Effect of Coaching to Increase Water Intake on Kidney Function Decline in Adults With Chronic Kidney Disease: The CKD WIT Randomized Clinical Trial.

Importance: In observational studies, increased water intake is associated with better kidney function. Objective: To determine the effect of coaching to increase water intake on kidney function in adults with chronic kidney disease. Design, Setting, and Participants: The CKD WIT (Chronic Kidney Disease Water Intake Trial) randomized clinical trial was conducted in 9 centers in Ontario, Canada, from 2013 until 2017 (last day of follow-up, May 25, 2017). Patients had stage 3 chronic kidney disease (estimated glomerular filtration rate [eGFR] 30-60 mL/min/1.73 m2 and microalbuminuria or macroalbuminuria) and a 24-hour urine volume of less than 3.0 L. Interventions: Patients in the hydration group (n = 316) were coached to drink more water, and those in the control group (n = 315) were coached to maintain usual intake. Main Outcomes and Measures: The primary outcome was change in kidney function (eGFR from baseline to 12 months). Secondary outcomes included 1-year change in plasma copeptin concentration, creatinine clearance, 24-hour urine albumin, and patient-reported overall quality of health (0 [worst possible] to 10 [best possible]). Results: Of 631 randomized patients (mean age, 65.0 years; men, 63.4%; mean eGFR, 43 mL/min/1.73 m2; median urine albumin, 123 mg/d), 12 died (hydration group [n = 5]; control group [n = 7]). Among 590 survivors with 1-year follow-up measurements (95% of 619), the mean change in 24-hour urine volume was 0.6 L per day higher in the hydration group (95% CI, 0.5 to 0.7; P < .001). The mean change in eGFR was -2.2 mL/min/1.73 m2 in the hydration group and -1.9 mL/min/1.73 m2 in the control group (adjusted between-group difference, -0.3 mL/min/1.73 m2 [95% CI, -1.8 to 1.2; P = .74]). The mean between-group differences (hydration vs control) in secondary outcomes were as follows: plasma copeptin, -2.2 pmol/L (95% CI, -3.9 to -0.5; P = .01); creatinine clearance, 3.6 mL/min/1.73 m2 (95% CI, 0.8 to 6.4; P = .01); urine albumin, 7 mg per day (95% CI, -4 to 51; P = .11); and quality of health, 0.2 points (95% CI, -0.3 to 0.3; P = .22). Conclusions and Relevance: Among adults with chronic kidney disease, coaching to increase water intake compared with coaching to maintain the same water intake did not significantly slow the decline in kidney function after 1 year. However, the study may have been underpowered to detect a clinically important difference. Trial Registration: clinicaltrials.gov Identifier: NCT01766687.

Patients' quality of life after stopping plasma exchange: a pilot study.

BACKGROUND: Plasma exchange is being widely used to treat various serious medical conditions. There has been very little follow-up data to describe the quality of life (QOL) of plasma exchange-recipients after active plasma exchange has stopped. OBJECTIVE: To assess the QOL of plasma exchange recipients after stopping plasma exchange. METHODS: A pilot study, based on responses to a postal questionnaire and clinical data obtained from the patients' charts, was carried out. The scores were computed from questionnaire responses and analyzed. RESULTS: The response rate was 59% with 58 patients completing a questionnaire three months after their final plasma exchange therapy. We identified significant heterogeneity in the quality of life of plasma exchange recipients after stopping plasma exchange therapy. This could be driven by different patient co-morbidities. We recommend that during follow up visits, a multi-disciplinary approach including consultation with a social worker might be considered for patients who may continue to have some limitations in their psychosocial activities post-discontinuation of plasma exchange. The high response rate to the questionnaire indicates that PLEX patients are interested in being involved in QOL studies, which suggests potential support for a prospective study of QOL with pre and post questionnaires and more detailed tracking of baseline co-morbidities.

A Quantitative and Qualitative Study on Patient and Physician Perceptions of Nephrology Telephone Consultation During COVID-19.

BACKGROUND: COVID-19 required rapid adoption of virtual modalities to provide care for patients with a chronic disease. Care was initially provided by telephone, which has not been evaluated for its effectiveness by patients and providers. This study reports patients' and nephrologists' perceptions and preferences surrounding telephone consultation in a chronic kidney disease (CKD) clinic. OBJECTIVE: To evaluate patient and physician perspectives on the key advantages and disadvantages of telephone consultations in a nephrology out-patient clinic setting. DESIGN: Cross-sectional observational survey study. SETTING: General nephrology clinic and a multidisciplinary kidney care clinic in London, Ontario, Canada. PARTICIPANTS: Patients with CKD who were fluent in English and participated in at least one telephone consultation with a nephrologist during the COVID-19 pandemic. METHODS AND MEASUREMENTS: Nephrologists' and participants' input facilitated the development of both patient and nephrologist surveys. Participants provided self-reported measures in 5 domains of satisfaction: user experience, technical quality, perceived effectiveness on well-being, perceived usefulness, and effect on interaction. Nephrologists provided self-reported measures within 6 categories: general experience, time management, medication changes, quality of care, job satisfaction, and challenges/strengths. Descriptive statistics were used to present data. Content analysis was performed on 2 open-ended responses. RESULTS: Of the 372 participants recruited, 235 participated in the survey (63% response). In all, 79% of the participants were ≥65 years old and 91% were white. Telephone consultation was a comfortable experience for 68%, and 73% felt it to be a safer alternative during the pandemic. Although 65% perceived no changes to health care access, most reported spending less time and fewer resources on transit and parking. Disadvantages to telephone consultation included a lack of physical examination and reduced patient-physician rapport. Eleven of 14 nephrologists were surveyed, with most reporting confidence in the use of telephone consultation. Physician barriers to telephone consultation included challenges with communications and lack of technology to support telephone clinics. LIMITATIONS: Our survey included a majority of older, white participants, which may not be generalizable to other participants particularly those of other ages and ethnicity. CONCLUSION: Although both patients and nephrologists adapted to telephone consultations, there remain opportunities to further explore populations and situations that would be better facilitated with an in-person visit. Future research in virtual care will require measurement of health care outcomes and economics. TRIAL REGISTRATION: Not applicable as this was a survey.

Patient attitudes towards the arteriovenous fistula: a qualitative study on vascular access decision making.

BACKGROUND: The use of arteriovenous fistulas (AVFs) among hemodialysis (HD) patients has been consistently associated with lower rates of morbidity and mortality; however, up to 30% of eligible patients refuse the creation or cannulation of an AVF. We aimed to understand the attitudes, beliefs, preferences and values of patients who refused creation or use of an AVF. METHODS: With qualitative methodology, we conducted semi-structured interviews with 13 HD patients (Canada, 2009), who previously refused creation or use of an AVF. Three independent analysts reviewed interview transcripts. RESULTS: We discovered three main themes that impacted the decision to refuse a fistula: (i) poor previous personal or vicarious experiences with the fistula, including cannulation, bleeding, time commitment and appearance; (ii) knowledge transfer and informed decision making. Patients identified information from other patients to be as important as information from health care workers, that information on vascular access (VA) was presented but not understood and that timing of information was crucial with information overload at the start of dialysis and (iii) maintenance of status quo and outlook on life. Some patients stated they live day-to-day without being influenced by the mortality risks with a catheter. CONCLUSIONS: AVF refusal is multifactorial and depends on individual patients. Although nephrologists consider the fistula to be the optimal VA, patients do not think in the same terms of reducing infection rates but focus on the practical day-to-day use of their VA and its influence on their quality of life and future outlook.

Is there a necessity for individual blood water corrections when conductivity-based access blood flow measurements are made?

BACKGROUND/AIMS: Access blood water flow rate (Qaw) can be measured during hemodialysis using an online effective ionic dialysance (EID) methodology. Fresenius employ this methodology in their 2008K dialysis machine. The machine computer converts Qaw to an access blood flow rate (Fresenius Qa) using a generic blood water constant (BWC). We wished to validate this BWC. METHODS: 18 patients had Fresenius Qa measurements using the EID and these were compared with a 'gold standard' ultrasound dilution methodology (Transonic Qa). Qa values were also obtained by removing the BWC from Fresenius Qa values to obtain the Qaw and recorrecting it with individualized patient factors using hematocrit and total protein values (HctTp Qa). The measurements were repeated after 1 h. RESULTS: There were no significant differences between Fresenius and Transonic, nor between HctTp and Transonic Qa values (p > 0.17). There were strong correlations between both sets of values (r > 0.856; p < 0.001). There was a significant correlation between the pairs of Transonic Qa values (r = 0.823; p < 0.007), but not for Fresenius Qa pairs (r = 0.573; p > 0.07). It was surmised that the BWC was not valid post-dialysis. CONCLUSION: The generic BWC is comparable to individualized blood water correction factors when Qa measures are made early in dialysis and prior to ultrafiltration treatment.

Lowering postdialysis plasma sodium (conductivity) to increase sodium removal in volume-expanded hemodialysis patients: a pilot study using a biofeedback software system.

BACKGROUND: Extracellular fluid expansion is common in hemodialysis patients. Aggressive fluid removal may lead to intradialytic complications. High dialysate sodium concentrations may lessen complications, but may increase extracellular volume. We hypothesized that decreasing plasma sodium concentration during dialysis will increase sodium removal and decrease extracellular volume. STUDY DESIGN: Pilot clinical trial. SETTING & PARTICIPANTS: 16 patients with end-stage kidney disease treated using thrice-weekly hemodialysis at a university teaching hospital hemodialysis unit. INTERVENTION: Stepwise decrease in postdialysis plasma sodium level (calculated as end-of-session plasma conductivity) over 4 phases effected by dialysate conductivity measurement cells and a biofeedback software system (Diacontrol; Hospal, www.hospal.it) that allowed alteration of dialysate inlet conductivity and calculation of plasma conductivity. OUTCOMES: Decrease in postdialysis plasma sodium (conductivity) levels, sodium removal, redistribution of body water, and effect of these on interdialytic weight gain and blood pressure. MEASUREMENTS: Plasma sodium and conductivity values (the latter measured in millisiemens per centimeter); ionic mass balance (sodium removal); bioelectrical impedance analysis measurements of body-water compartments and phase angle; interdialytic weight gain; and blood pressure. RESULTS: Plasma sodium concentrations at the end of dialysis were decreased from 137.8 (phase 1) to 135.6 mmol/L (phase 4) and end-of-session plasma conductivity values were decreased from 14.0 (phase 1) to 13.5 mS/cm (phase 4; all mean values). Ionic mass balance increased from 383 to 480 mmol. Extracellular water was significantly decreased, phase angle was increased, and blood pressure and interdialytic weight gain were decreased. Plasma sodium levels correlated significantly with plasma conductivity; thus, changes in postdialysis plasma sodium levels can be inferred from changes in end-of-session plasma conductivity values. LIMITATIONS: Small number of patients. No information for dietary sodium intake. CONCLUSION: To decrease extracellular volume, it may be necessary to add diffusive to convective sodium losses.

Effect of N-acetylcysteine on serum creatinine and kidney function: results of a randomized controlled trial.

BACKGROUND: Evidence for a protective effect of N-acetylcysteine (NAC) on acute and chronic kidney disease is equivocal, and controversy persists about whether NAC affects creatinine level independently of actual kidney function. Study objectives are to investigate whether NAC affects serum creatinine level independently of alterations in other measures of kidney function. STUDY DESIGN: Double-blind randomized controlled trial. SETTING & PARTICIPANTS: Patients with stage 3 chronic kidney disease (n = 60), Canada, 2007-2008. INTERVENTION: Participants were randomly allocated to receive 4 doses of oral NAC (each 1,200 mg) or placebo, administered at 12-hour intervals. OUTCOME: The primary outcome was change in serum creatinine level between baseline and 4 hours after the last treatment dose. In addition, changes in other parameters of kidney function were measured between baseline and 4, 24, or 48 hours after the last treatment dose. MEASUREMENTS: Serum creatinine, cystatin C, 24-hour urine protein and creatinine excretion, and creatinine clearance. RESULTS: 60 patients, mean age of 70 years, 75% men, 50% had diabetes, with mean creatinine clearance of 43.7 ± 18.8 (SD) mL/min were enrolled. Between baseline and 4 hours posttreatment, serum creatinine level decreased by 0.044 ± 0.15 mg/dL in the NAC group and 0.040 ± 0.18 mg/dL in the placebo group (95% CI for difference, -0.09 to 0.08; P = 0.9). No significant differences between groups were observed for change in serum creatinine, cystatin C, urine protein, urine creatinine, or creatinine clearance values at any time. LIMITATIONS: Blinding patients to orally administered liquid NAC is difficult and it is possible that patients receiving NAC were not sufficiently blinded. Effects of NAC beyond 48 hours of treatment were not evaluated. CONCLUSIONS: In this randomized controlled trial, NAC had no short-term effect on creatinine level and did not decrease urine protein excretion within 48 hours of treatment.

The Chronic Kidney Disease Water Intake Trial: Protocol of a Randomized Controlled Trial.

BACKGROUND: In observational studies, drinking more water associates with a slower rate of kidney function decline; whether the same is true in a randomized controlled trial is unknown. OBJECTIVE: To examine the 1-year effect of a higher vs usual water intake on estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease. DESIGN: Parallel-group randomized controlled trial. SETTING: Nine centers in Ontario, Canada. Enrollment and randomization occurred between May 2013 and May 2016; follow-up for the primary outcome will continue until June 2017. PARTICIPANTS: Adults (n = 631) with stage 3 chronic kidney disease (eGFR 30-60 mL/min/1.73 m2) and microalbuminuria. INTERVENTION: The high water intake group was coached to increase their oral water intake by 1.0 to 1.5 L/day (depending on sex and weight), over and above usual consumed beverages, for a period of 1 year. The control group was coached to maintain their usual water intake during this time. MEASURES: Participants provided 24-hour urine samples at baseline and at 6 and 12 months after randomization; urine samples were analyzed for volume, creatinine, osmolality, and the albumin-to-creatinine ratio. Blood samples were obtained at baseline and at 3- to 6-month intervals after randomization, and analyzed for creatinine, copeptin, osmolality, and electrolytes. Other measures collected included health-related quality of life, blood pressure, body mass index, and diet. PRIMARY OUTCOME: The between-group change in eGFR from baseline (prerandomization) to 12 months after randomization. SECONDARY OUTCOMES: Change in plasma copeptin concentration, 24-hour urine albumin-to-creatinine ratio, measured creatinine clearance, estimated 5-year risk of kidney failure (using the 4-variable Kidney Failure Risk Equation), and health-related quality of life. PLANNED ANALYSIS: The primary analysis will follow an intention-to-treat approach. The between-group change in eGFR will be compared using linear regression. Supplementary analyses will examine alternative definitions of eGFR change, including annual percentage change, rate of decline, and rapid decline (a P value <0.05 will be interpreted as statistically significant if there is concordance with the primary outcome). TRIAL REGISTRATION: This randomized controlled trial has been registered at www.clinicaltrials.gov; government identifier: NCT01766687.

MISE EN CONTEXTE: Dans les études observationnelles, on a remarqué une association entre un apport hydrique accru et un ralentissement de la détérioration de la fonction rénale. Cependant, nous ignorions si ce phénomène s'observait également lors d'essais contrôlés à répartition aléatoire. OBJECTIFS DE L'ÉTUDE: L'objectif était d'observer, sur une période d'un an, les effets d'un apport hydrique accru sur le débit de filtration glomérulaire estimé (DFGe) de patients atteints d'insuffisance rénale chronique (IRC) par rapport à l'apport hydrique habituel. MODÈLE DE L'ÉTUDE: Essai contrôlé à répartition aléatoire et à groupes parallèles. CADRE DE L'ÉTUDE: L'étude s'est tenue au sein de neuf centres hospitaliers de l'Ontario, au Canada. Le recrutement et la répartition des patients se sont échelonnés sur une période de trois ans, soit de mai 2013 à mai 2016. Le suivi des résultats primaires s'est poursuivi jusqu'en juin 2017. PARTICIPANTS: Un total de 631 adultes atteints d'insuffisance rénale de stade 3 (DFGe entre 30 et 60 mL/min/1,73 m2) et présentant une microalbuminurie. MÉTHODOLOGIE: Sur une période d'un an, nous avons demandé au groupe-test d'augmenter leur apport hydrique de 1 à 1,5 litre par jour, quantité établie selon le sexe et le poids du patient. Le groupe contrôle devait maintenir son apport hydrique au volume habituel. MESURES: Les participants devaient fournir des échantillons d'urine sur une période de 24 heures avant la répartition aléatoire, de même que six mois et douze mois après. Les échantillons d'urine ont été recueillis pour en mesurer le volume, le taux de créatinine et de copeptine, l'osmolarité et les électrolytes. Les autres paramètres analysés incluaient la pression sanguine, l'indice de masse corporelle (IMC), la diète et la qualité de vie générale des patients en considérant leur état de santé. RÉSULTAT PRIMAIRE ESCOMPTÉ: L'observation de variations entre les deux groupes au plan de la mesure de DFGe faite avant la répartition aléatoire et celle faite douze mois après. RÉSULTATS SECONDAIRES: Des variations dans la concentration plasmatique de copeptine, le ratio albumine-créatinine sur une période de 24 heures, la clairance de la créatinine, l'estimation du risque d'insuffisance rénale sur cinq (5) ans (en utilisant l'équation du risque d'insuffisance rénale à quatre variables) et la qualité de vie reliée à l'état de santé. ANALYSE PRÉVUE: L'analyse primaire suivra une approche d'analyse en intention de traiter. Les variations du DFGe entre les deux groupes seront comparées par analyse de covariance. Des analyses subséquentes se pencheront sur les différentes manières de définir les changements observés dans les mesures du DFGe, soit le pourcentage de la variation annuelle, le taux de déclin et le déclin rapide pour lequel une valeur de p plus faible que 0,05 sera interprétée comme étant significative statistiquement si elle concorde avec le résultat primaire. ENREGISTREMENT DE L'ESSAI CLINIQUE: Cet essai contrôlé à répartition aléatoire a été enregistré sur www.clinicaltrials.gov et le code d'identification du gouvernement est le NCT01766687.

Consecutive first-morning urine samples to measure change in the albumin-to-creatinine ratio: a pilot study of a home urine collection protocol.

BACKGROUND: Multiple first-morning urine samples are recommended for measuring the urine albumin-to-creatinine ratio (ACR); however, this can be challenging in community-based research. METHODS: The objectives of the study are to pilot-test a home urine collection protocol and examine how the average and variance of ACR varied with the number of urine collections and time to laboratory analysis. This is a prospective observational pilot study. This study was conducted in London, Ontario, Canada at the London Health Sciences Centre (2012-2013). The patients were adults with chronic kidney disease (mean estimated glomerular filtration rate, 36 mL/min/1.73 m(2)). Participants collected a first-morning 20-mL urine sample on three consecutive days. This process was repeated after 3 months. Samples were picked up by hospital courier and analyzed for ACR on the same day; additional aliquots were analyzed after a delay of 24-48 h (stored at 4 °C) and 3-9 months (stored at -80 °C). The geometric mean of the percentage change in ACR between baseline and 3 months was calculated and compared between single samples and the average of two vs. three consecutive samples. RESULTS: Of 31 patients enrolled, 26 (83.9 %) submitted all six urine samples. The geometric mean of ACR for three consecutive samples at baseline was 87, 83, and 80 mg/mmol, and the corresponding percentage increase from baseline to 3 months was 15 % (95 % confidence interval (CI), -9 to 46 %), 33 % (95 % CI, 10 to 59 %), and 22 % (95 % CI, -6 to 57 %). Compared with single urine collections at baseline and follow-up, averaging ACR values from two consecutive first-morning urine samples improved the sample variance and reduced the required sample size to detect a given treatment effect by approximately 30 %. No further gain in statistical efficiency was achieved with three urine samples. Results were similar when the laboratory analysis was delayed by 24-48 h, but a delay of 3-9 months resulted in systematic overestimation of the ACR. Our study's generalizability is limited by its small sample size and reliance on a clinic-based population from a single urban center. CONCLUSIONS: We successfully used a home urine collection protocol to obtain multiple first-morning urine samples in patients with chronic kidney disease. Statistical efficiency was improved by averaging ACR values from two consecutive first-morning urine samples at baseline and follow-up.

MISE EN CONTEXTE: Le prélèvement de la première urine du matin est recommandé pour procéder à l'analyse du ratio albumine/créatinine (RAC) chez les patients atteints d'insuffisance rénale chronique (IRC). Toutefois, cette procédure représente un défi dans le domaine de la recherche communautaire. OBJECTIFS DE L'ÉTUDE: Cette étude constitue un essai pilote qui visait à établir un protocole normalisé pour la collecte d'échantillons d'urine chez les patients atteints d'IRC. Cet essai pilote avait également pour objectif de caractériser les variations dans les valeurs moyennes et les valeurs d'écart à la moyenne des RAC en fonction du nombre de prélèvements effectués et du moment où ceux-ci sont analysés en laboratoire. CADRE ET TYPE D'ÉTUDE: Il s'agit d'une étude pilote prospective réalisée par observation. L'étude s'est tenue au London Health Science Center de London en Ontario, au Canada en 2012 et 2013. MÉTHODE: Les participants, des adultes atteints d'IRC (débit de filtration glomérulaire moyen de 36 mL/min/1,73 m2), ont procédé au prélèvement de 20 mL de la première urine du matin durant trois jours consécutifs. La procédure a été répétée après trois mois. À chaque fois, les échantillons étaient cueillis par un messager envoyé par l'hôpital pour leur analyse du RAC le jour-même. De chacun des échantillons reçus, deux aliquots étaient prélevés pour analyse ultérieure: un premier était conservé à 4 °C pour analyse dans les 24 à 48 heures, et un deuxième était congelé à −80 °C pour analyse du RAC de 3 à 9 mois suivant le prélèvement. La moyenne géométrique des pourcentages de variation du RAC entre les valeurs mesurées le jour-même et les valeurs mesurées après 3 mois a été calculée, on l'a ensuite comparée avec le RAC des échantillons individuels avec les moyennes de RAC obtenues pour deux et trois échantillons consécutifs. RÉSULTATS: Des 31 patients inclus dans l'étude, 83,9 % (n = 26) ont fourni les six échantillons d'urine requis pour analyse. Les moyennes géométriques des RAC pour les échantillons prélevés sur trois jours consécutifs s'élevaient à 87,83 et 80 mg/mmol, et les pourcentages correspondants à la variation entre le RAC au jour 1 et le RAC après 3 mois étaient respectivement de 15 % (95 % IC : −9 % à 46 %), de 33 % (95 % IC : 10 % à 59 %), et de 22 % (95 % IC : −6 % à 57 %). En comparant les RAC des échantillons individuels au jour 1 et après 3 mois avec la moyenne des RAC de deux échantillons prélevés consécutivement, un accroissement de la variance a été observé. De plus, cette comparaison a également permis de conclure qu'il était possible de détecter un effet thérapeutique donné dans un échantillon jusqu'à 30 % moins volumineux. Aucun avantage sur le plan de l'efficacité statistique n'a été amené par l'analyse de trois prélèvements consécutifs. Enfin, les résultats d'analyse du RAC de 24 à 48 heures suivant l'arrivée des échantillons n'a offert que peu de variation en comparaison avec les valeurs obtenues au jour 1. Par contre, dans le cas des échantillons analysés après 3 à 9 mois ceux-ci ont systématiquement entraîné une surévaluation de la mesure du RAC. LIMITES DE L'ÉTUDE: La possibilité de généralisation de la présente étude est limitée par son faible échantillonnage et par le fait qu'elle s'appuie sur une population clinique provenant d'une seule agglomération urbaine. CONCLUSIONS: L'essai pilote mené dans le but d'établir un protocole normalisé permettant aux patients atteints d'IRC de prélever des échantillons d'urine du matin à la maison a été couronné de succès. De plus, les résultats montrent que d'utiliser les moyennes de RAC de deux échantillons prélevés consécutivement permet d'accroître l'efficacité statistique tant pour les échantillons analysés au jour 1 que lors du suivi après 3 mois.

Perioperative N-acetylcysteine to prevent renal dysfunction in high-risk patients undergoing cabg surgery: a randomized controlled trial.

CONTEXT: Renal dysfunction is a complication of coronary artery bypass graft (CABG) surgery performed with cardiopulmonary bypass (CPB) that is associated with increased morbidity and mortality. N-acetylcysteine, an antioxidant and vasodilator, counteracts renal ischemia and hypoxia. OBJECTIVE: To determine whether perioperative intravenous (IV) N-acetylcysteine preserves renal function in high-risk patients undergoing CABG surgery with CPB compared with placebo. DESIGN, SETTING, AND PATIENTS: Randomized, quadruple blind, placebo-controlled trial (October 2003-September 2004) in operating rooms and general intensive care units (ICUs) of 2 Ontario tertiary care centers. The 295 patients required elective or urgent CABG and had at least 1 of the following: preexisting renal dysfunction, at least 70 years old, diabetes mellitus, impaired left ventricular function, or undergoing concomitant valve or redo surgery. INTERVENTIONS: Patients received 4 (2 intraoperative and 2 postoperative) doses of IV N-acetylcysteine (600 mg) (n = 148) or placebo (n = 147) over 24 hours. MAIN OUTCOME MEASURES: The primary outcome was the proportion of patients developing postoperative renal dysfunction, defined by an increase in serum creatinine level greater than 0.5 mg/dL (44 micromol/L) or a 25% increase from baseline within the first 5 postoperative days. Secondary outcomes included postoperative interventions and complications, the requirement for renal replacement therapy (RRT), adverse events, hospital mortality, and ICU and hospital length of stay. RESULTS: There was no difference in the proportion of patients with postoperative renal dysfunction (29.7% vs 29.0%, P = .89; relative risk [RR], 1.03 [95% confidence interval {CI}, 0.72-1.46]) in the N-acetylcysteine and placebo groups, respectively. We noted nonsignificant differences in postoperative interventions and complications, the need for RRT (0.7% vs 2.1%; P = .37), total (6.1% vs 9.6%; P = .26) and serious adverse events, hospital mortality (3.4% vs 2.7%; P>.99), and ICU and hospital length of stay between the N-acetylcysteine and placebo groups. A post hoc subgroup analysis of patients (baseline creatinine level >1.4 mg/dL [120 micromol/L]) showed a nonsignificant trend toward fewer patients experiencing postoperative renal dysfunction in the N-acetylcysteine group compared with the placebo group (25.0% vs 37.1%; P = .29). CONCLUSIONS: N-acetylcysteine did not prevent postoperative renal dysfunction, interventions, complications, or mortality in high-risk patients undergoing CABG surgery with CPB. Further research is required to identify CABG patients at risk for postoperative renal events, valid markers of renal dysfunction, and to establish renal thresholds associated with important clinical outcomes.

Prevalence of risk factors predisposing to foot problems in patients on hemodialysis.

A disturbingly high prevalence of single or bilateral lower extremity amputations in our program prompted us to conduct a study to identify the prevalence of risk factors that predispose patients on hemodialysis (HD) to foot problems. The study consisted of a one-time assessment of subjects' risk for and actual prevalence of amputation. The sample consisted of 232 subjects--56% male, 44% female. Ages ranged from 21-91 years, mean age 65.1 and median age 69 years. The most common comorbidities were hypertension (75%), coronary artery disease (50%), diabetes (42.2%), hyperlipidemia (34.9%), and peripheral vascular disease (27.2%), which are all established risk factors for peripheral arterial occlusive disease. Twenty-one percent of subjects were current smokers; 28% were former smokers. Nearly 13.4% of subjects had undergone amputations ranging from single toes to bilateral above knee amputations. Only 31% of subjects had both bilateral palpable pedal pulses present. Neuropathy, as evidenced by the inability to feel the application of monofilaments to 10 sites on each foot or the presence of symptoms, was present in 74.6% of subjects. Only 2.6% of subjects demonstrated comprehensive self-care behaviors (SCBs). With respect to subjects' ability for self-care, 75% of subjects had adequate vision, 60% adequate dexterity, and 55% adequate flexibility to perform self-care. Study findings confirmed impressions that patients are at considerable risk for foot complications. Implications for nursing practice include regular foot assessment, education for self-care, and referral to specialists when required.

Effect of increased water intake on plasma copeptin in patients with chronic kidney disease: results from a pilot randomised controlled trial.

OBJECTIVES: Increased water intake may have a beneficial effect on the kidney through suppression of plasma vasopressin. We examined the effect of increased water intake on plasma copeptin (a marker of vasopressin) over 6 weeks in patients with chronic kidney disease. DESIGN: Secondary analysis of a randomised controlled parallel-group pilot trial. SETTING: Canada, 2012-2013. PARTICIPANTS: 28 patients with stage 3 chronic kidney disease randomised (2:1) to a hydration (n=17) or control group (n=11). INTERVENTION: The hydration group was coached to increase water intake by up to 1.5 L/day for 6 weeks. The control group was asked to maintain regular water intake. MEASURES AND OUTCOMES: Participants provided blood and 24 h urine samples at baseline and 6 weeks. Change in plasma copeptin was compared within and between study groups. RESULTS: Participants were 64% male with a mean age of 62 years and an estimated glomerular filtration rate of 40 mL/min/1.73 m(2). Between baseline and 6 weeks, 24 h urine volume increased by 0.7 L/day in the hydration group, rising from 2.3 to 3.0 L/day (p=0.01), while decreasing by 0.3 L/day among controls, from 2.0 to 1.7 L/day (p=0.07); between-group difference: 0.9 L/day (95% CI 0.37 to 1.46; p=0.002). In the hydration group, median copeptin decreased by 3.6 pmol/L, from 15.0 to 10.8 pmol/L (p=0.005), while remaining stable among controls at 19 pmol/L (p=0.76; p=0.19 for the between-group difference in median change); the between-group difference in mean change was 5.4 pmol/L (95% CI -1.2 to 12.0; p=0.11). CONCLUSIONS: Adults with stage 3 chronic kidney disease can be successfully randomised to drink approximately 1 L more per day than controls. This increased water intake caused a significant decrease in plasma copeptin concentration. Our larger 12-month trial will examine whether increased water intake can slow renal decline in patients with chronic kidney disease. TRIAL REGISTRATION NUMBER: NCT01753466.

The chronic kidney disease Water Intake Trial (WIT): results from the pilot randomised controlled trial.

BACKGROUND AND OBJECTIVES: Increased water intake may benefit kidney function. Prior to initiating a larger randomised controlled trial (RCT), we examined the safety and feasibility of asking adults with chronic kidney disease (CKD) to increase their water intake. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: Beginning in October 2012, we randomly assigned 29 adults with stage 3 CKD (estimated glomerular filtration rate (eGFR) 30-60 mL/min/1.73 m(2) and albuminuria) to one of the two groups of water intake: hydration (n=18) or standard (n=11). We asked the hydration group to increase their water intake by 1.0-1.5 L/day (in addition to usual intake, depending on sex and weight) for 6 weeks, while the control group carried on with their usual intake. Participants collected a 24 h urine sample at baseline and at 2 and 6 weeks after randomisation. Our primary outcome was the between-group difference in change in 24 h urine volume from baseline to 6 weeks. RESULTS: (63%)of participants were men, 81% were Caucasians and the average age was 61 years (SD 14 years). The average baseline eGFR was 40 mL/min/1.73 m(2) (SD 11 mL/min/1.73 m(2)); the median albumin to creatinine ratio was 19 mg/mmol (IQR 6-74 mg/mmol). Between baseline and 6-week follow-up, the hydration group's average 24 h urine volume increased by 0.7 L/day (from 2.3 to 3.0 L/day) and the control group's 24 h urine decreased by 0.3 L/day (from 2.0 to 1.7 L/day; between-group difference in change: 0.9 L/day (95% CI 0.4 to 1.5; p=0.002)). We found no significant changes in urine, serum osmolality or electrolyte concentrations, or eGFR. No serious adverse events or changes in quality of life were reported. CONCLUSIONS: A pilot RCT indicates adults with stage 3 CKD can successfully and safely increase water intake by up to 0.7 L/day in addition to usual fluid intake. TRIAL REGISTRATION REGISTERED WITH CLINICAL TRIALSGOVERNMENT IDENTIFIER: NCT01753466.

Performance of the creatinine-based and the cystatin C-based glomerular filtration rate (GFR) estimating equations in a heterogenous sample of patients referred for nuclear GFR testing.

Cystatin C may be a more accurate marker of the glomerular filtration rate (GFR) than creatinine. We evaluated the performance of the creatinine-based abbreviated modification of diet in renal disease (MDRD), the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, and 6 cystatin C-based equations in estimating GFR (eGFR) in a heterogeneous sample of patients. Measured GFR (mGFR) was obtained from the plasma clearance of 99mtechnetium Diethylenetriaminepentaacetic acid in 42 adult patients referred for nuclear GFR testing (January to March 2008). We evaluated the bias, precision, and accuracy of the abbreviated MDRD, CKD-EPI, Filler, Grubb, Hoek, Larsson, Le Bricon, and Rule eGFR equations. Participants had a mean mGFR of 70.9 mL/min/1.73 m2 (range: 22-125 mL/min/1.73 m2), a median age of 57 years (interquartile range: 45, 66), were 62% male, and were 38% liver transplant recipients. Correlation coefficients between eGFRs and mGFR ranged from 0.65 to 0.87 (each P<0.001). The cystatin C-based Hoek equation had the best overall performance with a low bias (-1.4 mL/min/1.73 m2), good precision (13.3 mL/min/1.73 m2), and greatest accuracy, with 93% of values within 30% of mGFR. Although the CKD-EPI equation had the lowest bias (-0.6 mL/min/1.73 m2), it had poor precision (20.7 mL/min/1.73 m2) and low accuracy, with only 69% of values within 30% of mGFR. The Hoek equation remained accurate and had the least bias when patients were grouped according to the history of liver transplantation and the mGFR above or below 60 mL/min/1.73 m2. In this heterogeneous sample, the cystatin C-based Hoek equation performed the best overall, regardless of mGFR level or history of liver transplantation.

Hemodialysis in a satellite unit: clinical performance target attainment and health-related quality of life.

BACKGROUND AND OBJECTIVES: In Canada, patients are increasingly receiving hemodialysis (HD) in satellite units, which are closer to their community but further from tertiary care hospitals and their nephrologists. The process of care is different in the satellites with fewer visits from nephrologists and reliance on remote communication. The objective of this study is to compare clinical performance target attainment and health-related quality of life (HRQOL) in patients receiving HD in satellite versus in-center units. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: The London Health Sciences Centre in London, Ontario, Canada, has both tertiary care center and satellite HD units. All eligible patients who received dialysis treatment at one of these units as of July 24, 2008, were enrolled into a cross-sectional study (n = 522). Patient attainment of hemoglobin, albumin, calcium-phosphate (Ca-P) product, Kt/V, and vascular access targets were compared. Participants were also administered the Kidney Disease Quality of Life Short-Form questionnaire. RESULTS: Satellite patients were more likely to attain clinical performance targets for albumin (adjusted odds ratio [OR] = 4.87 [95% confidence interval [CI]: 2.13 to 11.14]), hemoglobin (OR = 1.59 [95% CI: 1.08 to 2.35]), and Ca-P product (OR = 2.02 [95% CI: 1.14 to 3.60]), as well as for multiple targets (P < 0.05). HRQOL scores were largely similar between groups. CONCLUSIONS: Patients receiving HD in a satellite unit were just as likely, or more likely, to demonstrate attainment of clinical performance targets as those dialyzing in-center, while maintaining a similar HRQOL. This supports the increased use of satellite units to provide care closer to the patient's community.

Effect of N-acetylcysteine on renal function in patients with chronic kidney disease.

BACKGROUND: N-acetylcysteine (NAC) is commonly administered to high-risk individuals to attenuate the risk of contrast-induced nephropathy in spite of the debate regarding its efficacy. In several studies serum creatinine decreased after exposure to NAC and contrast dye. The mechanism by which NAC attenuates the decline in renal function is not known. Studies in subjects with normal renal function suggest NAC may have an effect on tubular secretion. AIM: The aim of this study was to determine the effect of NAC on renal function, measured by serum creatinine and Cystatin C, in patients with stage 3 chronic kidney disease. METHOD: Serum creatinine and Cystatin C were measured prior to, 4, 24 and 48 h after the administration of 600 mg oral NAC in 30 patients. The protocol was repeated with the addition of 1200 mg oral cimetidine administered 3 h before NAC. RESULTS: Serum creatinine was not significantly different from baseline (186 +/- 65 micromol/L) to 4 h (185 +/- 62 micromol/L), 24 h (187 +/- 64 micromol/L) or 48 h (184 +/- 61 micromol/L) post NAC, nor were Cystatin C levels. Co-administration of cimetidine resulted in a significant rise in serum creatinine with no change in Cystatin C levels. CONCLUSION: This study failed to detect a change in serum creatinine or Cystatin C after a single dose of NAC in participants with stage 3 chronic kidney disease. Further randomized trials of multiple doses and longer follow up are needed to confirm these results.

Erythropoietin dose requirements when converting from subcutaneous to intravenous administration among patients on hemodialysis.

BACKGROUND: The optimal route for administration of exogenous erythropoietin remains controversial, particularly after the increased incidence in pure red cell aplasia. In Canada, the majority of hemodialysis units have converted to the intravenous route for administration of erythropoietin to potentially decrease the risk of pure red cell aplasia. OBJECTIVE: To compare the difference in the weight-adjusted, weekly erythropoietin dose (units/kg/wk) administered by the subcutaneous compared with the intravenous route in a chronic hemodialysis population followed for 12 months. METHODS: This prospective cohort study recruited patients receiving subcutaneous erythropoietin for at least 3 months while undergoing dialysis in a tertiary care hemodialysis program. Participants were switched to intravenous erythropoietin, and the average weekly dose was recorded at 1, 2, 3, 6, and 12 months. Anemia management and hemoglobin, iron, and delivered dialysis dose targets remained constant throughout the study. RESULTS: The erythropoietin dose increased by 24.5 units/kg/wk (95% CI 12.7 to 36.3; p < 0.001), representing a 20.2% increase (95% CI 10.5% to 29.9%; p < 0.001) 12 months after conversion from the subcutaneous to intravenous route of administration. Both patients with and without residual renal function at baseline required a significant increase in the intravenous dose. CONCLUSIONS: A 20.2% increase in erythropoietin dose was required to maintain hemoglobin targets between 11 and 12 g/dL after conversion from a subcutaneous to intravenous formulation. Healthcare funding agencies need to reexamine the cost benefit of using intravenous erythropoietin in the hemodialysis population with a low incidence of pure red cell aplasia.