American journal of physiology. Renal physiology最新文献

{"title":"Measuring nephron number in the healthy and diabetic rat kidney in vivo using MRI without contrast agents.","authors":"Edwin J Baldelomar, Jennifer R Charlton, Shella Keilhoz, Benjamin Kohn, Leslie D Wilson, Lingyun Ivy Xiong, Alan Garfinkel, Kevin M Bennett","doi":"10.1152/ajprenal.00088.2026","DOIUrl":"10.1152/ajprenal.00088.2026","url":null,"abstract":"<p><p>We investigated whether physiological oscillations detected by noncontrast resting-state magnetic resonance imaging (rsMRI) can be used to measure functional nephron number, nephron density, or estimated single-nephron glomerular filtration rate (eSNGFR) in vivo. We further investigated whether the observed oscillations below 0.05 Hz reflect tubuloglomerular feedback (TGF). First, we compared features of spectral power of oscillations in rsMRI with total nephron number, nephron density, glomerular filtration rate (GFR), and eSNGFR in healthy Sprague-Dawley rats (<i>n</i> = 20). We then compared features of spectral power to total nephron number in Zucker Diabetic Sprague-Dawley (ZDSD) rats (<i>n</i> = 8) with type-2 diabetes. Finally, we tested the hypothesis that spectral features associated with nephron number reflect TGF by comparing spectra before and after furosemide infusion, which blocks the Na-K-2Cl cotransporter required for TGF and attenuates TGF oscillations. In healthy rats, the median power of rsMRI oscillations below 0.05 Hz in the kidney cortex was significantly correlated (<i>P</i> < 0.05) with nephron number in all animals (<i>R</i>² = 0.68) and within sex groups (<i>R</i>², males = 0.71; <i>R</i>², females = 0.73). Median power in this range was inversely correlated with eSNGFR (<i>P</i> < 0.05, <i>R</i>² = 0.39). No spectral features were correlated with nephron density or GFR. In ZDSD rats with confirmed pathology, total power between 0.015 and 0.045 Hz was significantly correlated with nephron number (<i>R</i>² = 0.59, <i>P</i> < 0.05). In both male and female rats, furosemide caused a significant attenuation of power in rsMRI spectral peaks below 0.05 Hz throughout the cortex (<i>P</i> < 0.05). This work demonstrates the noninvasive, in vivo measurement of nephron number in healthy and diabetic rats using rsMRI, and the potential application of rsMRI to detect TGF-associated physiological fluctuations.<b>NEW & NOTEWORTHY</b> We previously showed that resting-state magnetic resonance imaging (rsMRI) detects spontaneous physiological oscillations in rat and human kidneys, potentially reflecting autoregulation mechanisms. Here, we apply rsMRI and show that the features of these oscillations can be used to measure nephron number in healthy and diabetic rats, and are associated with the tubuloglomerular feedback mechanism. Because the rsMRI scan is short (∼10 min) and noninvasive, it might be rapidly translated to measure nephron number and function in the clinic.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F643-F652"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147719181","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":"HIF-mediated regulation of glutathione-specific γ-glutamyl cyclotransferase 1 contributes to tubular cell death in renal ischemia-reperfusion injury.","authors":"Yoshitaka Kihira, Takujiro Homma, Shinji Matsunaga, Kunihisa Yamaguchi, Panagiota Tsounapi, Takehiro Yamaguchi, Yoshino Fujimura, Eiji Sato, Toshiaki Tamaki, Shuhei Tomita","doi":"10.1152/ajprenal.00179.2025","DOIUrl":"10.1152/ajprenal.00179.2025","url":null,"abstract":"<p><p>Renal ischemia-reperfusion (I/R) remains a leading cause of acute renal failure in both native and transplanted kidneys. Hypoxia-inducible factor (HIF)-1α is a protective factor against renal I/R injury (rIRI). However, the downstream mechanisms through which HIF-1α exerts its protective effects in rIRI remain to be fully elucidated. rIRI was induced in heterozygous HIF-1α knockout (hKO) mice. To establish an in vitro model of rIRI, a human tubular cell line (HK2) was subjected to hypoxia-reoxygenation (H/R). rIRI-induced hKO mice exhibited elevated serum creatinine levels compared with rIRI-induced wild-type (WT) mice. Furthermore, tubular cell death was observed earlier in WT mice during the initial phase of I/R, whereas it was reduced in hKO mice. Phagocytosis of damaged tubular cells by macrophages was diminished in hKO mice, suggesting that the clearance of cellular debris plays a critical role in renal tissue repair and regeneration. Furthermore, glutathione-specific γ-glutamyl cyclotransferase 1 (CHAC1), a known cell death inducer, was upregulated in the tubular cells of WT mice but not hKO mice following I/R. The overexpression of CHAC1 in HK2 cells induced cell death, whereas siRNA-mediated CHAC1 knockdown attenuated cell death in HK2 cells subjected to H/R. These findings collectively suggest that CHAC1 plays a pivotal role in regulating tubular cell death during rIRI. Our findings indicate that controlled cell death induction is essential for rIRI recovery. CHAC1, a key factor in this process, is a potential therapeutic target for rIRI.<b>NEW & NOTEWORTHY</b> Here, we reported that HIF-1α upregulates glutathione-specific γ-glutamyl cyclotransferase 1 (CHAC1), a regulator of cell death and oxidative stress, in rIRI. Our results suggested that CHAC1 plays a pivotal role in regulating tubular cell death during rIRI, and the controlled tubular cell death induced by CHAC1 is essential for rIRI recovery. This proposes novel mechanisms underlying rIRI recovery.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F653-F664"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147694138","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":"Remembering P. Darwin Bell, Editor-in-Chief, 2013-2020.","authors":"Pamela K Carmines, Edward W Inscho","doi":"10.1152/ajprenal.00105.2026","DOIUrl":"https://doi.org/10.1152/ajprenal.00105.2026","url":null,"abstract":"","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":"330 6","pages":"F665-F666"},"PeriodicalIF":3.4,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847262","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":"Transcription factor 21 deletion from podocyte precursors as a model for congenital nephrotic syndrome.","authors":"Vidhi Dalal, Yalu Zhou, Dilip K Deb, Benjamin R Thomson, Jonathan Nelson, Grace Ledogar, Sol Misener, Hiroshi Maekawa, Anthony Chang, Eunah Chung, Joo-Seop Park, Susan E Quaggin","doi":"10.1152/ajprenal.00490.2025","DOIUrl":"https://doi.org/10.1152/ajprenal.00490.2025","url":null,"abstract":"<p><p>Nephrotic syndrome is one of the most common causes of kidney disease in children. The glomerular and tubulointerstitial changes that occur in the kidney due to this state of high-grade proteinuria are incompletely understood. Here we report a mouse model of congenital nephrotic syndrome, induced by deletion of transcription factor 21 (<i>Tcf21</i>) from podocyte precursors, that can be used to study the injury sustained by young kidneys in response to nephrotic range proteinuria. <i>Tcf21</i> is required for normal podocyte development. Our laboratory previously showed that deletion of <i>Tcf21</i> from early podocyte progenitors abrogated the formation of normal foot processes in embryonic mice. We now show the post-natal phenotype of this deletion characterized by progressive nephrotic range proteinuria as early as 2 weeks of age. These mice developed worsening glomerulosclerosis and tubulointerstitial fibrosis, resulting in early mortality. Single cell RNA sequencing of kidneys from these mice demonstrated structural and developmental defects in podocytes caused by the absence of <i>Tcf21</i>. Parietal epithelial cells in mutant kidneys underwent secondary changes that have been shown to promote glomerular injury in other models of kidney disease. Additionally, we observed tubulointerstitial changes coincident with the massive proteinuria produced by this genetic model - namely, an expansion of fibroblasts accompanied by the appearance of a new injury cell state in the loop of Henle. These changes preceded the onset of severe, irreversible injury, presenting pathways that could be intervened upon early in disease to prevent progression of renal fibrosis.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847098","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":"Loss of Proximal Tubule Lactate Dehydrogenase A (LDHA) Exacerbates Nephrotoxic Acute Kidney Injury Through Metabolic Dysregulation.","authors":"Yan Lu, Anna A Zmijewska, Yanfeng Zhang, Gunars Osis, Matthew D Cheung, Landon Wilson, Yanlin Jiang, Sudeepthi Vejendla, Amie Traylor, Stephen Barnes, James F George, Anupam Agarwal","doi":"10.1152/ajprenal.00048.2026","DOIUrl":"https://doi.org/10.1152/ajprenal.00048.2026","url":null,"abstract":"<p><p>Acute kidney injury (AKI) involves abrupt loss of kidney function driven in part by proximal tubule metabolic stress, yet the role of glycolytic regulation in tubular injury susceptibility remains unclear. Lactate dehydrogenase A (LDHA) is a key regulator of glycolytic flux and redox balance, but its function in proximal tubules during AKI is poorly defined. In this work, we use a cisplatin-induced AKI model to investigate the role of proximal tubule LDHA in regulating metabolic responses and injury severity. Proximal tubule-specific LDHA knockout mice (PEPCK^CreLDHA^Δ/Δ) and LDHA^flox/flox controls were subjected to cisplatin-induced AKI. Untargeted metabolomics of kidney cortex and single-nucleus RNA sequencing (snRNA-seq) were performed to define metabolic and cell-specific transcriptional responses. Loss of proximal tubular LDHA exacerbated cisplatin-induced AKI, as evidenced by worsened kidney function and tubular injury, accompanied by increased expression of inflammatory markers following injury. The analysis also showed a distinct metabolic profile at baseline in LDHA-deficient kidneys, which became more pronounced after cisplatin exposure, with coordinated changes in purine and nucleotide metabolism, energy-related metabolites, and pathways linked to redox balance and mitochondrial function. snRNA-seq revealed intrinsic transcriptional changes within proximal tubule cells at baseline and after injury, reflecting cellular stress and metabolic remodeling without strong activation of classic inflammatory gene programs. Together, these findings identify proximal tubular LDHA as a key regulator of metabolic flexibility and injury tolerance in cisplatin-induced AKI, and suggest that disrupted coordination of glycolytic and nucleotide metabolism increases tubular vulnerability, highlighting metabolic regulation as a potential therapeutic target.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":""},"PeriodicalIF":3.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847070","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":"Increasing plasma sodium with Tolvaptan under regulated water intake: comparison with hypertonic saline.","authors":"Nabil William Sweis, Jennifer Tuazon, Yusra Cheema, Robert Rosa, Daniel Batlle, Gary Robertson","doi":"10.1152/ajprenal.00049.2026","DOIUrl":"10.1152/ajprenal.00049.2026","url":null,"abstract":"<p><p>In the treatment of hyponatremia, there is a potential risk of osmotic demyelination due to an excessively rapid rise in plasma sodium. We reasoned that a controlled rate of sodium increase could be achieved using a vasopressin antagonist like Tolvaptan while regulating water intake by under-replacing urine output by a constant amount relative to body weight. Studies were conducted in healthy male subjects in a clinical research unit to determine the effect of either 60 mg (<i>n</i> = 6) or 30 mg (<i>n</i> = 6) of Tolvaptan on plasma sodium, osmolality, plasma arginine vasopressin, thirst, and urine volume and osmolality. To regulate water intake, each subject ingested a volume of water equal to his urine output minus 5 mL/kg of his basal body weight every hour. Ten to 14 days later, the same subjects underwent a 6-h infusion of 3% saline, and the data were compared with the results with Tolvaptan. Both doses of Tolvaptan lowered urine osmolality and markedly increased free water clearance and urine output. Plasma sodium increased from 138 ± 0.6 to 144 ± 2.0 mEq/L and from 139 ± 0.8 to 144 ± 2.2 with Tolvaptan 60 and 30 mg, respectively, over 6 h of regulated water intake. When the same subjects were infused with hypertonic saline, the rise in plasma sodium and osmolality was nearly identical to that produced by Tolvaptan under regulated water intake. Tolvaptan can be used to achieve a controlled rise in plasma sodium by regulating water intake. Subjects with hyponatremia may benefit from this approach, which reduces their excess body water and is therefore a more physiologic way to correct hyponatremia.<b>NEW & NOTEWORTHY</b> This study shows that the rise in plasma sodium induced by the vasopressin V2-receptor antagonist Tolvaptan can be controlled by regulating water intake to under-replace urine output by a fixed amount per kilogram body weight in healthy subjects. This approach produced increases in plasma sodium that were comparable to hypertonic saline and provides a means to prevent rapid rises in plasma sodium beyond the target rate.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F530-F540"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147522944","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":"NBL1 associates with renal phenotypes in mice, but partial Nbl1 reduction does not ameliorate kidney disease.","authors":"Courtney N Willey, Rei Bufi, Yuka Takemon, Abigail Brackett, Alicia Warren, Samantha Spellacy, Daniel M Gatti, Susan Sheehan, Ron Korstanje","doi":"10.1152/ajprenal.00465.2025","DOIUrl":"10.1152/ajprenal.00465.2025","url":null,"abstract":"<p><p>Increased concentrations of neuroblastoma suppressor of tumorigenicity 1 (NBL1) in the blood have been associated with disease progression in diabetic kidney disease (DKD) and IgA nephropathy. However, it is unclear whether NBL1 is a causal factor for kidney disease and what is driving these increased concentrations in the blood. To test this, we evaluated <i>Nbl1</i> heterozygous knockout (<i>Nbl1^+/-</i>) mice in two models of kidney injury, X-linked Alport syndrome (XLAS) and chronic low-dose cisplatin treatment, and compared them with wild-type (WT) controls. In parallel, we assessed serum NBL1, kidney function, and damage, and performed a genetic analysis for the drivers of NBL1 concentrations in two independent cohorts of genetically diverse Diversity Outbred mice with XLAS (DO-XLAS), analyzing each cohort separately. Serum NBL1 was consistently associated with reduced glomerular filtration rate (GFR) across both DO-XLAS cohorts, whereas correlations with albumin-to-creatinine ratio (ACR) were variable between cohorts, and not consistently replicated. In both XLAS and cisplatin models, partial reduction of NBL1 (∼50%) in <i>Nbl1^+/-</i> mice did not alter GFR, ACR, or histological injury relative to WT controls. Genetic analysis of NBL1 concentrations in our DO-XLAS cohorts identified associations with loci on Chromosomes 4 and 17. Together, these findings indicate that elevated serum NBL1 reflects kidney injury and, under partial reduction, does not alter disease severity, consistent with NBL1 functioning as a biomarker rather than a causal driver of kidney disease.<b>NEW & NOTEWORTHY</b> Elevated NBL1 in blood correlates with end-stage kidney disease in humans with diabetic kidney disease. NBL1 also correlates with renal phenotypes in a cohort of genetically diverse mice with X-linked Alport syndrome. Studies in two different mouse models of kidney disease reveal that elevated NBL1 is not causal to kidney injury, positioning NBL1 as a biomarker with potential applicability across etiologies and clarifying its role as a consequence of renal pathology.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F582-F591"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576938","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":"Therapeutic effects of imidazoline 2 receptor activation on lower urinary tract dysfunction in a mouse model of spinal cord injury.","authors":"Mamoru Hashimoto, Sergei Karnup, Stephanie L Daugherty, Kang Jun Cho, Kanako Matsuoka, Shingo Kimura, Tadanobu Kamijo, Koichi Sugimoto, Nobutaka Shimizu, Hirotsugu Uemura, Kazutoshi Fujita, Jonathan M Beckel, Naoki Yoshimura","doi":"10.1152/ajprenal.00457.2025","DOIUrl":"10.1152/ajprenal.00457.2025","url":null,"abstract":"<p><p>This study evaluated the effects of the imidazoline I2 receptor (I2R) agonist 2-(2-benzofuranyl)-2-imidazoline (2BFI) on lower urinary tract dysfunction (LUTD) in a mouse spinal cord injury (SCI) model. Female mice were divided into three groups: spinal intact (SI), SCI with vehicle, and SCI with 2BFI beginning 2 wk postinjury. SCI was induced by complete Th8-9 spinal transection. Four weeks after SCI, conscious cystometrograms (CMG) and external urethral sphincter (EUS) electromyography (EMG) were recorded. L6-S1 dorsal root ganglia (DRG) were collected for qPCR analysis of TRPV1, tumor necrosis factor α (TNF-α), and inducible nitric oxide synthase (iNOS). In a separate group of animals, intrathecal (i.t.) 2BFI was tested during CMG/EMG in SCI. Organ bath studies assessed 2BFI-induced relaxation in bladder strips precontracted with KCl or carbachol. SCI mice showed increased nonvoiding contractions (NVCs) and reduced voiding efficiency versus SI. 2BFI significantly decreased NVCs, improved voiding efficiency, and prolonged EUS relaxation, evident as reduced EMG activity compared with vehicle. SCI-induced upregulation of TRPV1, TNF-α, and iNOS in DRG was significantly attenuated by 2BFI. I.t. 2BFI reduced residual urine and NVCs and increased EUS relaxation in SCI mice. In organ baths, 2BFI produced significant relaxation of precontracted bladder strips from both SI and SCI mice. I2R activation in the lumbosacral spinal cord and bladder may provide an effective therapeutic strategy for SCI-induced LUTD.<b>NEW & NOTEWORTHY</b> This study shows that selective activation of the imidazoline-2 receptor improves both detrusor overactivity and detrusor-sphincter dyssynergia after spinal cord injury. Systemic and intrathecal administration of 2BFI produced coordinated actions in the spinal cord and lower urinary tract, including enhanced relaxation of the external urethral sphincter, reduced inflammation mediated by C-fiber afferents, and direct relaxation of bladder smooth muscle, indicating a promising therapeutic target.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F592-F600"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147576906","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":"Publisher's note.","authors":"","doi":"10.1152/ajprenal.00118.2026_NOT","DOIUrl":"https://doi.org/10.1152/ajprenal.00118.2026_NOT","url":null,"abstract":"","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":"330 5","pages":"F641"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147847316","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 many roles of the calcium-sensing receptor in the kidney.","authors":"Miguel A Gutierrez-Gallardo, Jessica Paola Bahena-Lopez, David H Ellison, Gerardo Gamba","doi":"10.1152/ajprenal.00415.2025","DOIUrl":"10.1152/ajprenal.00415.2025","url":null,"abstract":"<p><p>The calcium-sensing receptor (CaSR) is a central regulator of renal mineral homeostasis and tubular function. Since the discovery of its expression in the kidney, numerous studies have demonstrated that its actions are finely distributed along the nephron. Through these segment-specific mechanisms, the CaSR orchestrates diverse physiological processes: contributes to the integrity of the filtration barrier, regulates proximal and distal tubular handling of essential ions such as calcium, magnesium, and sodium, and influences water transport and acid-base balance, integrating mineral metabolism with overall renal function. Collectively, these functions establish the CaSR as a key integrator of nephron physiology, linking calcium sensing to ion transport, cellular signaling, and renal protection under both physiological and pathological conditions.</p>","PeriodicalId":93867,"journal":{"name":"American journal of physiology. Renal physiology","volume":" ","pages":"F565-F581"},"PeriodicalIF":3.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147523002","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}