Statin safety in chinese: A population-based study of older adults

Background Compared to Caucasians, Chinese achieve a higher blood concentration of statin for a given dose. It remains unknown whether this translates to increased risk of serious statinassociated adverse events amongst Chinese patients. Methods We conducted a population-based retrospective cohort study of older adults (mean age, 74 years) newly prescribed a statin in Ontario, Canada between 2002 and 2013, where 19,033 Chinese (assessed through a validated surname algorithm) were matched (1:3) by propensity score to 57,099 non-Chinese. This study used linked healthcare databases. Findings The follow-up observation period (mean 1.1, maximum 10.8 years) was similar between groups, as were the reasons for censoring the observation period (end of follow-up, death, or statin discontinuation). Forty-seven percent (47%) of Chinese were initiated on a higher than recommended statin dose. Compared to non-Chinese, Chinese ethnicity did not associate with any of the four serious statin-associated adverse events assessed in this study [rhabdomyolysis hazard ratio (HR) 0.61 (95% CI 0.28 to 1.34), incident diabetes HR 1.02 (95% CI 0.80 to 1.30), acute kidney injury HR 0.90 (95% CI 0.72 to 1.13), or all-cause mortality HR 0.88 (95% CI 0.74 to 1.05)]. Similar results were observed in subgroups defined by statin type and dose. Conclusions We observed no higher risk of serious statin toxicity in Chinese than matched non-Chinese older adults with similar indicators of baseline health. Regulatory agencies should review available data, including findings from our study, to decide if a change in their statin dosing recommendations for people of Chinese ethnicity is warranted

The risk of stroke and stroke type in patients with atrial fibrillation and chronic kidney disease

Background: Atrial fibrillation (AF) and chronic kidney disease (CKD) are known to increase the risk of stroke. Objectives: We set out to examine the risk of stroke by kidney function and albuminuria in patients with and without AF. Design: Retrospective cohort study. Settings: Ontario, Canada. Participants: A total of 736 666 individuals (>40 years) from 2002 to 2015. Measurements: New-onset AF, albumin-to-creatinine ratio (ACR), and an estimated glomerular filtration rate (eGFR). Methods: A total of 39 120 matched patients were examined for the risk of ischemic, hemorrhagic, or any stroke event, accounting for the competing risk of all-cause mortality. Interaction terms for combinations of ACR/eGFR and the outcome of stroke with and without AF were examined. Results: In a total of 4086 (5.2%) strokes (86% ischemic), the presence of AF was associated with a 2-fold higher risk for any stroke event and its subtypes of ischemic and hemorrhagic stroke. Across eGFR levels, the risk of stroke was 2-fold higher with the presence of AF except for low levels of eGFR (eGFR < 30 mL/min/1.73 m2, hazard ratio [HR]: 1.38, 95% confidence interval [CI]: 0.99-1.92). Similarly across ACR levels, the risk of stroke was 2-fold higher except for high levels of albuminuria (ACR > 30 mg/g, HR: 1.61, 95% CI: 1.31-1.99). The adjusted risk of stroke with AF differed by combinations of ACR and eGFR categories (interaction P value = .04) compared with those without AF. Both stroke types were more common in patients with AF, and ischemic stroke rates differed significantly by eGFR and ACR categories. Limitations: Medication information was not included. Conclusions: Patients with CKD and AF are at a high risk of total, ischemic, and hemorrhagic strokes; the risk is highest with lower eGFR and higher ACR and differs based on eGFR and the degree of ACR

Association between angiotensin converting enzyme inhibitor or angiotensin receptor blocker use prior to major elective surgery and the risk of acute dialysis

Background: Some studies but not others suggest angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) use prior to major surgery associates with a higher risk of postoperative acute kidney injury (AKI) and death. Methods: We conducted a large population-based retrospective cohort study of patients aged 66 years or older who received major elective surgery in 118 hospitals in Ontario, Canada from 1995 to 2010 (n = 237,208). We grouped the cohort into ACEi/ARB users (n = 101,494) and non-users (n = 135,714) according to whether the patient filled at least one prescription for an ACEi or ARB (or not) in the 120 days prior to surgery. Our study outcomes were acute kidney injury treated with dialysis (AKI-D) within 14 days of surgery and all-cause mortality within 90 days of surgery. Results: After adjusting for potential confounders, preoperative ACEi/ARB use versus non-use was associated with 17% lower risk of post-operative AKI-D (adjusted relative risk (RR): 0.83; 95% confidence interval (CI): 0.71 to 0.98) and 9% lower risk of all-cause mortality (adjusted RR: 0.91; 95% CI: 0.87 to 0.95). Propensity score matched analyses provided similar results. The association between ACEi/ARB and AKI-D was significantly modified by the presence of preoperative chronic kidney disease (CKD) (P value for interaction < 0.001) with the observed association evident only in patients with CKD (CKD - adjusted RR: 0.62; 95% CI: 0.50 to 0.78 versus No CKD: adjusted RR: 1.00; 95% CI: 0.81 to 1.24). Conclusions: In this cohort study, preoperative ACEi/ARB use versus non-use was associated with a lower risk of AKI-D, and the association was primarily evident in patients with CKD. Large, multi-centre randomized trials are needed to inform optimal ACEi/ARB use in the peri-operative setting

Patient Engagement in Kidney Research: Opportunities and Challenges Ahead

Purpose of Review: Patient engagement in research is increasingly recognized as an important component of the research process and may facilitate translation of research findings. To heighten awareness on this important topic, this review presents opportunities and challenges of patient engagement in research, drawing on specific examples from 4 areas of Canadian kidney research conducted by New Investigators in the Kidney Research Scientist Core Education and National Training (KRESCENT) Program. Sources of Information: Research expertise, published reports, peer-reviewed articles, and research funding body websites. Methods: In this review, the definition, purpose, and potential benefits of patient engagement in research are discussed. Approaches toward patient engagement that may help with translation and uptake of research findings into clinical practice are highlighted. Opportunities and challenges of patient engagement are presented in both basic science and clinical research with the following examples of kidney research: (1) precision care in focal and segmental glomerulosclerosis, (2) systems biology approaches to improve management of chronic kidney disease and enhance kidney graft survival, (3) reducing the incidence of suboptimal dialysis initiation, and (4) use of patient-reported outcome measures (PROMs) and patient-reported experience measures (PREMs) in kidney practice. Key Findings: Clinical research affords more obvious opportunities for patient engagement. The most obvious step at which to engage patients is in the setting of research priorities. Engagement at all stages of the research cycle may prove to be more challenging, and requires a detailed plan, along with funds and infrastructure to ensure that it is not merely tokenistic. Basic science research is several steps removed from the clinical application and involves complex scientific concepts, which makes patient engagement inherently more difficult. Limitations: This is a narrative review of the literature that has been partly influenced by the perspectives and experiences of the authors and focuses on research conducted by the authors. The evidence base to support the suggested benefits of patient engagement in research is currently limited. Implications: The formal incorporation of patients’ priorities, perspectives, and experiences is now recognized as a key component of the research process. If patients and researchers are able to effectively work together, this could enhance research quality and efficiency. To effectively engage patients, proper infrastructure and dedicated funding are needed. Going forward, a rigorous evaluation of patient engagement strategies and their effectiveness will be needed

Bridging the gap: a Canadian perspective on translational kidney research

Abstract Purpose of review Chronic kidney disease affects approximately 3 million Canadians. Ongoing investment in high quality kidney research is needed to improve the care of patients with kidney disease. The barriers to translating such research are discussed in this review. Sources of information Personal knowledge, research funding body websites, and published reports. Findings In this review, we discuss the meaning of the term translational research and present some of the programs aimed at ensuring efficient translation of scientific discoveries with a discussion of the barriers to translation. We highlight some successes and barriers to kidney research translation using recent examples of research in Canadian nephrology. We present the following examples of kidney research: (1) research aimed at identifying the causative genes for inherited kidney diseases; (2) recent discoveries in cell-based therapies for kidney disease; (3) an examination of the impact of acute kidney injury in renal transplant patients; and (4) the development of a kidney failure risk equation to improve prognosis accuracy. Limitations This review focuses on research conducted by the authors. Implications The process of research translation is prolonged and challenging and therefore requires resources, patience, and careful planning. With increased awareness and understanding of the barriers to research translation, researchers and funding bodies can work together to increase the rate at which important research findings reach clinical practice and improve the care of patients with kidney disease

Risk Factors for Unplanned Dialysis Initiation: A Systematic Review of the Literature

Background: Unplanned dialysis initiation is common in patients with chronic kidney disease (CKD). Objective: To determine common definitions and patient risk factors for unplanned dialysis. Design: Systematic review. Setting: MEDLINE, EMBASE, and the Cochrane Library were searched from inception to February 2018. Patients: Studies that included incident chronic dialysis patients or patients with CKD that cited a definition or examined risk factors for unplanned dialysis were included. Measurements: Definitions and criteria for unplanned dialysis reported across studies. Patient characteristics associated with unplanned dialysis. Methods: Two reviewers independently extracted data using a standardized data abstraction form and assessed study quality using a modified New Castle Ottawa Scale. Results: From 2797 citations, 48 met eligibility criteria. Reported definitions for unplanned dialysis were variable. Most publications cited dialysis initiation under emergency conditions and/or with a central venous catheter. The association of patient characteristics with unplanned dialysis was reported in 26 studies, 18 were retrospective and 21 included incident dialysis patients. The most common risk factors in univariate analyses were (number of studies) increased age (n = 7), cause of kidney disease (n = 6), presence of cardiovascular disease (n = 7), lower serum hemoglobin (n = 9), lower serum albumin (n = 10), higher serum phosphate (n = 6), higher serum creatinine or lower estimated glomerular filtration rate (eGFR) at dialysis initiation (n = 7), late referral (n = 5), lack of dialysis education (n = 6), and lack of follow-up in a predialysis clinic prior to dialysis initiation (n = 5). A minority of studies performed multivariable analyses (n = 10); the most common risk factors were increased age (n = 4), increased comorbidity score (n = 3), late referral (n = 5), and lower eGFR at dialysis initiation (n = 3). Limitations: Comparison of results across studies was limited by inconsistent definitions for unplanned dialysis. High-quality data on patient risk factors for unplanned dialysis are lacking. Conclusions: Well-designed prospective studies to determine modifiable risk factors are needed. The lack of a consensus definition for unplanned dialysis makes research and quality improvement initiatives in this area more challenging

Validation of Administrative Database Codes for Acute Kidney Injury in Kidney Transplant Recipients

Background: Validation studies of acute kidney injury (AKI) diagnostic codes performed in the general population have shown poor sensitivity, but the accuracy of such codes in the kidney transplant population remains unknown. Objective: The objective of this study is to determine the accuracy of AKI diagnostic codes in kidney transplant recipients. We hypothesized that the sensitivity of diagnostic codes would be significantly greater in the kidney transplant population since these patients are closely followed by nephrologists and are more likely to have serum creatinine measured. Design: The design is a population-based retrospective cohort study using healthcare administrative and laboratory databases. Setting: The setting is in Southwestern Ontario and Ottawa, Ontario, Canada, from 2003 to 2012. Patients: We included first-time kidney transplant recipients admitted to hospital for whom serum creatinine was measured in hospital and within 6 months prior ( n = 524). Methods: Patients meeting the Acute Kidney Injury Network (AKIN) classification serum creatinine change criteria were classified as having AKI. We determined the sensitivity, specificity, and negative and positive predictive values for the ICD-10 -CA code for AKI when present as an admission diagnosis, most responsible diagnosis, or any diagnosis compared to a reference standard of AKI defined by the AKIN criteria (stage 1 or greater, stage 2 or greater, or stage 3). Results: Forty-five percent of included kidney transplant patients had a diagnosis of AKI. The most sensitive coding algorithm (reference standard AKIN stage 2 or greater, ICD -10 code present as any diagnosis) had a sensitivity of 42.1 % (95 % CI 31.7, 53.3), a specificity of 90.6 % (95 % CI 87.6, 93.0), and a positive likelihood ratio of 4.5. The median (IQR) rise in serum creatinine from baseline in patients with and without AKI codes was 104 (57 to 158) μmol/L and 16 (−3 to 41) μmol/L, respectively (Mann-Whitney test, p < 0.0001). Limitations: The low sensitivity of the AKI code may be due to an alternative diagnosis of acute rejection being assigned in certain cases. The cause of AKI could not be determined. Conclusions: Similar to the general population, the ICD-10 N17x code misses many kidney transplant patients with AKI during their hospitalization. This makes the code unusable for studying the incidence and consequences of AKI in hospitalized kidney transplant patients