{"title":"Renal nerves in physiology, pathophysiology and interoception","authors":"Louise C. Evans, Alex Dayton, John W. Osborn","doi":"10.1038/s41581-024-00893-3","DOIUrl":"https://doi.org/10.1038/s41581-024-00893-3","url":null,"abstract":"<p>Sympathetic efferent renal nerves have key roles in the regulation of kidney function and blood pressure. Increased renal sympathetic nerve activity is thought to contribute to hypertension by promoting renal sodium retention, renin release and renal vasoconstriction. This hypothesis led to the development of catheter-based renal denervation (RDN) for the treatment of hypertension. Two RDN devices that ablate both efferent and afferent renal nerves received FDA approval for this indication in 2023. However, in animal models, selective ablation of afferent renal nerves resulted in comparable anti-hypertensive effects to ablation of efferent and afferent renal nerves and was associated with a reduction in sympathetic nerve activity. Selective afferent RDN also improved kidney function in a chronic kidney disease model. Notably, the beneficial effects of RDN extend beyond hypertension and chronic kidney disease to other clinical conditions that are associated with elevated sympathetic nerve activity, including heart failure and arrhythmia. These findings suggest that the kidney is an interoceptive organ, as increased renal sensory nerve activity modulates sympathetic activity to other organs. Future studies are needed to translate this knowledge into novel therapies for the treatment of hypertension and other cardiorenal diseases.</p>","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"37 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142368964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Risk of kidney failure among patients with genetic kidney diseases","authors":"Susan J. Allison","doi":"10.1038/s41581-024-00896-0","DOIUrl":"10.1038/s41581-024-00896-0","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 11","pages":"705-705"},"PeriodicalIF":28.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metabolism at the crossroads of inflammation and fibrosis in chronic kidney disease","authors":"Verónica Miguel, Isaac W. Shaw, Rafael Kramann","doi":"10.1038/s41581-024-00889-z","DOIUrl":"https://doi.org/10.1038/s41581-024-00889-z","url":null,"abstract":"<p>Chronic kidney disease (CKD), defined as persistent (>3 months) kidney functional loss, has a growing prevalence (>10% worldwide population) and limited treatment options. Fibrosis driven by the aberrant accumulation of extracellular matrix is the final common pathway of nearly all types of chronic repetitive injury in the kidney and is considered a hallmark of CKD. Myofibroblasts are key extracellular matrix-producing cells that are activated by crosstalk between damaged tubules and immune cells. Emerging evidence indicates that metabolic alterations are crucial contributors to the pathogenesis of kidney fibrosis by affecting cellular bioenergetics and metabolite signalling. Immune cell functions are intricately connected to their metabolic characteristics, and kidney cells seem to undergo cell-type-specific metabolic shifts in response to damage, all of which can determine injury and repair responses in CKD. A detailed understanding of the heterogeneity in metabolic reprogramming of different kidney cellular subsets is essential to elucidating communication processes between cell types and to enabling the development of metabolism-based innovative therapeutic strategies against CKD.</p>","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"21 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142236209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Polygenic scores and their applications in kidney disease","authors":"Atlas Khan, Krzysztof Kiryluk","doi":"10.1038/s41581-024-00886-2","DOIUrl":"https://doi.org/10.1038/s41581-024-00886-2","url":null,"abstract":"<p>Genome-wide association studies (GWAS) have uncovered thousands of risk variants that individually have small effects on the risk of human diseases, including chronic kidney disease, type 2 diabetes, heart diseases and inflammatory disorders, but cumulatively explain a substantial fraction of disease risk, underscoring the complexity and pervasive polygenicity of common disorders. This complexity poses unique challenges to the clinical translation of GWAS findings. Polygenic scores combine small effects of individual GWAS risk variants across the genome to improve personalized risk prediction. Several polygenic scores have now been developed that exhibit sufficiently large effects to be considered clinically actionable. However, their clinical use is limited by their partial transferability across ancestries and a lack of validated models that combine polygenic, monogenic, family history and clinical risk factors. Moreover, prospective studies are still needed to demonstrate the clinical utility and cost-effectiveness of polygenic scores in clinical practice. Here, we discuss evolving methods for developing polygenic scores, best practices for validating and reporting their performance, and the study designs that will empower their clinical implementation. We specifically focus on the polygenic scores relevant to nephrology and other chronic, complex diseases and review their key limitations, necessary refinements and potential clinical applications.</p>","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"8 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142231346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chee Kay Cheung, Suceena Alexander, Heather N. Reich, Haresh Selvaskandan, Hong Zhang, Jonathan Barratt
{"title":"The pathogenesis of IgA nephropathy and implications for treatment","authors":"Chee Kay Cheung, Suceena Alexander, Heather N. Reich, Haresh Selvaskandan, Hong Zhang, Jonathan Barratt","doi":"10.1038/s41581-024-00885-3","DOIUrl":"https://doi.org/10.1038/s41581-024-00885-3","url":null,"abstract":"<p>IgA nephropathy (IgAN) is a common form of primary glomerulonephritis and represents an important cause of chronic kidney disease globally, with observational studies indicating that most patients are at risk of developing kidney failure within their lifetime. Several research advances have provided insights into the underlying disease pathogenesis, framed by a multi-hit model whereby an increase in circulating IgA1 that lacks galactose from its hinge region — probably derived from the mucosal immune system — is followed by binding of specific IgG and IgA antibodies, generating immune complexes that deposit within the glomeruli, which triggers inflammation, complement activation and kidney damage. Although treatment options are currently limited, new therapies are rapidly emerging that target different pathways, cells and mediators involved in the disease pathogenesis, including B cell priming in the gut mucosa, the cytokines APRIL and BAFF, plasma cells, complement activation and endothelin pathway activation. As more treatments become available, there is a realistic possibility of transforming the long-term outlook for many individuals with IgAN.</p>","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"2020 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A novel mechanism of sodium and fluid retention in liver disease","authors":"Ellen F. Carney","doi":"10.1038/s41581-024-00892-4","DOIUrl":"10.1038/s41581-024-00892-4","url":null,"abstract":"","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 10","pages":"635-635"},"PeriodicalIF":28.6,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142123521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reference-trial-informed design to explore treatment effects in trial-underrepresented subgroups","authors":"Paris J. Baptiste","doi":"10.1038/s41581-024-00888-0","DOIUrl":"https://doi.org/10.1038/s41581-024-00888-0","url":null,"abstract":"<p>Randomized controlled trials (RCT) are often regarded as the ‘gold standard’ of clinical evidence. However, their strict eligibility criteria can impact cohort diversity and limit the inclusion of some subgroups, including patients with comorbidities, older individuals or those from minority ethnic groups. Observational data, including data from electronic health records, can be used to bridge the gap in evidence but are subject to bias and confounding owing to the lack of randomization.</p><p>The ‘target trial’ emulation framework, which emulates the design of a hypothetical ‘target trial’ using observational data, has increasingly been used for causal inference<sup>1,2</sup>. Despite this approach implementing design decisions to limit the effects of bias and confounding, uncertainty remains as to whether the observed result aligns with those which would have been obtained in RCT settings. Using a specified existing RCT (the ‘reference trial’) offers an opportunity to add further validity to inferences. This goal is achieved by basing the target trial design on the reference trial and benchmarking findings from the emulated study against the reference trial results. This approach adds confidence to the results obtained from the observational study before extending analysis to trial-underrepresented groups.</p>","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"35 1","pages":""},"PeriodicalIF":41.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142118057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Towards an effective obstetric nephrology care: the Mansoura experience","authors":"Rasha Shemies","doi":"10.1038/s41581-024-00887-1","DOIUrl":"10.1038/s41581-024-00887-1","url":null,"abstract":"For women with kidney disease of childbearing age, kidney care should feature discussions of pregnancy, including informed counseling and support. Health disparities between regions with different levels of income are undeniable, but special care programs aimed at the early identification and management of patients at risk can greatly decrease the magnitude of the problem.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 12","pages":"767-767"},"PeriodicalIF":28.6,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}