Current Opinion in Nephrology and Hypertension最新文献

{"title":"Vasopressin, protein metabolism, and water conservation.","authors":"Joshua S Carty, Jason A Watts, Juan Pablo Arroyo","doi":"10.1097/MNH.0000000000001012","DOIUrl":"10.1097/MNH.0000000000001012","url":null,"abstract":"<p><strong>Purpose of review: </strong>Highlight the mechanisms through which vasopressin and hypertonic stress regulate protein metabolism.</p><p><strong>Recent findings: </strong>Mammals have an 'aestivation-like' response in which hypertonic stress increases muscle catabolism and urea productionVasopressin can directly regulate ureagenesis in the liver and the kidneyIn humans chronic hypertonic stress is associated with premature aging, diabetes, cardiovascular disease, and premature mortality.</p><p><strong>Summary: </strong>There is an evolutionarily conserved 'aestivation-like' response in humans in which hypertonic stress results in activation of the vasopressin system, muscle catabolism, and ureagenesis in order to promote water conservation.</p>","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":" ","pages":"512-517"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11290986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141455781","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}

{"title":"Aldosterone-independent regulation of K + secretion in the distal nephron.","authors":"John Demko, Robert Weber, David Pearce, Bidisha Saha","doi":"10.1097/MNH.0000000000001006","DOIUrl":"10.1097/MNH.0000000000001006","url":null,"abstract":"<p><strong>Purpose of review: </strong>Maintenance of plasma K + concentration within a narrow range is critical to all cellular functions. The kidneys are the central organ for K + excretion, and robust renal excretory responses to dietary K + loads are essential for survival. Recent advances in the field have challenged the view that aldosterone is at the center of K + regulation. This review will examine recent findings and propose a new mechanism for regulating K + secretion.</p><p><strong>Recent findings: </strong>Local aldosterone-independent response systems in the distal nephron are increasingly recognized as key components of the rapid response to an acute K + load, as well as playing an essential role in sustained responses to increased dietary K + . The master kinase mTOR, best known for its role in mediating the effects of growth factors and insulin on growth and cellular metabolism, is central to these aldosterone-independent responses. Recent studies have shown that mTOR, particularly in the context of the \"type 2\" complex (mTORC2), is regulated by K + in a cell-autonomous fashion.</p><p><strong>Summary: </strong>New concepts related to cell-autonomous K + signaling and how it interfaces with aldosterone-dependent regulation are emerging. The underlying signaling pathways and effectors of regulated K + secretion, as well as implications for the aldosterone paradox and disease pathogenesis are discussed.</p>","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":" ","pages":"526-534"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11290980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418208","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}

{"title":"The role of claudins in renal transepithelial transport and kidney disease.","authors":"Arnold Tsamo Tetou, Dorothee Günzel","doi":"10.1097/MNH.0000000000001003","DOIUrl":"10.1097/MNH.0000000000001003","url":null,"abstract":"<p><strong>Purpose of review: </strong>25 years after the discovery of claudins as the central constituents of tight junctions, the \"hunter-gatherer phase\" of claudin research is coming to an end. Deficiency in individual claudins as a cause of rare hereditary diseases is well documented. However, knowledge about the involvement of renal claudins in common kidney diseases and strategies to utilize claudins or their regulators for intervention are still scarce. The present review summarizes novel approaches to address these questions.</p><p><strong>Recent findings: </strong>Publicly accessible omics data provide new insights not only into general claudin expression patterns along the nephron, but also into sex-specific differences in claudin expression and into claudin dysregulation in renal injury. Computational association studies identify claudin variants as risk factors for kidney disease such as nephrolithiasis or loss of filtration capacity. The establishment of innovative cell culture and organoid models contributes to a better understanding of junctional and extra-junctional functions of individual claudins.</p><p><strong>Summary: </strong>The current studies lay the foundation for the identification of upstream regulators of renal claudin expression and thus for the development of new concepts for the treatment of kidney disease.</p>","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":" ","pages":"535-542"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897504","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}

{"title":"Cancer drugs and acute kidney injury: new therapies and new challenges.","authors":"Ittamar Gork, Fei Xiong, Abhijat Kitchlu","doi":"10.1097/MNH.0000000000001001","DOIUrl":"10.1097/MNH.0000000000001001","url":null,"abstract":"<p><strong>Purpose of review: </strong>Cancer therapies continue to evolve at a rapid pace and although novel treatments, including immunotherapies and targeted therapies have allowed for substantial improvements in cancer survival, they carry associated risks of acute kidney injury (AKI). We aim to summarize the existing literature on AKI associated with the spectrum of systemic cancer treatments, including conventional chemotherapies, newer immunotherapies, and the growing number of targeted cancer therapies, which may be associated with both AKI and 'pseudo-AKI'.</p><p><strong>Recent findings: </strong>Conventional cytotoxic chemotherapies (e.g. cisplatin and other platinum-based agents, methotrexate, pemetrexed, ifosfamide, etc.) with well recognized nephrotoxicities (predominantly tubulointerstitial injury) remain in widespread use. Immunotherapies (e.g., immune checkpoint inhibitors and CAR-T therapies) may be associated with kidney immune-related adverse events, most often acute interstitial nephritis, and rarely, glomerular disease. Recently, multiple targeted cancer therapies have been associated with reduced renal tubular secretion of creatinine, causing elevations in serum creatinine and apparent 'pseudo-AKI'. To complicate matters further, these agents have had biopsy-proven, 'true' kidney injury attributed to them in numerous case reports.</p><p><strong>Summary: </strong>Clinicians in nephrology and oncology must be aware of the various potential kidney risks with these agents and recognize those with clinically meaningful impact on both cancer and kidney outcomes.</p>","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":" ","pages":"474-485"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140850798","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}

{"title":"Therapeutic approaches for pulmonary hypertension in patients with chronic kidney disease.","authors":"Marcelle Tuttle, Mark J Sarnak, Sankar D Navaneethan","doi":"10.1097/MNH.0000000000001008","DOIUrl":"10.1097/MNH.0000000000001008","url":null,"abstract":"<p><strong>Purpose of review: </strong>Pulmonary hypertension is a common comorbidity in patients with chronic kidney disease (CKD), but therapeutic options are limited. We discuss the epidemiology of pulmonary hypertension in patients with CKD and review therapies for pulmonary hypertension with a focus on emerging treatments for pulmonary arterial hypertension (PAH).</p><p><strong>Recent findings: </strong>The definition of pulmonary hypertension has been updated to a lower threshold of mean pulmonary artery pressures of more than 20 mmHg, potentially leading to more patients with CKD to qualify for the diagnosis of pulmonary hypertension. Endothelin receptor antagonists, a class of medications, which demonstrated efficacy in patients with PAH, have been shown to slow progression of CKD, but their efficacy in lowering pulmonary artery pressures and their effects on reducing cardiovascular mortality in this population remains unproven. Sotatercept, a novel activin signaling inhibitor, which was previously studied in dialysis patients has been shown to increase exercise capacity in patients with PAH. These studies may lead to new specific therapies for pulmonary hypertension in patients with CKD.</p><p><strong>Summary: </strong>Pulmonary hypertension is common in patients with CKD. Although our understanding of factors leading to pulmonary hypertension in this population have evolved, evidence supporting disease-specific therapy in CKD is limited arguing for larger, long-term studies.</p>","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":" ","pages":"494-502"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11290985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426576","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}

{"title":"Postnatal renal tubule development: roles of tubular flow and flux.","authors":"Yi-Jing G Cheng, Chien-Chou Chen, Chih-Jen Cheng","doi":"10.1097/MNH.0000000000001007","DOIUrl":"10.1097/MNH.0000000000001007","url":null,"abstract":"<p><strong>Purpose of review: </strong>Postnatal renal tubule development is critical to adult kidney function. Several postnatal changes regulate the differentiation and proliferation of renal tubular cells. Here, we review the literature and our efforts on thick ascending limb (TAL) development in Bartter syndrome (BS).</p><p><strong>Recent findings: </strong>Glomerular filtrate quickly increases after birth, imposing fluid shear stress and circumferential stretch on immature renal tubules. Recent studies showed that kidney organoids under flow (superfusion) have better development of tubular structures and the expression of cilia and solute transporters. These effects are likely mediated by mechanosensors, such as cilia and the piezo1 channel. Improved renal oxygenation and sodium pump-dependent active transport can stimulate mitochondrial respiration and biogenesis. The functional coupling between transport and mitochondria ensures ATP supply for energy-demanding reactions in tubular cells, including cell cycle progression and proliferation. We recently discovered that postnatal renal medulla maturation and TAL elongation are impaired in Clc-k2-deficient BS mice. Primary cultured Clc-k2-deficient TAL cells have G1-S transition and proliferation delay. These developmental defects could be part of the early pathogenesis of BS and worsen the phenotype.</p><p><strong>Summary: </strong>Understanding how tubular flow and transepithelial ion fluxes regulate renal tubule development may improve the treatment of congenital renal tubulopathies.</p>","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":" ","pages":"518-525"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11290981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141442246","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}

{"title":"Revisiting resistant hypertension in kidney disease.","authors":"Shweta Bansal","doi":"10.1097/MNH.0000000000001002","DOIUrl":"10.1097/MNH.0000000000001002","url":null,"abstract":"<p><strong>Purpose of review: </strong>As compared to controlled or uncontrolled hypertension, resistant hypertension in patients with chronic kidney disease (CKD) poses a significantly increased healthcare burden due to greater target end-organ damage including cardiovascular disease and CKD progression. Patients with CKD have two to three times higher risk of developing resistant hypertension. True resistant hypertension needs to be distinguished from apparent treatment resistant hypertension (aTRH); however, it is usually not possible in epidemiological studies. Moreover, impact of contemporary guidelines changes in the target blood pressure (BP) goal to less than 130/80 mmHg remains to be determined.</p><p><strong>Recent findings: </strong>Up to half of patients with CKD meet aTRH criteria using 2017 ACC/AHA target BP less than 130/80 mmHg. Excess sodium retention in extracellular and tissue compartment remains the cornerstone cause of resistance to the treatment in CKD. Maximizing and optimizing the diuretic regimen in addition to dietary sodium restriction plays a critical role in these patients. Management requires a trustworthy provider-patient relationship facilitating identification and intervention for the barriers restricting the uptake of lifestyle modifications and medications. Recently, renal denervation has been approved and many other novel agents are on the horizon for treatment of true resistant hypertension associated with CKD.</p><p><strong>Summary: </strong>This review discusses the latest in the pathophysiology, definition, identification and treatment strategies of resistant hypertension in individuals with CKD. Further investigations are required to identify the prevalence, future implication and treatment outcome data for true resistant hypertension associated with CKD.</p>","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":" ","pages":"465-473"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11296285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140897501","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}

{"title":"Synergistic susceptibility to environmental lead toxicity in chronic kidney disease.","authors":"John Danziger","doi":"10.1097/MNH.0000000000000991","DOIUrl":"10.1097/MNH.0000000000000991","url":null,"abstract":"<p><strong>Purpose of review: </strong>While high levels of lead exposure, as occurs accidentally or occupationally, can cause toxicity across multiple organ systems, the hazard of commonly encountered levels of lead in the environment remains unresolved. Challenges to researching the health effects of lead include its complex interplay with renal function, rendering analyses at risk of unaccounted confounding, and the likely small effect size of environmental levels of exposure. While children are known to be disproportionately susceptible to lead toxicity, resulting in appropriately more stringent regulatory surveillance for those under 5 years old, emerging evidence suggests that those with chronic kidney disease (CKD) similarly are at a greater risk. This review summarizes the role of environmental lead toxicity as a potential cause and consequence of CKD.</p><p><strong>Recent findings: </strong>Whether environmental lead exposure causes CKD remains debatable, with little recent research advancing the conflicting, mostly cross-sectional, analyses from years ago. However, an emerging body of evidence suggests that CKD increases the susceptibility to lead toxicity. Higher circulating lead levels and lower urinary excretion result in greater lead accumulation in CKD, with simultaneous greater risk of clinically meaningful disease. Recent studies suggest that levels of lead found commonly in the United States drinking water supply, and currently permissible by the Environmental Protection Agency, associate with hematologic toxicity in those with advanced CKD. Whether environmental lead contamination may have additional negative health impact among this at-risk population, including cardiovascular and neurocognitive disease, warrants further study.</p><p><strong>Summary: </strong>The underlying pathophysiology of kidney disease synergizes the susceptibility to environmental lead toxicity for those with CKD. Low levels of exposure, as found commonly in the United States water supply, may have adverse health impact in CKD. Further research will be needed to determine if more stringent environmental regulations are warranted to protect the health of all.</p>","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":" ","pages":"543-550"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626266","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}

{"title":"Antineutrophil cytoplasmic antibody-associated vasculitis.","authors":"Raghunandan Konda, Arun Rajasekaran, Dana V Rizk","doi":"10.1097/MNH.0000000000001004","DOIUrl":"10.1097/MNH.0000000000001004","url":null,"abstract":"<p><strong>Purpose of review: </strong>This review focuses on latest developments in managing antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), a systemic autoimmune condition characterized by inflammation and necrosis of small blood vessels due to circulating autoantibodies that target neutrophilic granules.</p><p><strong>Recent findings: </strong>Our understanding of AAV pathogenesis has evolved in the past decades highlighting the central pathogenic roles of autoantibodies and complement activation. In parallel, the appreciation for glucocorticoid toxicity has led the research on crucial steroid-sparing therapeutic alternatives. Complement inhibitors (like avacopan) that have emerged are associated with better preservation of kidney function in AAV patients with severe kidney impairment. The role of plasma-exchange (PLEX) was revisited in updated guidelines that recommended its potential use in the context of diffuse alveolar hemorrhage associated hypoxia and severe kidney involvement, particularly with a serum creatinine level above 3.4 mg/dl. The ANCA Kidney Risk Score risk prediction and Glucocorticoid Toxicity Index score aid in identifying high-risk patients and individualizing management plans.</p><p><strong>Summary: </strong>Kidney involvement in AAV requires prompt diagnosis and initiation of immunosuppression to prevent irreversible nephron loss. Newer therapeutic targets are on the horizon and offer hope for personalized treatment strategies.</p>","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":" ","pages":"503-511"},"PeriodicalIF":2.2,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141087302","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}

{"title":"New insights into renal calcium-sensing receptor activation.","authors":"Henrik Dimke","doi":"10.1097/MNH.0000000000000998","DOIUrl":"10.1097/MNH.0000000000000998","url":null,"abstract":"<p><strong>Purpose of review: </strong>Activation of the calcium-sensing receptor (CASR) in the parathyroid gland suppresses the release of parathyroid hormone (PTH). Furthermore, activation of the renal CASR directly increases the urinary excretion of calcium, by inhibiting transepithelial calcium transport in the nephron. Gain-of-function mutations in the CASR gene lead to autosomal dominant hypocalcemia 1 (ADH1), with inappropriately low PTH levels and hypocalcemia, indicative of excessive activation of the parathyroid CASR. However, hypercalciuria is not always observed. The reason why the manifestation of hypercalciuria is not uniform among ADH1 patients is not well understood.</p><p><strong>Recent findings: </strong>Direct activation of the CASR in the kidney has been cumbersome to study, and an indirect measure to effectively estimate the degree of CASR activation following chronic hypercalcemia or genetic gain-of-function CASR activation has been lacking. Studies have shown that expression of the pore-blocking claudin-14 is strongly stimulated by the CASR in a dose-dependent manner. This stimulatory effect is abolished after renal Casr ablation in hypercalcemic mice, suggesting that claudin-14 abundance may gauge renal CASR activation. Using this marker has led to unexpected discoveries regarding renal CASR activation.</p><p><strong>Summary: </strong>These new studies have informed on renal CASR activation thresholds and the downstream CASR-regulated calcium transport mechanisms.</p>","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":" ","pages":"433-440"},"PeriodicalIF":3.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862386","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}