Pub Date : 2024-07-16DOI: 10.34067/KID.0000000000000512
Cramer J Kallem, Alaa A Alghwiri, Jonathan G Yabes, Maria-Eleni Roumelioti, Sarah Erickson, Bruce L Rollman, Steven Weisbord, Mark Unruh, Yoram Vodovotz, Manisha Jhamb, Jennifer L Steel
Background: Patient-reported symptoms are associated with inflammation biomarkers in many chronic diseases. We examined associations of inflammation biomarkers with pain, fatigue, and depression in patients with end-stage kidney disease (ESKD) and the effects of a Technology Assisted stepped Collaborative Care (TĀCcare) intervention on these biomarkers.
Methods: In the TĀCcare multi-site randomized control trial, data on patient-reported symptoms were collected at baseline, 3, and 6 months. Anti-inflammatory [interleukin 1 receptor agonist (IL-1RA), IL-10], pro-inflammatory [tumor necrosis factor alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP), IL-6] and regulatory [IL-2] biomarkers were assayed. Linear mixed-effects modeling was used to examine within- and between-group differences after adjusting for age, sex, race, and comorbidities.
Results: Among the 160 patients (mean age 58±14 years, 55% men, 52% white), there were no significant associations between inflammation biomarkers and pain, fatigue or depression at baseline. Both intervention and control group demonstrated reductions in IL-10 and IL-1RA over 6 months (β range=-1.22 to -0.40, p range=<0.001 to 0.02) At 3 months, the treatment group exhibited decreases in TNF-α (β=-0.22, p<0.001) and IL-2 (β=-0.71, p<0.001), whereas the control group showed increases in IL-6/IL-10 ratio (β=0.33, p=0.03). At 6 months, both groups exhibited decreases in IL-2 (β range=-0.66 to -0.57,p<0.001); the control group showed significant increases in the ratio of IL-6/IL-10 (β=0.75,p<0.001) and decrease in TNF-α (β=-0.16, p=0.02). Compared to controls, the treatment group demonstrated significantly decreased IL-2 at 3 months (β=-0.53, p<0.001). Significant interaction effects of treatment were observed on the association between changes in pro-inflammatory biomarkers (TNF-α and hs-CRP) levels and changes in symptom scores from baseline to 6 months.
Conclusions: The TĀCcare intervention had a short-term impact on reducing inflammatory burden in patients with ESKD. More studies are needed to confirm our findings and to determine if these biomarkers mediate the link between symptoms and disease progression.
背景:在许多慢性疾病中,患者报告的症状与炎症生物标志物有关。我们研究了终末期肾病(ESKD)患者的炎症生物标志物与疼痛、疲劳和抑郁的关系,以及技术辅助分步协作护理(TĀCcare)干预对这些生物标志物的影响:在TĀCcare多站点随机对照试验中,收集了基线、3个月和6个月时患者报告的症状数据。对抗炎性[白细胞介素 1 受体激动剂(IL-1RA)、IL-10]、促炎性[肿瘤坏死因子α(TNF-α)、高敏 C 反应蛋白(hs-CRP)、IL-6]和调节性[IL-2]生物标志物进行了检测。在对年龄、性别、种族和合并症进行调整后,采用线性混合效应模型来检验组内和组间差异:在160名患者(平均年龄58±14岁,55%为男性,52%为白人)中,炎症生物标志物与基线时的疼痛、疲劳或抑郁之间没有明显关联。干预组和对照组的IL-10和IL-1RA在6个月内均有下降(β范围=-1.22至-0.40,P范围=结论:TĀCcare干预对减轻ESKD患者的炎症负担有短期影响。还需要更多的研究来证实我们的发现,并确定这些生物标志物是否介导了症状和疾病进展之间的联系。
{"title":"Association of Symptoms and Collaborative Care Intervention (TĀCcare) with Systemic Inflammation Biomarkers in End-Stage Kidney Disease.","authors":"Cramer J Kallem, Alaa A Alghwiri, Jonathan G Yabes, Maria-Eleni Roumelioti, Sarah Erickson, Bruce L Rollman, Steven Weisbord, Mark Unruh, Yoram Vodovotz, Manisha Jhamb, Jennifer L Steel","doi":"10.34067/KID.0000000000000512","DOIUrl":"10.34067/KID.0000000000000512","url":null,"abstract":"<p><strong>Background: </strong>Patient-reported symptoms are associated with inflammation biomarkers in many chronic diseases. We examined associations of inflammation biomarkers with pain, fatigue, and depression in patients with end-stage kidney disease (ESKD) and the effects of a Technology Assisted stepped Collaborative Care (TĀCcare) intervention on these biomarkers.</p><p><strong>Methods: </strong>In the TĀCcare multi-site randomized control trial, data on patient-reported symptoms were collected at baseline, 3, and 6 months. Anti-inflammatory [interleukin 1 receptor agonist (IL-1RA), IL-10], pro-inflammatory [tumor necrosis factor alpha (TNF-α), high sensitivity C-reactive protein (hs-CRP), IL-6] and regulatory [IL-2] biomarkers were assayed. Linear mixed-effects modeling was used to examine within- and between-group differences after adjusting for age, sex, race, and comorbidities.</p><p><strong>Results: </strong>Among the 160 patients (mean age 58±14 years, 55% men, 52% white), there were no significant associations between inflammation biomarkers and pain, fatigue or depression at baseline. Both intervention and control group demonstrated reductions in IL-10 and IL-1RA over 6 months (β range=-1.22 to -0.40, p range=<0.001 to 0.02) At 3 months, the treatment group exhibited decreases in TNF-α (β=-0.22, p<0.001) and IL-2 (β=-0.71, p<0.001), whereas the control group showed increases in IL-6/IL-10 ratio (β=0.33, p=0.03). At 6 months, both groups exhibited decreases in IL-2 (β range=-0.66 to -0.57,p<0.001); the control group showed significant increases in the ratio of IL-6/IL-10 (β=0.75,p<0.001) and decrease in TNF-α (β=-0.16, p=0.02). Compared to controls, the treatment group demonstrated significantly decreased IL-2 at 3 months (β=-0.53, p<0.001). Significant interaction effects of treatment were observed on the association between changes in pro-inflammatory biomarkers (TNF-α and hs-CRP) levels and changes in symptom scores from baseline to 6 months.</p><p><strong>Conclusions: </strong>The TĀCcare intervention had a short-term impact on reducing inflammatory burden in patients with ESKD. More studies are needed to confirm our findings and to determine if these biomarkers mediate the link between symptoms and disease progression.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620353","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}
Pub Date : 2024-07-15DOI: 10.34067/KID.0000000000000496
Jianling Tao, Osamu Winget Yasui, Neil S Kamdar, Sijie Zheng, Rita A Popat, David H Rehkopf, Glenn M Chertow
Introduction: Plasmapheresis is currently recommended when antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) presents with severe kidney and/or lung involvement. This cross-sectional study aimed at describing characteristics of hospitalized patients diagnosed with AAV with severe kidney involvement undergoing plasmapheresis in the US.
Methods: We defined the study population as adults hospitalized for active kidney involvement with a new diagnosis of AAV (by subtype or unspecified). We established the cohort from the 2016-2020 National Inpatient Sample by ICD-10-CM codes. In this cross-sectional study, we described demographic and clinical characteristics, associated inpatient procedures, lengths of stay, hospital costs, and disposition at discharge comparing patients treated and not treated with plasmapheresis.
Results: We identified a total of 975 cases of hospitalized AAV with acute kidney involvement in the US treated by plasmapheresis over the 5-year period. Demographic characteristics of patients who received plasmapheresis were similar to those in patients who did not (n=5670). There were no regional differences in the proportion of patients who received plasmapheresis; however, plasmapheresis was deployed more frequently among patients admitted to urban teaching hospitals relative to rural and non-teaching hospitals. Cases treated with plasmapheresis were more likely to have had acute kidney injury (AKI) (96% vs. 90%, p=0.0007), AKI requiring dialysis (52% vs 16%, p<0.001), hypoxia (40% vs. 16%, p<0.0001), and respiratory failure requiring mechanical ventilation (13% vs. 3%, p=0.0003).
Conclusion: During 2016-2020, plasmapheresis was deployed in approximately 20% of patients being admitted for AAV and acute kidney involvement in the US. As standards of care and practice evolve, the role of plasmapheresis in the management of AAV with acute kidney involvement will require further study.
{"title":"Plasmapheresis in ANCA-Associated Vasculitis with Active Kidney Involvement in the United States (2016-2020): A Cross-Sectional Study.","authors":"Jianling Tao, Osamu Winget Yasui, Neil S Kamdar, Sijie Zheng, Rita A Popat, David H Rehkopf, Glenn M Chertow","doi":"10.34067/KID.0000000000000496","DOIUrl":"https://doi.org/10.34067/KID.0000000000000496","url":null,"abstract":"<p><strong>Introduction: </strong>Plasmapheresis is currently recommended when antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) presents with severe kidney and/or lung involvement. This cross-sectional study aimed at describing characteristics of hospitalized patients diagnosed with AAV with severe kidney involvement undergoing plasmapheresis in the US.</p><p><strong>Methods: </strong>We defined the study population as adults hospitalized for active kidney involvement with a new diagnosis of AAV (by subtype or unspecified). We established the cohort from the 2016-2020 National Inpatient Sample by ICD-10-CM codes. In this cross-sectional study, we described demographic and clinical characteristics, associated inpatient procedures, lengths of stay, hospital costs, and disposition at discharge comparing patients treated and not treated with plasmapheresis.</p><p><strong>Results: </strong>We identified a total of 975 cases of hospitalized AAV with acute kidney involvement in the US treated by plasmapheresis over the 5-year period. Demographic characteristics of patients who received plasmapheresis were similar to those in patients who did not (n=5670). There were no regional differences in the proportion of patients who received plasmapheresis; however, plasmapheresis was deployed more frequently among patients admitted to urban teaching hospitals relative to rural and non-teaching hospitals. Cases treated with plasmapheresis were more likely to have had acute kidney injury (AKI) (96% vs. 90%, p=0.0007), AKI requiring dialysis (52% vs 16%, p<0.001), hypoxia (40% vs. 16%, p<0.0001), and respiratory failure requiring mechanical ventilation (13% vs. 3%, p=0.0003).</p><p><strong>Conclusion: </strong>During 2016-2020, plasmapheresis was deployed in approximately 20% of patients being admitted for AAV and acute kidney involvement in the US. As standards of care and practice evolve, the role of plasmapheresis in the management of AAV with acute kidney involvement will require further study.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620354","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}
Pub Date : 2024-07-12DOI: 10.34067/kid.0000000000000510
M. I. Abdul Hafidz, Hasdy Haron, M. Z. Abdul Wahab
{"title":"Global Perspective on Kidney Transplantation in Malaysia","authors":"M. I. Abdul Hafidz, Hasdy Haron, M. Z. Abdul Wahab","doi":"10.34067/kid.0000000000000510","DOIUrl":"https://doi.org/10.34067/kid.0000000000000510","url":null,"abstract":"","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141652323","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}
Pub Date : 2024-07-08DOI: 10.34067/KID.0000000000000506
Osama El Shamy, Nicole Wyatt, Sagar Patel, Naief Abudaff, Robert Greevy, Andrew Guide, Ankur D Shah, Juan Pablo Arroyo, Thomas A Golper
Background: With the growing use of automated peritoneal dialysis (APD), it is important to improve our knowledge of the clinical patterns and physiology of APD treatment sessions. The ultrafiltration (UF) achieved during each cycle of an APD treatment is assumed to be relatively linear if the delivered prescription is the same. We set out to determine if that is indeed the case.
Methods: Single-center, cross-sectional study of prevalent PD patients. All adult APD patients (> 18 years of age), who had been on PD for >3 months, and >3 months on APD were included. Continuous ambulatory PD patients or those with peritonitis within 3 months of the consent date were excluded. Individual treatment data from 7 consecutive APD treatment sessions with consistent dialysate composition for each cycler exchange were collected for each subject.
Results: Thirty-nine subjects met the inclusion criteria and were enrolled. The probability of yielding a positive UF was 48.9% for cycle 1, rising to 90.5% by cycle 6. Adjusting for average dextrose concentration, dwell time, fill volume, solute transfer rate, and number of cycles, we observed that cycles 2 through 6 achieved progressively higher UF volumes than cycle 1 (p < 0.001). The first and last cycles demonstrated significantly different cycle UF volumes compared to a middle cycle (-230 ml and 277 ml, respectively, p < 0.001).
Conclusions: We observed a consistent increase in UF volumes achieved per cycle over the course of an APD treatment session with numerous clinical and physiologic implications. This provides the foundation for future studies investigating peritoneal inter-cycle variations and membrane physiology.
{"title":"Ultrafiltration Patterns during Automated Peritoneal Dialysis: Findings and Insights to Peritoneal Physiology.","authors":"Osama El Shamy, Nicole Wyatt, Sagar Patel, Naief Abudaff, Robert Greevy, Andrew Guide, Ankur D Shah, Juan Pablo Arroyo, Thomas A Golper","doi":"10.34067/KID.0000000000000506","DOIUrl":"https://doi.org/10.34067/KID.0000000000000506","url":null,"abstract":"<p><strong>Background: </strong>With the growing use of automated peritoneal dialysis (APD), it is important to improve our knowledge of the clinical patterns and physiology of APD treatment sessions. The ultrafiltration (UF) achieved during each cycle of an APD treatment is assumed to be relatively linear if the delivered prescription is the same. We set out to determine if that is indeed the case.</p><p><strong>Methods: </strong>Single-center, cross-sectional study of prevalent PD patients. All adult APD patients (> 18 years of age), who had been on PD for >3 months, and >3 months on APD were included. Continuous ambulatory PD patients or those with peritonitis within 3 months of the consent date were excluded. Individual treatment data from 7 consecutive APD treatment sessions with consistent dialysate composition for each cycler exchange were collected for each subject.</p><p><strong>Results: </strong>Thirty-nine subjects met the inclusion criteria and were enrolled. The probability of yielding a positive UF was 48.9% for cycle 1, rising to 90.5% by cycle 6. Adjusting for average dextrose concentration, dwell time, fill volume, solute transfer rate, and number of cycles, we observed that cycles 2 through 6 achieved progressively higher UF volumes than cycle 1 (p < 0.001). The first and last cycles demonstrated significantly different cycle UF volumes compared to a middle cycle (-230 ml and 277 ml, respectively, p < 0.001).</p><p><strong>Conclusions: </strong>We observed a consistent increase in UF volumes achieved per cycle over the course of an APD treatment session with numerous clinical and physiologic implications. This provides the foundation for future studies investigating peritoneal inter-cycle variations and membrane physiology.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559052","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}
Pub Date : 2024-07-08DOI: 10.34067/kid.0000000000000494
M. Shieu, Li Nien Chen, Harold J. Manley, Antonia Harford, C. Hsu, Daniel E. Weiner, Dana Miskulin, Doug Johnson, Eduardo Lacson
{"title":"SARS-CoV-2 Vaccination and Severe COVID-19 Infection and Reinfection Outcomes among ESRD Patients from A National Dialysis Provider","authors":"M. Shieu, Li Nien Chen, Harold J. Manley, Antonia Harford, C. Hsu, Daniel E. Weiner, Dana Miskulin, Doug Johnson, Eduardo Lacson","doi":"10.34067/kid.0000000000000494","DOIUrl":"https://doi.org/10.34067/kid.0000000000000494","url":null,"abstract":"","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141668772","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}
Background: In the past three years, cases of gross hematuria (GH) after the vaccination for coronavirus disease 2019 (COVID-19) in IgA nephropathy (IgAN) patients have been frequently reported worldwide. However, the post-event renal prognosis of these patients, their clinical backgrounds, and underlying mechanisms remain unknown. Therefore, we conducted a nationwide multicenter prospective cohort study in Japan.
Methods: We analyzed laboratory findings at the time of the first presentation to the hospital, and 3 and 6 months after in patients with GH after the vaccination, and histopathological findings in their kidney biopsy specimens. Moreover, changes in pathological biomarkers of IgAN such as galactose-deficient IgA1 (Gd-IgA1) and its immune complexes (ICs) were also evaluated.
Results: During the study period, 127 newly presenting with GH after the vaccination were enrolled, with a clear female bias (73.2%). GH was observed after the second or subsequent vaccinations in most patients (92.9%). Of the 37 patients undergoing kidney biopsy prior to the vaccination, 36 patients had been diagnosed with IgAN/IgA vasculitis (IgAV). In remaining 90 patients, 69 of the 70 who newly underwent kidney biopsy were diagnosed with IgAN (N=67)/IgAV (N=2). Their histopathology did not show a high incidence of acute lesions such as endocapillary hypercellularity and crescentic lesions. Most cases showed a temporary increase in proteinuria, but no sustained worsening in renal function. Among the biomarkers measured, serum Gd-IgA1 and ICs were comparable throughout the observation period, however, only urinary Gd-IgA1 was increased at the time of GH.
Conclusions: We found that GH after the vaccination is more likely to occur in IgAN/IgAV patients, with a female bias, but without progressive exacerbation of renal function. Although further investigation is needed regarding causal relationship between vaccination and GH, this study provides many insights into the molecular mechanisms of GH.
{"title":"Gross Hematuria after the COVID-19 mRNA Vaccination: Nationwide Multicenter Prospective Cohort Study in Japan.","authors":"Ryousuke Aoki, Yoshihito Nihei, Keiichi Matsuzaki, Hitoshi Suzuki, Masao Kihara, Asa Ogawa, Tomoya Nishino, Satoru Sanada, Shinya Yokote, Masahiro Okabe, Sayuri Shirai, Akihiro Fukuda, Junichi Hoshino, Daisuke Kondo, Takashi Yokoo, Naoki Kashihara, Ichiei Narita, Yusuke Suzuki","doi":"10.34067/KID.0000000000000498","DOIUrl":"https://doi.org/10.34067/KID.0000000000000498","url":null,"abstract":"<p><strong>Background: </strong>In the past three years, cases of gross hematuria (GH) after the vaccination for coronavirus disease 2019 (COVID-19) in IgA nephropathy (IgAN) patients have been frequently reported worldwide. However, the post-event renal prognosis of these patients, their clinical backgrounds, and underlying mechanisms remain unknown. Therefore, we conducted a nationwide multicenter prospective cohort study in Japan.</p><p><strong>Methods: </strong>We analyzed laboratory findings at the time of the first presentation to the hospital, and 3 and 6 months after in patients with GH after the vaccination, and histopathological findings in their kidney biopsy specimens. Moreover, changes in pathological biomarkers of IgAN such as galactose-deficient IgA1 (Gd-IgA1) and its immune complexes (ICs) were also evaluated.</p><p><strong>Results: </strong>During the study period, 127 newly presenting with GH after the vaccination were enrolled, with a clear female bias (73.2%). GH was observed after the second or subsequent vaccinations in most patients (92.9%). Of the 37 patients undergoing kidney biopsy prior to the vaccination, 36 patients had been diagnosed with IgAN/IgA vasculitis (IgAV). In remaining 90 patients, 69 of the 70 who newly underwent kidney biopsy were diagnosed with IgAN (N=67)/IgAV (N=2). Their histopathology did not show a high incidence of acute lesions such as endocapillary hypercellularity and crescentic lesions. Most cases showed a temporary increase in proteinuria, but no sustained worsening in renal function. Among the biomarkers measured, serum Gd-IgA1 and ICs were comparable throughout the observation period, however, only urinary Gd-IgA1 was increased at the time of GH.</p><p><strong>Conclusions: </strong>We found that GH after the vaccination is more likely to occur in IgAN/IgAV patients, with a female bias, but without progressive exacerbation of renal function. Although further investigation is needed regarding causal relationship between vaccination and GH, this study provides many insights into the molecular mechanisms of GH.</p>","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559050","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}
Pub Date : 2024-07-05DOI: 10.34067/kid.0000000000000497
MohamedH Hafez
{"title":"Global Perspective: Kidney Transplantation in North Africa","authors":"MohamedH Hafez","doi":"10.34067/kid.0000000000000497","DOIUrl":"https://doi.org/10.34067/kid.0000000000000497","url":null,"abstract":"","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141676401","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}
Pub Date : 2024-07-02DOI: 10.34067/kid.0000000000000491
Nicholas A. Shoctor, Makayla P. Brady, Kenneth R. McLeish, Rebecca R. Lightman, Leshaia Davis-Johnson, Conner Lynn, Anjali Dubbaka, Shweta Tandon, Michael W. Daniels, M. Rane, M. Barati, Dawn J. Caster, David W. Powell
Lupus nephritis (LN) occurs in over half of patients with systemic lupus erythematosus (SLE), but the cellular and molecular events that contribute to LN are not clearly defined. We reported previously that neutrophil degranulation participates in glomerular injury in mouse models of acute LN. The current study tests the hypothesis that glomerular recruitment and subsequent activation of neutrophils results in urine excretion of neutrophil granule constituents that are predictive of glomerular inflammation in proliferative LN. Urine and serum levels of 11 neutrophil granule proteins were measured by antibody-based array in proliferative LN patients and healthy donors (HD), and results were confirmed by ELISA. Glomerular neutrophil accumulation was assessed in LN patient biopsies who contributed urine for granule cargo quantitation and normal kidney tissue by microscopy. Degranulation was measured by flow cytometry in neutrophils isolated from LN patients and HD controls by cell surface granule markers CD63 (azurophilic), CC66b (specific) and CD35 (secretory). Nonparametric statistical analyses were performed and corrected for multiple comparisons. Eight granule proteins (myeloperoxidase, neutrophil elastase, azurocidin, olfactomedin-4, lactoferrin, alpha-1-acid glycoprotein 1 (α-1AG), MMP-9, and cathelicidin) were significantly elevated in urine from patients with active proliferative LN by array and/or ELISA, while only neutrophil elastase was increased in LN serum. Urine excretion of α-1AG declined in patients who achieved remission. The majority of LN glomeruli contained ≥ 3 neutrophils. Basal levels of specific granule markers were increased in neutrophils from LN patients, compared to HD controls. Serum from patients with active LN stimulated specific and secretory, but not azurophilic granule release by HD neutrophils. Circulating neutrophils in patients with LN are primed for enhanced degranulation. Glomerular recruitment of those primed neutrophils leads to release and urine excretion of neutrophil granule cargo that serves as a urine marker of active glomerular inflammation in proliferative LN.
{"title":"Increased Urine Excretion of Neutrophil Granule Cargo in Active Proliferative Lupus Nephritis","authors":"Nicholas A. Shoctor, Makayla P. Brady, Kenneth R. McLeish, Rebecca R. Lightman, Leshaia Davis-Johnson, Conner Lynn, Anjali Dubbaka, Shweta Tandon, Michael W. Daniels, M. Rane, M. Barati, Dawn J. Caster, David W. Powell","doi":"10.34067/kid.0000000000000491","DOIUrl":"https://doi.org/10.34067/kid.0000000000000491","url":null,"abstract":"\u0000 \u0000 Lupus nephritis (LN) occurs in over half of patients with systemic lupus erythematosus (SLE), but the cellular and molecular events that contribute to LN are not clearly defined. We reported previously that neutrophil degranulation participates in glomerular injury in mouse models of acute LN. The current study tests the hypothesis that glomerular recruitment and subsequent activation of neutrophils results in urine excretion of neutrophil granule constituents that are predictive of glomerular inflammation in proliferative LN.\u0000 \u0000 \u0000 \u0000 Urine and serum levels of 11 neutrophil granule proteins were measured by antibody-based array in proliferative LN patients and healthy donors (HD), and results were confirmed by ELISA. Glomerular neutrophil accumulation was assessed in LN patient biopsies who contributed urine for granule cargo quantitation and normal kidney tissue by microscopy. Degranulation was measured by flow cytometry in neutrophils isolated from LN patients and HD controls by cell surface granule markers CD63 (azurophilic), CC66b (specific) and CD35 (secretory). Nonparametric statistical analyses were performed and corrected for multiple comparisons.\u0000 \u0000 \u0000 \u0000 Eight granule proteins (myeloperoxidase, neutrophil elastase, azurocidin, olfactomedin-4, lactoferrin, alpha-1-acid glycoprotein 1 (α-1AG), MMP-9, and cathelicidin) were significantly elevated in urine from patients with active proliferative LN by array and/or ELISA, while only neutrophil elastase was increased in LN serum. Urine excretion of α-1AG declined in patients who achieved remission. The majority of LN glomeruli contained ≥ 3 neutrophils. Basal levels of specific granule markers were increased in neutrophils from LN patients, compared to HD controls. Serum from patients with active LN stimulated specific and secretory, but not azurophilic granule release by HD neutrophils.\u0000 \u0000 \u0000 \u0000 Circulating neutrophils in patients with LN are primed for enhanced degranulation. Glomerular recruitment of those primed neutrophils leads to release and urine excretion of neutrophil granule cargo that serves as a urine marker of active glomerular inflammation in proliferative LN.\u0000","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141688006","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}
Pub Date : 2024-07-01Epub Date: 2024-05-28DOI: 10.34067/KID.0000000000000468
Steven Fishbane, Juan-Jesus Carrero, Supriya Kumar, Eiichiro Kanda, Katarina Hedman, Richard Ofori-Asenso, Naoki Kashihara, Mikhail N Kosiborod, Mitja Lainscak, Carol Pollock, Peter Stenvinkel, David C Wheeler, Roberto Pecoits-Filho
{"title":"Hyperkalemia Burden and Treatment Pathways in Patients with CKD: Findings From the DISCOVER CKD Retrospective Cohort.","authors":"Steven Fishbane, Juan-Jesus Carrero, Supriya Kumar, Eiichiro Kanda, Katarina Hedman, Richard Ofori-Asenso, Naoki Kashihara, Mikhail N Kosiborod, Mitja Lainscak, Carol Pollock, Peter Stenvinkel, David C Wheeler, Roberto Pecoits-Filho","doi":"10.34067/KID.0000000000000468","DOIUrl":"10.34067/KID.0000000000000468","url":null,"abstract":"","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11296538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.34067/KID.0000000000000454
Miguel Bigotte Vieira
{"title":"Reducing Tacrolimus Levels to Improve Cognitive Function in Kidney Transplant Recipients.","authors":"Miguel Bigotte Vieira","doi":"10.34067/KID.0000000000000454","DOIUrl":"10.34067/KID.0000000000000454","url":null,"abstract":"","PeriodicalId":17882,"journal":{"name":"Kidney360","volume":null,"pages":null},"PeriodicalIF":3.2,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11296539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}