Current Opinion in Nephrology and Hypertension最新文献_第4页

Novel therapeutic approaches for phosphate regulation. 磷酸盐调节的新治疗方法。

IF 3.1 3区医学

Current Opinion in Nephrology and Hypertension Pub Date : 2026-09-01 Epub Date: 2026-05-15 DOI: 10.1097/MNH.0000000000001191

Laith Alzyood, Wei Chen

{"title":"Novel therapeutic approaches for phosphate regulation.","authors":"Laith Alzyood, Wei Chen","doi":"10.1097/MNH.0000000000001191","DOIUrl":"10.1097/MNH.0000000000001191","url":null,"abstract":"Purpose of review: Hyperphosphatemia in chronic kidney disease (CKD) is associated with vascular calcification and increased mortality. Despite widespread use of phosphate binders, treatment of hyperphosphatemia remains challenging and controversy persists regarding the optimal serum phosphate targets. This review summarizes recent clinical and experimental studies of phosphate-lowering therapies in CKD.Recent findings: To define the optimal phosphate target, the Pragmatic Trial of Higher vs. Lower Serum Phosphate Targets in Patients Undergoing Hemodialysis (HiLo) trial was conducted but was terminated early and underpowered. Oxylanthanum carbonate is a new lanthanum-based agent with phosphate-binding efficacy equivalent to lanthanum carbonate but smaller in pill size. Tenapanor, an inhibitor of paracellular phosphate transport, effectively lowers serum phosphate and reduces pill burden. AP306, formerly known as EOS789, an inhibitor of active transcellular phosphate transporters, lowers serum phosphate more effectively compared to sevelamer carbonate. As with existing phosphate binders, gastrointestinal side effects are common with these new phosphate-lowering agents. Lastly, synbiotic therapy modulates gut microbiota and reduces intestinal phosphate absorption in rats with CKD.Summary: Combining phosphate binders with agents that inhibit paracellular and transcellular intestinal phosphate absorption may improve the treatment of hyperphosphatemia while reducing pill burden in CKD. Defining optimal serum phosphate targets and the mortality benefits of phosphate lowering is essential to minimize treatment-related adverse effects.","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":" ","pages":"491-497"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel developments in untangling the significance of Epac signaling in the kidney. 解开肾脏Epac信号意义的新进展。

IF 3.1 3区医学

Current Opinion in Nephrology and Hypertension Pub Date : 2026-09-01 Epub Date: 2026-05-15 DOI: 10.1097/MNH.0000000000001198

Kyrylo Pyrshev, Oleg Zaika, Xiaodong Cheng, Oleh Pochynyuk

{"title":"Novel developments in untangling the significance of Epac signaling in the kidney.","authors":"Kyrylo Pyrshev, Oleg Zaika, Xiaodong Cheng, Oleh Pochynyuk","doi":"10.1097/MNH.0000000000001198","DOIUrl":"10.1097/MNH.0000000000001198","url":null,"abstract":"Purpose of review: Exchange proteins directly activated by cAMP (Epac1 and Epac2) are abundantly expressed in the glomerulus and epithelial cells of the renal tubule. Epac activity is rather benign at baseline, but it can be greatly potentiated in response to stress or during disease states. However, the significance of the Epac signaling cascade for kidney function is largely enigmatic. This review analyzes recently published evidence on the reno-protective actions of Epac1 and Epac2 isoforms in the pathology of glomerulonephritis and upon dietary acidification.Recent findings: Paralog-specific beneficial actions of Epac have been reported recently in the glomerulus and the collecting duct system. Activation of Epac1 promotes glycolysis and increases lactate production, thereby augmenting podocyte survival in an experimental model of glomerulonephritis. Dietary acidification greatly enhances renal Epac2, but not Epac1, expression to stimulate urinary acid excretion. Epac2 deficiency produces a distal renal tubule acidosis (RTA)-like phenotype associated with the inability to acidify urine due to impaired H + secretion by A-type intercalated cells.Summary: Activation of Epac1 and Epac2 isoforms is instrumental for defensive and adaptive responses in the pathophysiology of glomerulonephritis and metabolic acidosis. Further characterization and subsequent implementation of pharmacology-based treatments targeting individual Epac isoforms might be of considerable clinical importance.","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":" ","pages":"545-550"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of kir4.1/Kir5.1 in mediating the effect of angiotensin-II on Na-Cl-cotransporter. kir4.1/Kir5.1在介导血管紧张素- ii对na - cl -共转运蛋白影响中的作用。

IF 3.1 3区医学

Current Opinion in Nephrology and Hypertension Pub Date : 2026-09-01 Epub Date: 2026-06-03 DOI: 10.1097/MNH.0000000000001203

Wen-Hui Wang, Dao-Hong Lin

{"title":"The role of kir4.1/Kir5.1 in mediating the effect of angiotensin-II on Na-Cl-cotransporter.","authors":"Wen-Hui Wang, Dao-Hong Lin","doi":"10.1097/MNH.0000000000001203","DOIUrl":"10.1097/MNH.0000000000001203","url":null,"abstract":"Purpose of review: Angiotensin-II plays an important role in regulating thiazide-sensitive Na-Cl-cotransporter (NCC) encoded by Slc12A3. Moreover, inwardly-rectifying-K + (Kir) channels 4.1/Kir5.1 encoded by Kcnj10 and Kcnj16 have been shown to determine NCC expression/activity. This review discusses the role of Kir4.1/Kir5.1 of distal-convoluted-tubule (DCT) in mediating the effect of angiotensin-II on NCC expression/activity.Recent findings: Deletion of kidney-tubule AT1aR has no significant effect on baseline-activity of Kir4.1/Kir5.1 of DCT. However, angiotensin-II acutely stimulates Kir4.1/Kir5.1-activity and hyperpolarizes basolateral membrane predominantly in the late DCT but not in early-DCT. Angiotensin-II perfusion for 24-h stimulates NCC expression/activity, this effect is absent in kidney-tubule-specific Kir4.1-knockout mice. However, angiotensin-II perfusion for 7-days is still able to increase NCC expression/activity in kidney-tubule-specific Kir4.1-knockout mice. The deletion of AT1aR completely abolishes both short-term and long-term effects of angiotensin-II on NCC. Overnight-low-salt intake stimulates Kir4.1/Kir5.1 in DCT and NCC in wild-type mice. This effect is absent in AT1aR-knockout mice and overnight-low-salt increases renal-K + -excretion in AT1aR-knockout mice.Summary: AT1aR is not required for baseline-activity of Kir4.1/Kir5.1 but it mediates the Ang-II and the effect of low-salt-intake on Kir4.1/Kir5.1. Short-term Ang-II-induced stimulation of NCC requires Kir4.1/Kir5.1. However, Ang-II also stimulates NCC by Kir4.1/Kir5.1-independent mechanism. AT1aR plays a role in maintaining K + homeostasis during low-salt-intake.","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":" ","pages":"576-581"},"PeriodicalIF":3.1,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148204505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Parathyroid hormone levels: the lower the better the outcomes. 甲状旁腺激素水平：越低效果越好。

IF 3.1 3区医学

Current Opinion in Nephrology and Hypertension Pub Date : 2026-07-01 Epub Date: 2026-04-30 DOI: 10.1097/MNH.0000000000001188

Hirotaka Komaba

{"title":"Parathyroid hormone levels: the lower the better the outcomes.","authors":"Hirotaka Komaba","doi":"10.1097/MNH.0000000000001188","DOIUrl":"10.1097/MNH.0000000000001188","url":null,"abstract":"Purpose of review: Secondary hyperparathyroidism (SHPT) is a common complication of chronic kidney disease, particularly in patients receiving dialysis. Conventional management has emphasized avoiding excessively low PTH levels to prevent low-turnover bone disease, yet recent evidence challenges this approach. This review examines the potential of more intensive PTH control to improve skeletal and clinical outcomes.Recent findings: Although excessive suppression of PTH or low-turnover bone has been thought to impair bone strength, recent evidence indicates that intensive PTH reduction does not compromise bone integrity and may even reduce fracture risk. PTH-lowering interventions appear to limit further progression of SHPT-associated cortical porosity but cannot reverse established structural damage, underscoring the importance of early intervention. Low-turnover bone has also been hypothesized to impair calcium buffering and promote vascular calcification; however, its clinical impact seems limited in the era of widespread calcimimetic use or following parathyroidectomy. Furthermore, there is no clear evidence that excessive PTH suppression adversely affects nonskeletal organs influenced by SHPT.Summary: These findings suggest that the benefits of more intensive PTH control may outweigh potential risks, supporting a proactive management approach. Prospective interventional studies are needed to confirm whether this strategy can reduce fractures and improve survival without safety concerns.","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":" ","pages":"427-432"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Remission in diabetic kidney disease: current evidence and future directions. 糖尿病肾病的缓解：目前的证据和未来的方向。

IF 3.1 3区医学

Current Opinion in Nephrology and Hypertension Pub Date : 2026-07-01 Epub Date: 2026-05-03 DOI: 10.1097/MNH.0000000000001197

Michael Reaume, Navdeep Tangri

{"title":"Remission in diabetic kidney disease: current evidence and future directions.","authors":"Michael Reaume, Navdeep Tangri","doi":"10.1097/MNH.0000000000001197","DOIUrl":"10.1097/MNH.0000000000001197","url":null,"abstract":"Purpose of review: Diabetes is the leading cause of chronic kidney disease (CKD) worldwide. Diabetic kidney disease (DKD) has traditionally been viewed as a progressive condition characterized by declining estimated glomerular filtration rate (eGFR) and worsening albuminuria, with affected individuals facing substantially elevated risks of major adverse cardiovascular events and kidney failure. However, recent advances in pharmacologic therapies have demonstrated dramatic improvements in both cardiovascular and kidney outcomes. The objective of this review is to summarize the evidence for contemporary pharmacologic therapies in DKD, and to examine the emerging concept of disease remission in DKD.Recent findings: Randomized controlled trials of sodium-glucose cotransporter 2 inhibitors, non-steroidal mineralocorticoid receptor antagonists, and glucagon-like peptide-1 receptor agonists have demonstrated significant attenuation of eGFR decline and reductions in albuminuria. These findings have given rise to the hypothesis that, with guideline-directed therapy, some patients with DKD may achieve disease remission, defined by physiologic declines in eGFR and minimal (or resolved) albuminuria. Emerging evidence not only highlights the promise of this paradigm but also underscores the lack of standardized definitions and long-term outcome data.Summary: Emerging pharmacologic therapies are transforming DKD. Reframing DKD management from one of slowing progression to achieving remission could have important implications for clinical practice worldwide.","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":" ","pages":"480-489"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recent insights into the role of dietary phosphorus in the development and progression of chronic kidney disease-mineral and bone disorder. 膳食磷在慢性肾脏疾病-矿物质和骨骼疾病的发生和进展中的作用的最新见解。

IF 3.1 3区医学

Current Opinion in Nephrology and Hypertension Pub Date : 2026-07-01 Epub Date: 2026-04-30 DOI: 10.1097/MNH.0000000000001185

Orlando M Gutiérrez

{"title":"Recent insights into the role of dietary phosphorus in the development and progression of chronic kidney disease-mineral and bone disorder.","authors":"Orlando M Gutiérrez","doi":"10.1097/MNH.0000000000001185","DOIUrl":"10.1097/MNH.0000000000001185","url":null,"abstract":"Purpose of review: Dietary phosphorus is a central driver of chronic kidney disease-mineral and bone disorder (CKD-MBD). This review summarizes recent advances that clarify how differing forms and sources of dietary phosphorus influence bone and mineral metabolism, as well as related physiologic outcomes, in individuals with and without CKD.Recent findings: Controlled feeding studies across CKD and non-CKD populations demonstrate that reducing intake of highly bioavailable phosphorus - particularly from food additives - leads to consistent improvements in urinary phosphorus excretion, fibroblast growth factor 23, parathyroid hormone, and α-Klotho levels, with more pronounced benefits among individuals with CKD. Higher consumption of whole-grain phosphorus, which is less bioavailable, has been associated with lower cardiovascular and all-cause mortality risk and does not appear to adversely affect mineral metabolism in CKD. Additional population-based, physiologic, and translational studies further show that intake of added or highly bioavailable phosphorus is linked to greater adiposity, impaired mitochondrial ATP production, and abnormal mitochondrial responses during exercise. These observations suggest that bioavailable phosphorus has systemic metabolic effects extending beyond traditional CKD-MBD pathways.Summary: Highly bioavailable phosphorus additives disrupt mineral metabolism and contribute to broader metabolic dysfunction, supporting the need for updated dietary recommendations and further mechanistic and clinical investigation.","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":" ","pages":"447-452"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fibroblast growth factor 23 at the crossroads of mineral metabolism and bone disease. 成纤维细胞生长因子23在矿物质代谢和骨病的十字路口。

IF 3.1 3区医学

Current Opinion in Nephrology and Hypertension Pub Date : 2026-07-01 Epub Date: 2026-04-30 DOI: 10.1097/MNH.0000000000001193

Dominik Kentrup, Aline Martin

{"title":"Fibroblast growth factor 23 at the crossroads of mineral metabolism and bone disease.","authors":"Dominik Kentrup, Aline Martin","doi":"10.1097/MNH.0000000000001193","DOIUrl":"10.1097/MNH.0000000000001193","url":null,"abstract":"Purpose of review: Fibroblast growth factor 23 (FGF23) is an endocrine regulator of phosphate homeostasis produced by bone. This review aims to examine the role of FGF23 in bone biology, with a focus on its contributions to skeletal abnormalities in hereditary hypophosphatemia and chronic kidney disease (CKD).Recent findings: In hereditary hypophosphatemic disorders, FGF23 excess leads to renal phosphate wasting and impaired bone mineralization. Therapies targeting FGF23 demonstrated clear clinical benefits in restoring phosphate levels and improving skeletal defects. Recent evidence indicates that FGF23 may also exert direct effects on osteoblast differentiation independent of phosphate levels. In CKD, preclinical studies suggest that reducing FGF23 improves bone outcomes, but the contribution of FGF23 to altered osteoblast differentiation and bone loss in CKD remains to be tested directly.Summary: FGF23 contributes to bone disease both indirectly by regulating phosphate homeostasis and directly by inhibiting osteoblast differentiation. Targeting FGF23 represents a promising therapeutic approach, but in CKD, strategies blocking FGF23 must be carefully balanced against the risk of further disrupting phosphate balance. A better understanding of the mechanisms underlying the direct effects of FGF23 on bone is essential for the development of safe and effective treatments.","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":" ","pages":"406-412"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147812155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mesenchymal/stromal cell therapy in kidney diseases: an update. 肾脏疾病的间充质/基质细胞治疗：最新进展。

IF 3.1 3区医学

Current Opinion in Nephrology and Hypertension Pub Date : 2026-07-01 Epub Date: 2026-04-01 DOI: 10.1097/MNH.0000000000001184

Margaux Navez, Olivier Detry, François Jouret

{"title":"Mesenchymal/stromal cell therapy in kidney diseases: an update.","authors":"Margaux Navez, Olivier Detry, François Jouret","doi":"10.1097/MNH.0000000000001184","DOIUrl":"10.1097/MNH.0000000000001184","url":null,"abstract":"Purpose of review: This review synthesizes advanced preclinical and clinical studies published over the past 18 months evaluating mesenchymal stromal cells (MSCs) and MSC-derived products in kidney diseases. We focused on the translational relevance of MSC-based therapies against ischemia-reperfusion injury (IRI) and toxic acute kidney injury (AKI), as well as chronic kidney disease (CKD) progression in diabetic kidney disease (DKD) and lupus nephritis (LN).Recent findings: The renoprotective effects of MSC-based therapies are highly dependent on the timing of administration and the local pathological microenvironment. In IRI and AKI, therapeutic efficacy is confined to specific exposure windows and is driven by early modulation of mitochondrial dysfunction, inflammation and cell death. In DKD, MSCs from multiple sources consistently improve albuminuria, renal function and structural damage through anti-inflammatory, antifibrotic, autophagy-restoring and ferroptosis-inhibiting mechanisms. This nephroprotection appears to be largely independent of the glycaemic control. In LN, immune-contextual conditioning critically shapes the phenotypes of MSCs and MSC-derived extracellular vesicles (EVs), with optimized or engineered products outperforming the naïve approaches. In contrast, hypertension-related kidney disease illustrates how chronic ischemia and vascular remodelling limit MSC efficacy unless the underlying hemodynamic stress is corrected.Summary: Across diverse settings of acute and chronic kidney injury, MSC-based therapies act primarily as modulators of early pathogenic cascades rather than curative interventions for advanced damage. Their efficacy critically depends on timing, disease context and micro-environmental conditioning. Increasingly, cell-free strategies based on EVs offer scalable and potentially safer alternatives, supporting the translational development of context-adapted and combinatorial strategies.","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":" ","pages":"465-472"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147590544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Paracellular transport along the nephron in physiology and pathophysiology. 生理和病理生理学中沿肾元的细胞旁转运。

IF 3.1 3区医学

Current Opinion in Nephrology and Hypertension Pub Date : 2026-07-01 Epub Date: 2026-04-02 DOI: 10.1097/MNH.0000000000001183

Ali Sassi, Monika Gjorgjieva, Eric Feraille

{"title":"Paracellular transport along the nephron in physiology and pathophysiology.","authors":"Ali Sassi, Monika Gjorgjieva, Eric Feraille","doi":"10.1097/MNH.0000000000001183","DOIUrl":"10.1097/MNH.0000000000001183","url":null,"abstract":"Purpose of review: Tight junctions formed by claudins regulate paracellular permeability to sodium, chloride, calcium, magnesium, and water along the nephron, thereby enabling energy-efficient reabsorption of glomerular filtrate that limits tubular oxygen consumption.Recent findings: We review evidence from knockout models, cell lines, and single-cell analyses demonstrating highly segment-specific claudin functions along the nephron. In the proximal tubule, independent claudin-2 and claudin-10a pores mediate cation/water and anion permeability, respectively, and inducible claudin-2 deletion causes hypercalciuria and nephrocalcinosis. In the thick ascending limb, three functionally distinct cell populations express different claudin combinations, with claudin-10b driving paracellular Na + permeability and claudin-16/19 mediating Ca 2+ and Mg 2+ reabsorption. In the aldosterone-sensitive distal nephron, coupling between ENaC-ɣ and claudin-8 links transcellular Na + entry to the prevention of paracellular Na + back-leak independently of aldosterone, whereas aldosterone transcriptionally upregulates claudin-3 and claudin-8. Claudin-3 deficiency triggers compensatory upregulation of ENaC and claudins-4/8/10 to preserve sodium balance. Claudin-4 is upregulated in nephrotic syndrome and promotes NaCl retention. These findings reveal paracellular pathway's critical role in metabolic efficiency and tubulopathy pathogenesis.Summary: Claudins form segment-specific paracellular pathways that enable efficient ion and water reabsorption with low metabolic cost along the nephron. Mutations with loss of function of claudins cause tubulopathies with salt loss, hypomagnesemia, and/or nephrocalcinosis and kidney stones. Future studies using inducible and segment-specific models will be essential to identify strategies to restore paracellular transport in kidney disease.","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":" ","pages":"473-479"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147615875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New regulators of parathyroid hormone secretion. 甲状旁腺激素分泌的新调节因子。

IF 3.1 3区医学

Current Opinion in Nephrology and Hypertension Pub Date : 2026-07-01 Epub Date: 2026-05-28 DOI: 10.1097/MNH.0000000000001190

Tally Naveh-Many, Efrat Brook, Alia Hassan

{"title":"New regulators of parathyroid hormone secretion.","authors":"Tally Naveh-Many, Efrat Brook, Alia Hassan","doi":"10.1097/MNH.0000000000001190","DOIUrl":"10.1097/MNH.0000000000001190","url":null,"abstract":"Purpose of review: Parathyroid hormone (PTH) regulates mineral metabolism and bone strength. Beyond the well-characterized roles of calcium, phosphate, vitamin D, and fibroblast growth factor 23 (FGF23), emerging evidence identifies leptin as a previously under-recognized parathyroid regulator, Secondary hyperparathyroidism (SHP) is a major complication of chronic kidney disease (CKD) characterized by dysregulated PTH secretion and parathyroid hyperplasia. The intracellular signaling mechanisms driving SHP remain elusive. This review examines the role of leptin in PTH regulation and parathyroid physiology and highlights experimental and clinical evidence identifying mechanistic target of rapamycin complex 1 (mTORC1) as a critical regulator of parathyroid structure and function in CKD-SHP.Recent findings: Leptin has been shown to directly stimulate PTH secretion, at least in part by downregulating calcium-sensing receptor (CaSR) signaling, establishing a novel leptin-PTH axis. In experimental CKD, uremia triggers robust parathyroid mTORC1 activation, promoting cellular hyperplasia and PTH overproduction both of which are prevented and reversed by rapamycin. Genetic mouse models show that parathyroid-specific mTOR deletion impairs gland integrity and adaptive PTH responses, whereas constitutive mTORC1 activation via Tsc1 deletion induces autonomous gland enlargement and impaired secretory capacity. Clinically, kidney transplant recipients treated with mTOR inhibitors exhibit lower PTH levels and reduced SHP incidence compared to those receiving other immunosuppressants.Summary: mTORC1 is a central integrator of parathyroid growth, structural integrity and hormone secretion. Targeting mTORC1 signaling offers a promising therapeutic strategy for the prevention and management of CKD-associated SHP.","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":" ","pages":"419-426"},"PeriodicalIF":3.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148027891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0