Regional variation in incidence and prognosis of acute kidney injury : a Danish population-based cohort study

S.S. was supported by a Starter Grant for Clinical Lecturers from the Academy of Medical Sciences, Wellcome Trust, Medical Research Council, British Heart Foundation, Arthritis Research UK, the Royal College of Physicians and Diabetes UK [SGL020\1076].Peer reviewe

Control of confounding in the analysis phase – an overview for clinicians

In observational studies, control of confounding can be done in the design and analysis phases. Using examples from large health care database studies, this article provides the clinicians with an overview of standard methods in the analysis phase, such as stratification, standardization, multivariable regression analysis and propensity score (PS) methods, together with the more advanced high-dimensional propensity score (HD-PS) method. We describe the progression from simple stratification confined to the inclusion of a few potential confounders to complex modeling procedures such as the HD-PS approach by which hundreds of potential confounders are extracted from large health care databases. Stratification and standardization assist in the understanding of the data at a detailed level, while accounting for potential confounders. Incorporating several potential confounders in the analysis typically implies the choice between multivariable analysis and PS methods. Although PS methods have gained remarkable popularity in recent years, there is an ongoing discussion on the advantages and disadvantages of PS methods as compared to those of multivariable analysis. Furthermore, the HD-PS method, despite its generous inclusion of potential confounders, is also associated with potential pitfalls. All methods are dependent on the assumption of no unknown, unmeasured and residual confounding and suffer from the difficulty of identifying true confounders. Even in large health care databases, insufficient or poor data may contribute to these challenges. The trend in data collection is to compile more fine-grained data on lifestyle and severity of diseases, based on self-reporting and modern technologies. This will surely improve our ability to incorporate relevant confounders or their proxies. However, despite a remarkable development of methods that account for confounding and new data opportunities, confounding will remain a serious issue. Considering the advantages and disadvantages of different methods, we emphasize the importance of the clinical input and of the interplay between clinicians and analysts to ensure a proper analysis

Post-operative acute kidney injury and five-year risk of death, myocardial infarction, and stroke among elective cardiac surgical patients: a cohort study

IntroductionThe prognostic impact of acute kidney injury (AKI) on long-term clinical outcomes remains controversial. We examined the five-year risk of death, myocardial infarction, and stroke after elective cardiac surgery complicated by AKI.MethodsWe conducted a cohort study among adult elective cardiac surgical patients without severe chronic kidney disease and/or previous heart or renal transplant surgery using data from population-based registries. AKI was defined by the Acute Kidney Injury Network (AKIN) criteria as a 50% increase in serum creatinine from baseline level, acute creatinine rise of ≥26.5μmol/L (0.3mg/dL) within 48 hours, and/or initiation of renal replacement therapy within five days after surgery. We followed patients from the fifth post-operative day until myocardial infarction, stroke or death within five years. Five-year risk was computed by the cumulative incidence method and compared with hazards ratios (HR) from a Cox proportional hazards regression model adjusting for propensity score.ResultsA total of 287 (27.9%) of 1,030 patients developed AKI. Five-year risk of death was 26.5% (95% CI: 21.2 to 32.0) among patients with AKI and 12.1% (95% CI: 10.0 to 14.7) among patients without AKI. The corresponding adjusted HR of death was 1.6 (95% CI: 1.1 to 2.2). Five-year risk of myocardial infarction was 5.0% (95% CI: 2.9 to 8.1) among patients with AKI and 3.3% (95% CI: 2.1 to 4.8) among patients without AKI. Five-year risk of stroke was 5.0% (95% CI: 2.8 to 7.9) among patients with AKI and 4.2% (95% CI: 2.9 to 5.8) among patients without AKI. Adjusted HRs were 1.5 (95% CI: 0.7 to 3.2) of myocardial infarction and 0.9 (95% CI: 0.5 to 1.8) of stroke.ConclusionsAKI, within five days after elective cardiac surgery, was associated with increased five-year mortality and a statistically insignificant increased risk of myocardial infarction. No association was seen with the risk of stroke

Timing of renal replacement therapy and long-term risk of chronic kidney disease and death in intensive care patients with acute kidney injury

Abstract Background The optimal time to initiate renal replacement therapy (RRT) in intensive care unit (ICU) patients with acute kidney injury (AKI) is unclear. We examined the impact of early RRT on long-term mortality, risk of chronic kidney disease (CKD), and end-stage renal disease (ESRD). Methods This cohort study included all adult patients treated with continuous RRT in the ICU at Aarhus University Hospital, Skejby, Denmark (2005–2015). Data were obtained from a clinical information system and population-based registries. Early treatment was defined as RRT initiation at AKI stage 2 or below, and late treatment was defined as RRT initiation at AKI stage 3. Inverse probability of treatment (IPT) weights were computed from propensity scores. The IPT-weighted cumulative risk of CKD (estimated glomerular filtration rate < 60 ml/minute/1.73 m2), ESRD, and mortality was estimated and compared using IPT-weighted Cox regression. Results The mortality, CKD, and ESRD analyses included 1213, 303, and 617 patients, respectively. The 90-day mortality in the early RRT group was 53.6% compared with 46.0% in the late RRT group (HR 1.24, 95% CI 1.03–1.48). The 90-day to 5-year mortality was 37.7% and 41.5% in the early and late RRT groups, respectively (HR 0.95, 95% CI 0.70–1.29). The 5-year risk of CKD was 35.9% in the early RRT group and 44.9% in the late RRT group (HR 0.74, 95% CI 0.46–1.18). The 5-year risk of ESRD was 13.3% in the early RRT group and 16.7% in the late RRT group (HR 0.79, 95% CI 0.47–1.32). Conclusions Early initiation was associated with increased 90-day mortality. In patients surviving to day 90, early initiation was not associated with a major impact on long-term mortality or risk of CKD and ESRD. Despite potential residual confounding due to the observational design, our findings do not support that early RRT initiation is superior to late initiation

Kidney function before and after acute kidney injury: a nationwide population-based cohort study

Abstract Background Acute kidney injury (AKI) is a common and serious condition defined by a rapid decline in kidney function. Data on changes in long-term kidney function following AKI are sparse and conflicting. Therefore, we examined the changes in estimated glomerular filtration rate (eGFR) from before to after AKI in a nationwide population-based setting. Methods Using Danish laboratory databases, we identified individuals with first-time AKI defined by an acute increase in plasma creatinine (pCr) during 2010 to 2017. Individuals with three or more outpatient pCr measurements before and after AKI were included and cohorts were stratified by baseline eGFR (≥/&amp;lt;60 ml/min/1.73m2). Linear regression models were used to estimate and compare individual eGFR slopes and eGFR levels before and after AKI. Results Among individuals with a baseline eGFR ≥60 ml/min/1.73m2 (n = 64 805), first-time AKI was associated with a median difference in eGFR level of −5.6 ml/min/1.73m2 (interquartile range [IQR], −16.1 to 1.8) and a median difference in eGFR slope of −0.4 ml/min/1.73m2/year (IQR, −5.5 to 4.4). Correspondingly, among individuals with a baseline eGFR &amp;lt;60 ml/min/1.73m2 (n = 33 267), first-time AKI was associated with a median difference in eGFR level of −2.2 ml/min/1.73m2 (IQR, −9.2 to 4.3) and a median difference in eGFR slope of 1.5 ml/min/1.73m2/year (IQR, −2.9 to 6.5). Conclusion Among individuals with first-time AKI surviving to have repeated outpatient pCr measurements, AKI was associated with changes in eGFR level and eGFR slope for which the magnitude and direction depend on baseline eGFR. </jats:sec

Renin-angiotensin system blocker use and the risk of acute kidney injury after colorectal cancer surgery: a population-based cohort study.

OBJECTIVES:It is unknown whether preoperative use of ACE inhibitors (ACE-I) or angiotensin receptor blockers (ARBs) affects the risk of acute kidney injury (AKI) after colorectal cancer (CRC) surgery. We assessed the impact of preoperative ACE-I/ARB use on risk of AKI after CRC surgery. DESIGN:Observational cohort study. Patients were divided into three exposure groups-current, former and non-users-through reimbursed prescriptions within 365 days before the surgery. AKI within 7 days after surgery was defined according to the current Kidney Disease Improving Global Outcome consensus criteria. SETTING:Population-based Danish medical databases. PARTICIPANTS:A total of 9932 patients undergoing incident CRC surgery during 2005-2014 in northern Denmark were included through the Danish Colorectal Cancer Group Database. OUTCOME MEASURE:We computed cumulative incidence proportions (risk) of AKI with 95% CIs for current, former and non-users of ACE-I/ARB, including death as a competing risk. We compared current and former users with non-users by computing adjusted risk ratios (aRRs) using log-binomial regression adjusted for demographics, comorbidities and CRC-related characteristics. We stratified the analyses of ACE-I/ARB users to address any difference in impact within relevant subgroups. RESULTS:Twenty-one per cent were ACE-I/ARB current users, 6.4% former users and 72.3% non-users. The 7-day postoperative AKI risk for current, former and non-users was 26.4% (95% CI 24.6% to 28.3%), 25.2% (21.9% to 28.6%) and 17.8% (17.0% to 18.7%), respectively. The aRRs of AKI were 1.20 (1.09 to 1.32) and 1.16 (1.01 to 1.34) for current and former users, compared with non-users. The relative risk of AKI in current compared with non-users was consistent in all subgroups, except for higher aRR in patients with a history of hypertension. CONCLUSIONS:Being a current or former user of ACE-I/ARBs is associated with an increased risk of postoperative AKI compared with non-users. Although it may not be a drug effect, users of ACE-I/ARBs should be considered a risk group for postoperative AKI

Additional file 4: Table S4. of Timing of renal replacement therapy and long-term risk of chronic kidney disease and death in intensive care patients with acute kidney injury

Description of patients with and without baseline creatinine. (DOC 53 kb