Canadian Journal of Kidney Health and Disease最新文献

{"title":"De Novo Fibrinogen A Alpha Chain Amyloidosis in a Kidney Transplant Patient: Case Report and Literature Review.","authors":"Taqui Khaja,&nbsp;Luan Truong,&nbsp;George Nassar","doi":"10.1177/20543581231209207","DOIUrl":"10.1177/20543581231209207","url":null,"abstract":"<p><strong>Rationale: </strong><i>De Novo</i> transplant amyloidosis denotes the condition when a patient develops amyloidosis after transplantation but had not been diagnosed with the disease prior to transplantation. The incidence of <i>de novo</i> amyloidosis in kidney transplants is rare, but few published case reports have described the occurrence of <i>de novo</i> Amyloid A protein (AA) and Light Chain (AL) amyloidosis. However, <i>de novo</i> hereditary fibrinogen A alpha chain (AFib) has not been previously reported.</p><p><strong>Patient presentation: </strong>We present a 72-year-old man, a kidney transplant recipient, who developed progressive rise in his creatinine about 3 years after transplantation. He has long-standing diabetes mellitus type 2, obesity, and hypertension, so he did not have a kidney biopsy of his native kidneys prior to transplantation.</p><p><strong>Diagnosis: </strong>A kidney transplant biopsy was done that showed amyloidosis. Mass spectrophotometry confirmed it as AFib amyloidosis. Genetic testing of the patient revealed that he has fibrinogen A alpha gene (FGA) point mutation with a p.E545V variant.</p><p><strong>Interventions: </strong>Cardiac evaluation showed normal transthoracic echocardiogram. Cardiac magnetic resonance imaging (MRI) showed no involvement by amyloidosis. A peripheral nerve biopsy showed diabetic neuropathy. Thus, the kidney was the only organ involved by the disease. The kidney transplant was managed conservatively with blood pressure and diabetes control in addition to his usual immunosuppression regimen which was not altered. He is being treated with diuretics, angiotensin receptor inhibitors, and sodium glucose transport 2 inhibitors.</p><p><strong>Outcomes: </strong>Kidney transplant function exhibited only slow progression over 18 months since the diagnosis was confirmed. This slow progression is likely because the p.E545V point mutation variant is less aggressive than other gene deletion mutations and because our patient was judged to have been diagnosed early in the course of his disease.</p><p><strong>Teaching points: </strong>In this case report, we illustrate the findings and testing that confirmed the diagnosis of AFib amyloidosis. We summarize the clinical aspects, outcomes of the disease, and treatment options. We believe this case report is interesting because it is the first reported case of AFib amyloidosis in a kidney transplant recipient who was not known to have the disease prior to kidney transplantation.</p>","PeriodicalId":9426,"journal":{"name":"Canadian Journal of Kidney Health and Disease","volume":"10 ","pages":"20543581231209207"},"PeriodicalIF":1.7,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10619347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420918","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":"Risk and Timing of Major Bleeding Complications Requiring Intervention of the Percutaneous Kidney Biopsy With a Short Observation Protocol: A Retrospective Chart Review.","authors":"Melissa Schorr,&nbsp;Pavel S Roshanov,&nbsp;Jeremy Vandelinde,&nbsp;Andrew A House","doi":"10.1177/20543581231205334","DOIUrl":"10.1177/20543581231205334","url":null,"abstract":"<p><strong>Background: </strong>We previously published a retrospective study of kidney biopsies performed in a tertiary care hospital in London, Ontario from 2012 to 2017. This study resulted in a change of practice in our institution to shorter postbiopsy monitoring for outpatients as well as the development of a risk calculator to predict serious bleeding complications.</p><p><strong>Objective: </strong>The primary objective of this study was to determine whether this shorter monitoring time is adequate in the outpatient setting. A secondary objective was to validate the bleeding risk calculator in both inpatients and outpatients.</p><p><strong>Design: </strong>This was a retrospective chart review.</p><p><strong>Setting: </strong>This study was performed at a tertiary academic hospital in London, Ontario, Canada.</p><p><strong>Participants: </strong>This was a retrospective study of 400 adult patients who underwent kidney biopsy between April 30, 2018 and February 25, 2022 at a tertiary academic hospital in London, Canada.</p><p><strong>Methods: </strong>We retrospectively assessed frequency and timing of major bleeding complications in patients who underwent kidney biopsy. In secondary analyses, we examined the prediction performance of the risk calculator in discrimination and calibration.</p><p><strong>Results: </strong>Major bleeding occurred in 7 patients (1.8%). Five of these patients required blood transfusions (1.3%) and 2 required embolization (0.5%). In the outpatient setting, any major bleeding events were identified immediately (1 patient) or on the routine 2-hour ultrasounds (1 patient). The risk calculator showed good discrimination (C-statistic, 0.91, 95% confidence interval [CI] = [0.84 to 0.95]) and calibration (slope, 1.10, 95% CI = [0.47 to 1.74]; intercept, 95% CI = -0.02 [-0.79 to 0.75]), but with much uncertainty in the estimates.</p><p><strong>Limitations: </strong>The occurrence of only a few major bleeding events limits the reliability of our assessment of our risk calculator.</p><p><strong>Conclusions: </strong>There appears to be little yield in extending observation beyond 2 hours after an outpatient kidney biopsy with the use of immediate and 2-hour postbiopsy ultrasounds. The bleeding risk calculator (http://perioperativerisk.com/kbrc) warrants further validation.</p>","PeriodicalId":9426,"journal":{"name":"Canadian Journal of Kidney Health and Disease","volume":"10 ","pages":"20543581231205334"},"PeriodicalIF":1.7,"publicationDate":"2023-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10619350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420921","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":"Precision Medicine in Diabetic Kidney Disease: A Narrative Review Framed by Lived Experience.","authors":"Mallory L Downie,&nbsp;Arlene Desjarlais,&nbsp;Nancy Verdin,&nbsp;Tania Woodlock,&nbsp;David Collister","doi":"10.1177/20543581231209012","DOIUrl":"10.1177/20543581231209012","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Purpose of review: &lt;/strong&gt;Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease (CKD) for which many treatments exist that have been shown to prevent CKD progression and kidney failure. However, DKD is a complex and heterogeneous etiology of CKD with a spectrum of phenotypes and disease trajectories. In this narrative review, we discuss precision medicine approaches to DKD, including genomics, metabolomics, proteomics, and their potential role in the management of diabetes mellitus and DKD. A patient and caregivers of patients with lived experience with CKD were involved in this review.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Sources of information: &lt;/strong&gt;Original research articles were identified from MEDLINE and Google Scholar using the search terms \"diabetes,\" \"diabetic kidney disease,\" \"diabetic nephropathy,\" \"chronic kidney disease,\" \"kidney failure,\" \"dialysis,\" \"nephrology,\" \"genomics,\" \"metabolomics,\" and \"proteomics.\"&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A focused review and critical appraisal of existing literature regarding the precision medicine approaches to the diagnosis, prognosis, and treatment of diabetes and DKD framed by a patient partner's/caregiver's lived experience.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key findings: &lt;/strong&gt;Distinguishing diabetic nephropathy from CKD due to other types of DKD and non-DKD is challenging and typically requires a kidney biopsy for a diagnosis. Biomarkers have been identified to assist with the prediction of the onset and progression of DKD, but they have yet to be incorporated and evaluated relative to clinical standard of care CKD and kidney failure risk prediction tools. Genomics has identified multiple causal genetic variants for neonatal diabetes mellitus and monogenic diabetes of the young that can be used for diagnostic purposes and to specify antiglycemic therapy. Genome-wide-associated studies have identified genes implicated in DKD pathophysiology in the setting of type 1 and 2 diabetes but their translational benefits are lagging beyond polygenetic risk scores. Metabolomics and proteomics have been shown to improve diagnostic accuracy in DKD, have been used to identify novel pathways involved in DKD pathogenesis, and can be used to improve the prediction of CKD progression and kidney failure as well as predict response to DKD therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Limitations: &lt;/strong&gt;There are a limited number of large, high-quality prospective observational studies and no randomized controlled trials that support the use of precision medicine based approaches to improve clinical outcomes in adults with or at risk of diabetes and DKD. It is unclear which patients may benefit from the clinical use of genomics, metabolomics and proteomics along the spectrum of DKD trajectory.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Implications: &lt;/strong&gt;Additional research is needed to evaluate the role of the use of precision medicine for DKD management, including diagnosis, differentiation of diabetic nephropathy from other etiologies of DKD and CKD, sh","PeriodicalId":9426,"journal":{"name":"Canadian Journal of Kidney Health and Disease","volume":"10 ","pages":"20543581231209012"},"PeriodicalIF":1.7,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10619345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420920","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":"Multidisciplinary Support To Access living donor Kidney Transplant (MuST AKT): A Clinical Research Protocol for a Pilot Randomized Controlled Trial to Increase Living Kidney Donation.","authors":"Anne-Marie Selzler,&nbsp;Parastoo Molla Davoodi,&nbsp;Scott Klarenbach,&nbsp;Ngan N Lam,&nbsp;Terry Smith,&nbsp;Abigail Ackroyd,&nbsp;Natasha Wiebe,&nbsp;Bonnie Corradetti,&nbsp;Sharron Ferdinand,&nbsp;Dorothy Iyekekpolor,&nbsp;Gordon Smith,&nbsp;Nancy Verdin,&nbsp;Aminu K Bello,&nbsp;Kevin Wen,&nbsp;Soroush Shojai","doi":"10.1177/20543581231205340","DOIUrl":"10.1177/20543581231205340","url":null,"abstract":"<p><strong>Background: </strong>Living donor kidney transplantation (LDKT) is the optimal treatment for eligible patients with kidney failure, although it is underutilized. Contextually tailored patient- and family-centered interventions may be effective to increase LDKT.</p><p><strong>Objective: </strong>We outline a protocol to test the feasibility of the Multidisciplinary Support To Access living donor Kidney Transplant (MuST AKT) intervention designed to increase LDKT.</p><p><strong>Design: </strong>Non-blinded single-center pilot randomized controlled trial with a qualitative interview component.</p><p><strong>Setting: </strong>Academic transplant referral center in Northern Alberta Region with a population of more than 2 million in its catchment area.</p><p><strong>Patients: </strong>English-speaking patients of the age range 18 to 75 years who are referred for kidney transplantation are eligible to participate.</p><p><strong>Measurements: </strong>Feasibility will be assessed by indicators of recruitment, retention, and completion rates, treatment fidelity, adherence to intervention, engagement in intervention, and acceptability.</p><p><strong>Methods: </strong>Participants will be randomly assigned 1:1 to either standard care (control) or the experimental group who receive standard care plus the MuST AKT intervention, a person-centered program designed to assist and enable the kidney transplant candidate to achieve what is required to receive an LDKT. The intervention consists of an introductory session and 4 intervention sessions delivered in-person or virtually.</p><p><strong>Limitations: </strong>Inferences cannot be drawn regarding the efficacy/effectiveness of the MuST AKT intervention. This study is non-blinded.</p><p><strong>Conclusions: </strong>This pilot study is the first step in our broader initiative to increase LDKT in our health care jurisdiction. The results of this study will be used to inform the development of a future definitive randomized controlled trial.</p><p><strong>Trial registration number: </strong>NCT04666545.</p>","PeriodicalId":9426,"journal":{"name":"Canadian Journal of Kidney Health and Disease","volume":"10 ","pages":"20543581231205340"},"PeriodicalIF":1.7,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10619336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420919","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":"A Simple Exercise Program for Patients With End-Stage Kidney Disease to Improve Strength and Quality of Life: Clinical Research Protocol.","authors":"Rita S Suri,&nbsp;Louise Moist,&nbsp;Charmaine Lok,&nbsp;Catherine M Clase,&nbsp;Jennifer Harris,&nbsp;Robert D Reid,&nbsp;Tim Ramsay,&nbsp;Deborah Zimmerman","doi":"10.1177/20543581231205160","DOIUrl":"https://doi.org/10.1177/20543581231205160","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Most patients with end-stage kidney disease (ESKD) appreciate the importance of exercise and would like to increase their physical activity; however, they report a few key barriers, including (1) lack of physician advice to do so, (2) lack of safe and convenient programs (ie, appropriate for home or neighborhood), and (3) cost. Importantly, patients indicated in a previous survey that they would prefer an exercise program that improves muscle strength and symptoms, and are less interested in cardiovascular disease prevention.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;To test the feasibility of a simple, prescribed exercise program using Nordic walking poles in patients with ESKD treated with dialysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Design: &lt;/strong&gt;Randomized multicenter pilot trial of an exercise intervention that includes Nordic walking poles, personalized physician exercise prescriptions, pedometers, and access to exercise videos, compared with standard of care, in patients being treated with maintenance dialysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Setting: &lt;/strong&gt;Multicenter tertiary care centers in Canada.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Patients: &lt;/strong&gt;Ambulatory adult patients with ESKD treated with peritoneal dialysis or hemodialysis (HD) for at least 6 months at participating sites are potentially eligible. Inclusion criteria include ability to use Nordic walking poles (either de novo or in place of mobility aid) and to provide informed consent in English or in French. Exclusion criteria include (1) any absolute contraindication to exercise, (2) baseline step count &gt;8000 steps/day, (3) planned living donor kidney transplant, and (4) participation in another interventional trial that may affect the results of this study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This is a randomized multicenter pilot trial of an exercise intervention that consists of a prescription to exercise using Nordic walking poles, a pedometer to track activity, and access to exercise videos, with the comparator of standard of care (dialysis unit staff encouragement to exercise) in patients being treated with maintenance dialysis. Randomization is concealed and uses a 1:1 ratio for group assignment. Our specific aims are to determine the feasibility of patient recruitment, adherence to the exercise program (verified by step counts), and efficacy of the intervention on patient-important outcomes that were assessed as a priority by patients in a prior survey-specifically strength, fatigue, and sleep. We record days spent in hospital and loss of independent living to inform sample size calculations for a definitive trial of exercise in patient with ESKD treated with dialysis. Adverse events are closely monitored.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Outcomes: &lt;/strong&gt;Primary: Our recruitment goal is 90 to 150 patients over 27 months; adherence success will be defined if &gt;75% of randomized patients, excluding those who are transplanted or deceased, achieve &gt;80% of their prescribed steps at 6 and 12 months. Secondary Efficacy Ou","PeriodicalId":9426,"journal":{"name":"Canadian Journal of Kidney Health and Disease","volume":"10 ","pages":"20543581231205160"},"PeriodicalIF":1.7,"publicationDate":"2023-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10605660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71410726","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":"Burden and Risk Factors of Contrast-Associated Acute Kidney Injury in Hospitalized Zambian Children: A Prospective Cohort Study at the University Teaching Hospitals.","authors":"Hellen M'hango,&nbsp;Chishiba Kabengele,&nbsp;Veronica Sukuntu,&nbsp;Chisambo Mwaba","doi":"10.1177/20543581231205156","DOIUrl":"10.1177/20543581231205156","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Contrast-associated acute kidney injury (CAAKI) is defined as acute kidney injury (AKI) occurring within 72 hours of administration of contrast media (CM) and is linked to adverse outcomes including longer hospital stay, increased hospital mortality, and a higher risk of chronic kidney disease in later life. Risk factors for the development of CAAKI in the Zambian pediatric population have not been well studied.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;The objective of this study was to assess the burden of CAAKI, ascertain its risk factors, and describe short-term outcomes in hospitalized children at the University Teaching Hospitals (UTH) undergoing contrast-enhanced radiological investigations.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This was a prospective observational study of in-patients undergoing contrast-enhanced radiological procedures, between September 2020 and September 2021. The participants were recruited from the Children's Hospital, the Cancer Diseases Hospital, and the Pediatric Surgical Ward at the University Teaching Hospital in Lusaka, Zambia. The primary outcome variable was occurrence of AKI at 48 hours post CM administration. We used 2 criteria to define CAAKI in our study-the European Society of Urogenital Radiology (ESUR) and the Kidney Disease Improving Global Outcomes (KDIGO) 2012 criteria. Multivariable logistic regression models were formulated to assess for risk factors of CAAKI.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Of the 201 enrolled participants, 123 (61.2%) were male and the median age of the participants was 5 years (interquartile range [IQR] = 3-10). The mean hemoglobin was 103 g/L (standard deviation [SD] = 26), median creatinine was 30.9 µmol/l (IQR = 22.6-43), and the glomerular filtration rate (GFR) was 102.5 mL/min/1.73 m&lt;sup&gt;2&lt;/sup&gt; (IQR = 76.2-129.4). Forty-six (22.9%) developed CAAKI using the ESUR compared with 4.5% (9/201) using the KDIGO criteria. Independent risk factors of CAAKI were receiving a higher dose of CM (adjusted odds ratio [aOR] = 2.54; 95% confidence interval [CI] = [1.12-5.74]), prematurity (aOR = 4.6; 95% CI = [1.05-16.7]), and a higher eGFR (aOR= 1.01; 95% CI = [1.01-1.02]). Females had higher odds of CAAKI (aOR = 2.48; 95% CI = [1.18-5.18]) when compared with males. One CAAKI participant (2.2%) died; none of the participants who developed CAAKI and survived required dialysis and most of them (90%) were discharged before day 7. Day 7 eGFR results had returned to or near baseline values for those whose creatinine results were available.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;Using the ESUR criteria, a significant proportion (22.9%) of children undergoing contrast-enhanced computed tomography (CT) scans at the UTH developed CAAKI. In contrast, using the KDIGO criteria only 4.5% had CAAKI. Being born as a preterm baby, being female, having a higher eGFR at baseline, and receiving a higher dose of CM were found to be independent risk factors for CAAKI development in Zambian ch","PeriodicalId":9426,"journal":{"name":"Canadian Journal of Kidney Health and Disease","volume":"10 ","pages":"20543581231205156"},"PeriodicalIF":1.7,"publicationDate":"2023-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fb/b6/10.1177_20543581231205156.PMC10599111.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54227730","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":"Effects of Two Soluble ACE2-Fc Variants on Blood Pressure and Albuminuria in Hypertensive Mice: Research Letter.","authors":"Mayra Trentin-Sonoda,&nbsp;Joseph Zimpelmann,&nbsp;Karishma Tailor,&nbsp;John W Gillard,&nbsp;Nathan Yoganathan,&nbsp;Traian Sulea,&nbsp;Kevin D Burns","doi":"10.1177/20543581231207146","DOIUrl":"10.1177/20543581231207146","url":null,"abstract":"<p><strong>Background: </strong>Angiotensin-converting enzyme 2 (ACE2) hydrolyzes angiotensin (Ang) II to Ang-(1-7), promoting vasodilatation, and inhibiting oxidative stress and inflammation. Plasma membrane ACE2 is the receptor for all known SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) viral variants. In COVID-19 infection, soluble ACE2 variants may act as decoys to bind and neutralize the coronavirus, reducing its tissue infectivity. Furthermore, soluble ACE2 variants have been proposed as potential therapeutics for kidney disease and hypertensive disorders.</p><p><strong>Objective: </strong>Soluble ACE2 variants conjugated to human Fc domains and selected for high-potency viral SARS-CoV-2 neutralization were prepared and evaluated for ACE2 activity in vitro. Lead candidates were then tested for systemic ACE2 activity, stability, and effects on blood pressure and albuminuria in mice with Ang II-induced hypertension.</p><p><strong>Methods: </strong>ACE2 activity of 10 soluble ACE2 variants was first assessed in cell-free conditions using a fluorogenic substrate, or by Ang II hydrolysis to Ang-(1-7). Hypertension was induced in male or female mice by implantation of osmotic minipumps containing Ang II. Two lead ACE2 variants were injected intravenously (i.v.) into hypertensive mice, followed by measurements of blood pressure (tail-cuff plethysmography), albuminuria, and tissue ACE2 activity and protein (immunoblots).</p><p><strong>Results: </strong>Soluble ACE2-Fc variants demonstrated significant ACE2 enzymatic activity, with kinetics comparable with human recombinant ACE2. In hypertensive mice, single dose i.v. injection of ACE2-Fc variant K (10 mg/kg) significantly decreased systolic blood pressure at 24 hours, with partial lowering sustained to 48 hours, and tendency to reduce albuminuria at 72 hours. By contrast, ACE2-Fc variant I had no effect on blood pressure or albuminuria in hypertensive mice; ACE2-Fc variant K was detected by immunoblotting in plasma, kidney, heart, lung, liver, and spleen lysates 72 hours after injection, associated with significantly increased ACE2 activity in all tissues except kidney and spleen. Angiotensin-converting enzyme 2-Fc variant I had no effect on plasma ACE2 activity.</p><p><strong>Conclusions: </strong>Soluble ACE2-Fc variant K reduces blood pressure and tends to lower albuminuria in hypertensive mice. Furthermore, soluble ACE2-Fc variant K has prolonged tissue retention, associated with increased tissue ACE2 activity. The results support further studies directed at the therapeutic potential of soluble ACE2-Fc variant K for cardiovascular and kidney protection.</p>","PeriodicalId":9426,"journal":{"name":"Canadian Journal of Kidney Health and Disease","volume":"10 ","pages":"20543581231207146"},"PeriodicalIF":1.7,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/99/19/10.1177_20543581231207146.PMC10594958.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50160784","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":"Change Management Accompanying Implementation of Decision Support for Prevention of Acute Kidney Injury in Cardiac Catheterization Units: Program Report.","authors":"Bryan Ma,&nbsp;Matthew T James,&nbsp;Pantea A Javaheri,&nbsp;Denise Kruger,&nbsp;Michelle M Graham,&nbsp;Bryan J Har,&nbsp;Benjamin D Tyrrell,&nbsp;Shane Heavener,&nbsp;Clare Puzey,&nbsp;Eleanor Benterud","doi":"10.1177/20543581231206127","DOIUrl":"10.1177/20543581231206127","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Purpose of program: &lt;/strong&gt;Different models exist to guide successful implementation of electronic health tools into clinical practice. The Contrast Reducing Injury Sustained by Kidneys (Contrast RISK) initiative introduced an electronic decision support tool with physician audit and feedback into all of the cardiac catheterization facilities in Alberta, Canada, with the goal of preventing contrast-associated acute kidney injury (CA-AKI) following coronary angiography and intervention. This report describes the change management approaches used by the initiative and end-user's feedback on these processes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Sources of information and methods: &lt;/strong&gt;The Canada Health Infoway Change Management model was used to address 6 activities relevant to project implementation: governance and leadership, stakeholder engagement, communications, workflow analysis and integration, training and education, and monitoring and evaluation. Health care providers and invasive cardiologists from all sites completed preimplementation, usability, and postimplementation surveys to assess integration and change success.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Key findings: &lt;/strong&gt;Prior to implementation, 67% of health providers were less than satisfied with processes to determine appropriate contrast dye volumes, 47% were less than satisfied with processes for administering adequate intravenous fluids, and 68% were less than satisfied with processes to ensure follow-up of high-risk patients. 48% of invasive cardiologists were less than satisfied with preprocedural identification of patients at risk of acute kidney injury (AKI). Following implementation, there were significant increases among health providers in the odds of satisfaction with processes for identifying those at high risk of AKI (odds ratio [OR] 3.01, 95% confidence interval [CI] 1.36-6.66, &lt;i&gt;P&lt;/i&gt; = .007), quantifying the appropriate level of contrast dye for each patient (OR 6.98, 95% CI 3.06-15.91, &lt;i&gt;P&lt;/i&gt; &lt; .001), determining the optimal amount of IV fluid for each patient (OR 1.86, 95% CI 0.88-3.91, &lt;i&gt;P&lt;/i&gt; = .102), and following up of kidney function of high risk patients (OR 5.49, 95%CI 2.45-12.30, &lt;i&gt;P&lt;/i&gt; &lt; .001). There were also significant increases among physicians in the odds of satisfaction with processes for identifying those at high risk of AKI (OR 19.53, 95% CI 3.21-118.76, &lt;i&gt;P&lt;/i&gt; = .001), quantifying the appropriate level of contrast dye for each patient (OR 26.35, 95% CI 4.28-162.27, &lt;i&gt;P&lt;/i&gt; &lt; .001), and for following-up kidney function of high-risk patients (OR 7.72, 95% CI 1.62-36.84.30, &lt;i&gt;P&lt;/i&gt; = .010). Eighty-nine percent of staff perceived the initiative as being successful in changing clinical practices to reduce the risk of CA-AKI. Physicians uniformly agreed that the system was well-integrated into existing workflows, while 42% of health providers also agreed.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Implications: &lt;/strong&gt;The Canada Health Infoway Change Management model was an effective framework f","PeriodicalId":9426,"journal":{"name":"Canadian Journal of Kidney Health and Disease","volume":"10 ","pages":"20543581231206127"},"PeriodicalIF":1.7,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2e/18/10.1177_20543581231206127.PMC10588412.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49688810","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":"Atypical ADPKD Due to a <i>DNAJB11</i> Pathogenic Variant: An Educational Case Report.","authors":"Jessica Kachmar,&nbsp;Zaki El-Haffaf,&nbsp;Guillaume Bollée","doi":"10.1177/20543581231203054","DOIUrl":"10.1177/20543581231203054","url":null,"abstract":"<p><strong>Rationale: </strong>Due to next-generation sequencing, variants in new genes such as <i>DNAJB11</i> are recently being identified as causing atypical autosomal dominant polycystic kidney disease (ADPKD). It is important to describe phenotypes associated with these variants in order to increase awareness among clinicians, especially since genetic variability affects ADPKD severity.</p><p><strong>Presenting concerns of the patient: </strong>We describe a 55-year-old female patient of Haitian origin who presented with slowly deteriorating kidney function, microscopic hematuria, proteinuria, enlarged kidneys with innumerable small cysts, and a family history of chronic kidney disease and cysts. The phenotype was atypical for ADPKD caused by <i>PKD1</i> or <i>PKD2</i> variants, since cysts were of small size, kidneys were only moderately enlarged, and the patient had no extra-renal involvement suggestive of typical ADPKD such as liver cysts, pancreatic cysts, cranial aneurysms, or cardiac abnormalities.</p><p><strong>Diagnoses: </strong>A panel of genes was analyzed by next-generation massive sequencing techniques, including <i>DNAJB11, DZIP1L, GANAB, HNF1B, PKD1, PKD2</i>, and <i>PKHD1</i>. Genetic testing revealed a heterozygous variant in the <i>DNAJB11</i> gene (c.123 dup), which is predicted to result in premature protein termination (p. Lys42*) and was classified by the laboratory as likely pathogenic.</p><p><strong>Interventions: </strong>She was treated with candesartan 16 mg once daily to address her proteinuria.</p><p><strong>Outcomes: </strong>At the time of the most recent follow-up, her proteinuria has increased, and her kidney function continues to slowly deteriorate.</p><p><strong>Teaching points: </strong><i>DNAJB11</i> variants are a rare cause of atypical ADPKD. It is important to recognize the clinical features that help distinguish <i>DNAJB11</i> from <i>PKD1</i> and <i>PKD2</i> variants. Atypical ADPKD due to <i>DNAJB11</i> variants is usually characterized by small cysts, normal kidney size, proteinuria, progressive chronic kidney disease, and phenotypic overlap with autosomal dominant tubulointerstitial kidney disease (ADTKD). It may, however, present itself with enlarged kidneys as was seen in our patient. Genetic testing should be offered whenever a patient presents atypical features of ADPKD, which also requires increased awareness among clinicians regarding the various phenotypes of atypical ADPKD.</p>","PeriodicalId":9426,"journal":{"name":"Canadian Journal of Kidney Health and Disease","volume":"10 ","pages":"20543581231203054"},"PeriodicalIF":1.7,"publicationDate":"2023-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/57/63/10.1177_20543581231203054.PMC10585986.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49688809","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":"Nontargeted Native Renal Biopsy Adequacy: Preintervention Data From a Province-Wide, Multicentre, and Interdepartmental Audit.","authors":"James P Nugent,&nbsp;Mei Lin Z Bissonnette,&nbsp;Brian Gibney,&nbsp;Myriam Farah,&nbsp;Alison C Harris","doi":"10.1177/20543581231205161","DOIUrl":"https://doi.org/10.1177/20543581231205161","url":null,"abstract":"<p><strong>Background: </strong>Nontargeted renal biopsy is essential to diagnosis, classification, and prognostication of medical renal disease. Inadequate biopsies delay diagnosis, expose the patient to repeated biopsy, and increase costs.</p><p><strong>Objective: </strong>The purpose of this project is to characterize nontargeted renal biopsy specimen adequacy and identify areas for improvement.</p><p><strong>Design: </strong>This project was designed as a clinical audit of specimen adequacy rates of nontargeted renal biopsies from 13 hospitals, as well as a questionnaire of radiology and pathology department staff regarding current practices surrounding renal biopsies.</p><p><strong>Setting: </strong>Retrospective analysis of 2188 adult native renal biopsies was performed from January 1, 2018, to September 9, 2021, across 13 hospitals.</p><p><strong>Patients: </strong>Adult patients with medical renal disease undergoing a nontargeted renal biopsy were included.</p><p><strong>Methods: </strong>Retrospective analysis of 2188 adult native renal biopsies was performed from January 1, 2018, to September 9, 2021, across 13 hospitals. Adequacy was divided into 4 categories based on number of glomeruli received: ideally adequate (≥25 glomeruli), minimally adequate (15-24), suboptimal (<15 and diagnosis rendered), and inadequate (<15 and no diagnosis rendered). Two targets were chosen; target 1, to achieve a combined suboptimal and inadequate rate ≤ 10%, and target 2, to attain an ideally adequate rate ≥80%. Radiology department heads in the province were surveyed on biopsy equipment, technique, technologist support, and feasibility of possible interventions to enhance biopsy adequacy. Pathology department staff were surveyed on their education and experience.</p><p><strong>Results: </strong>Adequacy was as follows: ideally adequate 64.7%, minimally adequate 26.0%, suboptimal 7.9%, and inadequate 1.4%. The province (and 8/13 hospitals) met target 1 for native biopsies (9.3%). Two hospitals achieved target 2 for native biopsies. A key finding was that the 2 hospitals with the lowest target 1 scores did not have a technologist present at biopsy.</p><p><strong>Limitations: </strong>Survey data was used to assess biopsy technique at each hospital, and specific technique for each biopsy was not recorded. As such, a multivariate statistical analysis of specimen adequacy rates was not feasible. Data on complications was not collected.</p><p><strong>Conclusions: </strong>Preintervention the province was at target for limiting inadequate and suboptimal native biopsies. There was a substantial shortfall in the ideally adequate rate from the proposed target. Using insight from survey data, interventions with the greatest expected impact were identified and those that are feasible given limited resources will be implemented to improve sample adequacy.</p><p><strong>Trial registration: </strong>Not registered.</p>","PeriodicalId":9426,"journal":{"name":"Canadian Journal of Kidney Health and Disease","volume":"10 ","pages":"20543581231205161"},"PeriodicalIF":1.7,"publicationDate":"2023-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ca/f2/10.1177_20543581231205161.PMC10576420.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41232492","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}