DOIUrl":"10.1152/ajprenal.00362.2024","url":null,"abstract":"<p><p>Diabetic kidney disease is a complication in one out of three patients with diabetes. Aberrant glucose metabolism in diabetes leads to structural and functional damage in glomerular tissue and a systemic inflammatory immune response. Complex cellular signaling is at the core of metabolic and functional derangement. Unfortunately, the mechanism underlying the role of inflammation in glomerular endothelial cell dysfunction during diabetic kidney disease is not fully understood. Mathematical models in systems biology allow the integration of experimental evidence and cellular signaling networks to understand mechanisms involved in disease progression. This study developed a logic-based ordinary differential equations model to study inflammatory cross talk between macrophages and glomerular endothelial cells during diabetic kidney disease progression using a protein signaling network stimulated with glucose and lipopolysaccharide. This modeling approach reduced the biological parameters needed to study signaling networks. The model was fitted to and validated against available biochemical data from in vitro experiments. The model identified mechanisms for dysregulated signaling in macrophages and glomerular endothelial cells during diabetic kidney disease. In addition, the influence of signaling interactions on glomerular endothelial cell morphology through selective knockdown and downregulation was investigated. Simulation results showed that partial knockdown of VEGF receptor 1, PLC-γ, adherens junction proteins, and calcium partially improved intercellular junction integrity between glomerular endothelial cells. These findings contribute to understanding of signaling and molecular perturbations that affect glomerular endothelial cells in the early stage of diabetic kidney disease.<b>NEW & NOTEWORTHY</b> This work provides a novel analysis of signaling cross talk between macrophages and glomerular endothelial cells in the early stage of diabetic kidney disease. A logic-based mathematical modeling approach identified vital signaling molecules and interactions that regulate glucose-mediated inflammation in glomerular endothelial cells and cause endothelial dysfunction in the diabetic kidney. Simulated interactions among vascular endothelial growth factor receptor 1, nitric oxide, and calcium significantly affected the intercellular junction proteins between glomerular endothelial cells.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F202-F224"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12214709/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adequate salt intake is essential for candesartan-treated rats to maintain renal function.","authors":"Anni Xie, Leijuan Xiao, Mingzhuo Zhang, Haonan Duan, Zhiyun Ren, Ping Wang, Yutao Jia, Jianteng Xu, Xueqi Chen, Mingda Liu, Weiwan Wang, Ying Xue, Jizhuang Lou, Xiaoyan Wang","doi":"10.1152/ajprenal.00313.2024","DOIUrl":"https://doi.org/10.1152/ajprenal.00313.2024","url":null,"abstract":"<p><p>Dietary salt restriction and angiotensin-II receptor-1 blockade (ARB) are commonly recommended for patients with renal and cardiovascular diseases. To explore what salt diet was suitable for the ARB users and what measurements predicted acute kidney injury (AKI), we evaluated the impact of low (0.02%, LS), normal (0.4%, NS), and high (2%, HS)-salt diets on renal function and urinary exosomal sodium-hydrogen exchanger-3 (NHE3), sodium-potassium-chloride cotransporter-2 (NKCC2), sodium-chloride cotransporter (NCC), and aquaporin-1 (AQP1) in candesartan-treated rats. All rats were given candesartan (1 mg/kg/day, ip) except as indicated. Relative to NS control, increased serum creatinine (SCr) but decreased creatinine clearance (Ccr) was observed in consecutive LS rats for 7 days with morphological kidney abnormalities. Similar changes at <i>day 3</i> were observed in the food-switching rats from NS to LS with elevated urine osmolality and creatinine but decreased sodium concentrations. Urinary exosomal NHE3, NKCC2, NCC, and AQP1 were increased in the consecutive LS rats with elevated serum renin, angiotensin-II, and aldosterone. They were increased at <i>day 1</i> in food-switching rats, 2 days earlier than changes in SCr and Ccr, but similar to urine kidney injury molecule-1. Renal and apical-membranous NHE3 and NKCC2 were increased, but AQP1 was decreased with decreased renal angiotensinogen and angiotensin-II receptor type I (AT1R). A moderate HS reversed the changes seen in food-switching rats in SCr, Ccr, and urinary exosomal measurements and improved the kidney morphological abnormalities. Thus, dietary salt restriction induces a prerenal/reversible kidney injury in candesartan-treated rats; urinary exosomal NHE3, NKCC2, NCC, and AQP1 may serve as early biomarkers for the damage.<b>NEW & NOTEWORTHY</b> Dietary salt restriction in candesartan-treated rats increases serum creatinine and urinary KIM-1 but decreases creatinine clearance with renal morphological abnormalities. Urinary exosomal NHE3, NKCC2, NCC, and AQP1 increase 2 days earlier than the changes of serum creatinine and creatinine clearance. Moderate high-salt diet reverses those changes with improved renal morphology. Extreme salt restriction should be avoided during candesartan treatment; urinary exosomal NHE3, NKCC2, NCC, and AQP1 may serve as early predictors of the acute kidney injury.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":"328 6","pages":"F787-F799"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053426","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":"When ACE2 turns against the kidney: a paradox unveiled in heme-induced AKI.","authors":"Ying Fu, Zheng Dong","doi":"10.1152/ajprenal.00167.2025","DOIUrl":"10.1152/ajprenal.00167.2025","url":null,"abstract":"","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F828-F829"},"PeriodicalIF":0.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048660","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}