Transfusion Management of Incident Dialysis Patients in Canada: A Prospective Observational Study.

BACKGROUND: Several studies have demonstrated harm associated with using erythropoiesis-stimulating agents (ESA) to achieve higher hemoglobin (Hb) levels. Subsequently, more conservative use of ESAs has changed anemia therapy in patients with chronic renal failure. OBJECTIVE: The objectives were to identify transfusion rates in hemodialysis (HD) patients during the first year of therapy, to identify factors associated with the probability of transfusion, describe reasons for the transfusions, and identify the Hb values associated with each transfusion. An exploratory objective was to describe the age of red blood cell transfusions. DESIGN: This was a multicenter prospective observational cohort study. SETTING: There were 12 study sites in 5 Canadian provinces. The study was performed from 2012 to 2014. METHODS: The study patients were adult incident chronic HD patients in these centers. Patients with acute kidney injury, peritoneal dialysis, and planned transfer to satellite units were excluded. Patients had to receive at least 1 month of chronic HD to be eligible. Data for 3 months prior to HD were obtained by retrospective chart review. Prospectively, charts were reviewed monthly for 12 months for data abstraction. RESULTS: There were 314 patients enrolled and 79.9% completed 12 month follow-up. Ninety-four (29.9%) patients received at least 1 unit of blood. During the first 90 days, the transfusion episode rate was 148.4 per 100 patient-years compared with 62.6 per 100 patient-years post 90 days. The most frequent indication was a low Hb value (92%) with gastrointestinal bleeding, surgical blood loss, and fatigue accounting for 9.9%, 8.6%, and 4.5%, respectively. Some patients had >1 indication. The mean Hb values prior to transfusion episodes ranged from 75.3 to 78.6 g/L. Cox regression analysis on time to first transfusion and time to first hospitalization/death both showed an association with inpatient initiation of HD. Some 37.5% initiated HD as an inpatient and differed from those starting as an outpatient. They had less predialysis care and laboratory data suggested more inflammation. The mean and median ages of the blood units transfused were 24.9 (SD = 10.0) and 23 days (interquartile range = 17-33). CONCLUSIONS: This work reported the blood transfusion rate in incident HD patients in Canada during a period associated with conservative ESA prescription. The major indication for transfusion was a low Hb rather than clinical symptoms. Initiation of HD as an inpatient was independently associated with the probability of receiving a blood transfusion. These findings require further investigation.

CONTEXTE: Plusieurs études ont fait état de lésions associées à l'utilisation d'agents stimulant l'érythropoïèse (ASE) pour hausser le taux d'hémoglobine (Hb). Dès lors, une utilisation plus conservatrice des ASE a modifié le traitement de l'anémie chez les patients atteints d'insuffisance rénale chronique. OBJECTIFS DE L'ÉTUDE: L'étude visait à i) établir les taux de transfusion sanguine chez les patients hémodialysés au cours de la première année de traitement; ii) cerner les facteurs associés à la probabilité de recourir à une transfusion sanguine; iii) connaître les raisons de la transfusion; et iv) caractériser le taux d'hémoglobine au moment de l'intervention. En outre, un objectif exploratoire consistait à déterminer l'âge des érythrocytes transfusés. TYPE D'ÉTUDE: Il s'agit d'une étude de cohorte observationnelle prospective multicentrique. CADRE DE L'ÉTUDE: L'étude s'est tenue entre 2012 et 2014 sur douze sites répartis dans cinq provinces canadiennes. MÉTHODOLOGIE: Les patients adultes hémodialysés des centres participants ont été recrutés pour l'étude. Ont été exclus les patients atteints d'insuffisance rénale aiguë, les patients traités par dialyse péritonéale et les patients à être transférés vers une unité satellite. Pour être admissible, le patient devait recevoir un traitement d'hémodialyse continu pendant au moins un mois. On a rétrospectivement tiré des dossiers médicaux les données des trois mois précédant l'hémodialyse, puis on a extrait les données des dossiers médicaux chaque mois sur un an. RÉSULTATS: Un total de 314 patients a participé à l'étude et 79,9 % d'entre eux ont complété les 12 mois de suivi. Sur cette période, 94 patients (29,9 %) ont reçu au moins une transfusion sanguine. Au cours des 90 premiers jours, le taux d'épisodes transfusionnels était de 148,4 pour 100 années-patients, comparativement à 62,6 pour 100 années-patients pour le reste de l'étude. La raison la plus fréquente de recourir à une transfusion était un faible taux d'Hb (92 % des cas); les cas de saignements gastro-intestinaux, de perte de sang périchirurgicale et de fatigue comptaient quant à eux pour 9,9 %, 8,6 % et 4,5 % respectivement. Certains patients cumulant plus d'une indication. Le taux d'Hb moyen prétransfusion variait de 75,3 à 78,6 g/L. Une analyse de régression de Cox sur le temps écoulé jusqu'à la première transfusion et jusqu'à la première hospitalisation (ou le décès) du patient a montré une corrélation avec l'initiation d'un traitement d'hémodialyse chez les patients hospitalisés. Les sujets qui avaient initié leur traitement d'hémodialyse alors qu'ils étaient hospitalisés (37,5 %) ont reçu moins de soins prédialyse et présentaient davantage d'inflammation que les sujets qui avaient commencé leurs traitements d'hémodialyse en tant que patient externe. Enfin, l'âge moyen et l'âge médian des érythrocytes transfusés étaient de 24,9 jours (ÉT : 10,0) et de 23 jours (EIQ : 17 à 23). CONCLUSION: Notre étude a permis de connaître le taux de transfusions sanguines dans une population de patients hémodialysés canadiens au cours d'une période correspondant à une prescription conservatrice d'ASE. On a observé que la principale raison de transfusion était un faible taux d'Hb et non des symptômes cliniques. Enfin, une hémodialyse amorcée en cours d'hospitalisation a été associée à une probabilité accrue de transfusion sanguine. Nos constatations devraient faire l'objet d'études plus approfondies.

Ferric pyrophosphate citrate (Triferic™) administration via the dialysate maintains hemoglobin and iron balance in chronic hemodialysis patients.

BACKGROUND: Administration of ferric pyrophosphate citrate (FPC, Triferic™) via hemodialysate may allow replacement of ongoing uremic and hemodialysis-related iron losses. FPC donates iron directly to transferrin, bypassing the reticuloendothelial system and avoiding iron sequestration. METHODS: Two identical Phase 3, randomized, placebo-controlled trials (CRUISE 1 and 2) were conducted in 599 iron-replete chronic hemodialysis patients. Patients were dialyzed with dialysate containing 2 µM FPC-iron or standard dialysate (placebo) for up to 48 weeks. Oral or intravenous iron supplementation was prohibited, and doses of erythropoiesis-stimulating agents were held constant. The primary efficacy end point was the change in hemoglobin (Hgb) concentration from baseline to end of treatment (EoT). Secondary end points included reticulocyte hemoglobin content (CHr) and serum ferritin. RESULTS: In both trials, Hgb concentration was maintained from baseline to EoT in the FPC group but decreased by 0.4 g/dL in the placebo group (P < 0.001, combined results; 95% confidence interval [CI] 0.2-0.6). Placebo treatment resulted in significantly larger mean decreases from baseline in CHr (-0.9 pg versus -0.4 pg, P < 0.001) and serum ferritin (-133.1 µg/L versus -69.7 µg/L, P < 0.001) than FPC treatment. The proportions of patients with adverse and serious adverse events were similar in both treatment groups. CONCLUSIONS: FPC delivered via dialysate during hemodialysis replaces iron losses, maintains Hgb concentrations, does not increase iron stores and exhibits a safety profile similar to placebo. FPC administered by hemodialysis via dialysate represents a paradigm shift in delivering maintenance iron therapy to hemodialysis patients.

Efficacy of cinacalcet with low-dose vitamin D in incident haemodialysis subjects with secondary hyperparathyroidism.

BACKGROUND: Treatment with cinacalcet improves the control of secondary hyperparathyroidism (SHPT) and the achievement of calcium and phosphorus targets. Most data come from subjects receiving cinacalcet after several years of dialysis treatment. We therefore compared the efficacy of treatment with cinacalcet and low doses of active vitamin D to flexible doses of active vitamin D alone for the management of SHPT in patients recently initiating haemodialysis. METHODS: This open-label trial randomized subjects (n = 309) with parathyroid hormone (PTH) >300 pg/mL on dialysis for 3-12 months to either cinacalcet with low-dose active vitamin D, if prescribed (cinacalcet); or usual care without cinacalcet (control). Randomized subjects were stratified by PTH at screening (300-450, >450-600, >600 pg/mL) and by the use of active vitamin D at enrolment. Treatment duration was 12 months, with primary efficacy endpoint (mean PTH reduction ≥ 30% from baseline) assessed at 6 months. RESULTS: The mean [standard deviation (SD)] haemodialysis vintage at enrolment was 7.2 (2.7) months; 53% of subjects were not receiving active vitamin D at enrolment. There was a significant difference in the achievement of the primary endpoint (≥ 30% PTH reduction at 6 months) between cinacalcet-treated subjects and controls in both the entire cohort (63 versus 38%; n = 304; P < 0.0001) and the subgroup of subjects not receiving active vitamin D at enrolment (70 versus 44%; n = 161; P < 0.01). Hypocalcaemia and gastrointestinal adverse events were more commonly observed in cinacalcet-treated subjects. CONCLUSIONS: These results indicate that cinacalcet with low-dose active vitamin D, if prescribed, provides a more effective treatment approach than usual care without cinacalcet for SHPT in incident haemodialysis patients, even in relatively treatment-naive patients.

Interprovincial differences in the achievement of K/DOQI targets of mineral metabolism in Canada.

BACKGROUND: Abnormalities in mineral metabolism in chronic kidney disease are associated with increased morbidity and mortality. The Kidney Disease Outcomes Quality Initiative (K/DOQI) clinical practice guidelines were established in 2003 to address issues in the management of mineral and bone metabolism. The goal of this study was to compare (i) mineral metabolism control among Canadian haemodialysis (HD) patients with K/DOQI-defined targets and Dialysis Outcomes and Practice Patterns Study II (DOPPS II) data and (ii) the effect of different treatment strategies. METHODS: A cross-sectional study of 2215 HD patients was conducted. Phosphorus (P), calcium (Ca), intact parathyroid hormone (iPTH) and calcium-phosphate product (CaXP) were analysed. In addition, management was compared between provinces with more or less restricted access to the phosphate binder sevelamer. RESULTS: K/DOQI targets for P, Ca, iPTH and CaXP K/DOQI targets were met by 59.7%, 58.6%, 29.7% and 83.3%, respectively. A greater proportion of patients were within target compared with those in DOPPS II (2002-2004). Targets were more likely to be reached by patients residing in provinces with formularies allowing less restricted access to sevelamer: P: 61.8% vs 55.7% (P = 0.01); CaXP: 85.5% vs 79.1% (P = 0.0006). As expected, patients in provinces with more restrictive formularies were more often receiving doses of elemental calcium > 1.5 g/day than those with more open listings (62.1% vs 14.0%, P < 0.0001) and were less likely to receive sevelamer (14.1% vs 42.4%, P = 0.0001). CONCLUSION: Mineral metabolism parameters were more frequently within the target range amongst (i) patients in the current study compared with those in the DOPPS II era and (ii) patients in provinces with less restricted access to sevelamer.