Pub Date : 2024-05-01Epub Date: 2024-02-29DOI: 10.1097/MNH.0000000000000978
Kevin Bodker, Natalie Freidin, Nayan Arora
Purpose of this review: Metabolic acidosis is frequently encountered in patients with chronic kidney disease (CKD), with increasing prevalence as kidney function worsens. Treating electrolyte disturbances is the sine qua non of Nephrologists, and alkali therapy to normalize serum bicarbonate levels and slow progression of kidney disease has been embedded in clinical practice guidelines for decades on the basis of animal models and controversial clinical trials. This review will critically appraise the literature base for this recommendation and determine whether the available evidence supports this common practice, which is a timely endeavor considering the impending demotion of metabolic acidosis treatment from recommendation to practice point in forthcoming KDIGO guidelines.
Recent findings: Earlier, open-label, studies supporting the utility of sodium bicarbonate therapy to slow progression of chronic kidney disease have been challenged by more recent, blinded, studies failing to show benefit on CKD progression. This was further demonstrated in the absence of concomitant sodium administration with the hydrochloric acid binder veverimer, which failed to demonstrate benefit on renal death, end stage kidney disease or 40% reduction in estimated glomerular filtration rate in a large multicenter trial.
Summary: The current body of literature does not support the routine treatment of metabolic acidosis in patients with CKD and the authors agree with the forthcoming KDIGO guidelines to de-emphasize this common practice.
{"title":"A basic solution for a complex problem: does treatment of metabolic acidosis slow CKD progression?","authors":"Kevin Bodker, Natalie Freidin, Nayan Arora","doi":"10.1097/MNH.0000000000000978","DOIUrl":"10.1097/MNH.0000000000000978","url":null,"abstract":"<p><strong>Purpose of this review: </strong>Metabolic acidosis is frequently encountered in patients with chronic kidney disease (CKD), with increasing prevalence as kidney function worsens. Treating electrolyte disturbances is the sine qua non of Nephrologists, and alkali therapy to normalize serum bicarbonate levels and slow progression of kidney disease has been embedded in clinical practice guidelines for decades on the basis of animal models and controversial clinical trials. This review will critically appraise the literature base for this recommendation and determine whether the available evidence supports this common practice, which is a timely endeavor considering the impending demotion of metabolic acidosis treatment from recommendation to practice point in forthcoming KDIGO guidelines.</p><p><strong>Recent findings: </strong>Earlier, open-label, studies supporting the utility of sodium bicarbonate therapy to slow progression of chronic kidney disease have been challenged by more recent, blinded, studies failing to show benefit on CKD progression. This was further demonstrated in the absence of concomitant sodium administration with the hydrochloric acid binder veverimer, which failed to demonstrate benefit on renal death, end stage kidney disease or 40% reduction in estimated glomerular filtration rate in a large multicenter trial.</p><p><strong>Summary: </strong>The current body of literature does not support the routine treatment of metabolic acidosis in patients with CKD and the authors agree with the forthcoming KDIGO guidelines to de-emphasize this common practice.</p>","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139989579","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}
Pub Date : 2024-04-26DOI: 10.1097/MNH.0000000000000995
Guillaume Courbon, Valentin David
PURPOSE OF THE REVIEW Iron deficiency regulates the production of the bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23) but also its cleavage, to generate both intact (iFGF23) and C-terminal (Cter)-FGF23 peptides. Novel studies demonstrate that independently of the phosphaturic effects of iFGF23, Cter-FGF23 peptides play an important role in the regulation of systemic iron homeostasis. This review describes the complex interplay between iron metabolism and FGF23 biology. RECENT FINDINGS C-terminal (Cter) FGF23 peptides antagonize inflammation-induced hypoferremia to maintain a pool of bioavailable iron in the circulation. A key mechanism proposed is the down-regulation of the iron-regulating hormone hepcidin by Cter-FGF23. SUMMARY In this manuscript, we discuss how FGF23 is produced and cleaved in response to iron deficiency, and the principal functions of cleaved C-terminal FGF23 peptides. We also review possible implications anemia of chronic kidney disease (CKD).
{"title":"Fibroblast growth factor 23 is pumping iron: C-terminal-fibroblast growth factor 23 cleaved peptide and its function in iron metabolism.","authors":"Guillaume Courbon, Valentin David","doi":"10.1097/MNH.0000000000000995","DOIUrl":"https://doi.org/10.1097/MNH.0000000000000995","url":null,"abstract":"PURPOSE OF THE REVIEW\u0000Iron deficiency regulates the production of the bone-derived phosphaturic hormone fibroblast growth factor 23 (FGF23) but also its cleavage, to generate both intact (iFGF23) and C-terminal (Cter)-FGF23 peptides. Novel studies demonstrate that independently of the phosphaturic effects of iFGF23, Cter-FGF23 peptides play an important role in the regulation of systemic iron homeostasis. This review describes the complex interplay between iron metabolism and FGF23 biology.\u0000\u0000\u0000RECENT FINDINGS\u0000C-terminal (Cter) FGF23 peptides antagonize inflammation-induced hypoferremia to maintain a pool of bioavailable iron in the circulation. A key mechanism proposed is the down-regulation of the iron-regulating hormone hepcidin by Cter-FGF23.\u0000\u0000\u0000SUMMARY\u0000In this manuscript, we discuss how FGF23 is produced and cleaved in response to iron deficiency, and the principal functions of cleaved C-terminal FGF23 peptides. We also review possible implications anemia of chronic kidney disease (CKD).","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140652506","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}
Pub Date : 2024-04-25DOI: 10.1097/MNH.0000000000000993
T. Harrison, Meghan J Elliott, Marcello Tonelli
PURPOSE OF REVIEW Personalized approaches to care are increasingly common in clinical nephrology. Although risk prediction models are developed to estimate the risk of kidney-disease related outcomes, they infrequently consider the priorities of patients they are designed to help. RECENT FINDINGS This review discusses certain steps in risk prediction tool development where patients and their priorities can be incorporated. Considering principles of equity throughout the process has been the focus of recent literature. SUMMARY Applying a person-centred lens has implications for several aspects of risk prediction research. Incorporating the patient voice may involve partnering with patients as researchers to identify the target outcome for the tool and/or determine priorities for outcomes related to the kidney disease domain of interest. Assessing the list of candidate predictors for associations with inequity is important to ensure the tool will not widen disparity for marginalized groups. Estimating model performance using person-centred measures such as model calibration may be used to compare models and select a tool more useful to inform individual treatment decisions. Finally, there is potential to include patients and families in determining other elements of the prediction framework and implementing the tool once development is complete.
{"title":"Integrating the patient voice: patient-centred and equitable clinical risk prediction for kidney health and disease.","authors":"T. Harrison, Meghan J Elliott, Marcello Tonelli","doi":"10.1097/MNH.0000000000000993","DOIUrl":"https://doi.org/10.1097/MNH.0000000000000993","url":null,"abstract":"PURPOSE OF REVIEW\u0000Personalized approaches to care are increasingly common in clinical nephrology. Although risk prediction models are developed to estimate the risk of kidney-disease related outcomes, they infrequently consider the priorities of patients they are designed to help.\u0000\u0000\u0000RECENT FINDINGS\u0000This review discusses certain steps in risk prediction tool development where patients and their priorities can be incorporated. Considering principles of equity throughout the process has been the focus of recent literature.\u0000\u0000\u0000SUMMARY\u0000Applying a person-centred lens has implications for several aspects of risk prediction research. Incorporating the patient voice may involve partnering with patients as researchers to identify the target outcome for the tool and/or determine priorities for outcomes related to the kidney disease domain of interest. Assessing the list of candidate predictors for associations with inequity is important to ensure the tool will not widen disparity for marginalized groups. Estimating model performance using person-centred measures such as model calibration may be used to compare models and select a tool more useful to inform individual treatment decisions. Finally, there is potential to include patients and families in determining other elements of the prediction framework and implementing the tool once development is complete.","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140657957","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}
Pub Date : 2024-04-24DOI: 10.1097/MNH.0000000000000992
P. Evenepoel, Hanne Skou Jørgensen
PURPOSE OF REVIEW Defining the optimal parathyroid hormone (PTH) target in chronic kidney disease (CKD) is challenging, especially for bone outcomes, due to the substantial variability in the skeleton's response to PTH. Although PTH hyporesponsiveness is as integral a component of CKD-mineral bone disorder as elevated PTH levels, clinical awareness of this condition is limited. In this review, we will discuss factors and mechanisms contributing to PTH hyporesponsiveness in CKD. This knowledge may provide clues towards a personalized approach to treating secondary hyperparathyroidism in CKD. RECENT FINDINGS Indicates a link between disturbed phosphate metabolism and impaired skeletal calcium sensing receptor signaling as an important mediator of PTH hyporesponsiveness in CKD. Further, cohort studies with diverse populations point towards differences in mineral metabolism control, rather than genetic or environmental factors, as drivers of the variability of PTH responsiveness. IN SUMMARY Skeletal PTH hyporesponsiveness in CKD has a multifactorial origin, shows important interindividual variability, and is challenging to estimate in clinical practice. The variability in skeletal responsiveness compromises PTH as a biomarker of bone turnover, especially when considering populations that are heterogeneous in ethnicity, demography, kidney function, primary kidney disease and mineral metabolism control, and in patients treated with bone targeting drugs.
{"title":"Skeletal parathyroid hormone hyporesponsiveness: a neglected, but clinically relevant reality in chronic kidney disease.","authors":"P. Evenepoel, Hanne Skou Jørgensen","doi":"10.1097/MNH.0000000000000992","DOIUrl":"https://doi.org/10.1097/MNH.0000000000000992","url":null,"abstract":"PURPOSE OF REVIEW\u0000Defining the optimal parathyroid hormone (PTH) target in chronic kidney disease (CKD) is challenging, especially for bone outcomes, due to the substantial variability in the skeleton's response to PTH. Although PTH hyporesponsiveness is as integral a component of CKD-mineral bone disorder as elevated PTH levels, clinical awareness of this condition is limited. In this review, we will discuss factors and mechanisms contributing to PTH hyporesponsiveness in CKD. This knowledge may provide clues towards a personalized approach to treating secondary hyperparathyroidism in CKD.\u0000\u0000\u0000RECENT FINDINGS\u0000Indicates a link between disturbed phosphate metabolism and impaired skeletal calcium sensing receptor signaling as an important mediator of PTH hyporesponsiveness in CKD. Further, cohort studies with diverse populations point towards differences in mineral metabolism control, rather than genetic or environmental factors, as drivers of the variability of PTH responsiveness.\u0000\u0000\u0000IN SUMMARY\u0000Skeletal PTH hyporesponsiveness in CKD has a multifactorial origin, shows important interindividual variability, and is challenging to estimate in clinical practice. The variability in skeletal responsiveness compromises PTH as a biomarker of bone turnover, especially when considering populations that are heterogeneous in ethnicity, demography, kidney function, primary kidney disease and mineral metabolism control, and in patients treated with bone targeting drugs.","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140662437","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}
Pub Date : 2024-04-22DOI: 10.1097/mnh.0000000000000994
Lashodya V Dissanayake, Oleg Palygin, Alexander Staruschenko
Salt-sensitive (SS) hypertension and its associated kidney damage have been extensively studied, yet proper therapeutic strategies are lacking. The interest in altering the metabolome to affect renal and cardiovascular disease has been emerging. Here, we discuss the effect and potential mechanism behind the protective effect of lysine, an essential amino acid, on the progression of SS hypertension.
人们对盐敏感性高血压及其相关的肾损伤进行了广泛的研究，但却缺乏适当的治疗策略。通过改变代谢组来影响肾脏和心血管疾病的研究正在兴起。在此，我们讨论了赖氨酸（一种必需氨基酸）对 SS 高血压进展的保护作用及其背后的潜在机制。
{"title":"Lysine and salt-sensitive hypertension.","authors":"Lashodya V Dissanayake, Oleg Palygin, Alexander Staruschenko","doi":"10.1097/mnh.0000000000000994","DOIUrl":"https://doi.org/10.1097/mnh.0000000000000994","url":null,"abstract":"Salt-sensitive (SS) hypertension and its associated kidney damage have been extensively studied, yet proper therapeutic strategies are lacking. The interest in altering the metabolome to affect renal and cardiovascular disease has been emerging. Here, we discuss the effect and potential mechanism behind the protective effect of lysine, an essential amino acid, on the progression of SS hypertension.","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140623827","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}
Pub Date : 2024-04-12DOI: 10.1097/mnh.0000000000000987
Barbara Cellini
Primary hyperoxalurias (PHs) are rare disorders caused by the deficit of liver enzymes involved in glyoxylate metabolism. Their main hallmark is the increased excretion of oxalate leading to the deposition of calcium oxalate stones in the urinary tract. This review describes the molecular aspects of PHs and their relevance for the clinical management of patients.
{"title":"A molecular journey on the pathogenesis of primary hyperoxaluria.","authors":"Barbara Cellini","doi":"10.1097/mnh.0000000000000987","DOIUrl":"https://doi.org/10.1097/mnh.0000000000000987","url":null,"abstract":"Primary hyperoxalurias (PHs) are rare disorders caused by the deficit of liver enzymes involved in glyoxylate metabolism. Their main hallmark is the increased excretion of oxalate leading to the deposition of calcium oxalate stones in the urinary tract. This review describes the molecular aspects of PHs and their relevance for the clinical management of patients.","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140560544","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}
Pub Date : 2024-04-11DOI: 10.1097/mnh.0000000000000989
Anna Faivre, Sophie de Seigneux
This review critically examines the role of hypoxia in chronic kidney disease (CKD). While traditionally viewed as detrimental, recent insights suggest a more nuanced understanding of hypoxia's role during renal disease.
{"title":"The role of hypoxia in chronic kidney disease: a nuanced perspective.","authors":"Anna Faivre, Sophie de Seigneux","doi":"10.1097/mnh.0000000000000989","DOIUrl":"https://doi.org/10.1097/mnh.0000000000000989","url":null,"abstract":"This review critically examines the role of hypoxia in chronic kidney disease (CKD). While traditionally viewed as detrimental, recent insights suggest a more nuanced understanding of hypoxia's role during renal disease.","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140560534","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}
Pub Date : 2024-04-11DOI: 10.1097/mnh.0000000000000990
Matteo Bargagli, Sven Trelle, Olivier Bonny, Daniel G Fuster
Kidney stones are the most common condition affecting the kidney, and characterized by a high rate of recurrence. Thiazide and thiazide-like diuretics (thiazides) are commonly prescribed to prevent the recurrence of kidney stones. This review offers a comprehensive up-to-date assessment of the evidence supporting the use of thiazides for kidney stone recurrence prevention, highlights potential harms associated with treatment, and identifies areas of knowledge that require further investigation.
{"title":"Thiazides for kidney stone recurrence prevention.","authors":"Matteo Bargagli, Sven Trelle, Olivier Bonny, Daniel G Fuster","doi":"10.1097/mnh.0000000000000990","DOIUrl":"https://doi.org/10.1097/mnh.0000000000000990","url":null,"abstract":"Kidney stones are the most common condition affecting the kidney, and characterized by a high rate of recurrence. Thiazide and thiazide-like diuretics (thiazides) are commonly prescribed to prevent the recurrence of kidney stones. This review offers a comprehensive up-to-date assessment of the evidence supporting the use of thiazides for kidney stone recurrence prevention, highlights potential harms associated with treatment, and identifies areas of knowledge that require further investigation.","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140560763","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}
Pub Date : 2024-04-08DOI: 10.1097/mnh.0000000000000988
Xian Liao, Emilia Scheidereit, Christoph Kuppe
Kidney fibrosis is a key pathological aspect and outcome of chronic kidney disease (CKD). The advent of multiomic analyses using human kidney tissue, enabled by technological advances, marks a new chapter of discovery in fibrosis research of the kidney. This review highlights the rapid advancements of single-cell and spatial multiomic techniques that offer new avenues for exploring research questions related to human kidney fibrosis development.
{"title":"New tools to study renal fibrogenesis.","authors":"Xian Liao, Emilia Scheidereit, Christoph Kuppe","doi":"10.1097/mnh.0000000000000988","DOIUrl":"https://doi.org/10.1097/mnh.0000000000000988","url":null,"abstract":"Kidney fibrosis is a key pathological aspect and outcome of chronic kidney disease (CKD). The advent of multiomic analyses using human kidney tissue, enabled by technological advances, marks a new chapter of discovery in fibrosis research of the kidney. This review highlights the rapid advancements of single-cell and spatial multiomic techniques that offer new avenues for exploring research questions related to human kidney fibrosis development.","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140560541","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}
Pub Date : 2024-04-05DOI: 10.1097/mnh.0000000000000985
Sharon Huish, Smeeta Sinha
Vascular and valvular calcification are associated with cardiovascular morbidity and mortality in people with chronic kidney disease (CKD). Uncertainty exists regarding therapeutic strategies to attenuate calcification. This review outlines the pathophysiological mechanisms contributing to vascular and valvular calcification, considers the mechanisms of action of therapeutic interventions, and reports the latest outcomes from interventional studies.
{"title":"New therapeutic perspectives for vascular and valvular calcifications in chronic kidney disease.","authors":"Sharon Huish, Smeeta Sinha","doi":"10.1097/mnh.0000000000000985","DOIUrl":"https://doi.org/10.1097/mnh.0000000000000985","url":null,"abstract":"Vascular and valvular calcification are associated with cardiovascular morbidity and mortality in people with chronic kidney disease (CKD). Uncertainty exists regarding therapeutic strategies to attenuate calcification. This review outlines the pathophysiological mechanisms contributing to vascular and valvular calcification, considers the mechanisms of action of therapeutic interventions, and reports the latest outcomes from interventional studies.","PeriodicalId":10960,"journal":{"name":"Current Opinion in Nephrology and Hypertension","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140560542","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}
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