Impact of Bioelectrical Impedance-Guided Fluid Management and Vitamin D Supplementation on Left Ventricular Mass in Patients Receiving Peritoneal Dialysis: A Randomized Controlled Trial.

RATIONALE & OBJECTIVE: Hypervolemia and vitamin D deficiency occur frequently in patients receiving peritoneal dialysis and may contribute to left ventricular (LV) hypertrophy. The effect of bioelectrical impedance analysis (BIA)-guided volume management or vitamin D supplementation on LV mass among those receiving peritoneal dialysis is uncertain. STUDY DESIGN: Two-by-two factorial randomized controlled trial. SETTING & PARTICIPANTS: Sixty-five patients receiving maintenance peritoneal dialysis. INTERVENTION: BIA-guided volume management versus usual care and oral cholecalciferol 50,000 U weekly for 8 weeks followed by 10,000 U weekly for 44 weeks or matching placebo. OUTCOME: Change in LV mass at 1 year measured by cardiac magnetic resonance imaging. RESULTS: Total body water decreased by 0.9 + 2.4 (SD) L in the BIA group compared with a 1.5 ± 3.4 L increase in the usual care group (adjusted between-group difference: -2.4 [95% CI, -4.1 to -0.68] L, P = 0.01). LV mass increased by 1.3 ± 14.3 g in the BIA group and decreased by 2.4 ± 37.7 g in the usual care group (between-group difference: +2.2 [95% CI, -13.9 to 18.3] g, P = 0.8). Serum 25-hydroxyvitamin D concentration increased by a mean of 17.2 ± 30.8 nmol/L in the cholecalciferol group and declined by 8.2 ± 24.3 nmol/L in the placebo group (between-group difference: 28.3 [95% CI, 17.2-39.4] nmol/L, P < 0.001). LV mass decreased by 3.0 ± 28.1 g in the cholecalciferol group and increased by 2.0 ± 31.2 g in the placebo group (between-group difference: -4.5 [95% CI, -20.4 to 11.5] g, P = 0.6). LIMITATIONS: Relatively small sample size with larger than expected variation in change in LV mass. CONCLUSIONS: BIA-guided volume management had a modest impact on volume status with no effect on the change in LV mass. Vitamin D supplementation increased serum vitamin D concentration but had no effect on LV mass. FUNDING: Unrestricted Baxter International extramural grant and the Kidney Foundation of Canada. TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT01045980.

Combined preoperative plasma exchange and red blood cell exchange transfusion in a renal transplant patient with protein S deficiency and hemoglobin SC disease.

BACKGROUND: Protein S deficiency is associated with increased risk of venous thromboembolism, complicating the perioperative management of such patients. We present a patient with sickle cell disease (Hb SC genotype) and inherited protein S deficiency who underwent a living-donor renal transplant. To minimize thrombotic risk and sickle cell complications, both plasma exchange and red blood cell (RBC) exchange transfusion were performed pre-operatively. METHODS AND MATERIALS: Plasma exchange was utilized to increase protein S levels and to reduce the risk of post-operative venous thromboembolism, including allograft thrombosis, while RBC exchange was performed to reduce the risk of acute post-operative sickle cell disease complications. RESULTS: With the use of combined pre-operative plasma exchange and RBC exchange transfusion, this patient with protein S deficiency and Hb SC underwent a successful renal transplant without acute sickle cell complications or thrombotic complications. CONCLUSIONS: This case demonstrates the potential use of pre-operative plasma exchange in patients with protein S deficiency undergoing high thrombotic risk procedures.

Circulating heparin-like anticoagulants: Case report and review of literature.

We report a case of a 56-year-old woman with a history of idiopathic thrombocytopenic purpura (ITP) following splenectomy on mycophenolate mofetil (MMF), who developed moderate bleeding after stopping MMF. Her laboratory testing suggested the presence of an abnormal circulating heparin-like anticoagulant with demonstrable anti-Xa activity. She was initially treated with antifibrinolytic therapy and was subsequently started on MMF alongside intravenous immunoglobulin, which significantly improved her bleeding symptoms. The presence of abnormal circulating heparin-like anticoagulants is a rare cause of coagulopathy. Few cases exist in the literature, with nearly all occurring in the setting of hematologic or solid-organ malignancy. The mechanism by which these endogenous anticoagulants develop is unclear. Clinical manifestations range from mild bleeding and bruising to life-threatening hemorrhage refractory to conventional therapy. Diagnosis of a heparin-like anticoagulant is based on coagulation testing as well as exclusion of other exogenous anticoagulants, acquired inhibitors, and/or factor deficiencies.

Using bioimpedance analysis to assess intensive care unit patients with sepsis in the post-resuscitation period: a prospective multicentre observational study.

PURPOSE: Clinicians lack well-validated, non-invasive, objective tools to guide volume management in the post-resuscitative period. Bioimpedance analysis (BIA) represents a novel method for guiding fluid management. We studied the relationship of BIA vector length (VL), an indicator of volume status, to the need for mechanical ventilation in patients with sepsis. METHODS: This is a multicentre prospective observational study at four Canadian ICUs. We examined adult patients admitted to the ICU within 72 hr of a sepsis diagnosis. Patients underwent daily BIA measurements for 30 days, until discharge from the ICU, or until death. Our primary outcome was the ongoing need for invasive mechanical ventilation, and we examined the association with VL using a generalized estimating equation. Our secondary analyses were targeted to determine an association between VL and other measures of volume status and acute kidney injury (AKI). RESULTS: We enrolled 159 patients from four centres over 27 months. The mean (standard deviation [SD]) age was 64 (15) yr with a mean (SD) APACHE (acute physiology, age, chronic health evaluation) II score of 25 (10); 57% (n = 91) were male. A 50-unit (ohm·m) increase in VL over any time period was associated with a 30% decrease in the probability of requiring invasive mechanical ventilation (P < 0.03). Volume expansion, indicated by a shorter VL, correlated with higher edema scores (r = - 0.31; P < 0.001) and higher net 24-hr fluid balance (r = - 0.27, P < 0.001). Patients with AKI had a shorter overall VL (r = - 0.23; P = 0.003). CONCLUSIONS: An increase in VL over time is associated with a decrease in probability of requiring invasive mechanical ventilation. Vector length correlates with other commonly used volume assessment methods in post-resuscitation patients with sepsis.

WNT signaling is required for peritoneal membrane angiogenesis.

The wingless-type mouse mammary tumor virus integration site family (WNT) signaling pathway is involved in wound healing and fibrosis. We evaluated the WNT signaling pathway in peritoneal membrane injury. We assessed WNT1 protein expression in the peritoneal effluents of 54 stable peritoneal dialysis (PD) patients and WNT-related gene expression in ex vivo mesothelial cell cultures from 21 PD patients. In a transforming growth factor-ß (TGF-ß)-mediated animal model of peritoneal fibrosis, we evaluated regulation of the WNT pathway and the effect of WNT inhibition on peritoneal fibrosis and angiogenesis. WNT1 and WNT2 gene expression were positively correlated with peritoneal membrane solute transport in PD patients. In the mouse peritoneum, TGF-ß-induced peritoneal fibrosis was associated with increased expression of WNT2 and WNT4. Peritoneal ß-catenin protein was significantly upregulated after infection with adenovirus expressing TGF-ß (AdTGF-ß) along with elements of the WNT signaling pathway. Treatment with a ß-catenin inhibitor (ICG-001) in mice with AdTGF-ß-induced peritoneal fibrosis resulted in attenuation of peritoneal angiogenesis and reduced vascular endothelial growth factor. Similar results were also observed with the WNT antagonist Dickkopf-related protein (DKK)-1. In addition to this, DKK-1 blocked epithelial-mesenchymal transition and increased levels of the cell adhesion protein E-cadherin. We provide evidence that WNT signaling is active in the setting of experimental peritoneal fibrosis and WNT1 correlates with patient peritoneal membrane solute transport in PD patients. Intervention in this pathway is a possible therapy for peritoneal membrane injury.

Study of Cardiovascular Outcomes in Renal Transplantation: A Prospective, Multicenter Study to Determine the Incidence of Cardiovascular Events in Renal Transplant Recipients in Ontario, Canada.

BACKGROUND: Renal transplant recipients (RTRs) are at significantly higher risk for morbidity and mortality compared with the general population, largely attributed to cardiovascular disease (CVD). Previous estimates of CVD events have come from health care databases and retrospective studies. OBJECTIVE: The objective of this study was to prospectively determine the prevalence of risk factors and incidence of CVD events in a Canadian cohort of RTRs. DESIGN: Study of Cardiovascular Outcomes in Renal Transplantation (SCORe) was a prospective, longitudinal, multicenter observational study. SETTING: Adult RTRs were recruited from 6 participating transplant sites in Ontario, Canada. PATIENTS: Eligible patients were those receiving a living or deceased donor renal transplant. Patients who received simultaneous transplant of any other organ were excluded. MEASUREMENTS: Primary outcomes included myocardial infarction (MI) defined by American College of Cardiology (ACC-MI) criteria, and major adverse cardiac events (MACE), defined as cardiovascular (CV) death, ACC-MI, coronary revascularization, and nonhemorrhagic stroke. CV events were adjudicated by a single, independent cardiologist. METHODS: CV and transplant-specific risk factors that predict MACE and ACC-MI were identified by stepwise regression analysis using the Cox proportional hazards model. RESULTS: A total of 1303 patients enrolled across 6 transplant centers were followed for 4.5 ± 1.6 years (mean ± SD). Incidence of MACE was 7.0%, with significant independent predictors/risk factors including age, diabetes, coronary revascularization, nonhemorrhagic stroke, and renal replacement therapy (RRT). ACC-MI incidence was 4.0%, with significant independent predictors/risk factors including age, coronary revascularization, and duration of RRT in excess of the median value (2.91 years). LIMITATIONS: Patients were recruited from a single province, so may not reflect the experience of RTRs in other areas of Canada. CONCLUSIONS: Using a prospective design and rigorous methodology, this study found that the incidence of CV events after renal transplantation was elevated relative to the general Canadian population and was comparable with that reported in patient registries, thus helping validate the utility of retrospective analysis in this field. SCORe highlights the importance of monitoring RTRs for traditional cardiac and transplant-specific CV risk factors to help prevent CV morbidity and mortality. Further research is needed to investigate a broader range of potential risk factors and their combined effects on incident CV events.

CONTEXTE: Les receveurs d'une greffe rénale présentent un risque significativement plus élevé de morbidité et de mortalité que l'ensemble de la population, ceci est en grande partie attribuable aux maladies cardiovasculaires. Les estimations antérieures du nombre d'événements cardiovasculaires proviennent des bases de données du système de santé et des résultats d'études rétrospectives. OBJECTIF DE L'ÉTUDE: L'étude visait à mesurer de manière prospective la prévalence des facteurs de risque et l'incidence des événements cardiovasculaires dans une cohorte de patients receveurs d'une greffe rénale au Canada. TYPE D'ÉTUDE: L'étude SCORe consistait en une étude observationnelle longitudinale menée de façon prospective au sein de plusieurs centres hospitaliers. CADRE DE L'ÉTUDE: Les patients adultes receveurs d'une greffe rénale ont été recrutés dans six hôpitaux de la province de l'Ontario, au Canada. PATIENTS: Les patients qui avaient reçu une greffe rénale provenant d'un donneur vivant ou décédé ont été inclus dans l'étude. Les patients qui avaient reçu une greffe simultanée de tout autre organe ont été exclus. MESURES: Les principaux critères retenus incluaient un infarctus du myocarde répondant aux critères établis par l'American College of Cardiology (ACC-MI), des événements cardiaques majeurs indésirables (MACE) tels que le décès d'origine cardiovasculaire, l'ACC-MI, la revascularisation coronarienne et l'AVC non hémorragique. Ces événements cardiovasculaires ont été constatés par un cardiologue indépendant. MÉTHODOLOGIE: Les facteurs de risque, cardiovasculaires ou spécifiques à la transplantation, qui permettent de prédire les MACE et l'ACC-MI ont été identifiés à l'aide du modèle de risques proportionnels de Cox pour l'analyse de régression en étapes. RÉSULTATS: Les 1 303 patients recrutés au sein des six centres hospitaliers ont été suivis sur une moyenne de 1,6 an (SD ± 4,5). L'incidence de MACE était de 7,0%, avec des indicateurs prévisionnels indépendants et des facteurs de risque significatifs incluant l'âge, le diabète, la revascularisation coronarienne, l'AVC non hémorragique et la thérapie de remplacement rénale. L'incidence d'ACC-MI était de 4,0%, avec des indicateurs prévisionnels indépendants et des facteurs de risque significatifs incluant l'âge, la revascularisation coronarienne et une durée pour la thérapie de remplacement rénal excédant la valeur médiane (2,91 ans). LIMITES DE L'ÉTUDE: Les patients ont été recrutés dans une seule province, les résultats sont susceptibles de ne pas être représentatifs de la situation des receveurs d'une greffe rénale ailleurs au Canada. CONCLUSIONS: Grâce à un plan d'étude prospectif et à une méthodologie rigoureuse, nous avons déterminé que l'incidence des événements cardiovasculaires chez les receveurs d'une greffe rénale a été plus élevée que dans la population canadienne en général. Nous avons également constaté qu'elle était comparable à l'incidence rapportée dans les registres de patients, ce qui vient confirmer l'utilité des études rétrospectives dans ce domaine. Les résultats obtenus lors de l'étude SCORe mettent en lumière l'importance de faire un suivi auprès des receveurs d'une greffe rénale afin de détecter les facteurs de risque cardiovasculaires ou spécifiques à l'intervention, et ainsi aider à prévenir la mortalité et la morbidité liées aux maladies cardiovasculaires. D'autres recherches sont nécessaires afin d'examiner un plus large éventail de facteurs de risques potentiels et leurs effets concomitants sur les événements cardiovasculaires.

Assessment of Postresuscitation Volume Status by Bioimpedance Analysis in Patients with Sepsis in the Intensive Care Unit: A Pilot Observational Study.

Background. Bioimpedance analysis (BIA) is a novel method of assessing a patient's volume status. Objective. We sought to determine the feasibility of using vector length (VL), derived from bioimpedance analysis (BIA), in the assessment of postresuscitation volume status in intensive care unit (ICU) patients with sepsis. Method. This was a prospective observational single-center study. Our primary outcome was feasibility. Secondary clinical outcomes included ventilator status and acute kidney injury. Proof of concept was sought by correlating baseline VL measurements with other known measures of volume status. Results. BIA was feasible to perform in the ICU. We screened 655 patients, identified 78 eligible patients, and approached 64 for consent. We enrolled 60 patients (consent rate of 93.8%) over 12 months. For each 50-unit increase in VL, there was an associated 22% increase in the probability of not requiring invasive mechanical ventilation (IMV) (p = 0.13). Baseline VL correlated with other measures of volume expansion including serum pro-BNP levels, peripheral edema, and central venous pressure (CVP). Conclusion. It is feasible to use BIA to predict postresuscitation volume status and patient-important outcomes in septic ICU patients. Trial Registration. This trial is registered with clinicaltrials.gov NCT01379404 registered on June 7, 2011.

Coronary artery calcification, cardiovascular events, and death: a prospective cohort study of incident patients on hemodialysis.

BACKGROUND: Coronary calcification in patients with end-stage renal disease (ESRD) is associated with an increased risk of cardiovascular outcomes and death from all causes. Previous evidence has been limited by short follow-up periods and inclusion of a heterogeneous cluster of events in the primary analyses. OBJECTIVE: To describe coronary calcification in patients incident to ESRD, and to identify whether calcification predicts vascular events or death. DESIGN: Prospective substudy of an inception cohort. SETTING: Tertiary care haemodialysis centre in Ontario (St Joseph's Healthcare Hamilton). PARTICIPANTS: Patients starting haemodialysis who were new to ESRD. MEASUREMENTS: At baseline, clinical characterization and spiral computed tomography (CT) to score coronary calcification by the Agatston-Janowitz 130 scoring method. A primary outcome composite of adjudicated stroke, myocardial infarction, or death. METHODS: We followed patients prospectively to identify the relationship between cardiac calcification and subsequent stroke, myocardial infarction, or death, using Cox regression. RESULTS: We recruited 248 patients in 3 centres to our main study, which required only biochemical markers. Of these 164 were at St Joseph's healthcare, and eligible to participate in the substudy; of these, 51 completed CT scanning (31 %). Median follow up was 26 months (Q1, Q3: 14, 34). The primary outcome occurred in 16 patients; 11 in the group above the median and 5 in the group below (p = 0.086). There were 26 primary outcomes in 16 patients; 20 (77 %) events in the group above the coronary calcification median and 6 (23 %) in the group below (p = 0.006). There were 10 deaths; 8 in the group above the median compared with 2 in the group below (p = 0.04). The hazard ratios for coronary calcification above, compared with below the median, for the primary outcome composite were 2.5 (95 % CI 0.87, 7.3; p = 0.09) and 1.7 (95 % CI 0.55, 5.4; p = 0.4), unadjusted and adjusted for age, respectively. For death, the hazard ratios were 4.6 (95 % CI 0.98, 21.96; p = 0.054) and 2.4 (95 % CI 0.45, 12.97; p = 0.3) respectively. LIMITATIONS: We were limited by a small sample size and a small number of events. CONCLUSIONS: Respondent burden is high for additional testing around the initiation of dialysis. High coronary calcification in patients new to ESRD has a tendency to predict cardiovascular outcomes and death, though effects are attenuated when adjusted for age.

CONTEXTE: La calcification de l'artère coronaire chez les patients atteints d'insuffisance rénale terminale (IRT) est associée à un risque accru de troubles cardiovasculaires et de mortalité, toutes causes confondues. Les données précédemment recueillies se limitaient à un suivi de courte durée, de même qu'à l'inclusion de séries d'accidents non liés lors de l'analyse préliminaire. OBJECTIFS: Décrire la calcification de l'artère coronaire chez les patients atteints d'IRT et déterminer si la calcification de l'artère coronaire peut prédire des accidents vasculaires et la mort. TYPE D'ÉTUDE: Sous-étude prospective de cohorte selon le mode d'installation. CADRE: Une unité de soins tertiaires en dialyse, en Ontario (St Joseph's Healthcare Hamilton). PARTICIPANTS: Des patients qui sont nouvellement atteints d'IRT et qui entament une hémodialyse. MESURES: En début de traitement, une caractérisation clinique et une tomodensitométrie (TDM) hélicoïdale qui permettent de mesurer la calcification de l'artère coronaire sur 130, selon l'échelle d'Agatston-Janowitz. L'indicateur principal des résultats comprend l'AVC, l'infarctus du myocarde ou la mort. MÉTHODES: Nous avons suivi les patients de manière prospective, afin de cibler la relation entre la calcification de l'artère coronaire et l'AVC, l'infarctus du myocarde ou la mort subséquente, en utilisant la régression de Cox. RÉSULTATS: Nous avons recruté 248 patients dans trois unités, dans le cadre de l'étude principale, qui ne requérait que des biomarqueurs chimiques. De ces patients, 164 étaient de St Joseph's Healthcare, et étaient admissibles à la sous-étude; 51 avaient effectué une tomographie par ordinateur (31 %). Le suivi médian s'étendait sur 26 mois (Q1, Q3: 14, 34). L'indicateur principal a été observé chez 16 patients; 11 dans le groupe se trouvant au-dessus de la médiane, et 5 dans le groupe inférieur (p?=?0,086). On a observé 26 indicateurs principaux chez 16 patients; 20 (77 %) accidents dans le groupe se trouvant au-dessus de la médiane en ce qui a trait à la calcification et 6 (23 %) dans le groupe inférieur (p?=?0,006). Il y a eu 10 décès; 8 dans le groupe se trouvant au-dessus de la médiane et 2 dans le groupe inférieur (p?=?0,04). Les taux de risque de calcification de l'artère coronaire se trouvant au-dessus et sous la médiane, pour les indicateurs principaux, étaient respectivement de 2,5 (95 % IC 0,98; 21,96; p?=?0,054) et 2,4 (95 % IC 0,45, 12,97; p?=?0,3). LIMITES DE L'ÉTUDE: Nous avons été limités par la taille restreinte de l'échantillon, de même que par le petit nombre d'accidents. CONCLUSION: Le fardeau du répondant repose sur des examens supplémentaires au moment de commencer la dialyse. Un fort taux de calcification de l'artère coronaire chez les patients nouvellement atteints d'IRT tend à prédire des accidents cardiovasculaires et la mort, bien que les effets soient atténués après révision en fonction de l'âge.

Gremlin promotes peritoneal membrane injury in an experimental mouse model and is associated with increased solute transport in peritoneal dialysis patients.

The peritoneal membrane becomes damaged in patients on peritoneal dialysis (PD). Gremlin 1 (GREM1) inhibits bone morphogenic proteins (BMPs) and plays a role in kidney development and fibrosis. We evaluated the role of gremlin in peritoneal fibrosis and angiogenesis. In a cohort of 32 stable PD patients, GREM1 concentration in the peritoneal effluent correlated with measures of peritoneal membrane damage. AdGrem1, an adenovirus to overexpress gremlin in the mouse peritoneum, induced submesothelial thickening, fibrosis, and angiogenesis in C57BL/6 mice, which was associated with decreased expression of BMP4 and BMP7. There was evidence of mesothelial cell transition to a mesenchymal phenotype with increased α smooth muscle actin expression and suppression of E-cadherin. Some of the GREM1 effects may be reversed with recombinant BMP7 or a pan-specific transforming growth factor ß (TGF-ß) antibody. Neovascularization was not inhibited with a TGF-ß antibody, suggesting a TGF-ß-independent angiogenic mechanism. Swiss/Jackson Laboratory (SJL) mice, which are resistant to TGF-ß-induced peritoneal fibrosis, responded in a similar fashion to AdGrem1 as did C57BL/6 mice with fibrosis, angiogenesis, and mesothelial-to-mesenchymal transition. GREM1 was associated with up-regulated TGF-ß expression in both SJL and C57BL/6 mice, but SJL mice demonstrated a defective TGF-ß-induced GREM1 expression. In summary, GREM1 induces fibrosis and angiogenesis in mouse peritoneum and is associated with increased solute transport in these PD patients.

Estimated GFR reporting influences recommendations for dialysis initiation.

Automated reporting of estimated GFR (eGFR) with serum creatinine measurement is now common. We surveyed nephrologists in four countries to determine whether eGFR reporting influences nephrologists' recommendations for dialysis initiation. Respondents were randomly allocated to receive a survey of four clinical vignettes that included either serum creatinine concentration only or serum creatinine and the corresponding eGFR. For each scenario, the respondent was asked to rank his or her likelihood of recommending dialysis initiation on a modified 8-point Likert scale, ranging from 1 ("definitely not") to 8 ("definitely would"). Analysis of the 822 eligible responses received showed that the predicted likelihood of recommending dialysis increased by 0.55 points when eGFR was reported (95% confidence interval, 0.33 to 0.76), and this effect was larger for eGFRs >5 ml/min per 1.73 m(2) (P<0.001). Subgroup analyses suggested that physicians who had been in practice ≥13 years were more affected by eGFR reporting (P=0.03). These results indicate that eGFR reporting modestly increases the likelihood that dialysis is recommended, and physicians should be aware of this effect when assessing patients with severe CKD.

Mercury-associated nephrotic syndrome: a case report and systematic review of the literature.

Kidney injury from mercury is known to cause dose-related tubular dysfunction and idiosyncratic nephrotic syndrome according to various case reports. Motivated by a patient with subacute-onset nephrotic syndrome, histologic features of secondary focal segmental glomerulosclerosis, and concurrent mercury toxicity, we conducted a systematic review to explore renal histologic changes in patients with toxic mercury exposures and nephrotic syndrome. Data were extracted from a patient's clinical record. MEDLINE/Ovid was searched from 1950 to November 2010 using a prespecified search strategy. Two nephrology textbooks and the UpToDate online database also were searched. Inclusion criteria were studies of humans with nephrotic syndrome, nephrotic-range proteinuria, or kidney biopsy results reported. There were no exclusion criteria. We identified 27 other reports of 42 patients with nephrotic syndrome or nephrotic-range proteinuria. Of the 26 individuals, including our patient, who underwent kidney biopsy, histology showed glomerular disease in 21. Of these 20 biopsies, 4 showed minimal change disease and 15 showed membranous glomerulonephritis. Mercury exposure can lead to various glomerular lesions; we emphasize the importance of a careful occupational and dietary history in elucidating a cause for the undetermined nephrotic syndrome.

The fluid study protocol: a randomized controlled study on the effects of bioimpedance analysis and vitamin D on left ventricular mass in peritoneal dialysis patients.

OBJECTIVES: We will evaluate the effects of bioimpedance analysis-guided fluid management to reduce volume expansion, of vitamin D(3) supplementation, and of the combination of those techniques on decrease of left ventricular mass in peritoneal dialysis (PD) patients. DESIGN: This multicenter randomized controlled trial, with a 2 × 2 factorial design, will be conducted at PD clinics affiliated with 3 Canadian teaching hospitals. Consenting PD patients 18 years of age or older will be included. Patients will be excluded if they have contraindications to bioimpedance or magnetic resonance imaging, life or technique expectancy of less than 1 year, peritonitis within the preceding 3 months, or serum calcium above 2.55 mmol/L. INTERVENTION: The study will randomize 70 patients to bio-impedance-guided volume management or to usual care and to vitamin D(3) 50,000 U weekly for 8 doses, and then 10,000 U weekly or to matching placebo. MAIN OUTCOME MEASURES: The primary outcome will be change in left ventricular mass at 1 year as determined by cardiac magnetic resonance imaging. The secondary outcome will be a composite endpoint of death, nonfatal cardiovascular event, and transfer to hemodialysis for dialysis inadequacy or ultrafiltration failure. Other outcome measures will include blood pressure, quality of life, 6-minute walk test, inflammatory and fibrotic markers and their association with peritoneal membrane transport properties, and residual renal function. Patients will be followed for clinical outcomes for up to 3 years. CONCLUSIONS: This study will assess whether bioimpedance-directed volume management and vitamin D(3) supplementation can improve left ventricular mass in PD patients.

Management of hypophosphatemia in nocturnal hemodialysis with phosphate-containing enema: a technical study.

Hypophosphatemia is observed in patients undergoing nocturnal hemodialysis. Phosphate is commonly added to the dialysate acid bath, but systematic evaluation of the safety and reliability of this strategy is lacking. The objectives of this study were 4-fold. First, we determined whether predictable final dialysate phosphate concentrations could be achieved by adding varying amounts of Fleet® enema. Second, we assessed the stability of calcium (Ca) and phosphate dialysate levels under simulated nocturnal hemodialysis conditions. Third, we assessed for Ca-phosphate precipitate. Finally, we evaluated whether dialysate containing Fleet® enema met the current sterility standards. We added serial aliquots of enema to 4.5 L of dialysate acid concentrate and proportioned the solution on Gambro and Althin/Baxter dialysis machines for up to 8 hours. We measured dialysate phosphate, Ca, pH, and bicarbonate concentrations at baseline, and after simulated dialysis at 4 and 8 hours. We evaluated for precipitation visually and by assessing optical density at 620 nm. We used inoculation of agar to detect bacteria and Pyrotell reaction for endotoxin. For every 30 mL of Fleet® (1.38 mmol/mL of phosphate) enema added, the dialysate phosphate concentration increased by 0.2 mmol/L. There were no significant changes in dialysate phosphate, Ca, pH, and bicarbonate concentrations over 8 hours. No precipitate was observed in the dialysate by optical density measures at 620 nm for additions of up to 90 mL of enema. Bacterial and endotoxin testing met sterility standards. The addition of Fleet® enema to dialysate increases phosphate concentration in a predictable manner, and no safety problems were observed in our in vitro studies.

Waist-to-Hip Ratio, Cardiovascular Outcomes, and Death in Peritoneal Dialysis Patients.

Objectives. The primary objective of this study was to determine the relationship between waist-to-hip ratio (WHR), cardiovascular (CV) events, and mortality in peritoneal dialysis (PD) patients. A secondary objective was to investigate the association between abdominal obesity and systemic inflammatory markers. Methods. This is a prospective study of 22 prevalent PD patients. WHR was measured at baseline. C-reactive protein (CRP), tumour necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured. Main outcomes were first CV event and death from all causes. Survival analysis was used to examine the relationship between anthropomorphic measures and clinical outcomes. Results. Mean follow-up period was 3.1 years. In Kaplan-Meier analysis, survival was lower in those with higher WHR (P = .002). In Cox regression, WHR independently predicted mortality and first CV event after adjustment for known ischemic heart disease (hazard ratio [HR] 1.17, confidence interval [CI] 1.05-1.30 for death; HR 1.13, CI 1.01-1.26 for CV event). WHR correlated with serum TNF-α (r = 0.45; P = .05). Conclusion. The results of this study suggest WHR may be a risk factor for increased CV events and mortality in PD patients. Abdominal obesity is also associated with inflammatory markers. Larger studies are warranted to confirm these findings.

Impact of haemoglobin and erythropoietin dose changes on mortality: a secondary analysis of results from a randomized anaemia management trial.

BACKGROUND: Anaemia is a common complication of chronic kidney disease. A number of studies have identified an adverse association between haemoglobin (Hgb) variability and mortality. To date, no study has evaluated the impact of Hgb variability on mortality in the setting of a uniform Hgb target and erythropoiesis-stimulating agents (ESA) dosing strategy. METHODS: One hundred and fifty-four haemodialysis (HD) patients from a previous randomized anaemia management study were followed up for up to 6 years. The impact of Hgb variability and ESA dosing parameters on subsequent mortality risk were evaluated. RESULTS: More rapid rises in Hgb (Hgb deflect(pos)) and ESA dose increases were independently associated with mortality in multivariate analysis, whereas more rapid Hgb declines (Hgb deflect(neg)) and ESA dose decreases were not. Each gram per litre per week increase in Hgb deflect(pos) was associated with an adjusted hazard ratio (HR) of 1.23 (1.03-1.48), while for every 1000-unit increase in ESA dose, the adjusted HR was 1.12 (1.01-1.24). Factors associated with positive Hgb deflections included frequency and magnitude of ESA dose changes, baseline Hgb, patient weight and presence of an HD catheter. CONCLUSIONS: Rapid Hgb rises and greater average Eprex dose increases were independently associated with a higher mortality risk in HD patients after adjustment for baseline Hgb and Eprex dose. A randomized controlled trial evaluating different ESA dosing strategies in response to individual patient ESA responsiveness is needed.

Association between markers of inflammation, fibrosis and hypervolemia in peritoneal dialysis patients.

BACKGROUND/AIM: Volume expansion in peritoneal dialysis (PD) patients is associated with left ventricular hypertrophy. The link between inflammation and hypervolemia has not been extensively studied. The aim of this study was to determine if an association exists between hypervolemia and markers of inflammation in PD patients. METHODS: In this cross-sectional study of 22 prevalent PD patients, volume was determined by bioelectrical impedance analysis. Serum and peritoneal effluent interleukin-6 (IL-6) and peritoneal transforming growth factor (TGF)-beta(1) were measured. A fast peritoneal equilibration test determined peritoneal transport status. RESULTS: Bioimpedance-derived measures of hypervolemia correlated with peritoneal effluent IL-6 and TGF-beta(1). Peritoneal IL-6 was also associated with high peritoneal transport status. CONCLUSIONS: Markers of inflammation and fibrosis (peritoneal IL-6 and TGF-beta(1)) are associated with markers of hypervolemia.

A systematic review and meta-analysis of hypoglycemia and cardiovascular events: a comparison of glyburide with other secretagogues and with insulin.

OBJECTIVE: Glyburide is the most widely used sulfonylurea but has unique pharmacodynamic properties that may increase harm. We hypothesized that glyburide causes more hypoglycemia and cardiovascular events than other secretagogues or insulin. RESEARCH DESIGN AND METHODS: Data sources were Medline, Embase, Cochrane, and three other web-based clinical trial registers (1966-2005). Parallel, randomized, controlled trials in people with type 2 diabetes comparing glyburide monotherapy with monotherapy using secretagogues or insulin were selected. Outcomes were hypoglycemia, glycemic control, cardiovascular events, body weight, and death. Titles and abstracts of 1,806 publications were reviewed in duplicate and 21 relevant articles identified. Data on patient characteristics, interventions, outcomes, and validity were extracted in duplicate using predefined criteria. RESULTS: Glyburide was associated with a 52% greater risk of experiencing at least one episode of hypoglycemia compared with other secretagogues (relative risk 1.52 [95% CI 1.21-1.92]) and with 83% greater risk compared with other sulfonylureas (1.83 [1.35-2.49]). Glyburide was not associated with an increased risk of cardiovascular events (0.84 [0.56-1.26]), death (0.87 [0.70-1.07]), or end-of-trial weight (weighted mean difference 1.69 kg [95% CI -0.41 to 3.80]) compared with other secretagogues. Limitations included suboptimal reporting of original trials. Loss to follow-up exceeded 20% in some studies, and major hypoglycemia was infrequently reported. CONCLUSIONS: Glyburide caused more hypoglycemia than other secretagogues and other sulfonylureas. Glyburide was not associated with an increased risk of cardiovascular events, death, or weight gain.