Objective: Arteriovenous fistulas created for hemodialysis often fail to become usable and are fr... more Objective: Arteriovenous fistulas created for hemodialysis often fail to become usable and are frequently abandoned. This prospective trial evaluated the efficacy of vonapanitase, a recombinant human elastase, in increasing radiocephalic fistula use for hemodialysis and secondary patency. Methods: PATENCY-2 was a randomized, double-blind, placebo-controlled trial in patients on or approaching the need for hemodialysis undergoing radiocephalic arteriovenous fistula creation. Of 696 screened, 613 were randomized, and 603 were treated (vonapanitase n = 405, placebo n = 208). The study drug solution was applied topically to the artery and vein for 10 min immediately after fistula creation. The primary endpoints were fistula use for hemodialysis and secondary patency (fistula survival without abandonment). Other efficacy endpoints included unassisted fistula use for hemodialysis, primary unassisted patency, fistula maturation and unassisted maturation by ultrasound criteria, and fistula ...
Background and Aims The leading cause of mortality for patients with end-stage kidney disease (ES... more Background and Aims The leading cause of mortality for patients with end-stage kidney disease (ESKD) is cardiovascular disease (CVD). This is due, in part, to vascular calcification (VC) where calcium becomes deposited within arterial walls causing narrowing of the arteries and altering their flexibility. Matrix Gla protein (MGP), a vitamin k-dependent protein, is a key local inhibitor of VC and becomes up-regulated adjacent to sites of calcification. There is a very high prevalence of vitamin K deficiency in patients across the chronic kidney disease (CKD) spectrum and vitamin K has been shown to prevent VC in experimental models. To date, no trial has examined whether vitamin K supplementation prevents the progression of coronary artery calcification in patients with ESKD, a group in which high risk has been established. The aim of the iPACK-HD pilot study is to determine whether a trial to determine whether vitamin K has a favourable effect on coronary artery calcium (CAC) scores...
Canadian journal of kidney health and disease, 2018
Patients with chronic kidney disease (CKD) are asked to choose a renal replacement therapy or con... more Patients with chronic kidney disease (CKD) are asked to choose a renal replacement therapy or conservative management. Education and knowledge transfer play key roles in this decision-making process, yet they remain a partially met need. We sought to understand the dialysis modality decision-making process through exploration of the predialysis patient experience to better inform the educational process. Qualitative descriptive study. Kidney Care Centre of London Health Sciences Centre in London, Ontario, Canada. Twelve patients with CKD, with 4 patients on in-center hemodialysis, home hemodialysis, and peritoneal dialysis, respectively. Not applicable. We conducted semistructured interviews with each participant, along with any family members who were present. Interviews were transcribed verbatim. Conventional content analysis was used to analyze the transcripts for common themes. Representative quotes were decided via team consensus. A patient collaborator was part of the research...
The in-center dialysis unit and practice of dialysis, in the current multi-team approach, require... more The in-center dialysis unit and practice of dialysis, in the current multi-team approach, requires knowledge and skills in all the domains including medical expert, communicator, collaborator, scholar, health advocate, and leader. We are tasked as a community, to embrace and incentivize new innovations and technology to address these needs for our post graduate trainees. These innovations must address the basic principles of dialysis, quality improvement, technical and procedural skills as well as leadership and administration skills. The teaching methods and innovations must also be challenged to demonstrate the translation into adoption and improvements in practice to demonstrate success. This article will review the current state of the training curriculum in Nephrology for in-center hemodialysis and address some of the recent innovations.
The purpose of this manuscript is to describe a collaborative research initiative to explore the ... more The purpose of this manuscript is to describe a collaborative research initiative to explore the role of hydration in kidney health. Our understanding of the effects of hydration in health and disease is surprisingly limited, particularly when we consider the vital role of hydration in basic human physiology. Recent initiatives and research outcomes have challenged the global medical community to expand our knowledge about hydration, including the differences between water, sugared beverages and other consumables. Identification of the potential mechanisms contributing to the benefits of hydration has stimulated the global nephrology community to advance research regarding hydration for kidney health. Hydration and kidney health has been a focus of research for several research centers with a rapidly expanding world literature and knowledge. The International Society of Nephrology has collaborated with Danone Nutricia Research to promote development of kidney research initiatives, w...
Actuellement seule l'hydratation et la N-acétylcystéine se sont montrées efficaces pour d... more Actuellement seule l'hydratation et la N-acétylcystéine se sont montrées efficaces pour diminuer l'incidence de la néphropathie au produit de contraste radiologique. Nous avons étudié le rôle de la N-acétylcystéine et de divers protocoles d'hydratation chez des malades de chirurgie vasculaire soumis à une artériographie. Un essai monocentrique randomisé, contrôlé contre placebo, a été mené chez des malades ayant une dysfonction rénale pré-existante stable et subissant une artériographie élective en externe. Les malades ont été randomisés entre hydratation orale en externe et N-acétylcystéine, hydratation plus N-acétylcystéine ou notre traitement standard par hydratation intra-veineuse en hospitalisation seule. Deux malade sur 28 (7 %) qui avaient reçu une hydratation orale en externe et de la N-acétylcystéine ont fait une néphropathie au produit de contraste alors que deux sur 25 (8 %) qui avaient eu une hydratation en hospitalisation et de la N-acétylcystéine ont fait une néphropathie au produit de contraste et que deux sur 25 (8 %) qui ont eu le traitement standard par hydratation intra-veineuse seule en hospitalisation ont fait une néphropathie au produit de contraste. Il n'y avait pas de différence significative dans l'incidence de la néphropathie au produit de contraste entre les différents groupes. Aucun facteur de risque indépendant statistiquement significatif n'a été identifié parmi les malades qui ont fait une néphropathie au produit de contraste. La N-acétylcystéine n'a pas apporté un bénéfice supplémentaire aux malades traités par hydratation intra-veineuse en hospitalisation. L'hydratation orale associée à la N-acétylcystéine chez les malades externes était aussi efficace pour prévenir la néphropathie au produit de contraste que les traitements chez les malades hospitalisés et a évité une admission hospitalière couteuse.
Question In patients with hypertension having noncardiac surgery, is long-term -blocker treatment... more Question In patients with hypertension having noncardiac surgery, is long-term -blocker treatment associated with major adverse cardiovascular (CV) events (MACE) or mortality during the perioperative period? Methods Design Cohort study with linkage of national databases. Setting Denmark. Patients 55320 adults 20 years of age (mean age 66 y, {59%}* women) who had hypertension (based on the use of 2 of -blockers, reninangiotensin system [RAS] inhibitors, calcium antagonists, or thiazides) and had noncardiac surgeries. Exclusion criteria included liver disease, renal disease, secondary CV conditions, use of sotalol hydrochloride, or treatment with all 4 classes of study drugs. Risk factors Filled prescriptions for -blockers, RAS inhibitors, calcium antagonists, or thiazides in the 120 days before surgery. Outcomes MACE (CV death, nonfatal ischemic stroke, or nonfatal myocardial infarction) and mortality within 30 days after surgery. Main results Compared with RAS inhibitors plus thiazides, combinations of -blockers plus RAS inhibitors, calcium antagonists, or thiazides were associated with MACE and mortality (Table). Other outcomes are in the Table. Conclusion In patients with hypertension, -blocker treatment in combination with other antihypertensive drugs in the 120 days before noncardiac surgery was associated with increased risk for major adverse cardiovascular events and mortality compared with combinations that did not include a -blocker. Association between perioperative antihypertensive treatment and cardiovascular events and death in patients with hypertension having noncardiac surgery Antihypertensive treatments Adjusted odds ratio (95% CI) at 30 d after surgery MACE Mortality -blocker + RAS inhibitor 2.16 (1.54 to 3.04) 1.79 (1.33 to 2.42) -blocker + calcium antagonist 2.17 (1.48 to 3.17) 1.68 (1.20 to 2.35) -blocker + thiazide 1.56 (1.10 to 2.22) 1.65 (1.24 to 2.18) -blocker +2 others 1.22 (0.90 to 1.64) 1.31 (1.03 to 1.67) RAS inhibitor + calcium antagonist 1.12 (0.82 to 1.54) 1.15 (0.89 to 1.48) RAS inhibitor + thiazide + calcium antagonist 0.97 (0.73 to 1.29) 0.82 (0.64 to 1.05) Calcium antagonist + thiazide 1.02 (0.73 to 1.44) 1.24 (0.96 to 1.60) MACE = major adverse cardiovascular events; RAS = reninangiotensin system; CI defined in Glossary. Compared with RAS inhibitors + thiazides. Adjusted for sex, age, body mass index, year, comorbidities, pharmacotherapies, and surgery risk. Commentary Perioperative treatment with -blockers in noncardiac surgery remains controversial. 2 recent systematic reviews showed that perioperative initiation of -blockers was associated with both increases in all-cause mortality and cerebral vascular eventsprobably related to increased hypotension and bradycardiaand reductions in acute myocardial infarction and supraventricular tachycardia (1, 2). Variability of results within study cohorts was, in part, attributable to differences in surgical risk, type and dose of -blockade, and duration of -blocker exposure before surgery. Perioperative management of patients on long-term -blockers was not addressed, although current guidelines recommend continuing -blockers (3). The registry-based cohort study by Jrgensen and colleagues found that long-term use of -blockers plus other antihypertensive agents was associated with increased risk for MACE and all-cause mortality compared with combination therapy without -blockade. The findings are subject to the potential biases that threaten the validity of all observational studies. Although no between-group differences in baseline risk were identified, one wonders about confounding due to indication for -blocker use, which could result in a higher-risk cohort. Nonetheless, the outcomes are consistent with earlier reviews. -blockers are no longer considered first-line agents for hypertension; some guidelines do not even recommend them as second- or third-line agents because they are usually less effective than other treatments at reducing risk for CV events (4). The study by Jrgensen and colleagues identifies another area of uncertainty in the use of -blockers during the perioperative period. The existing literature is not sufficient to change practice. A clinical trial is needed to address the perioperative management of patients receiving long-term -blockers.
American journal of kidney diseases : the official journal of the National Kidney Foundation, Jan 12, 2015
Little is known about vascular access in patients starting hemodialysis therapy after kidney tran... more Little is known about vascular access in patients starting hemodialysis therapy after kidney transplant failure. Retrospective cohort study. Adult patients (aged ≥18 years) who started hemodialysis therapy in Ontario, Canada, from January 1, 2001, through December 31, 2010, after kidney transplant failure. Patient clinical and demographic characteristics. Proportion and timing of arteriovenous (AV) vascular access creation (fistula or graft) 12 months prior and up to 24 months after starting hemodialysis therapy. Event rates and outcome predictors. Our cohort included 683 patients with a mean age of 48 years and >50% with comorbidity index score < 3. In the 12 months predialysis and 24 months postdialysis, 16% and 47% of patients had an AV access created, respectively. In the postdialysis period, 13%, 26%, and 38% of patients had an AV access creation at 3, 6, and 12 months, respectively. History of coronary artery disease, diabetes mellitus, and peritoneal dialysis use prior ...
The hemodialysis vascular access surveillance controversy provides a case study of how enthusiasm... more The hemodialysis vascular access surveillance controversy provides a case study of how enthusiasm for a new test or treatment can lead to adoption of a false paradigm. Paradigms are the beliefs and assumptions shared by those in a field of knowledge, and are commonly included in clinical practice guidelines. The guidelines of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative recommend that arteriovenous vascular accesses undergo routine surveillance for detection and correction of stenosis. This recommendation is based on the paradigm that surveillance of access blood flow or dialysis venous pressure combined with correction of stenosis improves access outcomes. However, the quality of evidence that supports this paradigm has been widely criticized. We tested the validity of the surveillance paradigm by applying World Health Organization (WHO) criteria for evaluating screening tests to a literature review of published vascular access studies. These criteria i...
While randomized controlled trials (RCTs) are the gold standard for evidence in medicine, there i... more While randomized controlled trials (RCTs) are the gold standard for evidence in medicine, there is an overall paucity of RCTs in nephrology compared with other medical subspecialties. Consequently, the management of the dialysis population is often guided by nephrology clinical practice guidelines that are largely based on observational data or expert opinion. This review examines problems related to designing, conducting and completing RCTs in nephrology, highlighting major challenges, successes and frustrations, with specific examples as they pertain to the science of hemodialysis vascular access and their impact on clinical practice guidelines.
Objective: Arteriovenous fistulas created for hemodialysis often fail to become usable and are fr... more Objective: Arteriovenous fistulas created for hemodialysis often fail to become usable and are frequently abandoned. This prospective trial evaluated the efficacy of vonapanitase, a recombinant human elastase, in increasing radiocephalic fistula use for hemodialysis and secondary patency. Methods: PATENCY-2 was a randomized, double-blind, placebo-controlled trial in patients on or approaching the need for hemodialysis undergoing radiocephalic arteriovenous fistula creation. Of 696 screened, 613 were randomized, and 603 were treated (vonapanitase n = 405, placebo n = 208). The study drug solution was applied topically to the artery and vein for 10 min immediately after fistula creation. The primary endpoints were fistula use for hemodialysis and secondary patency (fistula survival without abandonment). Other efficacy endpoints included unassisted fistula use for hemodialysis, primary unassisted patency, fistula maturation and unassisted maturation by ultrasound criteria, and fistula ...
Background and Aims The leading cause of mortality for patients with end-stage kidney disease (ES... more Background and Aims The leading cause of mortality for patients with end-stage kidney disease (ESKD) is cardiovascular disease (CVD). This is due, in part, to vascular calcification (VC) where calcium becomes deposited within arterial walls causing narrowing of the arteries and altering their flexibility. Matrix Gla protein (MGP), a vitamin k-dependent protein, is a key local inhibitor of VC and becomes up-regulated adjacent to sites of calcification. There is a very high prevalence of vitamin K deficiency in patients across the chronic kidney disease (CKD) spectrum and vitamin K has been shown to prevent VC in experimental models. To date, no trial has examined whether vitamin K supplementation prevents the progression of coronary artery calcification in patients with ESKD, a group in which high risk has been established. The aim of the iPACK-HD pilot study is to determine whether a trial to determine whether vitamin K has a favourable effect on coronary artery calcium (CAC) scores...
Canadian journal of kidney health and disease, 2018
Patients with chronic kidney disease (CKD) are asked to choose a renal replacement therapy or con... more Patients with chronic kidney disease (CKD) are asked to choose a renal replacement therapy or conservative management. Education and knowledge transfer play key roles in this decision-making process, yet they remain a partially met need. We sought to understand the dialysis modality decision-making process through exploration of the predialysis patient experience to better inform the educational process. Qualitative descriptive study. Kidney Care Centre of London Health Sciences Centre in London, Ontario, Canada. Twelve patients with CKD, with 4 patients on in-center hemodialysis, home hemodialysis, and peritoneal dialysis, respectively. Not applicable. We conducted semistructured interviews with each participant, along with any family members who were present. Interviews were transcribed verbatim. Conventional content analysis was used to analyze the transcripts for common themes. Representative quotes were decided via team consensus. A patient collaborator was part of the research...
The in-center dialysis unit and practice of dialysis, in the current multi-team approach, require... more The in-center dialysis unit and practice of dialysis, in the current multi-team approach, requires knowledge and skills in all the domains including medical expert, communicator, collaborator, scholar, health advocate, and leader. We are tasked as a community, to embrace and incentivize new innovations and technology to address these needs for our post graduate trainees. These innovations must address the basic principles of dialysis, quality improvement, technical and procedural skills as well as leadership and administration skills. The teaching methods and innovations must also be challenged to demonstrate the translation into adoption and improvements in practice to demonstrate success. This article will review the current state of the training curriculum in Nephrology for in-center hemodialysis and address some of the recent innovations.
The purpose of this manuscript is to describe a collaborative research initiative to explore the ... more The purpose of this manuscript is to describe a collaborative research initiative to explore the role of hydration in kidney health. Our understanding of the effects of hydration in health and disease is surprisingly limited, particularly when we consider the vital role of hydration in basic human physiology. Recent initiatives and research outcomes have challenged the global medical community to expand our knowledge about hydration, including the differences between water, sugared beverages and other consumables. Identification of the potential mechanisms contributing to the benefits of hydration has stimulated the global nephrology community to advance research regarding hydration for kidney health. Hydration and kidney health has been a focus of research for several research centers with a rapidly expanding world literature and knowledge. The International Society of Nephrology has collaborated with Danone Nutricia Research to promote development of kidney research initiatives, w...
Actuellement seule l&#39;hydratation et la N-acétylcystéine se sont montrées efficaces pour d... more Actuellement seule l&#39;hydratation et la N-acétylcystéine se sont montrées efficaces pour diminuer l&#39;incidence de la néphropathie au produit de contraste radiologique. Nous avons étudié le rôle de la N-acétylcystéine et de divers protocoles d&#39;hydratation chez des malades de chirurgie vasculaire soumis à une artériographie. Un essai monocentrique randomisé, contrôlé contre placebo, a été mené chez des malades ayant une dysfonction rénale pré-existante stable et subissant une artériographie élective en externe. Les malades ont été randomisés entre hydratation orale en externe et N-acétylcystéine, hydratation plus N-acétylcystéine ou notre traitement standard par hydratation intra-veineuse en hospitalisation seule. Deux malade sur 28 (7 %) qui avaient reçu une hydratation orale en externe et de la N-acétylcystéine ont fait une néphropathie au produit de contraste alors que deux sur 25 (8 %) qui avaient eu une hydratation en hospitalisation et de la N-acétylcystéine ont fait une néphropathie au produit de contraste et que deux sur 25 (8 %) qui ont eu le traitement standard par hydratation intra-veineuse seule en hospitalisation ont fait une néphropathie au produit de contraste. Il n&#39;y avait pas de différence significative dans l&#39;incidence de la néphropathie au produit de contraste entre les différents groupes. Aucun facteur de risque indépendant statistiquement significatif n&#39;a été identifié parmi les malades qui ont fait une néphropathie au produit de contraste. La N-acétylcystéine n&#39;a pas apporté un bénéfice supplémentaire aux malades traités par hydratation intra-veineuse en hospitalisation. L&#39;hydratation orale associée à la N-acétylcystéine chez les malades externes était aussi efficace pour prévenir la néphropathie au produit de contraste que les traitements chez les malades hospitalisés et a évité une admission hospitalière couteuse.
Question In patients with hypertension having noncardiac surgery, is long-term -blocker treatment... more Question In patients with hypertension having noncardiac surgery, is long-term -blocker treatment associated with major adverse cardiovascular (CV) events (MACE) or mortality during the perioperative period? Methods Design Cohort study with linkage of national databases. Setting Denmark. Patients 55320 adults 20 years of age (mean age 66 y, {59%}* women) who had hypertension (based on the use of 2 of -blockers, reninangiotensin system [RAS] inhibitors, calcium antagonists, or thiazides) and had noncardiac surgeries. Exclusion criteria included liver disease, renal disease, secondary CV conditions, use of sotalol hydrochloride, or treatment with all 4 classes of study drugs. Risk factors Filled prescriptions for -blockers, RAS inhibitors, calcium antagonists, or thiazides in the 120 days before surgery. Outcomes MACE (CV death, nonfatal ischemic stroke, or nonfatal myocardial infarction) and mortality within 30 days after surgery. Main results Compared with RAS inhibitors plus thiazides, combinations of -blockers plus RAS inhibitors, calcium antagonists, or thiazides were associated with MACE and mortality (Table). Other outcomes are in the Table. Conclusion In patients with hypertension, -blocker treatment in combination with other antihypertensive drugs in the 120 days before noncardiac surgery was associated with increased risk for major adverse cardiovascular events and mortality compared with combinations that did not include a -blocker. Association between perioperative antihypertensive treatment and cardiovascular events and death in patients with hypertension having noncardiac surgery Antihypertensive treatments Adjusted odds ratio (95% CI) at 30 d after surgery MACE Mortality -blocker + RAS inhibitor 2.16 (1.54 to 3.04) 1.79 (1.33 to 2.42) -blocker + calcium antagonist 2.17 (1.48 to 3.17) 1.68 (1.20 to 2.35) -blocker + thiazide 1.56 (1.10 to 2.22) 1.65 (1.24 to 2.18) -blocker +2 others 1.22 (0.90 to 1.64) 1.31 (1.03 to 1.67) RAS inhibitor + calcium antagonist 1.12 (0.82 to 1.54) 1.15 (0.89 to 1.48) RAS inhibitor + thiazide + calcium antagonist 0.97 (0.73 to 1.29) 0.82 (0.64 to 1.05) Calcium antagonist + thiazide 1.02 (0.73 to 1.44) 1.24 (0.96 to 1.60) MACE = major adverse cardiovascular events; RAS = reninangiotensin system; CI defined in Glossary. Compared with RAS inhibitors + thiazides. Adjusted for sex, age, body mass index, year, comorbidities, pharmacotherapies, and surgery risk. Commentary Perioperative treatment with -blockers in noncardiac surgery remains controversial. 2 recent systematic reviews showed that perioperative initiation of -blockers was associated with both increases in all-cause mortality and cerebral vascular eventsprobably related to increased hypotension and bradycardiaand reductions in acute myocardial infarction and supraventricular tachycardia (1, 2). Variability of results within study cohorts was, in part, attributable to differences in surgical risk, type and dose of -blockade, and duration of -blocker exposure before surgery. Perioperative management of patients on long-term -blockers was not addressed, although current guidelines recommend continuing -blockers (3). The registry-based cohort study by Jrgensen and colleagues found that long-term use of -blockers plus other antihypertensive agents was associated with increased risk for MACE and all-cause mortality compared with combination therapy without -blockade. The findings are subject to the potential biases that threaten the validity of all observational studies. Although no between-group differences in baseline risk were identified, one wonders about confounding due to indication for -blocker use, which could result in a higher-risk cohort. Nonetheless, the outcomes are consistent with earlier reviews. -blockers are no longer considered first-line agents for hypertension; some guidelines do not even recommend them as second- or third-line agents because they are usually less effective than other treatments at reducing risk for CV events (4). The study by Jrgensen and colleagues identifies another area of uncertainty in the use of -blockers during the perioperative period. The existing literature is not sufficient to change practice. A clinical trial is needed to address the perioperative management of patients receiving long-term -blockers.
American journal of kidney diseases : the official journal of the National Kidney Foundation, Jan 12, 2015
Little is known about vascular access in patients starting hemodialysis therapy after kidney tran... more Little is known about vascular access in patients starting hemodialysis therapy after kidney transplant failure. Retrospective cohort study. Adult patients (aged ≥18 years) who started hemodialysis therapy in Ontario, Canada, from January 1, 2001, through December 31, 2010, after kidney transplant failure. Patient clinical and demographic characteristics. Proportion and timing of arteriovenous (AV) vascular access creation (fistula or graft) 12 months prior and up to 24 months after starting hemodialysis therapy. Event rates and outcome predictors. Our cohort included 683 patients with a mean age of 48 years and >50% with comorbidity index score < 3. In the 12 months predialysis and 24 months postdialysis, 16% and 47% of patients had an AV access created, respectively. In the postdialysis period, 13%, 26%, and 38% of patients had an AV access creation at 3, 6, and 12 months, respectively. History of coronary artery disease, diabetes mellitus, and peritoneal dialysis use prior ...
The hemodialysis vascular access surveillance controversy provides a case study of how enthusiasm... more The hemodialysis vascular access surveillance controversy provides a case study of how enthusiasm for a new test or treatment can lead to adoption of a false paradigm. Paradigms are the beliefs and assumptions shared by those in a field of knowledge, and are commonly included in clinical practice guidelines. The guidelines of the National Kidney Foundation Kidney Disease Outcomes Quality Initiative recommend that arteriovenous vascular accesses undergo routine surveillance for detection and correction of stenosis. This recommendation is based on the paradigm that surveillance of access blood flow or dialysis venous pressure combined with correction of stenosis improves access outcomes. However, the quality of evidence that supports this paradigm has been widely criticized. We tested the validity of the surveillance paradigm by applying World Health Organization (WHO) criteria for evaluating screening tests to a literature review of published vascular access studies. These criteria i...
While randomized controlled trials (RCTs) are the gold standard for evidence in medicine, there i... more While randomized controlled trials (RCTs) are the gold standard for evidence in medicine, there is an overall paucity of RCTs in nephrology compared with other medical subspecialties. Consequently, the management of the dialysis population is often guided by nephrology clinical practice guidelines that are largely based on observational data or expert opinion. This review examines problems related to designing, conducting and completing RCTs in nephrology, highlighting major challenges, successes and frustrations, with specific examples as they pertain to the science of hemodialysis vascular access and their impact on clinical practice guidelines.
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