Knowing a person's fracture risk according to their kidney function, gender, and age may influence clinical management and decision-making. Using healthcare databases from Ontario, Canada, we conducted a cohort study of 679,114 adults of 40 years and over (mean age 62 years) stratified at cohort entry by estimated glomerular filtration rate ((eGFR) 60 and over, 45-59, 30-44, 15-29, and under 15 ml/min per 1.73 m 2 ), gender, and age (40-65 and over 65 years). The primary outcome was the 3-year cumulative incidence of fracture (proportion of adults who fractured (hip, forearm, pelvis, or proximal humerus) at least once within 3-years of follow-up). Additional analyses examined the fracture incidence per 1000 person-years, hip fracture alone, stratification by prior fracture, stratification by eGFR and proteinuria, and 3-year cumulative incidence of falls with hospitalization. The 3-year cumulative incidence of fracture significantly increased in a graded manner in adults with a lower eGFR for both genders and both age groups. The 3-year cumulative incidence of fracture in women over 65 years of age across the 5 eGFR groups were 4.3%, 5.8%, 6.5%, 7.8%, and 9.6%, respectively. Corresponding estimates for men over 65 years were 1.6%, 2.0%, 2.7%, 3.8%, and 5.0%, respectively. Similar graded relationships were found for falls with hospitalization and additional analyses. Thus, many adults with chronic kidney disease will fall and fracture. Results can be used for prognostication and guidance of sample size requirements for fracture prevention trials.
Background and objectives The Fracture Risk Assessment Tool (FRAX) is widely used to predict the 10-year probability of fracture; however, the clinical utility of FRAX in CKD is unknown. This study assessed the predictive ability of FRAX in individuals with reduced kidney function compared with individuals with normal kidney function.Design, setting, participants, & measurements The discrimination and calibration (defined as the agreement between observed and predicted values) of FRAX were examined using data from the Canadian Multicentre Osteoporosis Study (CaMos). This study included individuals aged $40 years with an eGFR value at year 10 of CaMos (defined as baseline). The cohort was stratified by kidney function at baseline (eGFR,60 ml/min per 1.73 m 2 [72.2% stage 3a, 23.8% stage 3b, and 4.0% stage 4/5] versus $60 ml/min per 1.73 m 2 ) and followed individuals for a mean of 4.8 years for an incident major osteoporotic fracture (clinical spine, hip, forearm/wrist, or humerus).Results There were 320 individuals with an eGFR,60 ml/min per 1.73 m 2 and 1787 with an eGFR$60 ml/min per 1.73 m 2 . The mean age was 67610 years and 71% were women. The 5-year observed major osteoporotic fracture risk was 5.3% (95% confidence interval [95% CI], 3.3% to 8.6%) in individuals with an eGFR,60 ml/min per 1.73 m 2 , which was comparable to the FRAX-predicted fracture risk (6.4% with bone mineral density; 8.2% without bone mineral density). A statistically significant difference was not observed in the area under the curve values for FRAX in individuals with an eGFR,60 ml/min per 1.73 m 2 versus $60 ml/min per 1.73 m 2 (0.69 [95% CI, 0.54 to 0.83] versus 0.76 [95% CI, 0.70 to 0.82]; P=0.38).
There is poor consensus on the incidence and risk factors for fractures in kidney transplant recipients. Previous studies vary substantially in quality, fracture definitions, and the characteristics of recipients studied. Future research should clarify fracture incidence and risk, which will inform the design of future prevention trials and guide prognostication.
pared with never users. Cumulative use was not associated with increased odds of acute pancreatitis (P for trend among users = .49). Use of other antiarrhythmic drugs was not associated with acute pancreatitis (Table 2). Discussion | In this study of health care utilization data, use of amiodarone but not of other antiarrhythmic drugs was associated with a 50% increased odds of acute pancreatitis among patients with NVAF. The odds were almost doubled in the 12 months after amiodarone therapy initiation and did not depend on cumulative use of amiodarone. Considering an incidence of acute pancreatitis of 3 to 4 cases per 10 000 adults per year, 4 the observed association would result in approximately 1 to 2 additional cases of acute pancreatitis per 10 000 amiodarone users per year. A few isolated case reports of acute pancreatitis possibly linked to amiodarone use have been described in the literature. 1-3 The mechanisms responsible for this association are unknown, although direct cytotoxicity or immune-mediated pathways, as described for amiodarone-related pulmonary toxic effects, could be potential explanations. 5 Strengths of our study include the prospective assessment of medication use, the large sample size, and the availability of information on comorbidities and use of other medications potentially associated with increased risk of acute pancreatitis. Limitations are related to the use of health care utilization data: limited information on the validity of claims for acute pancreatitis, absence of clinical variables that characterize severity of the episode (eg, blood markers of acute pancreatitis), and the select group of patients included in this database. Our results indicate that acute pancreatitis could be an adverse effect of amiodarone use, an effect that may not be shared by other antiarrhythmic drugs. Even though the absolute risk of acute pancreatitis in the general population is low, health care professionals should be aware of this potential association in the treatment of patients with NVAF or acute pancreatitis. Further research should replicate our findings and determine potential mechanisms.
Despite transplant centers accepting recipients who are older with more comorbidities in recent years, the 3-year cumulative incidence of death or major cardiovascular event has remained stable over time.
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