Pub Date : 2024-10-24DOI: 10.1016/j.kint.2024.09.017
Sandra M Herrmann, Ala Abudayyeh, Shruti Gupta, Prakash Gudsoorkar, Nattawat Klomjit, Shveta S Motwani, Sabine Karam, Verônica T Costa E Silva, Sheikh B Khalid, Shuchi Anand, Jaya Kala, David E Leaf, Naoka Murakami, Arash Rashidi, Rimda Wanchoo, Abhijat Kitchlu
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer and are now the backbone of therapy for several malignancies. However, ICIs can cause a spectrum of renal immune-related adverse events including acute kidney injury (AKI), most commonly manifesting as acute interstitial nephritis (AIN), although glomerular disease and electrolyte disturbances have also been reported. In this position statement by the American Society of Onco-nephrology (ASON), we summarize the incidence and risk factors for ICI-AKI, pathophysiological mechanisms, and clinicopathologic features of ICI-AKI. We also discuss novel diagnostic approaches and promising biomarkers for ICI-AKI. From expert panel consensus, we provide clinical practice points for the initial assessment and diagnosis of ICI-AKI, management and immunosuppressive therapy, and consideration for rechallenge with ICI following AKI episodes. In addition, we explore ICI use in special populations, such as kidney transplant recipients, and propose key areas of focus for future research and clinical investigation.
{"title":"Diagnosis and management of immune checkpoint inhibitor-associated nephrotoxicity: a position statement from the American Society of Onco-nephrology.","authors":"Sandra M Herrmann, Ala Abudayyeh, Shruti Gupta, Prakash Gudsoorkar, Nattawat Klomjit, Shveta S Motwani, Sabine Karam, Verônica T Costa E Silva, Sheikh B Khalid, Shuchi Anand, Jaya Kala, David E Leaf, Naoka Murakami, Arash Rashidi, Rimda Wanchoo, Abhijat Kitchlu","doi":"10.1016/j.kint.2024.09.017","DOIUrl":"10.1016/j.kint.2024.09.017","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer and are now the backbone of therapy for several malignancies. However, ICIs can cause a spectrum of renal immune-related adverse events including acute kidney injury (AKI), most commonly manifesting as acute interstitial nephritis (AIN), although glomerular disease and electrolyte disturbances have also been reported. In this position statement by the American Society of Onco-nephrology (ASON), we summarize the incidence and risk factors for ICI-AKI, pathophysiological mechanisms, and clinicopathologic features of ICI-AKI. We also discuss novel diagnostic approaches and promising biomarkers for ICI-AKI. From expert panel consensus, we provide clinical practice points for the initial assessment and diagnosis of ICI-AKI, management and immunosuppressive therapy, and consideration for rechallenge with ICI following AKI episodes. In addition, we explore ICI use in special populations, such as kidney transplant recipients, and propose key areas of focus for future research and clinical investigation.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":3.784,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503094","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}
Pub Date : 2024-10-24DOI: 10.1016/j.kint.2024.10.012
Maya Machalitza, Hanna Debiec, Benedikt Krümpelmann, Nicoletta Ferru, Muhammed Elyesa Kilictas, Tobias B Huber, Linda Reinhard, Thorsten Wiech, Pierre Ronco, Elion Hoxha
{"title":"PCDH7-antibodies and PCDH7 immune deposits are mostly found in patients with PLA<sub>2</sub>R1- or NELL1-associated membranous nephropathy.","authors":"Maya Machalitza, Hanna Debiec, Benedikt Krümpelmann, Nicoletta Ferru, Muhammed Elyesa Kilictas, Tobias B Huber, Linda Reinhard, Thorsten Wiech, Pierre Ronco, Elion Hoxha","doi":"10.1016/j.kint.2024.10.012","DOIUrl":"10.1016/j.kint.2024.10.012","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":14.8,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503095","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":"An observational cohort study of kidney function evolution following increased BK viral replication.","authors":"Evert Cleenders, Maarten Coemans, Olga Mineeva-Sangwo, Priyanka Koshy, Dirk Kuypers, Geert Verbeke, Maarten Naesens","doi":"10.1016/j.kint.2024.10.013","DOIUrl":"10.1016/j.kint.2024.10.013","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":3.784,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503093","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}
Pub Date : 2024-10-24DOI: 10.1016/j.kint.2024.08.035
Max Brunkhorst, Lena Brunkhorst, Helge Martens, Svetlana Papizh, Martine Besouw, Corinna Grasemann, Serap Turan, Przemyslaw Sikora, Milan Chromek, Elisabeth Cornelissen, Marc Fila, Marc Lilien, Jeremy Allgrove, Thomas J Neuhaus, Mehmet Eltan, Laura Espinosa, Dirk Schnabel, Ibrahim Gokce, Juan David González-Rodríguez, Priyanka Khandelwal, Mandy G Keijzer-Veen, Felix Lechner, Maria Szczepańska, Marcin Zaniew, Justine Bacchetta, Francesco Emma, Dieter Haffner
Pathogenic variants in SLC34A1 and SLC34A3 encoding sodium-phosphate transporter 2a and 2c are rare causes of phosphate wasting. Since data on presentation and outcomes are scarce, we collected clinical, biochemical and genetic data via an online questionnaire and the support of European professional organizations. One hundred thirteen patients (86% children) from 90 families and 17 countries with pathogenic or likely pathogenic variants in SLC34A1 or SLC34A3 and a median follow-up of three years were analyzed. Biallelic SLC34A1 variant carriers showed polyuria, failure to thrive, vomiting, constipation, hypercalcemia and nephrocalcinosis in infancy, while biallelic SLC34A3 carriers presented in childhood or even adulthood with rickets/osteomalacia and/or osteopenia/osteoporosis, hypophosphatemia and, less frequently, nephrocalcinosis, while the prevalences of kidney stones were comparable. Adult biallelic SLC34A3 carriers had a six-fold increase chronic kidney disease (CKD) prevalence compared to the general population. All biallelic variant carriers shared a common biochemical pattern including elevated 1,25(OH)2D and alkaline phosphatase levels, suppressed parathyroid hormone (PTH), and hypercalciuria. Heterozygous carriers showed similar but less pronounced phenotypes. In biallelic SLC34A1 carriers, an attenuation of clinical features was observed after infancy, independent of treatment. Phosphate treatment was given in 55% of patients, median duration two years, and resulted in significant reduction, although not normalization, of alkaline phosphatase and of hypercalciuria but an increase in PTH levels, while 1,25(OH)2D levels remained elevated. Thus, our study indicates that biallelic SLC34A1 and SLC34A3 carriers show distinct, albeit overlapping phenotypes, with the latter having an increased risk of CKD in adulthood. Phosphate treatment may promote kidney phosphate loss and enhance 1,25(OH)2D synthesis via increased PTH production.
{"title":"Presentation and outcome in carriers of pathogenic variants in SLC34A1 and SLC34A3 encoding sodium-phosphate transporter NPT 2a and 2c.","authors":"Max Brunkhorst, Lena Brunkhorst, Helge Martens, Svetlana Papizh, Martine Besouw, Corinna Grasemann, Serap Turan, Przemyslaw Sikora, Milan Chromek, Elisabeth Cornelissen, Marc Fila, Marc Lilien, Jeremy Allgrove, Thomas J Neuhaus, Mehmet Eltan, Laura Espinosa, Dirk Schnabel, Ibrahim Gokce, Juan David González-Rodríguez, Priyanka Khandelwal, Mandy G Keijzer-Veen, Felix Lechner, Maria Szczepańska, Marcin Zaniew, Justine Bacchetta, Francesco Emma, Dieter Haffner","doi":"10.1016/j.kint.2024.08.035","DOIUrl":"10.1016/j.kint.2024.08.035","url":null,"abstract":"<p><p>Pathogenic variants in SLC34A1 and SLC34A3 encoding sodium-phosphate transporter 2a and 2c are rare causes of phosphate wasting. Since data on presentation and outcomes are scarce, we collected clinical, biochemical and genetic data via an online questionnaire and the support of European professional organizations. One hundred thirteen patients (86% children) from 90 families and 17 countries with pathogenic or likely pathogenic variants in SLC34A1 or SLC34A3 and a median follow-up of three years were analyzed. Biallelic SLC34A1 variant carriers showed polyuria, failure to thrive, vomiting, constipation, hypercalcemia and nephrocalcinosis in infancy, while biallelic SLC34A3 carriers presented in childhood or even adulthood with rickets/osteomalacia and/or osteopenia/osteoporosis, hypophosphatemia and, less frequently, nephrocalcinosis, while the prevalences of kidney stones were comparable. Adult biallelic SLC34A3 carriers had a six-fold increase chronic kidney disease (CKD) prevalence compared to the general population. All biallelic variant carriers shared a common biochemical pattern including elevated 1,25(OH)<sub>2</sub>D and alkaline phosphatase levels, suppressed parathyroid hormone (PTH), and hypercalciuria. Heterozygous carriers showed similar but less pronounced phenotypes. In biallelic SLC34A1 carriers, an attenuation of clinical features was observed after infancy, independent of treatment. Phosphate treatment was given in 55% of patients, median duration two years, and resulted in significant reduction, although not normalization, of alkaline phosphatase and of hypercalciuria but an increase in PTH levels, while 1,25(OH)<sub>2</sub>D levels remained elevated. Thus, our study indicates that biallelic SLC34A1 and SLC34A3 carriers show distinct, albeit overlapping phenotypes, with the latter having an increased risk of CKD in adulthood. Phosphate treatment may promote kidney phosphate loss and enhance 1,25(OH)<sub>2</sub>D synthesis via increased PTH production.</p>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":" ","pages":""},"PeriodicalIF":3.784,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503096","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}
Pub Date : 2024-10-18DOI: 10.1016/j.kint.2024.08.006
Ian B. Stanaway , Pavan K. Bhatraju , Jonathan Himmelfarb
{"title":"Corrigendum to “Acute kidney injury genetic risks: taking it 1 SNP at a time.” Kidney International 2024;106:188–190","authors":"Ian B. Stanaway , Pavan K. Bhatraju , Jonathan Himmelfarb","doi":"10.1016/j.kint.2024.08.006","DOIUrl":"10.1016/j.kint.2024.08.006","url":null,"abstract":"","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"106 5","pages":"Page 1002"},"PeriodicalIF":14.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486261","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}
Pub Date : 2024-10-18DOI: 10.1016/j.kint.2024.08.029
Nicholas G. Larkins , Jonathan C. Craig
Clinical risk prediction models are being generated at an increasing rate. One important component is the identification of groups for whom such models might require recalibration to retain their desired performance. To this end, an update of the postbiopsy International IgA Nephropathy Prediction Tool for children has been published in this issue of Kidney International. We review the methods used and generalizability in practice, along with broader concepts in model development and application.
临床风险预测模型的生成速度越来越快。其中一个重要的组成部分是确定哪些群体可能需要重新校准这些模型，以保持其理想的性能。为此，本期《国际肾脏》杂志发表了儿童活检后国际 IgA 肾病预测工具的更新版。我们回顾了在实践中使用的方法和可推广性，以及模型开发和应用中更广泛的概念。
{"title":"Using prediction models to improve care and communicate risk: updated modeling for children with IgA nephropathy","authors":"Nicholas G. Larkins , Jonathan C. Craig","doi":"10.1016/j.kint.2024.08.029","DOIUrl":"10.1016/j.kint.2024.08.029","url":null,"abstract":"<div><div>Clinical risk prediction models are being generated at an increasing rate. One important component is the identification of groups for whom such models might require recalibration to retain their desired performance. To this end, an update of the postbiopsy International IgA Nephropathy Prediction Tool for children has been published in this issue of <em>Kidney International</em>. We review the methods used and generalizability in practice, along with broader concepts in model development and application.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"106 5","pages":"Pages 790-792"},"PeriodicalIF":14.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486294","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}
Pub Date : 2024-10-18DOI: 10.1016/j.kint.2024.08.025
Marina Noris , Giuseppe Remuzzi
Cholesterol crystal embolism (CCE) is a complication of atherosclerosis and can cause microvascular obstruction in multiple organs. Because the consequences may be fatal, and there is no specific treatment, it is crucial to understand the mechanisms and identify treatment strategies. In this issue, Zhao et al., using a mouse model of kidney CCE, demonstrated that inhibition of C5a/C5aR prevented and resolved CCE-induced renal thrombosis and angiopathy. Although these findings must be extended to human condition, they offer hope for management of CCE syndrome.
{"title":"Looking into the cholesterol crystal ball: is complement the answer?","authors":"Marina Noris , Giuseppe Remuzzi","doi":"10.1016/j.kint.2024.08.025","DOIUrl":"10.1016/j.kint.2024.08.025","url":null,"abstract":"<div><div>Cholesterol crystal embolism (CCE) is a complication of atherosclerosis and can cause microvascular obstruction in multiple organs. Because the consequences may be fatal, and there is no specific treatment, it is crucial to understand the mechanisms and identify treatment strategies. In this issue, Zhao <em>et al.</em>, using a mouse model of kidney CCE, demonstrated that inhibition of C5a/C5aR prevented and resolved CCE-induced renal thrombosis and angiopathy. Although these findings must be extended to human condition, they offer hope for management of CCE syndrome.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"106 5","pages":"Pages 787-789"},"PeriodicalIF":14.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486303","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}
Pub Date : 2024-10-18DOI: 10.1016/j.kint.2024.08.024
Tomoki Yanagi , Hiroaki Kikuchi , Koh Takeuchi , Koichiro Susa , Takayasu Mori , Motoko Chiga , Kouhei Yamamoto , Asuka Furukawa , Takumi Kanazawa , Yuki Kato , Naohiro Takahashi , Takefumi Suzuki , Yutaro Mori , Benjamin C. Carter , Makiko Mori , Yuta Nakano , Tamami Fujiki , Yu Hara , Soichiro Suzuki , Fumiaki Ando , Eisei Sohara
Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a central kinase involved in energy homeostasis. Increased intracellular AMP levels result in AMPK activation through the binding of AMP to the γ-subunit of AMPK. Recently, we reported that AMP-induced AMPK activation is impaired in the kidneys in chronic kidney disease (CKD) despite an increase in the AMP/ATP ratio. However, the mechanisms by which AMP sensing is disrupted in CKD are unclear. Here, we identified mechanisms of energy homeostasis in which Unc-51-like kinase 1 (ULK1)-dependent phosphorylation of AMPKγ1 at Ser260/Thr262 promoting AMP sensitivity of AMPK. AMPK activation by AMP was impaired in Ulk1 knockout mice despite an increased AMP/ATP ratio. ULK1 expression is markedly downregulated in CKD kidneys, leading to AMP sensing failure. Additionally, MK8722, an allosteric AMPK activator, stimulated AMPK in the kidneys of a CKD mouse model (5/6th nephrectomy) via a pathway that is independent of AMP sensing. Thus, our study shows that MK8722 treatment significantly attenuates the deterioration of kidney function in CKD and may be a potential therapeutic option in CKD therapeutics.
{"title":"ULK1-regulated AMP sensing by AMPK and its application for the treatment of chronic kidney disease","authors":"Tomoki Yanagi , Hiroaki Kikuchi , Koh Takeuchi , Koichiro Susa , Takayasu Mori , Motoko Chiga , Kouhei Yamamoto , Asuka Furukawa , Takumi Kanazawa , Yuki Kato , Naohiro Takahashi , Takefumi Suzuki , Yutaro Mori , Benjamin C. Carter , Makiko Mori , Yuta Nakano , Tamami Fujiki , Yu Hara , Soichiro Suzuki , Fumiaki Ando , Eisei Sohara","doi":"10.1016/j.kint.2024.08.024","DOIUrl":"10.1016/j.kint.2024.08.024","url":null,"abstract":"<div><div>Adenosine monophosphate (AMP)-activated protein kinase (AMPK) is a central kinase involved in energy homeostasis. Increased intracellular AMP levels result in AMPK activation through the binding of AMP to the γ-subunit of AMPK. Recently, we reported that AMP-induced AMPK activation is impaired in the kidneys in chronic kidney disease (CKD) despite an increase in the AMP/ATP ratio. However, the mechanisms by which AMP sensing is disrupted in CKD are unclear. Here, we identified mechanisms of energy homeostasis in which Unc-51-like kinase 1 (ULK1)-dependent phosphorylation of AMPKγ1 at Ser260/Thr262 promoting AMP sensitivity of AMPK. AMPK activation by AMP was impaired in Ulk1 knockout mice despite an increased AMP/ATP ratio. ULK1 expression is markedly downregulated in CKD kidneys, leading to AMP sensing failure. Additionally, MK8722, an allosteric AMPK activator, stimulated AMPK in the kidneys of a CKD mouse model (5/6th nephrectomy) via a pathway that is independent of AMP sensing. Thus, our study shows that MK8722 treatment significantly attenuates the deterioration of kidney function in CKD and may be a potential therapeutic option in CKD therapeutics.</div></div>","PeriodicalId":17801,"journal":{"name":"Kidney international","volume":"106 5","pages":"Pages 887-906"},"PeriodicalIF":14.8,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142468937","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}
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