Peculiarities of Arteriovenous Prosthesis Functioning in Patients on Hemodialysis

Long-term and proper functioning of vascular access is necessary for renal replacement therapy in patients with chronic kidney disease (CKD). If it is impossible to form an arteriovenous fistula due to a pathologically changed structure of the vascular wall of peripheral arteries and veins, an arteriovenous prosthesis of various locations is implanted to form a permanent vascular access. However, the problem of long-term use of arteriovenous prostheses remains relevant, in particular, due to the prevalence of hemodynamic disorders, such as thrombosis, stenoses, and pseudoaneurysms. The aim of the study was a retrospective analysis of hemodynamic disorders and peculiarities of the use of arteriovenous prostheses as permanent vascular access in patients undergoing hemodialysis therapy. There were analyzed 586 medical records of inpatients and 103 discharge epicrisis of outpatients of the intensive nephrology department. Out of the 467 primary permanent vascular accesses formed for renal replacement therapy, 391 (83.72%) ones – were native arteriovenous fistulas (AVF) and 76 (16.27%) – were arteriovenous prostheses (AVP). It was found that the increase in the frequency of initial uncorrected and corrected primary loss of vascular access for AVF is the greatest during the first year of use and amounts to 35.53% and 26.32% of cases, respectively. Instead, the greatest increase in secondary loss of patency is observed during the first six months of using prostheses, which corresponds to 10.53% of patients. It is worth paying attention to the problem of concomitant pathology, in particular diabetes mellitus, arterial hypertension, calcification disease, which directly affect the state of the vascular wall and the functioning effectiveness of the vascular access. The obtained results indicate the necessity to review and supplement the existing methods of prevention of hemodynamic disorders of AVF during the first 6-12 months of their use in order to improve the quality of patients’ lives.Резюме. Для проведення замісної ниркової терапії у пацієнтів із хронічною хворобою нирок (ХХН) необхідне тривале та належне функціонування судинного доступу. При неможливості сформувати артеріовенозну фістулу внаслідок патологічно зміненої структури судинної стінки периферичних артерій та вен, для формування постійного судинного доступу проводиться імплантація артеріовенозного протеза різних локалізацій. Проте актуальною залишається проблема тривалого використання артеріовенозних протезів, зокрема, через поширеність гемодинамічних розладів, таких як тромбози, стенози та псевдоаневризми. Метою дослідження був ретроспективний аналіз гемодинамічних порушень та особливостей використання артеріовенозних протезів як постійного судинного доступу у хворих, які перебували на гемодіалізній терапії.  Проаналізовано 586 медичних карт стаціонарних хворих та 103 виписних епікризів амбулаторних хворих відділення інтенсивної нефрології. Із сформованих 467 первинних постійних судинних доступів для проведення замісної ниркової терапії 391 (83,72 %) – нативні артеріовенозні фістули (АВФ) та 76 (16,27 %) – артеріовенозні протези (АВП). Встановлено, що ріст частоти первинної некорегованої та корегованої первинних втрат судинного доступу для АВП є найбільшим протягом першого року використання та становить відповідно 35,53 % та 26,32 % випадків. Натомість найбільший ріст вторинної втрати прохідності спостерігається протягом перших шести місяців використання протезів, що відповідає 10,53 % пацієнтів. Варто звернути увагу на проблему супутньої патології, зокрема цукрового діабету, артеріальної гіпертензії, кальцинуючої хвороби, які безпосередньо впливають на стан судинної стінки та ефективність функціонування судинного доступу. Отримані результати свідчать про необхідність перегляду та доповнення існуючих методів профілактики гемодинамічних порушень роботи АВП протягом перших 6-12 місяців їхнього використання з метою покращення якості життя пацієнтів

Brecciation and Associated Mobile Submagmatic Emplacement of Alkali Feldspar Rich Rocks at Lake La Cloche, Harrow Twp, Ontario

N/AThesisBachelor of Science (BSc

Brecciation and Associated Mobile Submagmatic Emplacement of Alkali Feldspar Rich Rocks At Lake La Cloche, Harrow Twp, Ontario

Tensile fracturing and expansion possible relating to tectonic activity and faulting have in part controlled the emplacement of alkali feldspar rich rocks in Heronian sediments at Lake La Cloche, south of Massey, Ontario. The rocks include 1. albitite - composed almost entirely of low albite (Dr2-Abg95-An3) and minor dispersed hematite. 2. perthosite - containing separate phases of microcline and albite with mutual replacement textures. The seem to be physically separate but show similarities in spatial, textural and chemical aspects. They have been emplaced chiefly within a fracture zone at the top of the Mississagi quartzite. Perthosite is intimately related with 3. tuffisite - a somewhat mineralogically and modally variable rock emplaced as matrix within an irregular breccia pipe north of the fracture zone. The overall mineral assemblage is microcline + albite + perthite + epidote + chlorite + sericite+ hematite. Texturally it is reminiscent of crystal cuffs. Phenoclasts of the alkali feldspars (rounded, abraded) float in a hydrous silicate background. These phenoclasts are replicas of those in perthosite. Fragments of perthosite (phenoclast poor) were also found in tuffisite in one local. Tuffisite ranges from alkali feldspar poor to feldspar rich varieties. It is typically a silica poor alumina, lime, iron arid potash-rich rock. Tuffisite was probably emplaced as a fluidized mass. Some similarities to known fluidized bodies are present. These include rounding, attrition and fretting of the host rock, extensive penetration and exploitation of joints, bedding and planar weaknesses, internal sculpturing of the host rock, evidence for both mechanical and chemical emplacement. It may also be classed as a hydrothermalite. This refers to crytallization under submagmatic conditions, the pneumatolytic to hydrothermal range, hydroxyl minerals commonly developing. In this respect and others it is comparable with weilbergites, alkali feldspar-chlorite rocks within the Lahn region of Germany. Certain nearby breccia pipes and red feldspar rocks have been associated with alkalic igneous activity. (An alkaline rock province has been postulated along the North Shore of Lake Huron) Specif1cally soda rich fenite breccias are present at Nemag and Kusk lakes, 12 miles southwest of Sudbury. The red feldspar rock albitite is common along the North Shore. It is often adjacent or spatially related to diabase and has been interpreted accordingly in terms of genesis. Some albitites are not related spatially to di abase bodies and their emplacement has been controlled fracture systems. Their origin is more hazy. The author suggests two alternative interpretations dependent on whether alkali feldspars in tuffisite are considered to be primarily on- allochthonous. Alternative One - (Alkali feldspars primary): Perthosite and albitite are special fractionates, concentrated initially within the proto-tuffisite magma aj an al kali-volatile rich phase. These juvenile liquids were emplaced within a fracture zone at the top of the Mississagi. At about the same time tuffisite was emplaced within an irregular breccia pipe. The author throws open for argument the possibility that tuffisite is an upper crustal altered fenite breccia with associated red feldspar rock emplacement la fracture zones. Alternative Two-(Alkali feldspars allochthonous);Tuffisite is a hybrid rock type akin to a weilbergites (also interpreted as hybrid). Crystallization of red feldspar rocks within the pneumatolytic stage involved contamination in part by mafic material (possibly diabase). The resultant mechanical, chemical mixture was emplaced as a fluidized mass-tuffisite. More work needs to be done in determining which alternative is valid and what the exact relationships and sources of albitite, perthosite and tuffisite are.ThesisBachelor of Science (BSc

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to &lt;90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], &gt;300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of &lt;15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P&lt;0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P&lt;0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR) 25–75 mL/min per 1·73 m² of body surface area, and a urine albumin-to-creatinine ratio (UACR) of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders) were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days) or end-stage kidney disease (eGFR <15 mL/min per 1·73 m² sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure) in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325) or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%) of 1325 patients in the atrasentan group and 105 (7·9%) of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR] 0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%) of 1325 patients in the atrasentan group and 34 (2·6%) of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%) patients in the atrasentan group and 52 (3·9%) in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding AbbVi

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of bodysurface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2 ), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of endstage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years. (Funded by Janssen Research and Development; CREDENCE ClinicalTrials.gov number, NCT02065791.