Osteoporotic fracture rates in chronic hemodialysis and effect of heparin exposure: a retrospective cohort study.

BACKGROUND: Patients receiving chronic hemodialysis treatments are at a higher risk of fracture compared to the general population. While the use of heparin during dialysis is crucial to avoid thrombosis of the extracorporeal circuit, the association of unfractionated heparin (UFH) and the risk of osteoporotic fracture has been shown for many years. However, this association was not as clear for low-molecular-weight heparin (LMWH) and the few collected data originated from studies among pregnant women. Our aim was to measure osteoporotic fracture rate among hemodialysis patients and to evaluate the association of LMWH compared to UFH in hemodialysis. METHODS: A retrospective cohort study was conducted on data extracted from the RAMQ and Med-Echo databases from January 2007 to March 2013 with patients chronically hemodialyzed in 21 participating centers. Incidence rates for each fracture sites were measured per 1000 patient-year (p-y) and their 95% confidence intervals (CI). Osteoporotic fracture risk for a first event with LMWH compared to UFH was estimated using a cox proportional hazard model using demographics, comorbidities and drug use as covariates. RESULTS: 4796 patients undergoing chronic hemodialysis were identified. The incidence rate for all fracture sites was 22.7 /1000 p-y (95% CI: 19.6-26.1) and 12.8 /1000 p-y (95% CI: 10.5-15.4) for hip and femur fractures. We found a similar risk of osteoporotic fracture for LMWH compared to UFH (adjusted HR = 1.01; 95%CI: 0.72-1.42). Age and malignancy increased the risk of fracture while cerebrovascular disease decreased the risk of fracture. CONCLUSIONS: Compared to UFH, LMWH did not change the risk of osteoporotic fracture when used for the extracorporeal circuit anticoagulation in chronic hemodialysis.

Association Between Low-Molecular-Weight Heparin and Risk of Bleeding Among Hemodialysis Patients: A Retrospective Cohort Study.

BACKGROUND: Low-molecular-weight heparins (LMWH) replaced unfractionated heparin (UFH) in multiple indications. Although LMWH efficacy in hemodialysis was demonstrated through multiple studies, their safety remains controversial. The potential bioaccumulation in patients undergoing chronic hemodialysis raised the question of bleeding risk among this population. OBJECTIVE: The aim of this study was to evaluate bleeding risk among patients with chronic hemodialysis receiving LMWH or UFH for the extracorporeal circuit anticoagulation. DESIGN: We conducted a retrospective cohort study on data extracted from the Régie de l'assurance maladie du Québec (RAMQ) and Med-Echo databases from January 2007 to March 2013. SETTING: Twenty-one hemodialysis centers in the province of Québec, Canada. PATIENTS: Chronic hemodialysis patients. MEASUREMENTS: Bleeding risk evaluated by proportional Cox model for time-dependent exposure using demographics, comorbidities, and drug use as covariates. METHODS: Minor, major, and total bleeding events identified using International Classification of Diseases, Ninth Revision (ICD-9)/International Classification of Diseases, Tenth Revision (ICD-10) codes in the RAMQ and Med-Echo databases. Exposure status to LMWH or UFH was collected through surveys at the facility level. RESULTS: We identified 5322 prevalent and incident patients with chronic hemodialysis. The incidence rate for minor, major, and total bleeding was 9.45 events/1000 patient-year (95% confidence interval [CI]: 7.61-11.03), 24.18 events/1000 patient-year (95% CI: 21.52-27.08), and 32.88 events/1000 patient-year (95% CI: 29.75-36.26), respectively. We found similar risks of minor adjusted hazard ratio (HR: 1.04; 95% CI: 0.68-1.61), major (HR: 0.83; 95% CI: 0.63-1.10), and total bleeding (HR: 0.90; 95% CI: 0.72-1.14) when comparing LMWH with UFH. LIMITATIONS: Potential misclassification of patients' exposure status and possible underestimation of minor bleeding risk. CONCLUSION: LMWH was not associated with a higher minor, major, or total bleeding risk. LMWH did not increase the risk of bleeding compared with UFH for the extracorporeal circuit anticoagulation in hemodialysis. The convenience of use and predictable effect made LMWH a suitable alternative to UFH in hemodialysis.

CONTEXTE: Les héparines de faible poids moléculaire (HFPM) ont remplacé les héparines non fractionnées (HNF) dans de multiples indications. Quoique l'efficacité des HFPM en hémodialyse ait été démontrée par un grand nombre d'études, leur innocuité demeure controversée; la possible bioaccumulation des HFPM chez les patients en hémodialyse chronique soulève le risque d'hémorragie au sein de cette population. OBJECTIF DE L'ÉTUDE: Cette étude visait à évaluer le risque d'hémorragie dans une cohorte de patients en hémodialyse chronique et traités par HFPM ou HNF comme anticoagulant pour le circuit extracorporel. TYPE D'ÉTUDE: Nous avons mené une étude de cohorte rétrospective sur les données de janvier 2007 à mars 2013, extraites des bases de données de la RAMQ et de Med-Echo. CADRE: Les données proviennent de 21 centres d'hémodialyse de la province de Québec (Canada). SUJETS: Patients en hémodialyse chronique. MESURES: Le risque d'hémorragie a été évalué par un modèle proportionnel de Cox pour l'exposition en fonction du temps et avec les covariables suivantes : données démographiques, comorbidités existantes et usage de médicaments. MÉTHODOLOGIE: Les épisodes d'hémorragie mineure, majeure et totale ont été colligés à l'aide des codes de la CIM-9 et de la CIM-10 dans les bases de données de la RAMQ et de Med-Echo. Des sondages menés dans les établissements ont permis de déterminer l'exposition aux HFPM ou aux HNF. RÉSULTATS: Nous avons retenu un total de 5 322 cas incidents et prévalents de patients en hémodialyse chronique pour l'étude. Les taux d'incidence pour les hémorragies mineures, majeures et totales étaient de 9,45 événements par 1 000 années-patients (IC 95 % : 7,61-11,03), de 24,18 événements par 1 000 années-patients (IC 95 % : 21,52-27,08) et de 32,88 événements par 1 000 années-patients (IC 95 % : 29,75-36,26) respectivement. Nous avons observé un risque comparable d'hémorragie mineure (rapport de risque corrigé : 1,04; IC 95 % : 0,68-1,61), majeure (rapport de risque corrigé : 0,83; IC 95 % : 0,63-1,10) et totale (rapport de risque corrigé : 0,90; IC 95 % : 0,72-1,14) lorsque nous avons comparé les HFPM aux HNF. LIMITES: Nos résultats sont limités par les probables erreurs dans le classement de l'exposition des patients aux héparines, de même que par une possible sous-évaluation des risques d'hémorragies mineures. CONCLUSION: Les HFPM n'ont pas été associées à un risque accru d'hémorragies mineures, majeures ou totales. De plus, lorsqu'elles ont été utilisées comme anticoagulant du circuit extracorporel en hémodialyse, les HFPM n'ont pas augmenté le risque d'hémorragie par rapport aux HNF. Ainsi, la commodité d'utilisation et l'effet prévisible des HFPM en font une solution de remplacement adéquate aux HNF en hémodialyse.

Safety of low-molecular-weight heparin compared to unfractionated heparin in hemodialysis: a systematic review and meta-analysis.

BACKGROUND: Low molecular weight heparins (LMWH) have been extensively studied and became the treatment of choice for several indications including pulmonary embolism. While their efficacy in hemodialysis is considered similar to unfractionated heparin (UFH), their safety remains controversial mainly due to a risk of bioaccumulation in patients with renal impairment. The aim of this systematic review was to evaluate the safety of LMWH when compared to UFH for extracorporeal circuit (ECC) anticoagulation. METHODS: We used Pubmed, Embase, Cochrane central register of controlled trials, Trip database and NICE to retrieve relevant studies with no language restriction. We looked for controlled experimental trials comparing LMWH to UFH for ECC anticoagulation among end-stage renal disease patients undergoing chronic hemodialysis. Studies were kept if they reported at least one of the following outcomes: bleeding, lipid profile, cardiovascular events, osteoporosis or heparin-induced thrombocytopenia. Two independent reviewers conducted studies selection, quality assessment and data extraction with discrepancies solved by a third reviewer. Relative risk and 95% CI was calculated for dichotomous outcomes and mean weighted difference (MWD) with 95% CI was used to pool continuous variables. RESULTS: Seventeen studies were selected as part of the systematic. The relative risk for total bleeding was 0.76 (95% CI 0.26-2.22). The WMD calculated for total cholesterol was -28.70 mg/dl (95% CI -51.43 to -5.98), a WMD for triglycerides of -55.57 mg/dl (95% CI -94.49 to -16.66) was estimated, and finally LDL-cholesterol had a WMD of -14.88 mg/dl (95% CI -36.27 to 6.51). CONCLUSIONS: LMWH showed to be at least as safe as UFH for ECC anticoagulation in chronic hemodialysis. The limited number of studies reporting on osteoporosis and HIT does not allow any conclusion for these outcomes. Larger studies are needed to evaluate properly the safety of LMWH in chronic hemodialysis.

Association of erythropoiesis-stimulating agents and the incidence risk of cancer diagnosis among chronic dialysis patients: a nested case-control study.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are the cornerstone of the treatment for anemia in end-stage renal disease (ESRD) patients. Although a correlation has been established between ESAs and increased tumor growth among patients with cancer-related anemia, an association with a higher incidence of cancer among chronic dialysis patients remains relatively unclear. METHODS: We completed a nested case-control study in a cohort of 4574 patients who began chronic dialysis treatment between 1 January 2001 and 31 December 2007 in Quebec, Canada, utilizing dialysis registry and administrative databases exclusively to extract our data. We excluded patients with a prior diagnosis of cancer. Eligible cases were identified by the time of initial cancer diagnosis obtained from either the hospital's discharge or physician billing form. We then randomly selected up to 10 controls for each case. ESA exposure was evaluated between 6 and 9 months prior to the initial cancer diagnosis. The mean weekly exposure was used to categorize ESA usage as either a low dose (<30 µg/week), moderate dose (30-70 µg/week) or high dose (>70 µg/week). We estimated the association between ESAs and the risk of developing cancer using a multivariable conditional logistic regression. RESULTS: We identified 419 cases of cancer and 3895 matched controls during the study period. The use of ESAs was associated with a higher risk of cancer {odds ratio [OR] 1.04 [95% confidence interval (CI) 1.02-1.07]}. Specifically, patients in the high exposure group (>70 µg/week) had an increased risk of developing cancer [OR 1.77 (95% CI 1.18-2.66)] compared with patients in the unexposed group. CONCLUSION: High-dose ESA was associated with an increased incidence risk of new cancer diagnosis among chronic dialysis patients.