Alejandro Avello, Juan Guerrero-Mauvecin, Ana Belen Sanz
ABSTRACT Matrix metalloproteinase 7 (MMP-7) is a secreted endopeptidase involved in the degradation of extracellular matrix components and the activation of cytokines and growth factors. The regulation of MMP-7 can be transcriptionally regulated by AP-1 or Wnt/β-catenin or post-translationally by proteolytic activation. MMP-7 expression is low or absent in the healthy kidney, but is significantly upregulated in kidney injury, including AKI and CKD. The function of MMP-7 in kidney disease may differ for CKD and AKI; it may have a profibrotic role in CKD and an anti-apoptotic and regenerative function in AKI. Additionally, the potential of MMP-7 as a biomarker has been studied in different kidney diseases, and the results are promising. Recently, combined unbiased kidney proteomics and transcriptomics approaches identified kidney MMP-7 as the protein having the strongest association with both fibrosis and eGFR and confirmed the predictive role of plasma MMP-7 levels for kidney function decline in over 11 000 individuals. Additionally, urinary MMP-7, combined with urinary cystatin C (CysC) and retinol binding protein (RBP) was reported to provide information on tubular injury in focal segmental glomerulosclerosis and minimal change disease. We now present an overview of research on MMP-7 expression and function in kidney diseases and discuss its potential as a biomarker of kidney diseases.
{"title":"Urine MMP7 as a kidney injury biomarker","authors":"Alejandro Avello, Juan Guerrero-Mauvecin, Ana Belen Sanz","doi":"10.1093/ckj/sfad233","DOIUrl":"https://doi.org/10.1093/ckj/sfad233","url":null,"abstract":"ABSTRACT Matrix metalloproteinase 7 (MMP-7) is a secreted endopeptidase involved in the degradation of extracellular matrix components and the activation of cytokines and growth factors. The regulation of MMP-7 can be transcriptionally regulated by AP-1 or Wnt/β-catenin or post-translationally by proteolytic activation. MMP-7 expression is low or absent in the healthy kidney, but is significantly upregulated in kidney injury, including AKI and CKD. The function of MMP-7 in kidney disease may differ for CKD and AKI; it may have a profibrotic role in CKD and an anti-apoptotic and regenerative function in AKI. Additionally, the potential of MMP-7 as a biomarker has been studied in different kidney diseases, and the results are promising. Recently, combined unbiased kidney proteomics and transcriptomics approaches identified kidney MMP-7 as the protein having the strongest association with both fibrosis and eGFR and confirmed the predictive role of plasma MMP-7 levels for kidney function decline in over 11 000 individuals. Additionally, urinary MMP-7, combined with urinary cystatin C (CysC) and retinol binding protein (RBP) was reported to provide information on tubular injury in focal segmental glomerulosclerosis and minimal change disease. We now present an overview of research on MMP-7 expression and function in kidney diseases and discuss its potential as a biomarker of kidney diseases.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"14 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135552842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patrick Affeldt, Karl August Brensing, Eva Heger, Maike Wirtz, Gertrud Steger, Felix Carlo Koehler, Thomas Benzing, Dirk Stippel, Florian Klein, Christine Kurschat, Roman-Ulrich Müller, Veronica Di Cristanziano
{"title":"Neutralizing response against SARS-CoV-2 Omicron BA.5 and XBB.1.5 in hemodialysis patients","authors":"Patrick Affeldt, Karl August Brensing, Eva Heger, Maike Wirtz, Gertrud Steger, Felix Carlo Koehler, Thomas Benzing, Dirk Stippel, Florian Klein, Christine Kurschat, Roman-Ulrich Müller, Veronica Di Cristanziano","doi":"10.1093/ckj/sfad230","DOIUrl":"https://doi.org/10.1093/ckj/sfad230","url":null,"abstract":"","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"362 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135826935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ABSTRACT Meta-analyses offer an estimate of the overall effect size and help address the inconsistency in findings across studies. The risk is the overemphasis on statistical significance while underrepresenting or misinterpreting clinical significance. There's also a lack of standardized methods for quantifying and reporting clinical significance and these measures are often missing or inconsistently reported in many meta-analyses, making it difficult for readers to determine the clinical relevance of the findings. A major merit of Minutolo's meta-analysis is to formally evaluate efficacy and safety of Hypoxia Inducible Factor Prolyl Hydroxylase Inhibitors (HIF-PHI) as class and as single agents in comparison with ESA, by selecting from only phase-3 randomised clinical trials (RCTs) that compared HIF-PHIs with erythropoiesis-stimulating agents (ESAs) in dialysis and non-dialysis patients. From a clinical perspective, the primary evaluation in this meta-analysis should have been the percentage of patients able to reach and maintain the target haemoglobin (Hb) levels throughout the trials but only a few RCTs selected this primary end point. Any claimed superiority of one drug over another should consider the selected doses. The amount of iron administered to patients, their iron stores and level of inflammation are important confounding factors that affect the reliability of any comparison.
{"title":"Hypoxia inducible factor prolyl hydroxylase inhibitors: what a meta-analysis could tell us","authors":"Francesco Locatelli, Carmine Zoccali","doi":"10.1093/ckj/sfad229","DOIUrl":"https://doi.org/10.1093/ckj/sfad229","url":null,"abstract":"ABSTRACT Meta-analyses offer an estimate of the overall effect size and help address the inconsistency in findings across studies. The risk is the overemphasis on statistical significance while underrepresenting or misinterpreting clinical significance. There's also a lack of standardized methods for quantifying and reporting clinical significance and these measures are often missing or inconsistently reported in many meta-analyses, making it difficult for readers to determine the clinical relevance of the findings. A major merit of Minutolo's meta-analysis is to formally evaluate efficacy and safety of Hypoxia Inducible Factor Prolyl Hydroxylase Inhibitors (HIF-PHI) as class and as single agents in comparison with ESA, by selecting from only phase-3 randomised clinical trials (RCTs) that compared HIF-PHIs with erythropoiesis-stimulating agents (ESAs) in dialysis and non-dialysis patients. From a clinical perspective, the primary evaluation in this meta-analysis should have been the percentage of patients able to reach and maintain the target haemoglobin (Hb) levels throughout the trials but only a few RCTs selected this primary end point. Any claimed superiority of one drug over another should consider the selected doses. The amount of iron administered to patients, their iron stores and level of inflammation are important confounding factors that affect the reliability of any comparison.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136024136","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jolijn R van Leeuwen, Sophia Hafemann, Paul van der Boog, Diane van der Woude, Ton Rabelink, Y K Onno Teng
{"title":"The impact of reclassification by the 2022 ACR/EULAR classification criteria on risk factors for relapse in patients with ANCA-associated vasculitis","authors":"Jolijn R van Leeuwen, Sophia Hafemann, Paul van der Boog, Diane van der Woude, Ton Rabelink, Y K Onno Teng","doi":"10.1093/ckj/sfad225","DOIUrl":"https://doi.org/10.1093/ckj/sfad225","url":null,"abstract":"","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"32 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134997790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Simonetta Genovesi, Luca Porcu, Paola Rebora, Giorgio Slaviero, Gavino Casu, Silvio Bertoli, Flavio Airoldi, Monique Buskermolen, Maurizio Gallieni, Federico Pieruzzi, Giovanni Rovaris, Alberto Montoli, Emanuela Piccaluga, Giulio Molon, Federico Alberici, Marianna Adamo, Achille Gaspardone, Giuseppe D'Angelo, Pierluigi Merella, Giuseppe Vezzoli, Barbara Trezzi, Patrizio Mazzone
ABSTRACT Background The prevalence of atrial fibrillation (AF) in end stage kidney disease (ESKD) patients undergoing dialysis is high, however, the high risk of bleeding often hampers with a correct anticoagulation in ESKD patients with AF, despite high thromboembolic risk. Left atrial appendage (LAA) occlusion is a anticoagulation (OAT) for thromboembolism prevention in AF populations with high hemorrhagic risk. Methods and Results The purpose of the study was to evaluate the efficacy and safety of LAA occlusion in a cohort of dialysis patients undergoing the procedure (LAA occlusion cohort, n = 106), in comparison with two other ESKD cohorts, one taking warfarin (Warfarin cohort, n = 114) and the other without anticoagulation therapy (No-OAT cohort, n = 148). After a median follow-up of 4 years, a Cox regression model, adjusted for possible confounding factors, showed that the hazard ratios (HRs) of thromboembolic events in the LAA occlusion cohort were 0.19 (95%CI 0.04–0.96; p = 0.045) and 0.16 (95%CI 0.04–0.66; p = 0.011) as compared with Warfarin and No-OAT cohorts, respectively. The HR of bleeding in the LAA occlusion cohort was 0.37 (95%CI 0.16–0.83; p = 0.017) compared to Warfarin cohort, while there were no significant differences between the LAA occlusion and the No-OAT cohort (HR 0.51; 95%CI 0.23–1.12; p = 0.094). Adjusted Cox regression models showed lower mortality in patients undergoing LAA occlusion as compared with both the Warfarin cohort (HR 0.60; 95%CI 0.38–0.94; p = 0.027) and no-OAT cohort (HR 0.52; 95%CI 0.34–0.78; p = 0.002). Thromboembolic events in the LAA occlusion cohort were lower than expected according to the CHA2DS2VASc score (1.7 [95%CI 0.3–3.0] vs 6.7 events per 100 person/years, p < 0.001). Conclusion In ESKD patients with AF, LAA occlusion is safe and effective and is associated with reduced mortality compared with OAT or no therapy.
{"title":"Long term safety and efficacy of left atrial appendage occlusion in dialysis patients with atrial fibrillation: a multi-center, prospective, open label, observational study","authors":"Simonetta Genovesi, Luca Porcu, Paola Rebora, Giorgio Slaviero, Gavino Casu, Silvio Bertoli, Flavio Airoldi, Monique Buskermolen, Maurizio Gallieni, Federico Pieruzzi, Giovanni Rovaris, Alberto Montoli, Emanuela Piccaluga, Giulio Molon, Federico Alberici, Marianna Adamo, Achille Gaspardone, Giuseppe D'Angelo, Pierluigi Merella, Giuseppe Vezzoli, Barbara Trezzi, Patrizio Mazzone","doi":"10.1093/ckj/sfad221","DOIUrl":"https://doi.org/10.1093/ckj/sfad221","url":null,"abstract":"ABSTRACT Background The prevalence of atrial fibrillation (AF) in end stage kidney disease (ESKD) patients undergoing dialysis is high, however, the high risk of bleeding often hampers with a correct anticoagulation in ESKD patients with AF, despite high thromboembolic risk. Left atrial appendage (LAA) occlusion is a anticoagulation (OAT) for thromboembolism prevention in AF populations with high hemorrhagic risk. Methods and Results The purpose of the study was to evaluate the efficacy and safety of LAA occlusion in a cohort of dialysis patients undergoing the procedure (LAA occlusion cohort, n = 106), in comparison with two other ESKD cohorts, one taking warfarin (Warfarin cohort, n = 114) and the other without anticoagulation therapy (No-OAT cohort, n = 148). After a median follow-up of 4 years, a Cox regression model, adjusted for possible confounding factors, showed that the hazard ratios (HRs) of thromboembolic events in the LAA occlusion cohort were 0.19 (95%CI 0.04–0.96; p = 0.045) and 0.16 (95%CI 0.04–0.66; p = 0.011) as compared with Warfarin and No-OAT cohorts, respectively. The HR of bleeding in the LAA occlusion cohort was 0.37 (95%CI 0.16–0.83; p = 0.017) compared to Warfarin cohort, while there were no significant differences between the LAA occlusion and the No-OAT cohort (HR 0.51; 95%CI 0.23–1.12; p = 0.094). Adjusted Cox regression models showed lower mortality in patients undergoing LAA occlusion as compared with both the Warfarin cohort (HR 0.60; 95%CI 0.38–0.94; p = 0.027) and no-OAT cohort (HR 0.52; 95%CI 0.34–0.78; p = 0.002). Thromboembolic events in the LAA occlusion cohort were lower than expected according to the CHA2DS2VASc score (1.7 [95%CI 0.3–3.0] vs 6.7 events per 100 person/years, p &lt; 0.001). Conclusion In ESKD patients with AF, LAA occlusion is safe and effective and is associated with reduced mortality compared with OAT or no therapy.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"79 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135452544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
ABSTRACT Background Upacicalcet is a novel small-molecule calcimimetic agent developed for intravenous injection. Here, we evaluated the long-term efficacy and safety of upacicalcet treatment via intraindividual dose adjustment in haemodialysis patients with secondary hyperparathyroidism (SHPT). Methods A phase 2, multicentre, open-label, single-arm study was conducted. Upacicalcet was administered for 52 weeks; the starting dose was 50 μg thrice a week, and then adjusted to 25, 50, 100, 150, 200, 250, or 300 μg, according to the dose-adjustment method set in the protocol. The primary endpoint was the percentage of patients with serum intact parathyroid hormone (iPTH) level achieving a target range of 60–240 pg/mL (target achievement rate) at week 18. Results A total of 58 patients were administered upacicalcet. The target achievement rate of serum iPTH level at week 18 was 57.9%, which increased to 80.8% at week 52. The serum-corrected calcium (cCa) level decreased immediately after upacicalcet administration, but no further decrease was observed. Adverse events were observed in 94.8% of patients, and adverse drug reactions (ADRs) occurred in 20.7% of patients. The most common ADR was decreased adjusted calcium in eight patients; dizziness occurred as a serious ADR in one patient. The serum cCa level of patients who interrupted upacicalcet treatment at a serum cCa level of <7.5 mg/dL recovered to ≥7.5 mg/dL immediately after the interruption. Conclusions In haemodialysis patients with SHPT, upacicalcet doses of 25–300 μg for 52 weeks were found to be highly effective and well-tolerated, with minor safety concerns.
{"title":"Phase 2 study of upacicalcet in Japanese haemodialysis patients with secondary hyperparathyroidism: an intraindividual dose-adjustment study","authors":"Daijo Inaguma, Fumihiko Koiwa, Masanori Tokumoto, Masafumi Fukagawa, Shinji Yoneda, Hisami Yasuzawa, Kenji Asano, Keiko Hagita, Yosuke Inagaki, Daisuke Honda, Tadao Akizawa","doi":"10.1093/ckj/sfad213","DOIUrl":"https://doi.org/10.1093/ckj/sfad213","url":null,"abstract":"ABSTRACT Background Upacicalcet is a novel small-molecule calcimimetic agent developed for intravenous injection. Here, we evaluated the long-term efficacy and safety of upacicalcet treatment via intraindividual dose adjustment in haemodialysis patients with secondary hyperparathyroidism (SHPT). Methods A phase 2, multicentre, open-label, single-arm study was conducted. Upacicalcet was administered for 52 weeks; the starting dose was 50 μg thrice a week, and then adjusted to 25, 50, 100, 150, 200, 250, or 300 μg, according to the dose-adjustment method set in the protocol. The primary endpoint was the percentage of patients with serum intact parathyroid hormone (iPTH) level achieving a target range of 60–240 pg/mL (target achievement rate) at week 18. Results A total of 58 patients were administered upacicalcet. The target achievement rate of serum iPTH level at week 18 was 57.9%, which increased to 80.8% at week 52. The serum-corrected calcium (cCa) level decreased immediately after upacicalcet administration, but no further decrease was observed. Adverse events were observed in 94.8% of patients, and adverse drug reactions (ADRs) occurred in 20.7% of patients. The most common ADR was decreased adjusted calcium in eight patients; dizziness occurred as a serious ADR in one patient. The serum cCa level of patients who interrupted upacicalcet treatment at a serum cCa level of &lt;7.5 mg/dL recovered to ≥7.5 mg/dL immediately after the interruption. Conclusions In haemodialysis patients with SHPT, upacicalcet doses of 25–300 μg for 52 weeks were found to be highly effective and well-tolerated, with minor safety concerns.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"43 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135452546","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cédric Villain, Natalie Ebert, Tim Bothe, Muhammad Barghouth, Anna Pöhlmann, Anne-Katrin Fietz, Antonios Douros, Nina Mielke, Elke Schaeffner
ABSTRACT Background The Cockcroft–Gault equation (CrClC-G) is recommended for dose adjustment of direct oral anticoagulant drugs (DOACs) to kidney function. We aimed to assess whether defining DOAC dose appropriateness according to various kidney function estimators changed the associations between dose appropriateness and adverse events in older adults with atrial fibrillation (AF). Methods Participants of the Berlin Initiative Study with AF and treated with DOACs were included. We investigated CrClC-G and estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration and European Kidney Function Consortium equations based on creatinine and/or cystatin C. Marginal structural Cox models yielded confounder-adjusted hazard ratios for the risk of mortality, thromboembolism and bleeding associated with dose status. Results A total of 224 patients were included in the analysis (median age 87 years). Using CrClC-G, 154 (69%) had an appropriate dose of DOACs, 52 (23%) were underdosed and 18 (8%) were overdosed. During a 39-month median follow-up period, 109 (14.9/100 person-years) participants died, 25 (3.6/100 person-years) experienced thromboembolism and 60 (9.8/100 person-years) experienced bleeding. Dose status was not associated with mortality and thromboembolism, independent of the equation. Underdose status was associated with a lower risk of bleeding with all the equations compared with the appropriate dose group. In participants with discrepancies in dose status using CrClC-G and eGFR equations, the occurrence of endpoints did not differ between participants having an appropriate dose using CrClC-G or eGFR. Conclusion In older adults with AF, the association of DOAC dose status with adverse events did not differ when using CrClC-G or eGFR. Our results suggest that eGFR equations are not inferior to CrClC-G within this context.
{"title":"Kidney function estimators for drug dose adjustment of direct oral anticoagulants in older adults with atrial fibrillation","authors":"Cédric Villain, Natalie Ebert, Tim Bothe, Muhammad Barghouth, Anna Pöhlmann, Anne-Katrin Fietz, Antonios Douros, Nina Mielke, Elke Schaeffner","doi":"10.1093/ckj/sfad218","DOIUrl":"https://doi.org/10.1093/ckj/sfad218","url":null,"abstract":"ABSTRACT Background The Cockcroft–Gault equation (CrClC-G) is recommended for dose adjustment of direct oral anticoagulant drugs (DOACs) to kidney function. We aimed to assess whether defining DOAC dose appropriateness according to various kidney function estimators changed the associations between dose appropriateness and adverse events in older adults with atrial fibrillation (AF). Methods Participants of the Berlin Initiative Study with AF and treated with DOACs were included. We investigated CrClC-G and estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration and European Kidney Function Consortium equations based on creatinine and/or cystatin C. Marginal structural Cox models yielded confounder-adjusted hazard ratios for the risk of mortality, thromboembolism and bleeding associated with dose status. Results A total of 224 patients were included in the analysis (median age 87 years). Using CrClC-G, 154 (69%) had an appropriate dose of DOACs, 52 (23%) were underdosed and 18 (8%) were overdosed. During a 39-month median follow-up period, 109 (14.9/100 person-years) participants died, 25 (3.6/100 person-years) experienced thromboembolism and 60 (9.8/100 person-years) experienced bleeding. Dose status was not associated with mortality and thromboembolism, independent of the equation. Underdose status was associated with a lower risk of bleeding with all the equations compared with the appropriate dose group. In participants with discrepancies in dose status using CrClC-G and eGFR equations, the occurrence of endpoints did not differ between participants having an appropriate dose using CrClC-G or eGFR. Conclusion In older adults with AF, the association of DOAC dose status with adverse events did not differ when using CrClC-G or eGFR. Our results suggest that eGFR equations are not inferior to CrClC-G within this context.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"181 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135452543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Raghavan Murugan, Monique Y Boudreaux-Kelly, John A Kellum, Paul M Palevsky, Steven Weisbord
Abstract Background Contrast-associated acute kidney injury (CA-AKI) has been associated with a higher risk of cardiovascular (CV) events. We studied the risk of CV events in chronic kidney disease (CKD) patients undergoing angiography and whether biomarkers can predict such events. We also explored whether CA-AKI mediates the association of pre-angiography estimated glomerular filtration rate (eGFR) on CV events. Methods We analyzed participants from the Prevention of Serious Adverse Events following the Angiography (PRESERVE) trial. Urinary tissue inhibitor of matrix metalloproteinase [TIMP]-2 and insulin growth factor binding protein [IGFBP]-7, plasma brain-type natriuretic peptide (BNP), high sensitivity C-reactive protein (hs-CRP), and serum cardiac troponin-I (Tn-I) were assayed before and after angiography. We assessed the composite risk of CV events by day 90. Results Of the 922 participants, 119 (12.9%) developed CV events, and 73 (7.9%) developed CA-AKI. Most cases of CA-AKI (90%) were stage-1. There were no differences in urinary [TIMP-2]•[IGFBP7] concentrations or the proportion of patients with CA-AKI among those with and without CV events. Higher BNP, Tn-I, and hs-CRP were associated with CV events, but their discriminatory capacity was modest (AUROC < 0.7). CA-AKI did not mediate the association of the pre-angiography eGFR on CV events. Conclusions Most episodes of CA-AKI are stage-1 AKI and are not associated with CV events. Less severe CA-AKI episodes also did not mediate the risk of pre-angiography eGFR on CV events. Our findings suggest that most CV events after contrast procedures are due to underlying CKD and CV risk factors rather than less severe CA-AKI episodes and should help enhance the utilization of clinically indicated contrast procedures among high-risk patients with CKD. Further research is required to examine whether moderate-to-severe CA-AKI episodes are associated with CV events.
对比剂相关急性肾损伤(CA-AKI)与较高的心血管(CV)事件风险相关。我们研究了接受血管造影的慢性肾脏疾病(CKD)患者心血管事件的风险，以及生物标志物是否可以预测这些事件。我们还探讨了CA-AKI是否介导血管造影前估计的肾小球滤过率(eGFR)与CV事件的关联。方法我们分析了来自血管造影后严重不良事件预防(PRESERVE)试验的参与者。检测血管造影前后尿组织基质金属蛋白酶抑制剂(TIMP) -2、胰岛素生长因子结合蛋白(IGFBP) -7、血浆脑型利钠肽(BNP)、高敏c反应蛋白(hs-CRP)、血清心肌肌钙蛋白- i (Tn-I)。我们在第90天评估心血管事件的综合风险。结果在922名参与者中，119名(12.9%)发生CV事件，73名(7.9%)发生CA-AKI。大多数CA-AKI病例(90%)为1期。尿[TIMP-2]•[IGFBP7]浓度或伴有和不伴有CV事件的CA-AKI患者比例均无差异。较高的BNP、Tn-I和hs-CRP与CV事件相关，但它们的区分能力是适度的(AUROC <0.7)。CA-AKI不介导血管造影前eGFR与心血管事件的关联。结论:大多数CA-AKI发作为1期AKI，与CV事件无关。不太严重的CA-AKI发作也没有调节血管造影术前eGFR对心血管事件的影响。我们的研究结果表明，对比手术后的大多数CV事件是由于潜在的CKD和CV危险因素，而不是不太严重的CA-AKI发作，这应该有助于提高临床指示的对比手术在高危CKD患者中的应用。需要进一步的研究来检验中重度CA-AKI发作是否与CV事件相关。
{"title":"Contrast-associated acute kidney injury and cardiovascular events: a secondary analysis of PRESERVE cohort","authors":"Raghavan Murugan, Monique Y Boudreaux-Kelly, John A Kellum, Paul M Palevsky, Steven Weisbord","doi":"10.1093/ckj/sfad214","DOIUrl":"https://doi.org/10.1093/ckj/sfad214","url":null,"abstract":"Abstract Background Contrast-associated acute kidney injury (CA-AKI) has been associated with a higher risk of cardiovascular (CV) events. We studied the risk of CV events in chronic kidney disease (CKD) patients undergoing angiography and whether biomarkers can predict such events. We also explored whether CA-AKI mediates the association of pre-angiography estimated glomerular filtration rate (eGFR) on CV events. Methods We analyzed participants from the Prevention of Serious Adverse Events following the Angiography (PRESERVE) trial. Urinary tissue inhibitor of matrix metalloproteinase [TIMP]-2 and insulin growth factor binding protein [IGFBP]-7, plasma brain-type natriuretic peptide (BNP), high sensitivity C-reactive protein (hs-CRP), and serum cardiac troponin-I (Tn-I) were assayed before and after angiography. We assessed the composite risk of CV events by day 90. Results Of the 922 participants, 119 (12.9%) developed CV events, and 73 (7.9%) developed CA-AKI. Most cases of CA-AKI (90%) were stage-1. There were no differences in urinary [TIMP-2]•[IGFBP7] concentrations or the proportion of patients with CA-AKI among those with and without CV events. Higher BNP, Tn-I, and hs-CRP were associated with CV events, but their discriminatory capacity was modest (AUROC &lt; 0.7). CA-AKI did not mediate the association of the pre-angiography eGFR on CV events. Conclusions Most episodes of CA-AKI are stage-1 AKI and are not associated with CV events. Less severe CA-AKI episodes also did not mediate the risk of pre-angiography eGFR on CV events. Our findings suggest that most CV events after contrast procedures are due to underlying CKD and CV risk factors rather than less severe CA-AKI episodes and should help enhance the utilization of clinically indicated contrast procedures among high-risk patients with CKD. Further research is required to examine whether moderate-to-severe CA-AKI episodes are associated with CV events.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"71 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136354986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Louise Platen, Bo-Hung Liao, Myriam Tellenbach, Cho-Chin Cheng, Christopher Holzmann-Littig, Catharina Christa, Christopher Dächert, Verena Kappler, Romina Bester, Maia Lucia Werz, Emely Schönhals, Eva Platen, Peter Eggerer, Laëtitia Tréguer, Claudius Küchle, Christoph Schmaderer, Uwe Heemann, Oliver T Keppler, Lutz Renders, Matthias Christoph Braunisch, Ulrike Protzer
Background Individuals on hemodialysis are more vulnerable to SARS-CoV-2 infection than the general population due to end-stage kidney disease-induced immunosuppression. Methods 26 hemodialysis patients experiencing SARS-CoV-2 infection after 3rd vaccination were matched 1:1 to 26 out of 92 SARS-CoV-2 naives by age, sex, dialysis vintage and immunosuppressive drugs receiving a 4th vaccination with an mRNA-based vaccine. A competitive surrogate neutralization assay was used to monitor vaccination success. To determine infection neutralization titers, Vero-E6 cells were infected with SARS-CoV-2 variants of concern (VoC), Omicron sub-lineage BA.1, BA.5, and BQ.1.1. 50% inhibitory concentration (IC50, serum dilution factor 1:x) was determined before, four weeks after and 6 months after the 4th vaccination. Results 52 hemodialysis patients received four COVID-19 vaccinations and were followed up for a median of 6.3 months. Patient characteristics did not differ between the matched cohorts. Patients without a SARS-CoV-2 infection had a significant reduction of real virus neutralization capacity for all Omicron sub-lineages after six months (p<0.001 each). Those patients with a virus infection did not experience a reduction of real virus neutralization capacity after six months. Compared to the other Omicron VoC the BQ.1.1 sub-lineage had the lowest virus neutralization capacity. Conclusions SARS-CoV-2-naive hemodialysis patients had significantly decreased virus neutralization capacity six months after the 4th vaccination whereas patients with a SARS-CoV-2 infection had no change in neutralization capacity. This was independent of age, sex, dialysis vintage and immunosuppression. Therefore, in infection-naive hemodialysis patients a fifth COVID-19 vaccination might be reasonable 6 months after the 4th vaccination.
{"title":"Longitudinal SARS-CoV-2 neutralization of Omicron BA.1, BA.5 and BQ.1.1 after four vaccinations and the impact of breakthrough infections in haemodialysis patients","authors":"Louise Platen, Bo-Hung Liao, Myriam Tellenbach, Cho-Chin Cheng, Christopher Holzmann-Littig, Catharina Christa, Christopher Dächert, Verena Kappler, Romina Bester, Maia Lucia Werz, Emely Schönhals, Eva Platen, Peter Eggerer, Laëtitia Tréguer, Claudius Küchle, Christoph Schmaderer, Uwe Heemann, Oliver T Keppler, Lutz Renders, Matthias Christoph Braunisch, Ulrike Protzer","doi":"10.1093/ckj/sfad147","DOIUrl":"https://doi.org/10.1093/ckj/sfad147","url":null,"abstract":"Background Individuals on hemodialysis are more vulnerable to SARS-CoV-2 infection than the general population due to end-stage kidney disease-induced immunosuppression. Methods 26 hemodialysis patients experiencing SARS-CoV-2 infection after 3rd vaccination were matched 1:1 to 26 out of 92 SARS-CoV-2 naives by age, sex, dialysis vintage and immunosuppressive drugs receiving a 4th vaccination with an mRNA-based vaccine. A competitive surrogate neutralization assay was used to monitor vaccination success. To determine infection neutralization titers, Vero-E6 cells were infected with SARS-CoV-2 variants of concern (VoC), Omicron sub-lineage BA.1, BA.5, and BQ.1.1. 50% inhibitory concentration (IC50, serum dilution factor 1:x) was determined before, four weeks after and 6 months after the 4th vaccination. Results 52 hemodialysis patients received four COVID-19 vaccinations and were followed up for a median of 6.3 months. Patient characteristics did not differ between the matched cohorts. Patients without a SARS-CoV-2 infection had a significant reduction of real virus neutralization capacity for all Omicron sub-lineages after six months (p<0.001 each). Those patients with a virus infection did not experience a reduction of real virus neutralization capacity after six months. Compared to the other Omicron VoC the BQ.1.1 sub-lineage had the lowest virus neutralization capacity. Conclusions SARS-CoV-2-naive hemodialysis patients had significantly decreased virus neutralization capacity six months after the 4th vaccination whereas patients with a SARS-CoV-2 infection had no change in neutralization capacity. This was independent of age, sex, dialysis vintage and immunosuppression. Therefore, in infection-naive hemodialysis patients a fifth COVID-19 vaccination might be reasonable 6 months after the 4th vaccination.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"96 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135841871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Li Luo, Yuanhang Yang, Lyanne M Kieneker, Roemer J Janse, Alessandro Bosi, Faizan Mazhar, Rudolf A de Boer, Geertruida H de Bock, Ron T Gansevoort, Juan-Jesus Carrero
ABSTRACT Background Studies investigating the association of chronic kidney disease and cancer have focused on estimated glomerular filtration (eGFR) rather than on albuminuria. This study aimed to examine whether albuminuria is associated with cancer incidence, and whether this association is independent of eGFR. Methods We included subjects of the Stockholm Creatinine Measurements (SCREAM) project without a history of cancer—250 768 subjects with at least one urine albumin–creatinine ratio (ACR) test (primary cohort) and 433 850 subjects with at least one dipstick albuminuria test (secondary cohort). Albuminuria was quantified as KDIGO albuminuria stages. The primary outcome was overall cancer incidence. Secondary outcomes were site-specific cancer incidence rates. Multivariable Cox proportional hazards regression models adjusted for confounders including eGFR to calculate hazard ratios and 95% confidence intervals (HRs, 95% CIs). Results During a median follow-up of 4.3 (interquartile range 2.0–8.2) years, 21 901 subjects of the ACR cohort developed de novo cancer. In multivariable analyses, adjusting among others for eGFR, subjects with an ACR of 30–299 mg/g or ≥300 mg/g had a 23% (HR 1.23; 95% CI 1.19–1.28) and 40% (HR 1.40; 95% CI 1.31–1.50) higher risk of developing cancer, respectively, when compared with subjects with an ACR <30 mg/g. This graded, independent association was also observed for urinary tract, gastrointestinal tract, lung and hematological cancer incidence (all P < .05). Results were similar in the dipstick albuminuria cohort. Conclusions Albuminuria was associated with the risk of cancer independent of eGFR. This association was primarily driven by a higher risk of urinary tract, gastrointestinal tract, lung and hematological cancers.
背景:研究慢性肾脏疾病和癌症相关性的研究主要集中在肾小球滤过(eGFR)的估计上，而不是蛋白尿。本研究旨在探讨蛋白尿是否与癌症发病率相关，以及这种关联是否独立于eGFR。方法纳入无癌症史的斯德哥尔摩肌酐测量(SCREAM)项目的受试者，250 768例至少进行过一次尿白蛋白-肌酐比值(ACR)试验(主要队列)，433 850例至少进行过一次尿白蛋白试验(次要队列)。蛋白尿量化为KDIGO蛋白尿分期。主要结果是总体癌症发病率。次要结果是部位特异性癌症发病率。多变量Cox比例风险回归模型校正混杂因素，包括eGFR，计算风险比和95%置信区间(hr, 95% ci)。结果在中位随访4.3年(四分位数间隔2.0-8.2年)期间，ACR队列中有21,901名受试者发生了新发癌症。在多变量分析中，调整eGFR等因素，ACR为30-299 mg/g或≥300 mg/g的受试者有23% (HR 1.23;95% CI 1.19-1.28)和40% (HR 1.40;(95% CI 1.31-1.50)，与ACR为30mg /g的受试者相比，患癌症的风险更高。尿路、胃肠道、肺癌和血液学癌症的发病率也观察到这种分级的独立关联(P <. 05)。试纸蛋白尿组的结果相似。结论蛋白尿与癌症风险相关，与eGFR无关。这种关联主要是由泌尿道、胃肠道、肺癌和血液学癌症的高风险引起的。
{"title":"Albuminuria and the risk of cancer: the Stockholm CREAtinine Measurements (SCREAM) project","authors":"Li Luo, Yuanhang Yang, Lyanne M Kieneker, Roemer J Janse, Alessandro Bosi, Faizan Mazhar, Rudolf A de Boer, Geertruida H de Bock, Ron T Gansevoort, Juan-Jesus Carrero","doi":"10.1093/ckj/sfad145","DOIUrl":"https://doi.org/10.1093/ckj/sfad145","url":null,"abstract":"ABSTRACT Background Studies investigating the association of chronic kidney disease and cancer have focused on estimated glomerular filtration (eGFR) rather than on albuminuria. This study aimed to examine whether albuminuria is associated with cancer incidence, and whether this association is independent of eGFR. Methods We included subjects of the Stockholm Creatinine Measurements (SCREAM) project without a history of cancer—250 768 subjects with at least one urine albumin–creatinine ratio (ACR) test (primary cohort) and 433 850 subjects with at least one dipstick albuminuria test (secondary cohort). Albuminuria was quantified as KDIGO albuminuria stages. The primary outcome was overall cancer incidence. Secondary outcomes were site-specific cancer incidence rates. Multivariable Cox proportional hazards regression models adjusted for confounders including eGFR to calculate hazard ratios and 95% confidence intervals (HRs, 95% CIs). Results During a median follow-up of 4.3 (interquartile range 2.0–8.2) years, 21 901 subjects of the ACR cohort developed de novo cancer. In multivariable analyses, adjusting among others for eGFR, subjects with an ACR of 30–299 mg/g or ≥300 mg/g had a 23% (HR 1.23; 95% CI 1.19–1.28) and 40% (HR 1.40; 95% CI 1.31–1.50) higher risk of developing cancer, respectively, when compared with subjects with an ACR &lt;30 mg/g. This graded, independent association was also observed for urinary tract, gastrointestinal tract, lung and hematological cancer incidence (all P &lt; .05). Results were similar in the dipstick albuminuria cohort. Conclusions Albuminuria was associated with the risk of cancer independent of eGFR. This association was primarily driven by a higher risk of urinary tract, gastrointestinal tract, lung and hematological cancers.","PeriodicalId":18987,"journal":{"name":"NDT Plus","volume":"67 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135999378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：