Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association最新文献

{"title":"Immune checkpoint inhibitor-associated hypercalcaemia.","authors":"Hassan Izzedine,&nbsp;Thibaud Chazal,&nbsp;Rimda Wanchoo,&nbsp;Kenar D Jhaveri","doi":"10.1093/ndt/gfaa326","DOIUrl":"https://doi.org/10.1093/ndt/gfaa326","url":null,"abstract":"<p><p>Immune checkpoint inhibitors (CPIs) have recently become a cornerstone for the treatment of different advanced cancers. These drugs have the ability to reactivate the immune system against tumour cells but can also trigger a myriad of side effects, termed immune-related adverse events (irAEs). Although there are numerous reports of CPI-related endocrinopathies, hypercalcaemia as a suspected irAE is not well documented. The mechanisms of CPI hypercalcaemia are not clearly established. However, in our review, four distinct causes emerged: endocrine disease-related, sarcoid-like granuloma, humoral hypercalcaemia due to parathyroid-related hormone and hyperprogressive disease following CPI initiation. Prompt recognition of hypercalcaemia and the institution of therapy can be lifesaving, affording the opportunity to address the underlying aetiology. In this review we discuss the incidence, diagnosis and management of immune-related hypercalcaemia in oncological patients receiving CPI agents.</p>","PeriodicalId":520717,"journal":{"name":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","volume":" ","pages":"1598-1608"},"PeriodicalIF":6.1,"publicationDate":"2022-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39096231","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}

{"title":"Serum matrix metalloproteinase 7 and accelerated glomerular filtration rate decline in a general non-diabetic population.","authors":"Inger T Enoksen,&nbsp;Dmitri Svistounov,&nbsp;Jon V Norvik,&nbsp;Vidar T N Stefansson,&nbsp;Marit D Solbu,&nbsp;Bjørn O Eriksen,&nbsp;Toralf Melsom","doi":"10.1093/ndt/gfab251","DOIUrl":"https://doi.org/10.1093/ndt/gfab251","url":null,"abstract":"<p><strong>Background: </strong>Age-related reduction of glomerular filtration rate (GFR) is a major contributor to the global chronic kidney disease (CKD) epidemic. We investigated whether baseline serum levels of the pro-fibrotic matrix metalloproteinase 2 (MMP2), MMP7 and their inhibitor, tissue inhibitor of metalloproteinase 1 (TIMP1), which mediates fibrosis development in aging animals, were associated with GFR decline in a general non-diabetic population.</p><p><strong>Methods: </strong>In the Renal Iohexol Clearance Survey, we measured GFR using iohexol clearance in 1627 subjects aged 50-64 years without self-reported diabetes, kidney or cardiovascular disease. After a median of 5.6 years, 1324 had follow-up GFR measurements. Using linear mixed models and logistic regression analyses, we evaluated the association of MMP7, MMP2 and TIMP1 with the mean GFR decline rate, risk of accelerated GFR decline (defined as subjects with the 10% steepest GFR slopes: ≥1.8 mL/min/1.73 m2/year) and incident CKD [GFR <60 mL/min/1.73 m2 and/or urinary albumin to creatinine ratio (ACR) ≥3.0 mg/mmol].</p><p><strong>Results: </strong>Higher MMP7 levels (per standard deviation increase of MMP7) were associated with steeper GFR decline rates [-0.23 mL/min/1.73 m2/year (95% confidence interval -0.34 to -0.12)] and increased risk of accelerated GFR decline and incident CKD [odds ratios 1.58 (1.30-1.93) and 1.45 (1.05-2.01), respectively, in a model adjusted for age, sex, baseline GFR, ACR and cardiovascular risk factors]. MMP2 and TIMP1 showed no association with GFR decline or incident CKD.</p><p><strong>Conclusions: </strong>The pro-fibrotic biomarker MMP7, but not MMP2 or TIMP1, is associated with increased risk of accelerated GFR decline and incident CKD in middle-aged persons from the general population.</p>","PeriodicalId":520717,"journal":{"name":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","volume":" ","pages":"1657-1667"},"PeriodicalIF":6.1,"publicationDate":"2022-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0a/24/gfab251.PMC9395374.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39346200","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}

{"title":"Kidney biopsy chronicity grading in antineutrophil cytoplasmic antibody-associated vasculitis.","authors":"Marta Casal Moura,&nbsp;Fernando C Fervenza,&nbsp;Ulrich Specks,&nbsp;Sanjeev Sethi","doi":"10.1093/ndt/gfab250","DOIUrl":"https://doi.org/10.1093/ndt/gfab250","url":null,"abstract":"<p><strong>Background: </strong>Kidney biopsy is valuable for prognostic assessment of renal outcomes in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) with glomerulonephritis (AAV-GN) but the impact of chronic changes is not determined.</p><p><strong>Methods: </strong>We conducted a retrospective cohort study of myeloperoxidase (MPO)- or proteinase 3 (PR3)-ANCA-positive patients with AAV and active renal disease. We applied the Mayo Clinic Chronicity Score (MCCS) and validated and evaluated its implications on outcome prediction in AAV-GN.</p><p><strong>Results: </strong>We analyzed 329 patients with kidney biopsies available to score. The extent of chronicity was graded by MCCS as minimal [102 (31.0%)], mild [106 (32.2%)], moderate [86 (26.1%)] and severe [35 (10.6%)]. The MCCS grades correlated with the degree of renal function impairment at presentation [mean estimated glomerular filtration rate (eGFR) 48.3 versus 29.2 versus 23.7 versus 18.5 mL/min/1.73 m2, respectively; P < 0.0001]. Higher degrees of the individual components of the MCCS (glomerulosclerosis, interstitial fibrosis, tubular atrophy and arteriosclerosis) were associated with lower median eGFR (P < 0.0001) and decreased event-free [kidney failure (KF) and death] survival (P = 0.002, P < 0.0001, P < 0.0001 and P = 0.017, respectively). Patients with lower MCCS grades recovered renal function more frequently (P < 0.0001). Increasing MCCS grades were associated with decreased renal recovery (P = 0.001), more frequent events and shorter time to KF (P < 0.0001), KF and death (P < 0.0001) and death (P = 0.042), independent of the remission induction treatment used (cyclophosphamide or rituximab). The MCCS stratified renal outcomes for each MCCS grade and can be used in clinical practice as a cutoff for KF prediction (MCCS ≥4).</p><p><strong>Conclusions: </strong>Chronic changes on kidney histology independently predict renal function, outcomes and response to treatment in AAV-GN.</p>","PeriodicalId":520717,"journal":{"name":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","volume":" ","pages":"1710-1721"},"PeriodicalIF":6.1,"publicationDate":"2022-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/82/4f/gfab250.PMC9395375.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39348667","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}

{"title":"Kidney transplantation in patients with multiple myeloma: narrative analysis and review of the last two decades.","authors":"David W Chitty,&nbsp;Monique A Hartley-Brown,&nbsp;Mersema Abate,&nbsp;Richa Thakur,&nbsp;Rimda Wanchoo,&nbsp;Kenar D Jhaveri,&nbsp;Vinay Nair","doi":"10.1093/ndt/gfaa361","DOIUrl":"https://doi.org/10.1093/ndt/gfaa361","url":null,"abstract":"<p><p>There have been significant advances in the treatment of multiple myeloma in the last two decades. Approximately 25% of patients with newly diagnosed myeloma have some degree of kidney impairment. During the course of illness, nearly 50% of myeloma patients will develop kidney disease. Moreover, ∼10% of myeloma patients have advanced kidney disease requiring dialysis at presentation. Hemodialysis is associated with a significantly reduced overall survival (OS). In the setting of prolonged long-term OS due to the use of newer immunotherapeutic agents in the treatment of myeloma, patients with myeloma and advanced kidney disease may benefit from more aggressive management with kidney transplantation (KTx). Unfortunately, most data regarding outcomes of KTx in patients with myeloma come from single-center case series. With the advent of novel treatment choices, it remains unclear if outcomes of kidney transplant recipients with myeloma have improved in recent years. In this descriptive systematic review, we coalesced published patient data over the last 20 years to help inform clinicians and patients on expected hematologic and KTx outcomes in this complex population. We further discuss the future of KTx in patients with paraproteinemia.</p>","PeriodicalId":520717,"journal":{"name":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","volume":" ","pages":"1616-1626"},"PeriodicalIF":6.1,"publicationDate":"2022-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/ndt/gfaa361","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38691170","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}

{"title":"Safety and efficacy of dapagliflozin in patients with focal segmental glomerulosclerosis: a prespecified analysis of the dapagliflozin and prevention of adverse outcomes in chronic kidney disease (DAPA-CKD) trial.","authors":"David C Wheeler,&nbsp;Niels Jongs,&nbsp;Bergur V Stefansson,&nbsp;Glenn M Chertow,&nbsp;Tom Greene,&nbsp;Fan Fan Hou,&nbsp;Anna Maria Langkilde,&nbsp;John J V McMurray,&nbsp;Peter Rossing,&nbsp;Michal Nowicki,&nbsp;István Wittmann,&nbsp;Ricardo Correa-Rotter,&nbsp;C David Sjöström,&nbsp;Robert D Toto,&nbsp;Hiddo J L Heerspink","doi":"10.1093/ndt/gfab335","DOIUrl":"https://doi.org/10.1093/ndt/gfab335","url":null,"abstract":"<p><strong>Background: </strong>Despite renin-angiotensin-aldosterone system blockade and immunosuppressive treatment, focal segmental glomerulosclerosis (FSGS) often progresses to kidney failure. The objective of this prespecified analysis of the dapagliflozin and prevention of adverse outcomes in chronic kidney disease trial (DAPA-CKD) was to assess efficacy and safety of dapagliflozin in a small subgroup of participants with FSGS confirmed by kidney biopsy.</p><p><strong>Methods: </strong>In DAPA-CKD, patients with an estimated glomerular filtration rate (eGFR) 25-75 mL/min/1.73 m2 and urinary albumin:creatinine ratio (UACR) 200-5000 mg/g (22.6-565 mg/mol) were randomized to dapagliflozin 10 mg once daily or placebo as an adjunct to standard care and followed for median 2.4 years. The primary composite endpoint was sustained eGFR decline ≥50%, end-stage kidney disease, or kidney or cardiovascular death. The endpoint of interest for this analysis was eGFR slope (acute effects from baseline to Week 2 and chronic effects from Week 2 to end of treatment).</p><p><strong>Results: </strong>Of 104 participants with biopsy-confirmed FSGS, 45 were randomized to dapagliflozin and 59 to placebo. Mean (standard deviation) age was 54.0 (14.3) years, mean eGFR 41.9 (11.5) mL/min/1.73 m2 and median (interquartile range) UACR 1248 (749-2211) mg/g. The primary outcome occurred in 4 (8.9%) and 7 (11.9%) participants randomized to dapagliflozin and placebo, respectively [hazard ratio 0.62, 95% confidence interval (95% CI) 0.17, 2.17]. Dapagliflozin led to a larger acute reduction (standard error) in eGFR compared with placebo (-4.5, 95% CI -5.9 to -3.1 versus -0.9, -2.1 to 0.4 mL/min/1.73 m2/2 weeks). Thereafter, mean rates of chronic eGFR decline with dapagliflozin and placebo were -1.9 (-3.0, -0.9) and -4.0 (-4.9, -3.0) mL/min/1.73 m2/year, respectively (difference 2.0, 95% CI 0.6 to 3.5, mL/min/1.73 m2/year). Adverse events leading to study drug discontinuation were similar in both groups; there were fewer serious adverse events with dapagliflozin.</p><p><strong>Conclusions: </strong>Among DAPA-CKD participants with FSGS, dapagliflozin reduced the rate of chronic decline of eGFR compared with placebo, although this difference was not statistically significant.</p>","PeriodicalId":520717,"journal":{"name":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","volume":" ","pages":"1647-1656"},"PeriodicalIF":6.1,"publicationDate":"2022-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/62/4c/gfab335.PMC9395378.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39681022","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}

{"title":"Associations of cardiovascular disease and blood pressure with cognition in hemodialysis patients: The Osaka Dialysis Complication Study.","authors":"Tetsuo Shoji,&nbsp;Hisako Fujii,&nbsp;Katsuhito Mori,&nbsp;Shinya Nakatani,&nbsp;Yuki Nagata,&nbsp;Tomoaki Morioka,&nbsp;Masaaki Inaba,&nbsp;Masanori Emoto","doi":"10.1093/ndt/gfab247","DOIUrl":"https://doi.org/10.1093/ndt/gfab247","url":null,"abstract":"<p><strong>Background: </strong>Previous studies have reported mixed results regarding the contributions of cardiovascular disease (CVD) and blood pressure (BP) to cognitive impairment in chronic kidney disease.</p><p><strong>Methods: </strong>This was a cross-sectional study in 1213 patients on maintenance hemodialysis from 17 dialysis units in Japan. The main exposures were prior CVD and BP components including systolic BP (SBP) and diastolic BP (DBP). The outcome was low cognitive function evaluated with the Modified Mini-Mental State (3MS) examination with a cut-off level of 3MS <80.</p><p><strong>Results: </strong>The median age was 67 years, median duration of dialysis was 71 months, 37% were women, 39% had diabetic kidney disease and 36% had any pre-existing CVD. Median (interquartile range) of 3MS score was 91 (82-97), and 240 patients (20%) had 3MS <80. Logistic regression analysis showed that 3MS <80 was associated with the presence of any prior CVD, particularly prior stroke. 3MS <80 was associated with lower DBP but not with SBP. When patients were stratified by the presence of prior stroke, lower DBP, higher age and lower education level were factors associated with 3MS <80 in both subgroups. In the subgroup of patients without prior stroke, diabetic kidney disease was an additional factor associated with 3MS <80. CVDs other than stroke were not associated with 3MS in either subgroup.</p><p><strong>Conclusions: </strong>Prior stroke and lower DBP were associated with 3MS <80 in hemodialysis patients. These findings support the hypothesis that these vascular factors contribute to low cognitive performance in patients undergoing hemodialysis.</p>","PeriodicalId":520717,"journal":{"name":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","volume":" ","pages":"1758-1767"},"PeriodicalIF":6.1,"publicationDate":"2022-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39369474","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}

{"title":"SGLT2 inhibition requires reconsideration of fundamental paradigms in chronic kidney disease, 'diabetic nephropathy', IgA nephropathy and podocytopathies with FSGS lesions.","authors":"Hans-Joachim Anders,&nbsp;Anna Julie Peired,&nbsp;Paola Romagnani","doi":"10.1093/ndt/gfaa329","DOIUrl":"https://doi.org/10.1093/ndt/gfaa329","url":null,"abstract":"<p><p>In 2020, the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial first demonstrated that inhibition of the sodium-glucose transporter-2 (SGLT2) with dapagliflozin attenuates the progression of chronic kidney disease (CKD) with proteinuria in patients with or without diabetes at an unprecedented effect size. These results have far-reaching implications for a series of traditional concepts in Nephrology. It now became obvious that CKD with and without diabetes involves a predominant SGLT2-driven pathophysiology compared with the other pathogenic pathways currently under consideration. As SGLT2 inhibition is similarly efficacious in diabetic and non-diabetic CKD with proteinuria, treating CKD rather than 'diabetic nephropathy' becomes the central paradigm. Indeed, in older adults with type 2 diabetes, CKD is rather of multifactorial origin. As the DAPA-CKD trial included more patients with immunoglobulin A nephropathy (IgAN) than any of the previous IgAN trials, dual renin-angiotensin/SGLT2 inhibition may become the new standard. The same applies for patients with podocytopathy-related focal segmental glomerulosclerosis lesions. From now on, IgAN and podocytopathy trials without SGLT2 inhibition as background therapy and without glomerular filtration rate decline as primary outcome criterion will be of limited value. These and other potential implications will trigger broad discussions and secondary research activities with conclusions difficult to predict today. However, one is for sure: Nephrology after the DAPA-CKD trial will be not the same as it was before. Finally!</p>","PeriodicalId":520717,"journal":{"name":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","volume":" ","pages":"1609-1615"},"PeriodicalIF":6.1,"publicationDate":"2022-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1093/ndt/gfaa329","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38706627","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}

{"title":"Association of blood pressure with cardiovascular outcome and mortality: results from the KNOW-CKD study.","authors":"Jee Young Lee,&nbsp;Jung Tak Park,&nbsp;Young Su Joo,&nbsp;Changhyun Lee,&nbsp;Hae-Ryong Yun,&nbsp;Tae Ik Chang,&nbsp;Yeong-Hoon Kim,&nbsp;WooKyung Chung,&nbsp;Tae-Hyun Yoo,&nbsp;Shin-Wook Kang,&nbsp;Sue K Park,&nbsp;Dong Wan Chae,&nbsp;Kook-Hwan Oh,&nbsp;Seung Hyeok Han","doi":"10.1093/ndt/gfab257","DOIUrl":"https://doi.org/10.1093/ndt/gfab257","url":null,"abstract":"<p><strong>Background: </strong>Optimal blood pressure (BP) control is a major therapeutic strategy to reduce adverse cardiovascular events (CVEs) and mortality in patients with chronic kidney disease (CKD). We studied the association of BP with adverse cardiovascular outcome and all-cause death in patients with CKD.</p><p><strong>Methods: </strong>Among 2238 participants from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD), 2226 patients with baseline BP measurements were enrolled. The main predictor was systolic BP (SBP) categorized by five levels: <110, 110-119, 120-129, 130-139 and ≥140 mmHg. The primary endpoint was a composite outcome of all-cause death or incident CVEs. We primarily used marginal structural models (MSMs) using averaged and the most recent time-updated SBPs.</p><p><strong>Results: </strong>During the follow-up of 10 233.79 person-years (median 4.60 years), the primary composite outcome occurred in 240 (10.8%) participants, with a corresponding incidence rate of 23.5 [95% confidence interval (CI) 20.7-26.6]/1000 patient-years. MSMs with averaged SBP showed a U-shaped relationship with the primary outcome. Compared with time-updated SBP of 110-119 mmHg, hazard ratios (95% CI) for <110, 120-129, 130-139 and ≥140 mmHg were 2.47 (1.48-4.11), 1.29 (0.80-2.08), 2.15 (1.26-3.69) and 2.19 (1.19-4.01), respectively. MSMs with the most recent SBP also showed similar findings.</p><p><strong>Conclusions: </strong>In Korean patients with CKD, there was a U-shaped association of SBP with the risk of adverse clinical outcomes. Our findings highlight the importance of BP control and suggest a potential hazard of SBP <110 mmHg.</p>","PeriodicalId":520717,"journal":{"name":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","volume":" ","pages":"1722-1730"},"PeriodicalIF":6.1,"publicationDate":"2022-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39378524","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}

{"title":"Glomerular deposition of galactose-deficient IgA1-containing immune complexes via glomerular endothelial cell injuries.","authors":"Yuko Makita, Hitoshi Suzuki, Daisuke Nakano, Hiroyuki Yanagawa, Toshiki Kano, Jan Novak, Akira Nishiyama, Yusuke Suzuki","doi":"10.1093/ndt/gfac204","DOIUrl":"10.1093/ndt/gfac204","url":null,"abstract":"<p><strong>Background: </strong>Galactose-deficient immunoglobulin A1 (Gd-IgA1) plays a crucial role in the development of IgA nephropathy (IgAN). However, the pathological role of Gd-IgA1-containing immune complexes (ICs) and the mechanism of deposition in the mesangial region remain unclear.</p><p><strong>Methods: </strong>To examine the deposition of Gd-IgA1-containing ICs in the mesangial region through glomerular endothelial cell injury, we evaluated the alteration of renal microvascular endothelial glycocalyx in nude mice injected with Gd-IgA1-IgG ICs. Human renal glomerular endothelial cells (HRGECs) were used to assess the potential capacity of Gd-IgA1-IgG ICs to activate endothelial cells.</p><p><strong>Results: </strong>Nude mice injected with Gd-IgA1-containing ICs showed podocyte and endothelial cell injuries, with IgA, IgG and C3 depositions in glomerular capillaries and the mesangium. Moreover, albuminuria and hematuria were induced. Real-time glycocalyx imaging showed that renal microvascular glycocalyx was decreased immediately after injection of Gd-IgA1-containing ICs and then mesangial IgA deposition was increased. After coculture of Gd-IgA1-containing ICs with HRGECs, messenger RNA expression levels of endothelial adhesion molecules and proinflammatory mediators were upregulated significantly.</p><p><strong>Conclusion: </strong>Gd-IgA1-IgG ICs had a high affinity for glomerular endothelial cells, which resulted in glomerular filtration barrier dysfunction mediated by glycocalyx loss. Furthermore, Gd-IgA1-IgG ICs accelerated the production of adhesion factors and proinflammatory cytokines in glomerular endothelial cells. The glomerular endothelial cell injury induced by Gd-IgA1-containing ICs may enhance the permeability of Igs in the mesangial region and subsequent inflammatory responses in the pathogenesis of IgAN.</p>","PeriodicalId":520717,"journal":{"name":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","volume":" ","pages":"1629-1636"},"PeriodicalIF":0.0,"publicationDate":"2022-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9395370/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40390471","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}

{"title":"Urinary biomarkers predict progression and adverse outcomes of acute kidney injury in critical illness.","authors":"Stephen Duff,&nbsp;Ruairi Irwin,&nbsp;Jean Maxime Cote,&nbsp;Lynn Redahan,&nbsp;Blaithin A McMahon,&nbsp;Brian Marsh,&nbsp;Alistair Nichol,&nbsp;Sinead Holden,&nbsp;Peter Doran,&nbsp;Patrick T Murray","doi":"10.1093/ndt/gfab263","DOIUrl":"https://doi.org/10.1093/ndt/gfab263","url":null,"abstract":"<p><strong>Background: </strong>Acute kidney injury (AKI) is common in hospitalized patients and is associated with high morbidity and mortality. The Dublin Acute Biomarker Group Evaluation study is a prospective cohort study of critically ill patients (n = 717). We hypothesized that novel urinary biomarkers would predict progression of AKI and associated outcomes.</p><p><strong>Methods: </strong>The primary (diagnostic) analysis assessed the ability of biomarkers levels at the time of early Stage 1 or 2 AKI to predict progression to higher AKI stage, renal replacement therapy (RRT) or death within 7 days of intensive care unit admission. In the secondary (prognostic) analysis, we investigated the association between biomarker levels and RRT or death within 30 days.</p><p><strong>Results: </strong>In total, 186 patients had an AKI within 7 days of admission. In the primary (diagnostic) analysis, 8 of the 14 biomarkers were independently associated with progression. The best predictors were cystatin C [adjusted odds ratio (aOR) 5.2; 95% confidence interval (CI) 1.3-23.6], interleukin-18 (IL-18; aOR 5.1; 95% CI 1.8-15.7), albumin (aOR 4.9; 95% CI 1.5-18.3) and neutrophil gelatinase-associated lipocalin (NGAL; aOR 4.6; 95% CI 1.4-17.9). Receiver-operating characteristics and net reclassification index analyses similarly demonstrated improved prediction by these biomarkers. In the secondary (prognostic) analysis of Stages 1-3 AKI cases, IL-18, NGAL, albumin and monocyte chemotactic protein-1 were also independently associated with RRT or death within 30 days.</p><p><strong>Conclusions: </strong>Among 14 novel urinary biomarkers assessed, cystatin C, IL-18, albumin and NGAL were the best predictors of Stages 1-2 AKI progression. These biomarkers, after further validation, may have utility to inform diagnostic and prognostic assessment and guide management of AKI in critically ill patients.</p>","PeriodicalId":520717,"journal":{"name":"Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association","volume":" ","pages":"1668-1678"},"PeriodicalIF":6.1,"publicationDate":"2022-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39391961","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}