Publications by authors named "Swapnil Hiremath"

175 Publications

Finerenone: Fiddling With Hyperkalemia?

Am J Kidney Dis 2021 Aug 13. Epub 2021 Aug 13.

Department of Medicine, University of Ottawa, Ottawa, Canada.

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http://dx.doi.org/10.1053/j.ajkd.2021.07.006DOI Listing
August 2021

Association Between Attempted Arteriovenous Fistula Creation and Mortality in People Starting Hemodialysis via a Catheter: A Multicenter, Retrospective Cohort Study.

Can J Kidney Health Dis 2021 30;8:20543581211032846. Epub 2021 Jul 30.

Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, AB, Canada.

Background: In North America, most people start hemodialysis via a central venous catheter ("catheter"). These patients are counseled to undergo arteriovenous fistula ("fistula") creation within weeks of starting hemodialysis because fistulas are associated with improved survival.

Objectives: To determine whether attempting to create a fistula in patients who start hemodialysis via a catheter is associated with improved mortality. We also sought to determine whether differences in baseline patient characteristics, vascular procedures for access-related complications, or days in hospital may confound or mediate the relationship between attempted fistula creation and mortality.

Design: Multicenter, retrospective cohort study.

Setting: Six dialysis programs located in Ontario, Alberta, and Manitoba.

Patients: Patients aged ≥18 years who initiated hemodialysis via a catheter between January 1, 2004, and May 31, 2012, who had not had a previous attempt at fistula creation. We excluded those who had a life expectancy less than 1 year, who transitioned to peritoneal dialysis within 6 months of starting dialysis, and people who started hemodialysis via a graft.

Measurements: Attempted fistula creation, all-cause mortality, patient characteristics and comorbidities, vascular procedures for access-related complications, and days spent in hospital.

Methods: We used survival methods, including marginal structural models, to account for immortal time bias and time-varying confounding.

Results: In total, 1832 patients initiated hemodialysis via a catheter during the study period and met inclusion criteria. Of these patients, 565 (31%) underwent an attempt at fistula creation following hemodialysis start. As compared to those who did not receive a fistula attempt, these people were younger, had fewer comorbidities, and were more likely to have started dialysis as an outpatient and to have received pre-dialysis care. In a marginal structural model controlling for baseline characteristics and comorbidities, attempted fistula creation was associated with a significantly lower mortality (hazard ratio [HR] = 0.53; 95% confidence interval [CI] = 0.43-0.66). This effect did not appear to be confounded or mediated by differences in the number of days spent in hospital or vascular procedures for access-related complications. It also remained similar in analyses restricted to patients who survived at least 6 months (HR = 0.60; 95% CI = 0.47-0.77) and to patients who started hemodialysis as an outpatient (HR = 0.48; 95% CI = 0.33-0.68).

Limitations: There is likely residual confounding and treatment selection bias.

Conclusions: In this multicenter cohort study, attempting fistula creation in people who started hemodialysis via a catheter was associated with significantly reduced mortality. This reduction in mortality could not be explained by differences in patient characteristics or comorbidities, days spent in hospital, or vascular procedures for access-related complications. Residual confounding or selection bias may explain the observed benefits of fistulas for hemodialysis access.

Trial Registration: Not applicable (cohort study).
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http://dx.doi.org/10.1177/20543581211032846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326626PMC
July 2021

N-Acetylcysteine Interference With Creatinine Measurement: An In Vitro Analysis.

Kidney Int Rep 2021 Jul 19;6(7):1973-1976. Epub 2021 Apr 19.

Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

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http://dx.doi.org/10.1016/j.ekir.2021.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258456PMC
July 2021

Blood pressure measurement: Should technique define targets?

J Clin Hypertens (Greenwich) 2021 Aug 16;23(8):1538-1546. Epub 2021 Jul 16.

Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

Accurate assessment of blood pressure (BP) is the cornerstone of hypertension management. The objectives of this study were to quantify the effect of medical personnel presence during BP measurement by automated oscillometric BP (AOBP) and to compare resting office BP by AOBP to daytime average BP by 24-h ambulatory BP monitoring (ABPM). This study is a prospective randomized cross-over trial, conducted in a referral population. Patients underwent measurements of casual and resting office BP by AOBP. Resting BP was measured as either unattended (patient alone in the room during resting and measurements) or as partially attended (nurse present in the room during measurements) immediately prior to and after 24-h ABPM. The primary outcome was the effect of unattended 5-min rest preceding AOBP assessment as the difference between casual and resting BP measured by the Omron HEM 907XL. Ninety patients consented and 78 completed the study. The mean difference between the casual and Omron unattended systolic BP was 7.0 mm Hg (95% confidence interval [CI] 4.5, 9.5). There was no significant difference between partially attended and unattended resting office systolic BP. Resting office BP (attended and partially attended) underestimated daytime systolic BP load from 24-h ABPM. The presence or absence of medical personnel does not impact casual office BP which is higher than resting office AOBP. The requirement for unattended rest may be dropped if logistically challenging. Casual and resting office BP readings by AOBP do not capture the complexity of information provided by the 24-h ABPM.
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http://dx.doi.org/10.1111/jch.14324DOI Listing
August 2021

Review of Early Immune Response to SARS-CoV-2 Vaccination Among Patients With CKD.

Kidney Int Rep 2021 Sep 6;6(9):2292-2304. Epub 2021 Jul 6.

Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

The effects of the coronavirus disease-2019 (COVID-19) pandemic, particularly among those with chronic kidney disease (CKD), who commonly have defects in humoral and cellular immunity, and the efficacy of vaccinations against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are uncertain. To inform public health and clinical practice, we synthesized published studies and preprints evaluating surrogate measures of immunity after SARS-CoV-2 vaccination in patients with CKD, including those receiving dialysis or with a kidney transplant. We found 35 studies (28 published, 7 preprints), with sample sizes ranging from 23 to 1140 participants and follow-up ranging from 1 week to 1 month after vaccination. Seventeen of these studies enrolled a control group. In the 22 studies of patients receiving dialysis, the development of antibodies was observed in 18% to 53% after 1 dose and in 70% to 96% after 2 doses of mRNA vaccine. In the 14 studies of transplant recipients, 3% to 59% mounted detectable humoral or cellular responses after 2 doses of mRNA vaccine. After vaccination, there were a few reported cases of relapse or glomerulonephritis, and acute transplant rejection, suggesting a need for ongoing surveillance. Studies are needed to better evaluate the effectiveness of SARS-CoV-2 vaccination in these populations. Rigorous surveillance is necessary for detection of long-term adverse effects in patients with autoimmune disease and transplant recipients. For transplant recipients and those with suboptimal immune responses, alternate vaccination platforms and strategies should be considered. As additional data arise, the NephJC COVID-19 page will continue to be updated (http://www.nephjc.com/news/covid-vaccine).
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http://dx.doi.org/10.1016/j.ekir.2021.06.027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257418PMC
September 2021

Performance of the Aldosterone to Renin Ratio as a Screening Test for Primary Aldosteronism.

J Clin Endocrinol Metab 2021 Jul;106(8):2423-2435

Department of Medicine (Division of Nephrology) and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON,Canada.

Context: The aldosterone to renin ratio (ARR) is the guideline-recommended screening test for primary aldosteronism. However, there are limited data in regard to the diagnostic performance of the ARR.

Objective: To evaluate the sensitivity and specificity of the ARR as a screening test for primary aldosteronism.

Methods: We searched the MEDLINE, Embase, and Cochrane databases until February 2020. Observational studies assessing ARR diagnostic performance as a screening test for primary aldosteronism were selected. To limit verification bias, only studies where dynamic confirmatory testing was implemented as a reference standard regardless of the ARR result were included. Study-level data were extracted and risk of bias and applicability were assessed using the QUADAS-2 tool.

Results: Ten studies, involving a total of 4110 participants, were included. Potential risk of bias related to patient selection was common and present in half of the included studies. The population base, ARR positivity threshold, laboratory assay, and reference standard for confirmatory testing varied substantially between studies. The reported ARR sensitivity and specificity varied widely with sensitivity ranging from 10% to 100% and specificity ranging from 70% to 100%. Notably, 3 of the 10 studies reported an ARR sensitivity of <50%, suggesting a limited ability of the ARR to adequately identify patients with primary aldosteronism.

Conclusions: ARR performance varied widely based on patient population and diagnostic criteria, especially with respect to sensitivity. Therefore, no single ARR threshold for interpretation could be recommended. Limitations in accuracy and reliability of the ARR must be recognized in order to appropriately inform clinical decision-making.
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http://dx.doi.org/10.1210/clinem/dgab348DOI Listing
July 2021

Sex differences in the vascular access of hemodialysis patients: a cohort study.

Clin Kidney J 2021 May 6;14(5):1412-1418. Epub 2020 Sep 6.

Libin Cardiovascular Institute, Department of Cardiac Sciences, University of Calgary, Calgary, AB, Canada.

Background: We describe differences for probability of receiving a fistula attempt, achieving fistula use, remaining catheter-free and the rate of access-related procedures as a function of sex.

Methods: Prospectively collected vascular access data on incident dialysis patients from five Canadian programs using the Dialysis Measurement Analysis and Reporting System to determine differences in fistula-related outcomes between women and men. The probability of receiving a fistula attempt and the probability of fistula use were determined using binary logistic regression. Catheter and fistula procedure rates were described using Poisson regression. We studied time to fistula attempt and time to fistula use, accounting for competing risks.

Results: We included 1446 (61%) men and 929 (39%) women. Men had a lower body mass index (P < 0.001) and were more likely to have coronary artery disease (P < 0.001) and peripheral vascular disease (p < 0.001). A total of 688 (48%) men and 403 (43%) women received a fistula attempt. Women were less likely to receive a fistula attempt by 6 months {odds ratio [OR] 0.64 [95% confidence interval (CI) 0.52-0.79]} and to achieve catheter-free use of their fistula by 1 year [OR 0.38 (95% CI 0.27-0.53)]. At an average of 2.30 access procedures per person-year, there is no difference between women and men [incidence rate ratio (IRR) 0.97 (95% CI 0.87-1.07)]. Restricting to those with a fistula attempt, women received more procedures [IRR 1.16 (95% CI 1.04-1.30)] attributed to increased catheter procedures [IRR 1.50 (95% CI 1.27-1.78)]. There was no difference in fistula procedures [IRR women versus men 0.96 (95% CI 0.85-1.07)].

Conclusion: Compared with men, fewer women undergo a fistula attempt. This disparity increases after adjusting for comorbidities. Women have the same number of fistula procedures as men but are less likely to successfully use their fistula.
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http://dx.doi.org/10.1093/ckj/sfaa132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087139PMC
May 2021

Scoping review of COVID-19-related systematic reviews and meta-analyses: can we really have confidence in their results?

Postgrad Med J 2021 Feb 26. Epub 2021 Feb 26.

NICHD, National Institutes of Health, Bethesda, Maryland, USA

Aim: The aim of this study was to systematically appraise the quality of a sample of COVID-19-related systematic reviews (SRs) and discuss internal validity threats affecting the COVID-19 body of evidence.

Design: We conducted a scoping review of the literature. SRs with or without meta-analysis (MA) that evaluated clinical data, outcomes or treatments for patients with COVID-19 were included.

Main Outcome Measures: We extracted quality characteristics guided by A Measurement Tool to Assess Systematic Reviews-2 to calculate a qualitative score. Complementary evaluation of the most prominent published limitations affecting the COVID-19 body of evidence was performed.

Results: A total of 63 SRs were included. The majority were judged as a critically low methodological quality. Most of the studies were not guided by a pre-established protocol (39, 62%). More than half (39, 62%) failed to address risk of bias when interpreting their results. A comprehensive literature search strategy was reported in most SRs (54, 86%). Appropriate use of statistical methods was evident in nearly all SRs with MAs (39, 95%). Only 16 (33%) studies recognised heterogeneity in the definition of severe COVID-19 as a limitation of the study, and 15 (24%) recognised repeated patient populations as a limitation.

Conclusion: The methodological and reporting quality of current COVID-19 SR is far from optimal. In addition, most of the current SRs fail to address relevant threats to their internal validity, including repeated patients and heterogeneity in the definition of severe COVID-19. Adherence to proper study design and peer-review practices must remain to mitigate current limitations.
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http://dx.doi.org/10.1136/postgradmedj-2020-139392DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918809PMC
February 2021

A Systematic Review of the Effect of N-Acetylcysteine on Serum Creatinine and Cystatin C Measurements.

Kidney Int Rep 2021 Feb 3;6(2):396-403. Epub 2020 Dec 3.

The Ottawa Hospital, Ottawa, Ontario, Canada.

Introduction: N-acetylcysteine (NAC) is an antioxidant that can regenerate glutathione and is primarily used for acetaminophen overdose. NAC has been tested and used for preventing iatrogenic acute kidney injury or slowing the progression of chronic kidney disease, with mixed results. There are conflicting reports that NAC may artificially lower measured serum creatinine without improving kidney function, potentially by assay interference. Given these mixed results, we conducted a systematic review of the literature to determine whether there is an effect of NAC on kidney function as measured with serum creatinine and cystatin C.

Methods: A literature search was conducted to identify all study types reporting a change in serum creatinine after NAC administration. The primary outcome was change in serum creatinine after NAC administration. The secondary outcome was a change in cystatin C after NAC administration. Subgroup analyses were conducted to assess effect of creatinine assay (Jaffe vs. non-Jaffe and intravenous vs. oral).

Results: Six studies with a total of 199 participants were eligible for the systematic review and meta-analysis. There was a small but significant decrease in serum creatinine after NAC administration overall (weighted mean difference [WMD], -2.80 μmol/L [95% confidence interval {CI} -5.6 to 0.0];  = 0.05). This was greater with non-Jaffe methods (WMD, -3.24 μmol/L [95% CI -6.29 to -0.28];  = 0.04) than Jaffe (WMD, -0.51 μmol/L [95% CI -7.56 to 6.53];  = 0.89) and in particular with intravenous (WMD, -31.10 μmol/L [95% CI -58.37 to -3.83];  = 0.03) compared with oral NAC (WMD, -2.5 μmol/L [95% CI -5.32 to 0.32];  = 0.08). There was no change in cystatin C after NAC administration.

Discussion: NAC causes a decrease in serum creatinine but not in cystatin C, suggesting analytic interference rather than an effect on kidney function. Supporting this, the effect was greater with non-Jaffe methods of creatinine estimation. Future studies of NAC should use the Jaffe method of creatinine estimation when kidney outcomes are being reported. Even in clinical settings, the use of an enzymatic assay when high doses of intravenous NAC are being used may result in underdiagnosis or delayed diagnosis of acute kidney injury.
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http://dx.doi.org/10.1016/j.ekir.2020.11.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7879108PMC
February 2021

Canadian Association of Paediatric Nephrologists COVID-19 Rapid Response: Guidelines for Management of Acute Kidney Injury in Children.

Can J Kidney Health Dis 2021 5;8:2054358121990135. Epub 2021 Feb 5.

Department of Paediatrics, Division of Nephrology, University of Toronto, ON, Canada.

Purpose: This article provides guidance on managing acute kidney injury (AKI) and kidney replacement therapy (KRT) in pediatrics during the COVID-19 pandemic in the Canadian context. It is adapted from recently published rapid guidelines on the management of AKI and KRT in adults, from the Canadian Society of Nephrology (CSN). The goal is to provide the best possible care for pediatric patients with kidney disease during the pandemic and ensure the health care team's safety.

Information Sources: The Canadian Association of Paediatric Nephrologists (CAPN) COVID-19 Rapid Response team derived these rapid guidelines from the CSN consensus recommendations for adult patients with AKI. We have also consulted specific documents from other national and international agencies focused on pediatric kidney health. We identified additional information by reviewing the published academic literature relevant to pediatric AKI and KRT, including recent journal articles and preprints related to COVID-19 in children. Finally, our group also sought expert opinions from pediatric nephrologists across Canada.

Methods: The leadership of the CAPN, which is affiliated with the CSN, solicited a team of clinicians and researchers with expertise in pediatric AKI and acute KRT. The goal was to adapt the guidelines recently adopted for Canadian adult patients for pediatric-specific settings. These included specific COVID-19-related themes relevant to AKI and KRT in a Canadian setting, as determined by a group of kidney disease experts and leaders. An expert group of clinicians in pediatric AKI and acute KRT reviewed the revised pediatric guidelines.

Key Findings: (1) Current Canadian data do not suggest an imminent threat of an increase in acute KRT needs in children because of COVID-19; however, close coordination between nephrology programs and critical care programs is crucial as the pandemic continues to evolve. (2) Pediatric centers should prepare to reallocate resources to adult centers as needed based on broader health care needs during the COVID-19 pandemic. (3) Specific suggestions pertinent to the optimal management of AKI and KRT in COVID-19 patients are provided. These suggestions include but are not limited to aspects of fluid management, KRT vascular access, and KRT modality choice. (4) Considerations to ensure adequate provision of KRT if resources become scarce during the COVID-19 pandemic.

Limitations: We did not conduct a formal systematic review or meta-analysis. We did not evaluate our specific suggestions in the clinical environment. The local context, including how the provision of care for AKI and acute KRT is organized, may impede the implementation of many suggestions. As knowledge is advancing rapidly in the area of COVID-19, suggestions may become outdated quickly. Finally, most of the literature for AKI and KRT in COVID-19 comes from adult data, and there are few pediatric-specific studies.

Implications: Given that most acute KRT related to COVID-19 is likely to be required in the pediatric intensive care unit initial setting, close collaboration and planning between critical care and pediatric nephrology programs are needed. Our group will update these suggestions with a supplement if necessary as newer evidence becomes available that may change or add to the recommendations provided.
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http://dx.doi.org/10.1177/2054358121990135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868478PMC
February 2021

Inter-arm difference in blood pressure in patients referred to tertiary hypertension center: Prevalence, risk factors, and relevance to physicians.

J Clin Hypertens (Greenwich) 2020 08 9;22(8):1513-1517. Epub 2020 Aug 9.

Department of Nephrology, University of Ottawa, Ottawa, ON, Canada.

The prevalence of inter-arm BP difference is high in hypertension and is associated with adverse cardiovascular outcomes. We performed a retrospective chart review of prevalent patients in the Ottawa Hospital Hypertension Center to assess for prevalence, risk factors, and whether finding of inter-arm BP difference >10 mmHg leads to investigations of the aorta and aortic arch. Inter-arm BP difference among 493 patients was present in 16.2% (95% confidence interval [CI]13.3-19.9%), and it was associated with presence of peripheral arterial disease. Physicians did not investigate ascending aorta and aortic arch for causes of the clinically significant inter-arm BP difference.
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http://dx.doi.org/10.1111/jch.13978DOI Listing
August 2020

Proliferation of Papers and Preprints During the Coronavirus Disease 2019 Pandemic: Progress or Problems With Peer Review?

Adv Chronic Kidney Dis 2020 09 6;27(5):418-426. Epub 2020 Aug 6.

Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, ON, Canada. Electronic address:

The coronavirus disease 2019 (COVID-19) pandemic has spread exponentially throughout the world in a short period, aided by our hyperconnected world including global trade and travel. Unlike previous pandemics, the pace of the spread of the virus has been matched by the pace of publications, not just in traditional journals, but also in preprint servers. Not all publication findings are true, and sifting through the firehose of data has been challenging to peer reviewers, editors, as well as to consumers of the literature, that is, scientists, healthcare workers, and the general public. There has been an equally exponential rise in the public discussion on social media. Rather than decry the pace of change, we suggest the nephrology community should embrace it, making deposition of research into preprint servers the default, encouraging prepublication peer review more widely of such preprint studies, and harnessing social media tools to make these actions easier and seamless.
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http://dx.doi.org/10.1053/j.ackd.2020.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409832PMC
September 2020

Ashwagandha and Kidney Transplant Rejection.

Kidney Int Rep 2020 Dec 3;5(12):2375-2378. Epub 2020 Oct 3.

Division of Nephrology, Department of Medicine, the Ottawa Hospital, Ottawa, Ontario, Canada.

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http://dx.doi.org/10.1016/j.ekir.2020.09.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710824PMC
December 2020

Albuminuria as a risk factor for acute kidney injury: what is the evidence?

Nephrol Dial Transplant 2020 12;35(12):2026-2029

Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada.

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http://dx.doi.org/10.1093/ndt/gfaa276DOI Listing
December 2020

Intravenous Albumin for Mitigating Hypotension and Augmenting Ultrafiltration during Kidney Replacement Therapy.

Clin J Am Soc Nephrol 2021 05 28;16(5):820-828. Epub 2020 Oct 28.

Division of Nephrology, Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada

Among its many functions, owing to its oversized effect on colloid oncotic pressure, intravascular albumin helps preserve the effective circulatory volume. Hypoalbuminemia is common in hospitalized patients and is found especially frequently in patients who require KRT either for AKI or as maintenance hemodialysis. In such patients, hypoalbuminemia is strongly associated with morbidity, intradialytic hypotension, and mortality. Intravenous albumin may be administered in an effort to prevent or treat hypotension or to augment fluid removal, but this practice is controversial. Theoretically, intravenous albumin administration might prevent or treat hypotension by promoting plasma refilling in response to ultrafiltration. However, clinical trials have demonstrated that albumin administration is not nearly as effective a volume expander as might be assumed according to its oncotic properties. Although intravenous albumin is generally considered to be safe, it is also very expensive. In addition, there are potential risks to using it to prevent or treat intradialytic hypotension. Some recent studies have suggested that hyperoncotic albumin solutions may precipitate or worsen AKI in patients with sepsis or shock; however, the overall evidence supporting this effect is weak. In this review, we explore the theoretical benefits and risks of using intravenous albumin to mitigate intradialytic hypotension and/or enhance ultrafiltration and summarize the current evidence relating to this practice. This includes studies relevant to its use in patients on maintenance hemodialysis and critically ill patients with AKI who require KRT in the intensive care unit. Despite evidence of its frequent use and high costs, at present, there are minimal data that support the routine use of intravenous albumin during KRT. As such, adequately powered trials to evaluate the efficacy of intravenous albumin in this setting are clearly needed.
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http://dx.doi.org/10.2215/CJN.09670620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259476PMC
May 2021

Use of the FRAIL Questionnaire in Patients With End-Stage Kidney Disease.

Can J Kidney Health Dis 2020 16;7:2054358120952904. Epub 2020 Sep 16.

Department of Medicine, Ottawa Hospital, University of Ottawa, Ontario, Canada.

Background: Frailty is a clinical phenotype of decreased physiologic reserve that is associated with increased morbidity and mortality. The most meaningful way to assess frailty in patients with end-stage kidney disease (ESKD) is unknown.

Objective: To assess the prevalence of frailty in ESKD patients using the easy-to-administer FRAIL scale and, to determine its association with mortality, transplantation, and hospitalization.

Design: A cohort study was used.

Setting: The Ottawa Hospital, Ottawa, Ontario, Canada, was the setting of this study.

Patients: All eligible adult ESKD patients treated with dialysis from August to November 2017 at The Ottawa Hospital were invited to participate.

Measurements: The FRAIL scale.

Methods: Eligible patients completed an exercise survey with FRAIL questions embedded within the instrument. Number of comorbid illnesses was determined from the electronic medical record and weight loss was calculated from target weight in the patients' dialysis prescription. Mortality, transplant status, and hospitalizations were ascertained from the electronic medical record 18 months later; differences by frailty status were evaluated using descriptive statistics. Kaplan-Meier and Cox regression models were used to examine the association between frailty and transplant.

Results: Of 476 ESKD patients screened, 261 participated; 101 receiving peritoneal dialysis, 135 intermittent hemodialysis, and 25 home hemodialysis. Thirty-nine, 145, and 77 were frail, pre-frail, and not frail, respectively. Employment status, ethnicity, and comorbid illnesses differed significantly by frailty status, but mortality did not. In univariate analysis, frail patients were less likely to be listed for ( = .05) and to receive a kidney transplant ( = .02). However, after adjusting for age and modality, frailty was not statistically associated with a decreased likelihood of transplant (Hazard Ratio: 0.15; confidence interval [CI], 0.02-1.15; = .068). The results were similar when accounting for the competing risk of death ( = .060). Frail patients were more likely to be hospitalized ( = .01) and spend more time in the hospital ( = .04).

Limitations: Single-center design with a relatively short follow-up and small sample size limiting the number of variables that could be assessed in analysis. We also excluded patients who were unable to communicate in English or French and those patients with physical limitations such as amputations, potentially affecting generalizability.

Conclusions: Frail ESKD patients as identified by the FRAIL scale are less likely to receive a renal transplant; this association diminished statistically after adjusting for age and modality and when accounting for the competing risk of death. Frail patients were at increased risk of hospitalization. Further study with larger patient numbers and longer follow-up is needed to determine the usefulness of the FRAIL scale in predicting adverse outcomes.

Trial Registration: Not required as this was an observational study.
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http://dx.doi.org/10.1177/2054358120952904DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502991PMC
September 2020

SGLT2 Inhibitors in Resistant Hypertension: A Sweet Solution.

Am J Hypertens 2020 12;33(12):1071-1074

Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

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http://dx.doi.org/10.1093/ajh/hpaa100DOI Listing
December 2020

Kidney, Cardiac, and Safety Outcomes Associated With α-Blockers in Patients With CKD: A Population-Based Cohort Study.

Am J Kidney Dis 2021 02 11;77(2):178-189.e1. Epub 2020 Sep 11.

Department of Medicine (Division of Nephrology) and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada; The Institute of Clinical Evaluative Sciences, Ontario, Canada.

Rationale & Objectives: Alpha-blockers (ABs) are commonly prescribed for control of resistant or refractory hypertension in patients with and without chronic kidney disease (CKD). The association between AB use and kidney, cardiac, mortality, and safety-related outcomes in CKD remains unknown.

Study Design: Population-based retrospective cohort study.

Settings & Participants: Ontario (Canada) residents 66 years and older treated for hypertension in 2007 to 2015 without a prior prescription for an AB.

Exposures: New use of an AB versus new use of a non-AB blood pressure (BP)-lowering medication.

Outcomes: 30% or greater estimated glomerular filtration rate (eGFR) decline; dialysis initiation or kidney transplantation (kidney replacement therapy); composite of acute myocardial infarction, coronary revascularization, congestive heart failure, or atrial fibrillation; safety (hypotension, syncope, falls, and fractures) events; and mortality.

Analytical Approach: New users of ABs (doxazosin, terazosin, and prazosin) were matched to new users of non-ABs by a high dimensional propensity score. Cox proportional hazards and Fine and Gray models were used to examine the association of AB use with kidney, cardiac, mortality, and safety outcomes. Interactions by eGFR categories (≥90, 60-89, 30-59, and<30mL/min/1.73m) were explored.

Results: Among 381,120 eligible individuals, 16,088 were dispensed ABs and matched 1:1 to non-AB users. AB use was associated with higher risk for≥30% eGFR decline (HR, 1.14; 95% CI, 1.08-1.21) and need for kidney replacement therapy (HR, 1.28; 95% CI, 1.13-1.44). eGFR level did not modify these associations, P interaction=0.3and 0.3, respectively. Conversely, AB use was associated with lower risk for cardiac events, which was also consistent across eGFR categories (HR, 0.92; 95% CI, 0.89-0.95; P interaction=0.1). AB use was also associated with lower mortality risk, but only among those with eGFR<60mL/min/1.73m (P interaction<0.001): HRs were 0.85 (95% CI, 0.78-0.93) and 0.71 (95% CI, 0.64-0.80) for eGFR of 30 to 59 and<30mL/min/1.73m, respectively.

Limitations: Observational design, BP measurement data unavailable.

Conclusions: AB use in CKD is associated with higher risk for kidney disease progression but lower risk for cardiac events and mortality compared with alternative BP-lowering medications.
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http://dx.doi.org/10.1053/j.ajkd.2020.07.018DOI Listing
February 2021

Contrast and acute kidney injury: what is left to enhance?

Nephrol Dial Transplant 2020 Sep 10. Epub 2020 Sep 10.

Division of Nephrology, Department of Medicine, University of Ottawa, Canada and Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.

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http://dx.doi.org/10.1093/ndt/gfaa183DOI Listing
September 2020

Haemoperfusion should only be used for COVID-19 in the context of randomized trials.

Nat Rev Nephrol 2020 12;16(12):697-699

Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria.

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http://dx.doi.org/10.1038/s41581-020-00352-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478103PMC
December 2020

COVID-19 Extrapulmonary illness - The Impact of COVID-19 on Nephrology care.

Dis Mon 2020 Sep 25;66(9):101057. Epub 2020 Jul 25.

University of Ottawa, Ottawa, Canada.

Coronavirus disease-2019 (COVID-19) has caused a pandemic that has affected millions of people worldwide. COVID-19 is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and is spread by close contact and by respiratory droplets. It has also impacted different aspects of caring for people with kidney disease, including those with acute kidney injury (AKI), chronic kidney disease (CKD), those requiring kidney replacement therapy (KRT), and those with a kidney transplant. All of these patients are considered high risk. The lessons learned from the COVID-19 pandemic will hopefully serve to protect patients with kidney disease in a similar situation in the future.
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http://dx.doi.org/10.1016/j.disamonth.2020.101057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381936PMC
September 2020

CSN COVID-19 Rapid Review Program: Management of Acute Kidney Injury.

Can J Kidney Health Dis 2020 15;7:2054358120941679. Epub 2020 Jul 15.

Division of Nephrology, Department of Medicine, Western University, London, ON, Canada.

Purpose: Severe acute kidney injury (AKI) is a potential complication of COVID-19-associated critical illness. This has implications for the management of COVID-19-associated AKI and the resulting increased need for kidney replacement therapy (KRT) in the intensive care unit (ICU) and elsewhere in the hospital. The Canadian Society of Nephrology COVID-19 Rapid Review Team has sought to collate and synthesize currently available resources to inform ethically justifiable decisions. The goal is the provision of the best possible care for the largest number of patients with kidney disease while considering how best to ensure the safety of the health care team.

Information Sources: Local, provincial, national, and international guidance and planning documents related to the COVID-19 pandemic; guidance documents available from nephrology and critical care-related professional organizations; recent journal articles and preprints related to the COVID-19 pandemic; expert opinion from nephrologists from across Canada.

Methods: A working group of kidney specialist physicians was established with representation from across Canada. Kidney physician specialists met via teleconference and exchanged e-mails to refine and agree on the proposed suggestions in this document.

Key Findings: (1) Nephrology programs should work with ICU programs to plan for the possibility that up to 30% or more of critically ill patients with COVID-19 admitted to ICU will require kidney replacement therapy (KRT). (2) Specific suggestions pertinent to the optimal management of AKI and KRT in patients with COVID-19. These suggestions include, but are not limited to, aspects of fluid management, KRT vascular access, and KRT modality choice. (3) We describe considerations related to ensuring adequate provision of KRT, should resources become scarce during the COVID-19 pandemic.

Limitations: A systematic review or meta-analysis was not conducted. Our suggestions have not been specifically evaluated in the clinical environment. The local context, including how the provision of acute KRT is organized, may impede the implementation of many suggestions. Knowledge is advancing rapidly in the area of COVID-19 and suggestions may become outdated quickly.

Implications: Given that most acute KRT related to COVID-19 is likely to be required initially in the ICU setting, close collaboration and planning between critical care and nephrology programs is required. Suggestions may be updated as newer evidence becomes available.
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http://dx.doi.org/10.1177/2054358120941679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364799PMC
July 2020

Effects of CPAP on Blood Pressure and Sympathetic Activity in Patients With Diabetes Mellitus, Chronic Kidney Disease, and Resistant Hypertension.

CJC Open 2020 Jul 27;2(4):258-264. Epub 2020 Mar 27.

Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.

Background: Patients with obstructive sleep apnea (OSA) have increased sympathetic activity and frequently also have resistant hypertension (HTN). Treatment of OSA with continuous positive airway pressure (CPAP) decreases awake and sleep blood pressure (BP) and sympathetic activity. This study was designed to assess the effect of treatment of OSA with CPAP on sympathetic activity and BP in patients with diabetes mellitus (DM), chronic kidney disease (CKD), and resistant HTN.

Methods: This was a randomized, double-blind, sham-controlled trial. Patients with DM, CKD, and resistant HTN were randomized to treatment with a therapeutic or subtherapeutic CPAP for 6 weeks. They underwent 24-hour ambulatory BP monitoring and assessment of muscle sympathetic nerve activity before and after 6 weeks on treatment.

Results: Treatment with therapeutic CPAP caused significant decreases in awake systolic and diastolic BP from 144 to 136 mm Hg ( 0.004) and from 79 to 74 mm Hg ( 0.004) and in sleep BP from 135 to 119 mm Hg ( 0.045) and from 75 to 65 mm Hg ( 0.015) compared with treatment with subtherapeutic CPAP. In contrast, treatment with therapeutic CPAP did not decrease sympathetic activity as assessed from muscle sympathetic nerve activity.

Conclusions: Decrease in BP by treatment with CPAP in patients with DM, CKD, and OSA indicates the contribution of OSA to severity of HTN in this clinical scenario. Decrease in BP in the absence of changes in sympathetic activity is suggestive that other mechanisms induced by OSA play a larger role in the maintenance of HTN in these patients.
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http://dx.doi.org/10.1016/j.cjco.2020.03.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365815PMC
July 2020

Preprint Servers in Kidney Disease Research: A Rapid Review.

Clin J Am Soc Nephrol 2021 03 17;16(3):479-486. Epub 2020 Jul 17.

Division of Nephrology, Department of Medicine, St. Joseph's Healthcare Hamilton, McMaster University, Hamilton, Ontario, Canada

Preprint servers, such as arXiv and bioRxiv, have disrupted the scientific communication landscape by providing rapid access to research before peer review. medRxiv was launched as a free online repository for preprints in the medical, clinical, and related health sciences in 2019. In this review, we present the uptake of preprint server use in nephrology and discuss specific considerations regarding preprint server use in medicine. Distribution of kidney-related research on preprint servers is rising at an exponential rate. Survey of nephrology journals identified that 15 of 17 (88%) are publishing original research accepted submissions that have been uploaded to preprint servers. After reviewing 52 clinically impactful trials in nephrology discussed in the online Nephrology Journal Club (NephJC), an average lag of 300 days was found between study completion and publication, indicating an opportunity for faster research dissemination. Rapid review of papers discussing benefits and risks of preprint server use from the researcher, publisher, or end user perspective identified 53 papers that met criteria. Potential benefits of biomedical preprint servers included rapid dissemination, improved transparency of the peer review process, greater visibility and recognition, and collaboration. However, these benefits come at the risk of rapid spread of results not yet subjected to the rigors of peer review. Preprint servers shift the burden of critical appraisal to the reader. Media may be especially at risk due to their focus on "late-breaking" information. Preprint servers have played an even larger role when late-breaking research results are of special interest, such as during the global coronavirus disease 2019 pandemic. Coronavirus disease 2019 has brought both the benefits and risks of preprint servers to the forefront. Given the prominent online presence of the nephrology community, it is poised to lead the medicine community in appropriate use of preprint servers.
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http://dx.doi.org/10.2215/CJN.03800320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011003PMC
March 2021

Misleading Numbers: Is the Risk of Acute Kidney Injury with COVID-19 Truly This Low?

Am J Nephrol 2020 29;51(7):574-575. Epub 2020 Jun 29.

Division of Nephrology, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada,

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http://dx.doi.org/10.1159/000508088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7360499PMC
August 2020

Resistant Hypertension in a Dialysis Patient.

Hypertension 2020 08 29;76(2):278-287. Epub 2020 Jun 29.

From the Department of Renal Medicine, Royal Infirmary of Edinburgh (P.J.G., T.E.F., N.D.).

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15022DOI Listing
August 2020
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