Are you SURE about your vascular access? Exploring factors influencing vascular access decisions with chronic hemodialysis patients and their nurses.

A major decision for patients with stage 5 chronic kidney disease (CKD) relates to vascular access (VA) for treatment. Patients who receive pre-dialysis care often defer making a decision, which results in initiation of hemodialysis (HD) with a central venous catheter (CVC) in an urgent or emergent situation. Little is known about how individuals make decisions around VA. In this context, a mixed-methods study was undertaken to explore uncertainty related to changing their VA from an existing CVC to a graft or fistula. Quantitative assessment was measured using the SURE tool and interviews with patients and nurses were conducted. Results revealed that none of the 16 patient participants reported uncertainty. Qualitative findings revealed that patient decisions about access were impacted by observations, experiences, and dialogue in the hemodialysis unit. Study findings have important implications including the challenge of reconciling epidemiologic population-based risk measurement to the individual patient's situation. Moreover, the SURE tool was viewed as a mechanism to open a dialogue to confirm patients' decisions and provide further education and/or support following HD initiation.

Development of competencies for the use of bedside ultrasound for assessment and cannulation of hemodialysis vascular access.

Use of ultrasound for hemodialysis vascular access assessment and real-time cannulation requires specialized training. In order to obtain basic hand-eye coordination, theoretical sessions on ultrasound use, as well as practical sessions using phantom models are recommended prior to its use in the clinical setting with patients. New users of this technology need to consider that all competencies can be achieved with daily use of ultrasound at the bedside. It takes approximately 500 guided cannulations to achieve the highest level of competency described above.

Self-reported MeasUrement of Physical and PsychosOcial Symptoms Response Tool (SUPPORT-dialysis): systematic symptom assessment and management in patients on in-centre haemodialysis - a parallel arm, non-randomised feasibility pilot study protocol.

INTRODUCTION: Patients with kidney failure experience symptoms that are often under-recognised and undermanaged. These symptoms negatively impact health-related quality of life and are associated with adverse clinical outcomes. Regular symptom assessment, using electronic patient reported outcomes measure (ePROMs) linked to systematic symptom management, could improve such outcomes. Clinical implementation of ePROMs have been successful in routine oncology care, but not used for patients on dialysis. In this study, we describe a pilot study of ePROM-based systematic symptom monitoring and management intervention in patients treated with in-centre haemodialysis. METHODS AND ANALYSIS: This is a parallel-arm, controlled pilot of adult patients receiving in-centre maintenance haemodialysis. Participants in the intervention arm will complete ePROMs once a month for 6 months. ePROMs will be scored real time and the results will be shared with participants and with the clinical team. Moderate-severe symptoms will be flagged using established cut-off scores. Referral options for those symptoms will be shared with the clinical team, and additional symptom management resources will also be provided for both participants and clinicians. Participants in the control arm will be recruited at a different dialysis unit, to prevent contamination. They will receive usual care, except that they will complete ePROMs without the presentation of results to participants of the clinical team. The primary objectives of the pilot are to assess (1) the feasibility of a larger, randomised clinical effectiveness trial and (2) the acceptability of the intervention. Interviews conducted with participants and staff will be assessed using a content analysis approach. ETHICS AND DISSEMINATION: Ethical approval for this study was obtained from the University Health Network (REB#21-5199) and the William Osler Health System (#23-0005). All study procedures will be conducted in accordance with the standards of University Health Network research ethics board and with the 1964 Helsinki declaration and its later amendments. Results of this study will be shared with participants, patients on dialysis and other stakeholders using lay language summaries, oral presentations to patients and nephrology professionals. We will also be publishing the results in a peer-reviewed journal and at scientific meetings. PROTOCOL VERSION: 4 (16 November 2022). TRIAL REGISTRATION NUMBER: NCT05515991.

Renal and retinal effects of enalapril and losartan in type 1 diabetes.

BACKGROUND: Nephropathy and retinopathy remain important complications of type 1 diabetes. It is unclear whether their progression is slowed by early administration of drugs that block the renin-angiotensin system. METHODS: We conducted a multicenter, controlled trial involving 285 normotensive patients with type 1 diabetes and normoalbuminuria and who were randomly assigned to receive losartan (100 mg daily), enalapril (20 mg daily), or placebo and followed for 5 years. The primary end point was a change in the fraction of glomerular volume occupied by mesangium in kidney-biopsy specimens. The retinopathy end point was a progression on a retinopathy severity scale of two steps or more. Intention-to-treat analysis was performed with the use of linear regression and logistic-regression models. RESULTS: A total of 90% and 82% of patients had complete renal-biopsy and retinopathy data, respectively. Change in mesangial fractional volume per glomerulus over the 5-year period did not differ significantly between the placebo group (0.016 units) and the enalapril group (0.005, P=0.38) or the losartan group (0.026, P=0.26), nor were there significant treatment benefits for other biopsy-assessed renal structural variables. The 5-year cumulative incidence of microalbuminuria was 6% in the placebo group; the incidence was higher with losartan (17%, P=0.01 by the log-rank test) but not with enalapril (4%, P=0.96 by the log-rank test). As compared with placebo, the odds of retinopathy progression by two steps or more was reduced by 65% with enalapril (odds ratio, 0.35; 95% confidence interval [CI], 0.14 to 0.85) and by 70% with losartan (odds ratio, 0.30; 95% CI, 0.12 to 0.73), independently of changes in blood pressure. There were three biopsy-related serious adverse events that completely resolved. Chronic cough occurred in 12 patients receiving enalapril, 6 receiving losartan, and 4 receiving placebo. CONCLUSIONS: Early blockade of the renin-angiotensin system in patients with type 1 diabetes did not slow nephropathy progression but slowed the progression of retinopathy. (ClinicalTrials.gov number, NCT00143949.)

Effect of fish oil supplementation on graft patency and cardiovascular events among patients with new synthetic arteriovenous hemodialysis grafts: a randomized controlled trial.

CONTEXT: Synthetic arteriovenous grafts, an important option for hemodialysis vascular access, are prone to recurrent stenosis and thrombosis. Supplementation with fish oils has theoretical appeal for preventing these outcomes. OBJECTIVE: To determine the effect of fish oil on synthetic hemodialysis graft patency and cardiovascular events. DESIGN, SETTING, AND PARTICIPANTS: The Fish Oil Inhibition of Stenosis in Hemodialysis Grafts (FISH) study, a randomized, double-blind, controlled clinical trial conducted at 15 North American dialysis centers from November 2003 through December 2010 and enrolling 201 adults with stage 5 chronic kidney disease (50% women, 63% white, 53% with diabetes), with follow-up for 12 months after graft creation. INTERVENTIONS: Participants were randomly allocated to receive fish oil capsules (four 1-g capsules/d) or matching placebo on day 7 after graft creation. MAIN OUTCOME MEASURE: Proportion of participants experiencing graft thrombosis or radiological or surgical intervention during 12 months' follow-up. RESULTS: The risk of the primary outcome did not differ between fish oil and placebo recipients (48/99 [48%] vs 60/97 [62%], respectively; relative risk, 0.78 [95% CI, 0.60 to 1.03; P = .06]). However, the rate of graft failure was lower in the fish oil group (3.43 vs 5.95 per 1000 access-days; incidence rate ratio [IRR], 0.58 [95% CI, 0.44 to 0.75; P < .001]). In the fish oil group, there were half as many thromboses (1.71 vs 3.41 per 1000 access-days; IRR, 0.50 [95% CI, 0.35 to 0.72; P < .001]); fewer corrective interventions (2.89 vs 4.92 per 1000 access-days; IRR, 0.59 [95% CI, 0.44 to 0.78; P < .001]); improved cardiovascular event-free survival (hazard ratio, 0.43 [95% CI, 0.19 to 0.96; P = .04]); and lower mean systolic blood pressure (-3.61 vs 4.49 mm Hg; difference, -8.10 [95% CI, -15.4 to -0.85]; P = .01). CONCLUSIONS: Among patients with new hemodialysis grafts, daily fish oil ingestion did not decrease the proportion of grafts with loss of native patency within 12 months. Although fish oil improved some relevant secondary outcomes such as graft patency, rates of thrombosis, and interventions, other potential benefits on cardiovascular events require confirmation in future studies. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN15838383.

Arteriovenous fistulas for hemodialysis: application of high-frequency US to assess vein wall morphology for cannulation readiness.

PURPOSE: To determine whether venous wall thickness and hoop (circumferential) stress, as determined with high-frequency ultrasonography (US), can predict cannulation readiness in arteriovenous fistulas (AVFs). MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained for this prospective study. To determine the US appearance of the venous wall, an AVF specimen was excised and scanned in a bath of degassed lactated Ringer solution with a 55-MHz probe. The appearance of the wall at high-frequency US was correlated with histologic findings. High-frequency (40-55-MHz) US was used to image the near-field AVF venous wall of 14 men (mean age, 59 years ± 11 [standard deviation]) and six women (mean age, 55 years ± 14) with newly created AVFs within 1 week of cannulation between January 2008 and December 2009. Measurements of the intima-media thickness (IMT) were generated by three independent observers who were blinded to outcomes. Intraclass correlation analysis was performed. Cannulation readiness was defined as no extravasation during the first dialysis treatment. RESULTS: By using high-frequency US, the IMT was defined as the sum of a thin echogenic blood-intima interface and a uniform hypoechoic media. The mean IMT of the no extravasation group (0.16 mm ± 0.03) was greater than that of the extravasation group (0.10 mm ± 0.02) (P < .001). A minimum threshold IMT of 0.13 mm (P < .001) was associated with successful cannulation. The mean hoop stress of the no extravasation group (246 kPa ± 57) was lower than that of the extravasation group (530 kPa ± 199) (P < .001). A maximum hoop stress threshold of 248 kPa was associated with successful cannulation (P = .009). CONCLUSION: Venous IMT and hoop stress assessed with high-frequency US can predict cannulation readiness in AVFs that are clinically deemed mature.

Exploring the impact of a decision support intervention on vascular access decisions in chronic hemodialysis patients: study protocol.

BACKGROUND: In patients with Stage 5 Chronic Kidney Disease who require renal replacement therapy a major decision concerns modality choice. However, many patients defer the decision about modality choice or they have an urgent or emergent need of RRT, which results in them starting hemodialysis with a Central Venous Catheter. Thereafter, efforts to help patients make more timely decisions about access choices utilizing education and resource allocation strategies met with limited success resulting in a high prevalent CVC use in Canada. Providing decision support tailored to meet patients' decision making needs may improve this situation. The Registered Nurses Association of Ontario has developed a clinical practice guideline to guide decision support for adults living with Chronic Kidney Disease (Decision Support for Adults with Chronic Kidney Disease.) The purpose of this study is to determine the impact of implementing selected recommendations this guideline on priority provincial targets for hemodialysis access in patients with Stage 5 CKD who currently use Central Venous Catheters for vascular access. METHODS/DESIGN: A non-experimental intervention study with repeated measures will be conducted at St. Michaels Hospital in Toronto, Canada. Decisional conflict about dialysis access choice will be measured using the validated SURE tool, an instrument used to identify decisional conflict. Thereafter a tailored decision support intervention will be implemented. Decisional conflict will be re-measured and compared with baseline scores. Patients and staff will be interviewed to gain an understanding of how useful this intervention was for them and whether it would be feasible to implement more widely. Quantitative data will be analyzed using descriptive and inferential statistics. Statistical significance of difference between means over time for aggregated SURE scores (pre/post) will be assessed using a paired t-test. Qualitative analysis with content coding and identification of themes will be conducted for the focus group and patient interview data. DISCUSSION: Coupling the SURE tool with a decision support system structured so that a positive test result triggers providers to help patients through the decision-making process and/or refer patients to appropriate resources could benefit patients and ensure they have the opportunity to make informed HD access choices.

Glutathione and riboflavin status in supplemented patients undergoing home nocturnal hemodialysis versus standard hemodialysis.

BACKGROUND: Patients on conventional hemodialysis (HD) have elevated markers of oxidative stress and chronic inflammation, which may contribute to a high prevalence of cardiovascular disease. Glutathione (GSH), an important intracellular antioxidant, requires cysteine as a rate-limiting amino acid for its synthesis and riboflavin for its regeneration. OBJECTIVES: We aimed to examine whether erythrocyte GSH (eGSH) concentrations and riboflavin status are influenced by the increased dialysis dose provided to vitamin-supplemented patients receiving home nocturnal hemodialysis (HNHD) (6-8 hours/session, 5-7 nights/week) compared with patients on standard hemodialysis (SHD) (4 hours/session, 3 days/week). METHOD: This was a cross-sectional comparative study involving 30 patients undergoing SHD or HNHD regimens and a group of 15 healthy control subjects (HC). We measured eGSH concentration by liquid chromatography-tandem mass spectrometry, riboflavin status by eGSH reductase activity coefficient (EGRAC) as well as plasma total cysteine (Cys) and total homocysteine (Hcy), vitamin C by high-performance liquid chromatography, and C-reactive protein (CRP) by standard method. Estimated dietary protein and energy intakes were determined by 3-day food records, and nutritional status was assessed by subjective global assessment (SGA). RESULTS: There were no significant differences among groups in eGSH concentration, EGRAC, dietary protein intake, and SGA score. SHD patients had significantly higher plasma Cys (P < .001) and Hcy compared with HNHD and HC groups (P = .048). Vitamin C was significantly lower (P = .01) and CRP significantly higher (P = .048) in both HD groups compared with HC. CONCLUSION: eGSH concentration appears to be unaffected by dialysis dose in well-nourished HD patients.

Molecular comparison of Mycobacterium avium isolates from clinical and environmental sources.

We collected Mycobacterium avium isolates from clinical and drinking-water sources and compared isolates among themselves and to each other using molecular methods. Four clinical isolates were related to water isolates. Groups of indistinguishable clinical isolates were identified. The groups of identical clinical isolates suggest a common source of exposure.

Randomized pilot study to compare metal needles versus plastic cannulae in the development of complications in hemodialysis access.

BACKGROUND: Hemodialysis requires needle insertions every treatment. Needle injury (mechanical or hemodynamic) may cause complications (aneurysms/stenosis) that compromise dialysis delivery requiring interventions. Metal needles have a sharp slanted "V"-shaped cutting tip; plastic cannulae have a dull round tip and four side holes. Preliminary observations demonstrated a difference in intradialytic blood flow images and mean Doppler velocities at cannulation sites between the two devices. Complications from mechanical and hemodynamic trauma requiring interventions were compared in each group. MATERIALS AND METHODS: In all, 33 patients (13 females and 17 new accesses) were randomized to metal group (n = 17) and plastic group (n = 16). Mechanical trauma was minimized by having five nurses performing ultrasound-guided cannulations. Complications were identified by the clinician and addressed by the interventionalists, both blinded to study participation. Patients were followed for up to 12 months. RESULTS: Baseline characteristics were not significant. Procedures to treat complications along cannulation segments increased from 0.41 to 1.29 per patient (metal group) and decreased from 1.25 to 0.69 per patient (plastic group; p = 0.004). The relative risks of having an intervention (relative risk = 1.5, 95% confidence interval = 0.88-2.67) and having an infiltration during hemodialysis (relative risk = 2.26, 95% confidence interval = 1.03-4.97) were higher for metal needles. Time to first intervention trended in favor of plastic cannula (p = 0.069). Cost of supplies for these interventions was approximately CAD$20,000 lower for the plastic group. CONCLUSION: Decreased burden of illness related to cannulation (less infiltrations during hemodialysis) and Qb were associated with plastic cannulae. Decreased procedure costs were suggested during the study period in the plastic group.

An Adjustable Dalteparin Sodium Dose Regimen for the Prevention of Clotting in the Extracorporeal Circuit in Hemodialysis: A Clinical Trial of Safety and Efficacy (the PARROT Study).

BACKGROUND: Dalteparin sodium, a low-molecular-weight heparin, is indicated for prevention of clotting in the extracorporeal circuit during hemodialysis (HD). Product labeling recommends a fixed single-bolus dose of 5000 international units (IU) for HD sessions lasting up to 4 hours, but adjustable dosing may be beneficial in clinical practice. OBJECTIVE: The aim of the PARROT study was to investigate the safety and efficacy of an adjustable dose of dalteparin in patients with end-stage renal disease requiring 3 to 4 HD sessions per week. DESIGN: A 7-week, open-label, multicenter study with a single treatment arm, conducted between October 2013 and March 2016. SETTING: Ten sites in Canada. PATIENTS: A total of 152 patients with end-stage renal disease requiring 3 to 4 HD sessions per week. MEASUREMENTS: The primary outcome was the proportion of HD sessions completed without premature termination due to inadequate anticoagulation. METHODS: All participants initially received a dose of 5000 IU dalteparin, which could be adjusted at subsequent HD sessions when clinically indicated, by increment or decrement of 500 or 1000 IU, with no specified dose limits. RESULTS: Patients were followed for 256 patient-months. Nearly all (99.9%; 95% confidence interval [CI]: 99.7-100) evaluable HD sessions were completed without premature clotting. Dose was adjusted for more than half (52.3%) of participants, mostly owing to clotting or access compression time >10 minutes. Median dalteparin dose was 5000 IU (range: 500-13 000 IU). There were no major bleeds, and minor bleeding was reported in 2.3% of all HD sessions. There was no evidence of bioaccumulation. LIMITATIONS: This short-term study, with a single treatment arm, was designed to optimize dalteparin dose using a flexible dosing schedule; it was not designed to specifically evaluate dalteparin dose minimization, provide a direct comparison of dalteparin versus unfractionated heparin, or provide information on long-term safety for flexible dalteparin dosing. Patients were excluded if they were at high risk of bleeding, including those on anticoagulants and those on antiplatelet agents other than aspirin <100 mg/d. CONCLUSIONS: Overall, an adjustable dalteparin sodium dose regimen allowed safe completion of HD, with clinical benefits over fixed dosing. TRIAL REGISTRATION: ClinicalTrials.gov NCT01879618, registered June 13, 2013.

CONTEXTE: La daltéparine sodique, une héparine de faible poids moléculaire, est indiquée pour prévenir la formation de caillots dans le circuit extracorporel durant l'hémodialyse (HD). Pour une séance de dialyse d'une durée maximale de quatre heures, l'étiquette du produit recommande une dose fixe de 5 000 unités internationales (U.I.) administrée en bolus. Cependant, il est possible qu'il puisse être bénéfique d'ajuster la dose en pratique. OBJECTIF: Le but de l'étude PARROT était d'analyser l'innocuité et l'efficacité d'une dose ajustable de daltéparine chez des patients atteints d'insuffisance rénale terminale (IRT) et nécessitant trois à quatre séances d'HD par semaine. TYPE D'ÉTUDE: Il s'agit d'une étude ouverte et multicentrique à traitement unique d'une durée de sept semaines couvrant la période entre octobre 2013 et mars 2016. CADRE: L'étude a eu lieu dans dix centres de dialyse au Canada. SUJETS: L'étude a inclus 152 patients atteints d'IRT et nécessitant trois à quatre séances d'HD par semaine. MESURES: Le résultat principal était la proportion de séances d'HD complétées, non interrompues de manière prématurée en raison d'une anticoagulation inadéquate. MÉTHODOLOGIE: Tous les participants ont initialement reçu 5000 U.I. de daltéparine, dose qui a pu être ajustée lors des séances subséquentes, lorsqu'indiqué par le contexte clinique, à raison d'augmentation ou de réduction de 500 ou 1 000 U.I., sans spécification quant aux doses limites. RÉSULTATS: Les patients ont été suivis sur une période de 256 mois-patients. Pratiquement toutes les séances d'HD évaluables (99,9 %; IC 95 % : 99,7-100) ont été complétées sans coagulation prématurée. La dose de daltéparine a été ajustée pour plus de la moitié (52,3 %) des participants, essentiellement en raison de coagulation ou d'un besoin de procéder à une compression de l'accès vasculaire au-delà de 10 minutes. La dose médiane de daltéparine était de 5 000 U.I. (entre 500 et 13 000 U.I.). Aucune hémorragie majeure n'a été rapportée, mais une hémorragie mineure est survenue dans 2,3 % de toutes les séances d'HD analysées. Aucune bioaccumulation n'a été détectée. LIMITES: Cette étude de courte durée à traitement unique a été conçue pour optimiser le dosage de daltéparine à l'aide d'un schéma de posologie flexible. Elle ne visait pas à évaluer spécifiquement la minimisation de la dose ou à fournir des informations sur l'innocuité à long terme d'une posologie flexible pour la daltéparine. Également, les patients à haut risque d'hémorragie ont été exclus de l'étude, notamment ceux qui prenaient des anticoagulants ou des antiplaquettaires autres qu'une dose quotidienne de moins de 100 mg d'aspirine. CONCLUSION: Dans l'ensemble, un schéma posologique flexible pour la daltéparine sodique a permis de compléter les séances d'HD de façon sécuritaire, en plus de fournir des avantages cliniques par rapport à une dose fixe.

The relationship of diabetic retinopathy to preclinical diabetic glomerulopathy lesions in type 1 diabetic patients: the Renin-Angiotensin System Study.

Few epidemiological data exist regarding the correlation of anatomic measures of diabetic retinopathy and nephropathy, especially early in the disease processes. The aim of this study was to examine the association of severity of diabetic retinopathy with histological measures of diabetic nephropathy in normoalbuminuric patients with type 1 diabetes. The study included participants (n = 285) in the Renin-Angiotensin System Study (RASS; a multicenter diabetic nephropathy primary prevention trial) who were aged >/=16 years and had 2-20 years of type 1 diabetes with normal baseline renal function measures. Albumin excretion rate (AER), blood pressure, serum creatinine, and glomerular filtration rate (GFR) were measured using standardized protocols. Diabetic retinopathy was determined by masked grading of 30 degrees color stereoscopic fundus photographs of seven standard fields using the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. Baseline renal structural parameters, e.g., fraction of the glomerulus occupied by the mesangium or mesangial fractional volume [Vv(Mes/glom)] and glomerular basement membrane width, were assessed by masked electron microscopic morphometric analyses of research percutaneous renal biopsies. No retinopathy was present in 36%, mild nonproliferative diabetic retinopathy in 53%, moderate to severe nonproliferative diabetic retinopathy in 9%, and proliferative diabetic retinopathy in 2% of the cohort. Retinopathy was not related to AER, blood pressure, serum creatinine, or GFR. All renal anatomical end points were associated with increasing severity of diabetic retinopathy, while controlling for other risk factors. These data demonstrate a significant association between diabetic retinopathy and preclinical morphologic changes of diabetic nephropathy in type 1 diabetic patients.

The relation of ambulatory blood pressure and pulse rate to retinopathy in type 1 diabetes mellitus: the renin-angiotensin system study.

PURPOSE: To examine the association of ambulatory blood pressure (ABP) and ambulatory pulse rate (APR) with diabetic retinopathy (DR) in persons with type 1 diabetes in the Renin-Angiotensin System Study (RASS), a multicenter primary diabetic nephropathy (DN) prevention trial. DESIGN: Cross-sectional study. PARTICIPANTS: One hundred ninety-four normotensive RASS participants in 3 centers who are 16 years of age or older with type 1 diabetes mellitus (DM) of 2 to 20 years' duration. METHODS: Ambulatory blood pressure and APR were monitored using standardized protocols. Patients were defined as nondippers if the night-to-day ratios for both systolic and diastolic blood pressures were >0.9. Diabetic retinopathy was determined by masked grading of 30 degrees color stereoscopic fundus photographs of 7 standard fields using the Early Treatment Diabetic Retinopathy Study severity scale. MAIN OUTCOME MEASURE: Severity of DR. RESULTS: No DR was present in 32%, mild nonproliferative DR (NPDR) was present in 55%, and moderate to severe NPDR or proliferative DR was present in 13% of the cohort. Neither 24-hour systolic ABP or diastolic ABP, daytime systolic or diastolic ABP, nor nighttime diastolic ABP were related to severity of DR. Statistically significant associations were found between nighttime systolic ABP and mean ABP and DR. Among those with no DR, 19% were nondippers; for those with mild NPDR, 28% were nondippers; and for those with severe NPDR or proliferative DR, 36% were nondippers (P = 0.08). The ratio of nighttime to daytime APR, but not the 24-hour APR or daytime or nighttime APR, was related positively to the severity of DR. In multivariable analyses, only the nighttime systolic ABP was related to severity of DR (P<0.05). CONCLUSIONS: These data suggest that ABP, especially during the night, may provide a better measure than clinical BP regarding the relationship of BP to the severity of retinopathy in normotensive persons with type 1 DM without clinical DN.

Correlation between fractional reabsorption of sodium and erythropoietin dose in peritoneal dialysis patients.

BACKGROUND: Erythropoietin (EPO) deficiency of chronic renal failure (CRF) may be a functional consequence of decreased glomerular filtration rate and fractional reabsorption of sodium (FR(Na)). Decreased FR(Na) reduces renal oxygen consumption and increases tissue oxygen pressure, resulting in less EPO production. We hypothesized that, in CRF patients, there is a positive relationship between EPO production and FR(Na) and that, in such patients receiving EPO, a negative correlation is expected between FR(Na) and EPO dose. METHODS: Creatinine clearance, FR(Na), serum iron, transferrin, transferrin saturation, ferritin, and intact parathyroid hormone (iPTH) levels were measured in 91 peritoneal dialysis patients. The correlation between EPO dose and FR(Na) was studied. RESULTS: Mean EPO dose was 7076 +/- 4821 units/week and mean FR(Na) was 93.40% +/- 6.14%. A negative correlation was found between EPO dose and FR(Na) (r = -0.28, p < 0.01), and a positive correlation was found between both ferritin and iPTH and EPO dose (r = 0.39, p < 0.001 and r = 0.35, p < 0.002 respectively). After adjusting for the effect of creatinine clearance, ferritin, and iPTH, there was still a significant correlation between EPO dose and FR(Na) (p < 0.05). CONCLUSION: In CRF patients there is a negative correlation between FR(Na) and EPO dose, which supports the hypothesis that EPO deficiency may be related to the decreased renal oxygen-consuming work of sodium reabsorption.

The salvage of aneurysmal fistulae utilizing a modified buttonhole cannulation technique and multiple cannulators.

We describe the St Michael's Hospital (SMH) modified buttonhole (BH) cannulation technique as a method that offers a solution for fistulae with aneurysmal dilatation due to repetitive cannulation in a restricted area. This is a prospective cohort study of 14 chronic hemodialysis (HD) patients with problematic fistulae (marked aneurysmal formation and thinning of the overlying skin, bleeding during treatment, and prolonged hemostasis post-HD) because of repetitive, localized cannulation. Each patient was followed for 12 months. The protocol was as follows: creation of tunnel tracks by 1 to 3 experienced cannulators per patient, using sharp needles. After the tunnel tracks were established and cannulation was easily achieved with dull needles, additional cannulators were incorporated with the guidance of a mentor. Bleeding from cannulation sites during dialysis ceased within 2 weeks and skin damage resolved within 6 months in all patients. Hemostasis time postdialysis decreased from 24 to 15 min. Cannulation pain scores decreased significantly. Access flows and dynamic venous pressure measurements remained unchanged. No interventions were required to maintain access patency. In 2 cases, the aneurysms became much less evident. Complications included one episode of septic arthritis and one contact dermatitis. A third patient developed acute bacterial endocarditis 9 months following completion of her follow-up. The SMH modified BH cannulation technique can salvage problematic fistulae, prevent further damage, and induce healing of the skin in the areas of repetitive cannulation. This technique can be successfully achieved by multiple cannulators in a busy full-care HD unit.

Impact of needles in vascular access for hemodialysis.

This article reviews pragmatic aspects of cannulation practice and types of cannulation devices, as well as their impact in vascular access for hemodialysis. Hemodialysis treatment requires successful insertion of two needles for each dialysis treatment. The first needle is the arterial needle; it removes blood with toxin accumulation from the patient and delivers it to the dialysis machine. The second needle, called the venous needle, returns the purified blood from the dialyzer to the patient. Mechanical and hemodynamic trauma related to needle insertions will be discussed.

Mechanisms and management of toxicities associated with high-dose interferon alfa-2b therapy.

PURPOSE: The toxicity associated with adjuvant high-dose interferon-alfa-2b therapy (HDI) for high-risk melanoma can lead to premature discontinuation. It is important to understand the expected adverse events and their underlying mechanisms and to anticipate and aggressively manage toxicity during treatment in order to ensure that patients receive the maximum therapeutic benefit. METHODS: The toxicity profile of HDI was reviewed by examining data from the United States cooperative group trials. Available published data related to the potential mechanisms responsible for the observed adverse events are discussed, and comprehensive recommendations for managing side effects are presented. RESULTS: The HDI regimen is associated with acute constitutional symptoms, chronic fatigue, myelosuppression, elevated liver enzyme levels, and neurologic symptoms. The majority of patients tolerate 1 year of therapy with an understanding of the anticipated toxicities in conjunction with appropriate dose modifications and supportive care. Ongoing monitoring for liver dysfunction and hematologic toxicity is critical to ensure safety. Many of the toxicities associated with interferon-alfa (IFN-alpha) seem to be the result of endogenous cytokines and their effects on the neuroendocrine system. Recent data have also demonstrated that IFN-alpha suppresses the activity of specific CYP450 isoenzymes and that this correlates with discrete toxicities. Pharmacologic interventions are under study for fatigue and depression. An increased understanding of the mechanisms of IFN-alpha-associated toxicity will lead to more rational and effective supportive care and improved quality of life. CONCLUSION: Continued research in this area should lead to improvements in the safety and tolerability of adjuvant therapy for melanoma.

Differential effect of IFNalpha-2b on the cytochrome P450 enzyme system: a potential basis of IFN toxicity and its modulation by other drugs.

PURPOSE: High-dose IFNalpha-2b therapy (HDI) is the standard of adjuvant therapy for patients with high-risk melanoma, but toxicities of this regimen have limited its application. IFNs affect cytochrome P450 (CYP) enzymes, which metabolize many endogenous (e.g., steroids, fatty acids) and exogenous (e.g., drugs) substrates. No systematic studies have been performed to evaluate the effect of HDI on CYP enzymes. A significant inhibitory effect of HDI on CYP enzymes would increase the potential for adverse drug reactions and altered homeostasis through effects on hormone metabolism. METHODS: To evaluate the potential effect of HDI on CYP enzymes, 17 patients with high-risk melanoma were treated with HDI, and CYP enzyme activity was measured by administration of selectively metabolized probe drugs over time (days -6, +1, +26, and +52 of HDI). Probe drugs and/or metabolites were quantified and used to derive indexes of enzyme activity. RESULTS: The results indicate that HDI differentially impairs CYP-mediated metabolism, having no effect on some enzymes (CYP2E1) and substantial effects on others (CYP1A2; median 60% decrease). A significant association was found between the magnitude of CYP inhibition and the occurrence of side effects including fever and neurological toxicity, which may form a novel basis of the underlying pathophysiology of some IFNalpha-2b-induced toxicity. CONCLUSION: These data suggest that strategies to minimize the impairment of CYP enzymes could alter the toxicity profile of HDI and augment its therapeutic utility, and that recognition of these potential interactions is important in the therapeutic application of IFNs.