{"title":"Not every organ ticks the same","authors":"Khaoula Talbi, Anette Melk","doi":"10.1038/s41581-024-00842-0","DOIUrl":"10.1038/s41581-024-00842-0","url":null,"abstract":"A new study describes the development of proteomics-based ageing clocks that calculate the biological age of specific organs and define features of extreme ageing associated with age-related diseases. Their findings support the notion that plasma proteins can be used to monitor the ageing rates of specific organs and disease progression.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 7","pages":"431-432"},"PeriodicalIF":28.6,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639752","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}
Bianca A. Nguyen, Matthew R. Alexander, David G. Harrison
{"title":"Immune mechanisms in the pathophysiology of hypertension","authors":"Bianca A. Nguyen, Matthew R. Alexander, David G. Harrison","doi":"10.1038/s41581-024-00838-w","DOIUrl":"10.1038/s41581-024-00838-w","url":null,"abstract":"Hypertension is a leading risk factor for morbidity and mortality worldwide. Despite current anti-hypertensive therapies, most individuals with hypertension fail to achieve adequate blood pressure control. Moreover, even with adequate control, a residual risk of cardiovascular events and associated organ damage remains. These findings suggest that current treatment modalities are not addressing a key element of the underlying pathology. Emerging evidence implicates immune cells as key mediators in the development and progression of hypertension. In this Review, we discuss our current understanding of the diverse roles of innate and adaptive immune cells in hypertension, highlighting key findings from human and rodent studies. We explore mechanisms by which these immune cells promote hypertensive pathophysiology, shedding light on their multifaceted involvement. In addition, we highlight advances in our understanding of autoimmunity, HIV and immune checkpoints that provide valuable insight into mechanisms of chronic and dysregulated inflammation in hypertension. This Review outlines the roles of innate and adaptive immune cells in hypertension. The authors discuss the mechanisms and important properties of immune cells that contribute to hypertension pathogenesis, such as memory and plasticity.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 8","pages":"530-540"},"PeriodicalIF":28.6,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140639953","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":"Considerations of sex as a binary variable in clinical algorithms","authors":"Dinushika Mohottige, Samira Farouk, Tonia Poteat, Asa Radix, Selma Feldman Witchel","doi":"10.1038/s41581-024-00840-2","DOIUrl":"10.1038/s41581-024-00840-2","url":null,"abstract":"Clinical algorithms that are used to guide medical decision-making often include sex as a variable. However, binary considerations of sex and/or gender might introduce bias due to potentially inaccurate assumptions about sex and gender-specific physiology, hormones and exposures. An equity-focused approach to sex and gender is essential when using clinical algorithms to ensure health equity across populations.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 6","pages":"347-348"},"PeriodicalIF":41.5,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140637530","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}
Alexander Staruschenko, R. Todd Alexander, Michael J. Caplan, Daria V. Ilatovskaya
{"title":"Calcium signalling and transport in the kidney","authors":"Alexander Staruschenko, R. Todd Alexander, Michael J. Caplan, Daria V. Ilatovskaya","doi":"10.1038/s41581-024-00835-z","DOIUrl":"10.1038/s41581-024-00835-z","url":null,"abstract":"The kidney plays a pivotal role in regulating calcium levels within the body. Approximately 98% of the filtered calcium is reabsorbed in the nephron, and this process is tightly controlled to maintain calcium homeostasis, which is required to facilitate optimal bone mineralization, preserve serum calcium levels within a narrow range, and support intracellular signalling mechanisms. The maintenance of these functions is attributed to a delicate balance achieved by various calcium channels, transporters, and calcium-binding proteins in renal cells. Perturbation of this balance due to deficiency or dysfunction of calcium channels and calcium-binding proteins can lead to severe complications. For example, polycystic kidney disease is linked to aberrant calcium transport and signalling. Furthermore, dysregulation of calcium levels can promote the formation of kidney stones. This Review provides an updated description of the key aspects of calcium handling in the kidney, focusing on the function of various calcium channels and the physiological stimuli that control these channels or are communicated through them. A discussion of the role of calcium as an intracellular second messenger and the pathophysiology of renal calcium dysregulation, as well as a summary of gaps in knowledge and future prospects, are also included. Calcium reabsorption along the nephron is essential for calcium homeostasis and whole-body electrolyte balance. Here, Staruschenko et al. highlight signalling pathways and molecules involved in renal calcium handling in health and disease, and discuss progress in the integration of systems-level and molecular understanding of calcium transport and regulation.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 8","pages":"541-555"},"PeriodicalIF":28.6,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140621675","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}
Christian Hinze, Svjetlana Lovric, Philip F. Halloran, Jonathan Barasch, Kai M. Schmidt-Ott
{"title":"Epithelial cell states associated with kidney and allograft injury","authors":"Christian Hinze, Svjetlana Lovric, Philip F. Halloran, Jonathan Barasch, Kai M. Schmidt-Ott","doi":"10.1038/s41581-024-00834-0","DOIUrl":"10.1038/s41581-024-00834-0","url":null,"abstract":"The kidney epithelium, with its intricate arrangement of highly specialized cell types, constitutes the functional core of the organ. Loss of kidney epithelium is linked to the loss of functional nephrons and a subsequent decline in kidney function. In kidney transplantation, epithelial injury signatures observed during post-transplantation surveillance are strong predictors of adverse kidney allograft outcomes. However, epithelial injury is currently neither monitored clinically nor addressed therapeutically after kidney transplantation. Several factors can contribute to allograft epithelial injury, including allograft rejection, drug toxicity, recurrent infections and postrenal obstruction. The injury mechanisms that underlie allograft injury overlap partially with those associated with acute kidney injury (AKI) and chronic kidney disease (CKD) in the native kidney. Studies using advanced transcriptomic analyses of single cells from kidney or urine have identified a role for kidney injury-induced epithelial cell states in exacerbating and sustaining damage in AKI and CKD. These epithelial cell states and their associated expression signatures are also observed in transplanted kidney allografts, suggesting that the identification and characterization of transcriptomic epithelial cell states in kidney allografts may have potential clinical implications for diagnosis and therapy. This Review describes parallels in the injury mechanisms that underlie acute kidney injury, chronic kidney disease and allograft injury, and explains how our understanding of the molecular changes that occur in epithelia in the context of kidney disease may contribute to the therapeutic targeting of specific epithelial cell phenotypes for the treatment of transplantation complications.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 7","pages":"447-459"},"PeriodicalIF":28.6,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140603902","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":"Thiazides in kidney transplant recipients: skin in the game","authors":"Steven Van Laecke","doi":"10.1038/s41581-024-00839-9","DOIUrl":"10.1038/s41581-024-00839-9","url":null,"abstract":"Clinical trial data suggest that thiazides and thiazide-like drugs could be beneficial for blood-pressure lowering in patients with severe chronic kidney disease. However, prolonged exposure to these photosensitizing drugs could translate into increased risk of squamous cell carcinoma and post-transplant diabetes in the already extremely vulnerable kidney transplant population.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 6","pages":"351-352"},"PeriodicalIF":41.5,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140607838","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}
Carmine Zoccali, Francesca Mallamaci, Liz Lightstone, Vivek Jha, Carol Pollock, Katherine Tuttle, Peter Kotanko, Andrzej Wiecek, Hans Joachim Anders, Giuseppe Remuzzi, Kamyar Kalantar-Zadeh, Adeera Levin, Raymond Vanholder
{"title":"A new era in the science and care of kidney diseases","authors":"Carmine Zoccali, Francesca Mallamaci, Liz Lightstone, Vivek Jha, Carol Pollock, Katherine Tuttle, Peter Kotanko, Andrzej Wiecek, Hans Joachim Anders, Giuseppe Remuzzi, Kamyar Kalantar-Zadeh, Adeera Levin, Raymond Vanholder","doi":"10.1038/s41581-024-00828-y","DOIUrl":"10.1038/s41581-024-00828-y","url":null,"abstract":"Notable progress in basic, translational and clinical nephrology research has been made over the past five decades. Nonetheless, many challenges remain, including obstacles to the early detection of kidney disease, disparities in access to care and variability in responses to existing and emerging therapies. Innovations in drug development, research technologies, tissue engineering and regenerative medicine have the potential to improve patient outcomes. Exciting prospects include the availability of new drugs to slow or halt the progression of chronic kidney disease, the development of bioartificial kidneys that mimic healthy kidney functions, and tissue engineering techniques that could enable transplantable kidneys to be created from the cells of the recipient, removing the risk of rejection. Cell and gene therapies have the potential to be applied for kidney tissue regeneration and repair. In addition, about 30% of kidney disease cases are monogenic and could potentially be treated using these genetic medicine approaches. Systemic diseases that involve the kidney, such as diabetes mellitus and hypertension, might also be amenable to these treatments. Continued investment, communication, collaboration and translation of innovations are crucial to realize their full potential. In addition, increasing sophistication in exploring large datasets, implementation science, and qualitative methodologies will improve the ability to deliver transformational kidney health strategies. Despite notable progress in basic, clinical and translational nephrology research in the past 50 years, many challenges remain. In this Review, the authors provide an overview of the current status and future directions in nephrology research and patient care.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 7","pages":"460-472"},"PeriodicalIF":28.6,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140346157","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}
Daniël H. van Raalte, Petter Bjornstad, David Z. I. Cherney, Ian H. de Boer, Paola Fioretto, Daniel Gordin, Frederik Persson, Sylvia E. Rosas, Peter Rossing, Jennifer A. Schaub, Katherine Tuttle, Sushrut S. Waikar, Hiddo J. L. Heerspink
{"title":"Combination therapy for kidney disease in people with diabetes mellitus","authors":"Daniël H. van Raalte, Petter Bjornstad, David Z. I. Cherney, Ian H. de Boer, Paola Fioretto, Daniel Gordin, Frederik Persson, Sylvia E. Rosas, Peter Rossing, Jennifer A. Schaub, Katherine Tuttle, Sushrut S. Waikar, Hiddo J. L. Heerspink","doi":"10.1038/s41581-024-00827-z","DOIUrl":"10.1038/s41581-024-00827-z","url":null,"abstract":"Diabetic kidney disease (DKD), defined as co-existing diabetes and chronic kidney disease in the absence of other clear causes of kidney injury, occurs in approximately 20–40% of patients with diabetes mellitus. As the global prevalence of diabetes has increased, DKD has become highly prevalent and a leading cause of kidney failure, accelerated cardiovascular disease, premature mortality and global health care expenditure. Multiple pathophysiological mechanisms contribute to DKD, and single lifestyle or pharmacological interventions have shown limited efficacy at preserving kidney function. For nearly two decades, renin–angiotensin system inhibitors were the only available kidney-protective drugs. However, several new drug classes, including sodium glucose cotransporter-2 inhibitors, a non-steroidal mineralocorticoid antagonist and a selective endothelin receptor antagonist, have now been demonstrated to improve kidney outcomes in people with type 2 diabetes mellitus. In addition, emerging preclinical and clinical evidence of the kidney-protective effects of glucagon-like-peptide-1 receptor agonists has led to the prospective testing of these agents for DKD. Research and clinical efforts are geared towards using therapies with potentially complementary efficacy in combination to safely halt kidney disease progression. As more kidney-protective drugs become available, the outlook for people living with DKD should improve in the next few decades. Several new drug classes have been demonstrated to improve kidney outcomes in people with diabetes mellitus. Here, the authors examine the evidence for the efficacy and safety of combination treatment to reduce the progression of diabetic kidney disease.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 7","pages":"433-446"},"PeriodicalIF":28.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140343431","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}
Anna Francis, Meera N. Harhay, Albert C. M. Ong, Sri Lekha Tummalapalli, Alberto Ortiz, Agnes B. Fogo, Danilo Fliser, Prabir Roy-Chaudhury, Monica Fontana, Masaomi Nangaku, Christoph Wanner, Charu Malik, Anne Hradsky, Dwomoa Adu, Sunita Bavanandan, Ana Cusumano, Laura Sola, Ifeoma Ulasi, Vivekanand Jha, American Society of Nephrology, European Renal Association, International Society of Nephrology
{"title":"Chronic kidney disease and the global public health agenda: an international consensus","authors":"Anna Francis, Meera N. Harhay, Albert C. M. Ong, Sri Lekha Tummalapalli, Alberto Ortiz, Agnes B. Fogo, Danilo Fliser, Prabir Roy-Chaudhury, Monica Fontana, Masaomi Nangaku, Christoph Wanner, Charu Malik, Anne Hradsky, Dwomoa Adu, Sunita Bavanandan, Ana Cusumano, Laura Sola, Ifeoma Ulasi, Vivekanand Jha, American Society of Nephrology, European Renal Association, International Society of Nephrology","doi":"10.1038/s41581-024-00820-6","DOIUrl":"10.1038/s41581-024-00820-6","url":null,"abstract":"Early detection is a key strategy to prevent kidney disease, its progression and related complications, but numerous studies show that awareness of kidney disease at the population level is low. Therefore, increasing knowledge and implementing sustainable solutions for early detection of kidney disease are public health priorities. Economic and epidemiological data underscore why kidney disease should be placed on the global public health agenda — kidney disease prevalence is increasing globally and it is now the seventh leading risk factor for mortality worldwide. Moreover, demographic trends, the obesity epidemic and the sequelae of climate change are all likely to increase kidney disease prevalence further, with serious implications for survival, quality of life and health care spending worldwide. Importantly, the burden of kidney disease is highest among historically disadvantaged populations that often have limited access to optimal kidney disease therapies, which greatly contributes to current socioeconomic disparities in health outcomes. This joint statement from the International Society of Nephrology, European Renal Association and American Society of Nephrology, supported by three other regional nephrology societies, advocates for the inclusion of kidney disease in the current WHO statement on major non-communicable disease drivers of premature mortality. Addressing the burden of non-communicable diseases is a global public health priority. In this joint Consensus Statement, the American Society of Nephrology, the European Renal Association and the International Society of Nephrology highlight the need to recognize kidney disease as a key driver of premature mortality, in addition to other non-communicable diseases already prioritized by the World Health Organization.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 7","pages":"473-485"},"PeriodicalIF":28.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41581-024-00820-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140343289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Kidney disease: a global health priority","authors":"","doi":"10.1038/s41581-024-00829-x","DOIUrl":"10.1038/s41581-024-00829-x","url":null,"abstract":"The prevalence of kidney disease and its associated morbidity and mortality continue to rise. This crisis cannot be tackled unless kidney disease is made a global public health priority.","PeriodicalId":19059,"journal":{"name":"Nature Reviews Nephrology","volume":"20 7","pages":"421-423"},"PeriodicalIF":28.6,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41581-024-00829-x.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140349604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}