American journal of physiology. Renal physiology最新文献

{"title":"Revisiting voltage-coupled H⁺ secretion in the collecting duct.","authors":"Niklas Ayasse, Peder Berg, Mads V Sørensen, Samuel L Svendsen, Alan M Weinstein, Jens Leipziger","doi":"10.1152/ajprenal.00023.2024","DOIUrl":"10.1152/ajprenal.00023.2024","url":null,"abstract":"<p><p>Experimental studies have shown that V-type ATPase-driven H⁺ secretion is dependent on transepithelial voltage. On this basis, the \"voltage hypothesis\" of urinary acidification by the collecting duct was derived. Accordingly, it has been supposed that the lumen-negative potential created by the reabsorption of Na⁺ via the epithelial Na⁺ channel (ENaC) enhances electrogenic H⁺ secretion via V-type H⁺-ATPase. This concept continues to be widely used to explain acid/base disorders. Importantly, however, a solid proof of principle for the voltage hypothesis in physiologically relevant situations has not been reached. Rather, it has been challenged by recent in vivo functional studies. In this review, we outline the arguments and experimental observations explaining why voltage-coupled H⁺ secretion in the collecting duct often appears poorly applicable for rationalizing changes in H⁺ secretion as a function of more or less ENaC function in the collecting duct.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F931-F945"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11918339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334172","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":"Faster bladder filling in rats reduces detrusor overactivity but worsens (i.e., decreases) bladder compliance.","authors":"Wei He, Nick Slavik, Jacob Braun, Farshad Samadifam, James A Hokanson","doi":"10.1152/ajprenal.00209.2024","DOIUrl":"10.1152/ajprenal.00209.2024","url":null,"abstract":"<p><p>The impact of bladder filling rate on cystometric outcomes remains unclear. Clinically, faster bladder filling is believed to increase the likelihood of observing detrusor overactivity (DO) in those with bladder dysfunction, although evidence of this is lacking. We executed this study to clarify how changes in bladder filling rate impact cystometric parameters. Urethane-anesthetized female CD rats (<i>n</i> = 19) underwent bladder filling at five different fill rates, a baseline rate scaled to have a filling phase of ∼7 min (in line with our previous work) and scaled rates of 1/3×, 2×, 4×, and 8× that speed. Contrary to expectations, filling at faster rates decreased the likelihood of observing detrusor overactivity, with 4× and 8× filling rates demonstrating less detrusor overactivity than the baseline (1×) rate (<i>P</i> = 0.0091 for 4× and <i>P</i> = 0.019 for 8×). However, faster filling rates did decrease bladder compliance. Filling at 4× and 8× demonstrated decreased bladder compliance compared to 1× (<i>P</i> = 0.032 for 4× and <i>P</i> < 0.0001 for 8×). Finally, increasing the filling rate led to increases in bladder capacity at 4× (<i>P</i> = 0.034) and 8× (<i>P</i> = 0.0066) relative to 1×. These results suggest that, contrary to expectations, faster filling may not be more effective at eliciting detrusor overactivity (i.e., not a better diagnostic approach). As reductions in detrusor overactivity and increases in bladder capacity are critical parameters for evaluating preclinical therapeutics, faster filling may impair the ability to demonstrate further improvements.<b>NEW & NOTEWORTHY</b> Little is known about the effects of different bladder filling rates on cystometric results. Various sources have suggested that faster filling is \"provocative\" to the bladder. However, in this study we varied bladder filling rates in anesthetized rats and observed less detrusor overactivity with faster filling, not more. We explain this discrepancy as a miscommunication about what being provocative means, where faster filling leads to worse bladder compliance (as we observed), not more detrusor overactivity.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F985-F993"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482800","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":"5/6 Nephrectomy impairs acute kaliuretic responses and predisposes to postprandial hyperkalemia.","authors":"Kuang-Yu Wei, Martin Gritter, A H Jan Danser, Liffert Vogt, Martin H de Borst, Joris I Rotmans, Pedro Henrique Imenez Silva, Ewout J Hoorn","doi":"10.1152/ajprenal.00195.2024","DOIUrl":"10.1152/ajprenal.00195.2024","url":null,"abstract":"<p><p>The susceptibility of patients with chronic kidney disease to develop postprandial hyperkalemia suggests alterations in normal kidney sodium (Na⁺) and potassium (K⁺) handling, but the exact nature of these changes is largely unknown. To address this, we analyzed the natriuretic and kaliuretic responses to diuretics and acute K⁺ loading in rats who underwent 5/6 nephrectomy (5/6Nx) and compared this with the response in sham-operated rats. The natriuretic and kaliuretic responses to furosemide, hydrochlorothiazide, and amiloride were largely similar between 5/6Nx and sham rats except for a significantly reduced kaliuretic response to hydrochlorothiazide in 5/6Nx rats. Acute dietary K⁺ loading with either 2.5% potassium chloride or 2.5% potassium citrate caused lower natriuretic and kaliuretic responses in 5/6Nx rats compared with sham rats. This resulted in significantly higher plasma K⁺ concentrations in 5/6Nx rats, which were accompanied by corresponding increases in plasma aldosterone. Acute K⁺ loading caused dephosphorylation of Ste20-related proline/alanine-rich kinase and the sodium-chloride cotransporter both in sham and 5/6Nx rats. In contrast, the acute K⁺ load decreased the Na⁺/hydrogen exchanger 3 and increased serum- and glucocorticoid-regulated kinase 1 and the α-subunit of the epithelial sodium channel (ENaC) only in sham rats. Together, our data show that 5/6Nx impairs the natriuretic and kaliuretic response to an acute dietary K⁺ load, which is further characterized by a loss of ENaC adaptation and the development of postprandial hyperkalemia.<b>NEW & NOTEWORTHY</b> Rats who underwent 5/6 nephrectomy demonstrate a reduced ability to excrete an acute K⁺ load with the development of postprandial hyperkalemia. 5/6 Nephrectomy attenuates K⁺-induced natriuresis and impairs ENaC regulation despite intact NCC dephosphorylation and increased plasma aldosterone. This offers a potential explanation for why patients with chronic kidney disease are predisposed to postprandial hyperkalemia.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F1005-F1012"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482797","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":"Identification of natriuretic peptide receptor A-related gene expression signatures in podocytes in vivo reveals baseline control of protective pathways.","authors":"Mia Jensen, Elena-Sofia Heinl, Anna Federlein, Uwe Schwartz, Lars Lund, Kirsten Madsen, Boye L Jensen, Frank Schweda","doi":"10.1152/ajprenal.00394.2023","DOIUrl":"10.1152/ajprenal.00394.2023","url":null,"abstract":"<p><p>Natriuretic peptide receptor-A (NPR-A) is the principal receptor for the natriuretic peptides atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Targeted deletion of NPR-A in mouse glomerular podocytes significantly enhances renal injury in vivo in the DOCA-salt experimental model. It was therefore hypothesized that natriuretic peptides exert a direct protective effect on glomerular barrier integrity through activation of NPR-A and modulation of gene expression patterns in podocytes. Green fluorescence-positive podocytes from mice with a conditional deletion of <i>Npr1</i> encoding NPR-A were isolated by fluorescence-activated cell sorting (FACS). Differentially expressed genes (DEGs) in podocytes were identified by RNA sequencing of podocytes from wild-type and NPR-A-deleted mice. Enrichment analysis was performed on the DEGs using Gene Ontology (GO) terms. Identified transcripts were validated by real-time PCR and ELISA of cultured isolated human and mouse glomeruli. In addition, the effect of natriuretic peptides on podocyte migration was investigated by measuring the outgrowth of podocytes from cultured glomeruli. A total of 158 DEGs were identified with 81 downregulated DEGs and 77 upregulated DEGs in <i>Npr1</i>-deficient podocytes. Among the downregulated genes were protein S and semaphorin 3G, which are known to have protective effects in podocytes. Protein S was also expressed in and secreted from isolated human glomeruli. GO enrichment analysis revealed that the upregulated DEGs in NPR-A deficient podocytes were associated with cell migration and motility. In line, BNP significantly decreased podocyte outgrowth from cultured glomeruli. In conclusion, endogenous levels of natriuretic peptides in mice support baseline protective pathways at glomerular podocytes such as protein S and suppress podocyte migration.<b>NEW & NOTEWORTHY</b> A combination of fluorescence-activated cell sorting and RNA sequencing identified 158 changed gene products in adult mouse kidneys with and without podocyte-specific deletion of the natriuretic peptide receptor A. Downregulated products included protein S and semaphorin 3G, both with proven renoprotective impact, whereas upregulated products were related to mobility of podocytes. Protein S was produced and released from human and murine isolated glomeruli, and atrial natriuretic peptide (ANP) led to decreased migration of podocytes.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F806-F821"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303165","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":"Corrigendum for Ma et al., Volume 327, 2024, p. F250.","authors":"","doi":"10.1152/ajprenal.00130.2024_COR","DOIUrl":"10.1152/ajprenal.00130.2024_COR","url":null,"abstract":"","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":"327 5","pages":"F725"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482803","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":"Anatomic and functional evidence for renal autonomic innervation in normotensive and hypertensive rats.","authors":"Min Dai, Cai-Yu Li, Jing-Xiao Wang, Xiao-Yu Xu, Shi-Xiu Sun, Ying Kang, Ai-Dong Chen, Ying Han, Guo-Qing Zhu","doi":"10.1152/ajprenal.00133.2024","DOIUrl":"10.1152/ajprenal.00133.2024","url":null,"abstract":"<p><p>Renal denervation (RDN) has been used for treating resistant hypertension. A few recent studies have shown vagal innervation of kidneys causing confusion. This study aimed to provide anatomical and functional evidence for renal autonomic innervation. Experiments were performed in male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Pseudorabies virus (PRV) in the paraventricular nucleus and rostral ventrolateral medulla was prevented by bilateral RDN, but not subdiaphragmatic vagotomy. PRV did not appear in the dorsal motor nucleus of the vagus and nucleus tractus solitarii 72 h after renal injection of PRV. Adrenergic fibers were approximately seven times more than cholinergic fibers in the main renal artery (MRA) and its first (1RA) and second grade (2RA) branches. Adrenergic fibers in 1RA were more than those in MRA and 2RA. Tyrosine hydroxylase immunoreactivity in these arteries was higher in SHR than in WKY. Norepinephrine (NE) increased and α-receptor antagonist reduced vascular ring tension of renal arteries. The effect of NE was greater in 1RA and 2RA than in MRA, which was prevented by α-receptor antagonist. Acetylcholine (ACh) or blockage of β-receptors, M receptors, or N receptors had no significant effects on vascular ring tension and the effect of NE. Renal blood flow was reduced by electrical stimulation of renal nerves but not affected by stimulation of the subdiaphragmatic vagus. These results provide anatomical and functional evidence that kidneys are innervated and renal blood flow is regulated by renal sympathetic nerves rather than the vagus. Renal vasoconstriction is regulated by NE and adrenergic fibers rather than ACh or cholinergic fibers in WKY and SHR.<b>NEW & NOTEWORTHY</b> Kidneys are innervated by renal nerves rather than the vagus. Adrenergic fibers in renal arteries are about seven times more than cholinergic fibers. Renal vasoconstriction is regulated by norepinephrine and adrenergic fibers rather than acetylcholine or cholinergic fibers. Renal blood flow is regulated by renal sympathetic nerves and is not affected by the vagus. These findings provide anatomical and functional evidence for renal autonomic innervation in normotensive and hypertensive rats.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F885-F898"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303163","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":"Acute kidney injury results in long-term alterations of kidney lymphatics in mice.","authors":"Gelare Ghajar-Rahimi, Daria Barwinska, Grace E Whipple, Malgorzata M Kamocka, Shehnaz Khan, Seth Winfree, Jennifer Lafontaine, Reham H Soliman, Arin L Melkonian, Anna A Zmijewska, Matthew D Cheung, Amie M Traylor, Yanlin Jiang, Zhengqin Yang, Subhashini Bolisetty, Abolfazl Zarjou, Timmy Lee, James F George, Tarek M El-Achkar, Anupam Agarwal","doi":"10.1152/ajprenal.00120.2024","DOIUrl":"10.1152/ajprenal.00120.2024","url":null,"abstract":"<p><p>The long-term effects of a single episode of acute kidney injury (AKI) induced by bilateral ischemia-reperfusion injury (BIRI) on kidney lymphatic dynamics are not known. The purpose of this study was to determine if alterations in kidney lymphatics are sustained in the long term and how they relate to inflammation and injury. Mice underwent BIRI as a model of AKI and were followed up to 9 mo. Although kidney function markers normalized following initial injury, histological analysis revealed sustained tissue damage and inflammation for up to 9 mo. Transcriptional analysis showed both acute and late-stage lymphangiogenesis, supported by increased expression of lymphatic markers, with unique signatures at each phase. Expression of <i>Ccl21a</i> was distinctly upregulated during late-stage lymphangiogenesis. Three-dimensional tissue cytometry confirmed increased lymphatic vessel abundance, particularly in the renal cortex, at early and late timepoints postinjury. In addition, the study identified the formation of tertiary lymphoid structures composed of CCR7⁺ lymphocytes and observed changes in immune cell composition over time, suggesting a complex and dynamic response to AKI involving tissue remodeling and immune cell involvement. This study provides new insights into the role of lymphatics in the progression of AKI to chronic kidney disease.<b>NEW & NOTEWORTHY</b> Here, we perform the first, comprehensive study of long-term lymphatic dynamics following a single acute kidney injury (AKI) event. Using improved three-dimensional image analysis and an expanded panel of transcriptional markers, we identify multiple stages of lymphatic responses with distinct transcriptional signatures, associations with the immune microenvironment, and collagen deposition. This research advances kidney lymphatic biology, emphasizing the significance of longitudinal studies in understanding AKI and the transition to chronic kidney disease.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F869-F884"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142334169","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":"Chronic mistimed feeding results in renal fibrosis and disrupted circadian blood pressure rhythms.","authors":"Jazmine I Benjamin, Paramita Pati, Tha Luong, Xiaofen Liu, Carmen De Miguel, Jennifer S Pollock, David M Pollock","doi":"10.1152/ajprenal.00047.2024","DOIUrl":"10.1152/ajprenal.00047.2024","url":null,"abstract":"<p><p>Circadian disruption is a disturbance in biological timing, which can occur within or between different organizational levels, ranging from molecular rhythms within specific cells to the misalignment of behavioral and environmental cycles. Previous work from our group showed that less than 1 wk of food restriction to the light (inactive) period is sufficient to invert diurnal blood pressure rhythms in mice. However, kidney excretory rhythms and functions remained aligned with the light-dark cycle. Shift workers have an increased risk of cardiovascular disease that may different between sexes and often have irregular mealtimes, making the possibility of mistimed feeding as a potential contributor to the development of kidney disease. Thus, we hypothesized that chronic mistimed food intake would result in adverse cardiorenal effects, with sex differences in severity. Here, we show that chronic circadian disruption via mistimed feeding results in renal fibrosis and aortic stiffness in a sex-dependent manner. Our results indicate the importance of meal timing for the maintenance of blood pressure rhythms and kidney function, particularly in males. Our results also demonstrate that females are better able to acclimate to circadian-related behavioral change. <b>NEW & NOTEWORTHY</b> Circadian disruption through mistimed feeding resulted in nondipping blood pressure, renal fibrosis, and arterial stiffness that were less severe in females versus males. Mice fed exclusively during the daytime maintain their circadian rhythms of locomotor activity regardless of their loss of blood pressure rhythms. Although these mice ate less food, they maintained body weight, suggesting inefficiencies in overall metabolism. These findings demonstrate the importance of maintaining optimal food intake patterns to prevent cardiorenal pathophysiology.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F683-F696"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115828","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":"Macrophage SPAK deletion limits a low potassium-induced kidney inflammatory program.","authors":"Aihua Wu, Yahua Zhang, Fabian Bock, Juan Pablo Arroyo, Eric Delpire, Ming-Zhi Zhang, Raymond C Harris, Andrew S Terker","doi":"10.1152/ajprenal.00175.2024","DOIUrl":"10.1152/ajprenal.00175.2024","url":null,"abstract":"<p><p>Inadequate dietary potassium (K⁺) consumption is a significant contributor to poor cardiovascular outcomes. A diet with reduced K⁺ content has been shown to cause salt-sensitive increases in blood pressure. More recently, we have also shown that reductions in blood K⁺ can cause direct kidney injury, independent of dietary sodium (Na⁺) content. Here, we investigated the role of the kinase Ste20p-related proline-alanine-rich kinase (SPAK) in this kidney injury response. We observed that global SPAK deletion protected the kidney from the damaging effects of a diet high in Na⁺ and low in K⁺. We hypothesized that kidney macrophages were contributing to the injury response and that macrophage-expressed SPAK is essential in this process. We observed SPAK protein expression in isolated macrophages in vitro. Culture in K⁺-deficient medium increased SPAK phosphorylation and caused SPAK to localize to cytosolic puncta, reminiscent of with-no-lysine kinase (WNK) bodies identified along the distal nephron epithelium. WNK1 also adopted a punctate staining pattern under low K⁺ conditions, and SPAK phosphorylation was prevented by treatment with the WNK inhibitor WNK463. Macrophage-specific SPAK deletion in vivo protected against the low K⁺-mediated renal inflammatory and fibrotic responses. Our results highlight an important role for macrophages and macrophage-expressed SPAK in the propagation of kidney damage that occurs in response to reduced dietary K⁺ consumption.<b>NEW & NOTEWORTHY</b> Global Ste20p-related proline alanine-rich kinase (SPAK) deletion protects against harmful kidney effects of dietary K⁺ deficiency. Exposure to low K⁺ conditions increases SPAK phosphorylation and induces SPAK to adopt a punctate staining pattern. Macrophage-specific deletion of SPAK confers protection to low K⁺-induced kidney injury in vivo. Macrophage-expressed SPAK plays a key role in the development of kidney injury in response to a low K⁺ diet.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F899-F909"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303177","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":"Transition from acute kidney injury to chronic kidney disease: mechanisms, models, and biomarkers.","authors":"Tingfang Zhang, Robert E Widdop, Sharon D Ricardo","doi":"10.1152/ajprenal.00184.2024","DOIUrl":"10.1152/ajprenal.00184.2024","url":null,"abstract":"<p><p>Acute kidney injury (AKI) and chronic kidney disease (CKD) are increasingly recognized as interconnected conditions with overlapping pathophysiological mechanisms. This review examines the transition from AKI to CKD, focusing on the molecular mechanisms, animal models, and biomarkers essential for understanding and managing this progression. AKI often progresses to CKD due to maladaptive repair processes, persistent inflammation, and fibrosis, with both conditions sharing common pathways involving cell death, inflammation, and extracellular matrix (ECM) deposition. Current animal models, including ischemia-reperfusion injury (IRI) and nephrotoxic damage, help elucidate these mechanisms but have limitations in replicating the complexity of human disease. Emerging biomarkers such as kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and soluble tumor necrosis factor receptors (TNFRs) show promise in early detection and monitoring of disease progression. This review highlights the need for improved animal models and biomarker validation to better mimic human disease and enhance clinical translation. Advancing our understanding of the AKI-to-CKD transition through targeted therapies and refined research approaches holds the potential to significantly improve patient outcomes.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F788-F805"},"PeriodicalIF":0.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303178","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}