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Rationale & Objective: Clinical guidelines define chronic kidney disease (CKD) as abnormalities of kidney structure or function for>3 months. Assessment of the duration criterion may be implemented in different ways, potentially impacting estimates of disease incidence or prevalence in the population, individual diagnosis, and treatment decisions, especially for more severe cases. We investigated differences in incidence and prognosis of CKD stage G4 identified by 1 of 4 algorithms., Study Design: Population-based cohort study in Alberta, Canada., Setting & Participants: Residents>18 years old with incident CKD stage G4 (eGFR 15-29mL/min/1.73m 2 ) diagnosed between April 1, 2015, and March 31, 2018, based on administrative and laboratory data., Exposure: Four outpatient eGFR-based algorithms, increasing in stringency, for defining cohorts with CKD G4 were evaluated: (1) a single test, (2) first eGFR<30mL/min/1.73m 2 and a second eGFR 15-29mL/min/1.73m 2 measured>90 days apart (2 tests), (3) ≥2 eGFR measurements of<30mL/min/1.73m 2 sustained for>90 days (qualifying period) and the last eGFR in the qualifying period of 15-29mL/min/1.73m 2 (relaxed sustained), and (4) ≥2 consecutive measurements of 15-29mL/min/1.73m 2 for>90 days (rigorous sustained)., Outcome: Time to the earliest of death, eGFR improvement (a sustained increase in eGFR to≥30mL/min/1.73m 2 for>90 days and>25% increase from the index eGFR), or kidney failure., Analytical Approach: For each of the 4 cohorts, incidence rates and event-specific cumulative incidence functions at 1 year from cohort entry were estimated., Results: The incidence rates of CKD G4 decreased as algorithms became more stringent, from 190.7 (single test) to 79.9 (rigorous sustained) per 100,000 person-years. The 2 cohorts based on sustained reductions in eGFR were of comparable size and 1-year event-specific probabilities. The 2 cohorts based on a single test and a 2-test sequence were larger and experienced higher probabilities of eGFR improvement., Limitations: A short follow-up period of 1 year and a predominantly White population., Conclusions: The use of more stringent algorithms for defining CKD G4 results in substantially lower estimates of disease incidence, the identification of a group with a lower probability of eGFR improvement, and a higher risk of kidney failure. These findings can inform implementation decisions of disease definitions in clinical reporting systems and research studies., Plain-Language Summary: Although guidelines recommend>3 months to define chronic kidney disease (CKD), the methods for defining specific stages, particularly G4 (eGFR 15-29mL/min/1.73m 2 ) when referral to nephrology services is recommended, have been implemented differently across studies and surveillance programs. We studied differences in incidence and prognosis of CKD G4 cohorts identified by 4 algorithms using administrative and outpatient laboratory databases in Alberta, Canada. We found that, compared with a single-test definition, more stringent definitions resulted in a lower disease incidence and identified a group with worse short-term kidney outcomes. These findings highlight the impact of the choice of algorithm used to define CKD G4 on disease burden estimates at the population level, on individual prognosis, and on treatment/referral decisions., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Importance: Using the same level of estimated glomerular filtration rate (eGFR) to define chronic kidney disease (CKD) regardless of patient age may classify many elderly people with a normal physiological age-related eGFR decline as having a disease., Objective: To compare the outcomes associated with CKD as defined by a fixed vs an age-adapted eGFR threshold., Design, Setting, and Participants: This population-based cohort study was conducted in Alberta, Canada and used linked administrative and laboratory data from adults with incident CKD from April 1, 2009, to March 31, 2017, defined by a sustained reduction in eGFR for longer than 3 months below a fixed or an age-adapted eGFR threshold. Non-CKD controls were defined as being 65 years or older with a sustained eGFR of 60 to 89 mL/min/1.73 m2 for longer than 3 months and normal/mild albuminuria. The follow-up ended on March 31, 2019. The data were analyzed from February to April 2020., Exposures: A fixed eGFR threshold of 60 vs thresholds of 75, 60, and 45 mL/min/1.73 m2 for age younger than 40, 40 to 64, and 65 years or older, respectively., Main Outcomes and Measures: Competing risks of kidney failure (kidney replacement initiation or sustained eGFR <15 mL/min/1.73 m2 for >3 months) and death without kidney failure., Results: The fixed and age-adapted CKD cohorts included 127 132 (69 546 women [54.7%], 57 586 men [45.3%]) and 81 209 adults (44 582 women [54.9%], 36 627 men [45.1%]), respectively (537 vs 343 new cases per 100 000 person-years). The fixed-threshold cohort had lower risks of kidney failure (1.7% vs 3.0% at 5 years) and death (21.9% vs 25.4%) than the age-adapted cohort. A total of 53 906 adults were included in both cohorts. Of the individuals included in the fixed-threshold cohort only (n = 72 703), 54 342 (75%) were 65 years or older and had baseline eGFR of 45 to 59 mL/min/1.73 m2 with normal/mild albuminuria. The 5-year risks of kidney failure and death among these elderly people were similar to those of non-CKD controls, with a risk of kidney failure of 0.12% or less in both groups across all age categories and a risk of death at 69, 122, 279, and 935 times higher than the risk of kidney failure for 65 to 69, 70 to 74, 75 to 79, and 80 years or older, respectively., Conclusions and Relevance: This cohort study of adults with CKD suggests that the current criteria for CKD that use the same eGFR threshold for all ages may result in overestimation of the CKD burden in an aging population, overdiagnosis, and unnecessary interventions in many elderly people who have age-related loss of eGFR.

Rationale & Objective: Kidney disease is associated with an increased risk for postoperative morbidity and mortality. However, the incidence of major surgery on a population level is unknown. We aimed to determine the incidence of major surgery by level of kidney function., Study Design: Retrospective cohort study with entry from January 1, 2008, through December 31, 2009, and outcome surveillance from January 1, 2010, through December 31, 2016., Setting & Participants: Population-based study using administrative health data from Alberta, Canada; adults with an outpatient serum creatinine measurement or receiving maintenance dialysis formed the study cohort., Exposure: Participants were categorized into 6 estimated glomerular filtration rate (eGFR) categories: ≥60 (G1-G2), 45 to 59 (G3a), 30 to 44 (G3b), 15 to 29 (G4), and<15mL/min/1.73m 2 with (G5D) and without (G5) dialysis. eGFR was examined as a time-varying exposure based on means of measurements within 3-month ascertainment periods throughout the study period., Outcome: Major surgery defined as surgery requiring admission to the hospital for at least 24 hours., Analytical Approach: Incidence rates (IRs) for overall major surgery were estimated using quasi-Poisson regression and adjusted for age, sex, income, location of residence, albuminuria, and Charlson comorbid conditions. Age- and sex-stratified IRs of 13 surgery subtypes were also estimated., Results: 1,455,512 cohort participants were followed up for a median of 7.0 (IQR, 5.3) years, during which time 241,989 (16.6%) underwent a major surgery. Age and sex modified the relationship between eGFR and incidence of surgery. Men younger than 65 years receiving maintenance dialysis experienced the highest rates of major surgery, with an adjusted IR of 243.8 (95% CI, 179.8-330.6) per 1,000 person-years. There was a consistent trend of increasing surgery rates at lower eGFRs for most subtypes of surgery., Limitations: Outpatient preoperative serum creatinine measurement was necessary for inclusion and outpatient surgical procedures were not included., Conclusions: People with reduced eGFR have a significantly higher incidence of major surgery compared with those with normal eGFR, and age and sex modify this increased risk. This study informs our understanding of how surgical burden changes with differing levels of kidney function., (Copyright © 2020 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Aims: Patients with chronic kidney disease (CKD) have been under-represented in stable ischaemic heart disease (SIHD) trials despite their heightened risk of cardiovascular mortality. We examine associations between kidney disease, treatment selection, and long-term survival in patients with SIHD., Methods and Results: SIHD patients with angiographically significant stenosis (≥70%) were categorized by renal function [dialysis-dependent, severe CKD [estimated glomerular filtration rate (eGFR) < 30], mild-moderate CKD (eGFR 30-59), and no CKD (eGFR ≥ 60)] and by treatment groups [revascularization ≤3 months of angiogram (percutaneous coronary intervention or coronary artery bypass surgery) vs. medical therapy]. The association between renal function category and treatment on long-term survival was examined and adjusted for differences in age, sex, co-morbidities, and coronary anatomy. Of the 17 910 SIHD patients, 0.7% (n = 118) were dialysis-dependent, 1.2% (n = 215) severe CKD, 12.0% (n = 2157) mild-moderate CKD, and 86.1% (n = 15420) no CKD. The presence of CKD was associated with significantly lower adjusted odds of receiving revascularization [reference no CKD: dialysis-dependent: odds ratio (OR) 0.52 (0.35, 0.79), severe (non-dialysis) CKD: OR 0.54 (0.40, 0.73), and mild-moderate CKD: OR 0.80 (0.71, 0.89)]. Over a median follow-up of 8.0 (interquartile range 3.2) years, patients with progressive CKD had higher long-term mortality (dialysis-dependent, 53.4%; severe CKD, 30.2%; mild-moderate CKD, 22.2%; no CKD, 11.9%, Ptrend < 0.0001). Revascularization was associated with improved long-term survival [adjusted hazard ratio (HR): dialysis-dependent: HR 0.29 (0.15, 0.55), severe CKD: HR 0.63 (0.36, 1.08), mild-moderate CKD: HR 0.49 (0.40, 0.60), and no CKD: HR 0.47 (0.42, 0.52)] (Pinteraction < 0.001)., Conclusion: In SIHD, the presence of CKD was accompanied by lower revascularization rates and a higher risk of mortality. However, revascularization in CKD was associated with improved long-term survival.

Patients with severely decreased glomerular filtration rate (GFR) (i.e., chronic kidney disease [CKD] G4+) are at increased risk for kidney failure, cardiovascular disease (CVD) events (including heart failure), and death. However, little is known about the variability of outcomes and optimal therapeutic strategies, including initiation of kidney replacement therapy (KRT). Kidney Disease: Improving Global Outcomes (KDIGO) organized a Controversies Conference with an international expert group in December 2016 to address this gap in knowledge. In collaboration with the CKD Prognosis Consortium (CKD-PC) a global meta-analysis of cohort studies (n = 264,515 individuals with CKD G4+) was conducted to better understand the timing of clinical outcomes in patients with CKD G4+ and risk factors for different outcomes. The results confirmed the prognostic value of traditional CVD risk factors in individuals with severely decreased GFR, although the risk estimates vary for kidney and CVD outcomes. A 2- and 4-year model of the probability and timing of kidney failure requiring KRT was also developed. The implications of these findings for patient management were discussed in the context of published evidence under 4 key themes: management of CKD G4+, diagnostic and therapeutic challenges of heart failure, shared decision-making, and optimization of clinical trials in CKD G4+ patients. Participants concluded that variable prognosis of patients with advanced CKD mandates individualized, risk-based management, factoring in competing risks and patient preferences., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: Current guidelines recommend staging acute kidney injury (AKI) according to the serum creatinine (SCr) or urine output (UO) criteria that achieve the highest stage. There is little information about the implications of adding UO to SCr measurements for staging AKI outside intensive care units and after cardiac surgery., Methods: We performed a cohort study of all adults without end-stage renal disease who underwent major noncardiac surgery between January 2005 and March 2011 in Calgary, AB, Canada. Participants required at least two SCr and UO measurements to be included. We examined the implications of adding UO to SCr to stage AKI based on Kidney Disease: Improving Global Outcomes criteria. Logistic and linear regression models were used to examine the associations between AKI stage and 30-day mortality or hospital length of stay (LOS), respectively., Results: A total of 4229 (17%) surgical patients had sufficient SCr and UO measurements for inclusion in the cohort. The apparent incidence of postoperative AKI substantially increased with the addition of UO to SCr criteria (8.1% with SCr alone versus 64.0% with SCr and UO). Mortality for a given stage of AKI was lower when UO was added to SCr criteria (0.3, 3.2, 1.9 and 3.0% for no AKI and Stages 1, 2 and 3, respectively) versus with SCr alone (1.2, 4.2, 15.4 and 12.8%). However, among participants without AKI based on the SCr criterion, the odds of mortality and mean LOS both significantly increased with lower UO. Models that reclassified AKI stage based on UO in addition SCr criteria had the best discrimination for mortality and LOS., Conclusions: Adding UO to SCr criteria substantially increases the apparent incidence of AKI on hospital wards and significantly changes the prognostic implications of AKI identification and staging. These measures should not be considered equivalent criteria in AKI staging., (© The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Background: Using a community-based cohort we sought to investigate the association between change in estimated glomerular filtration rate (eGFR) and risk of incident cardiovascular disease including congestive heart failure (CHF), acute myocardial infarction (AMI), and stroke., Methods: We identified 479,126 adults without a history of cardiovascular disease who had at least 3 outpatient eGFR measurements over a 4 year period in Alberta, Canada. Change in eGFR was estimated as the absolute annual rate of change (categorized as ≤-5, -4, -3, -2, -1, 0, 1, 2, 3, 4, and ≥5 mL/min/1.73 m2/year). In a sensitivity analysis we also estimated change as the annual percentage change (categorized as ≤-7, -6 to -5, -4 to -3, -2 to -1, 0, 1 to 2, 3 to 4, 5 to 6, and ≥7%/year). The adjusted risk of incident CHF, AMI, and stroke associated with each category of change in eGFR was estimated, using no change in eGFR as the reference,, Results: There were 2622 (0.6%) CHF, 3463 (0.7%) AMI, and 2768 (0.6%) stroke events over a median follow-up of 2.5 years. Compared to participants with stable eGFR, those with the greatest decline (≤-5 mL/min/1.73 m2/year) had more than a two-fold increased risk of CHF (HR 2.57; 95% CI: 2.28 to 2.89). Risk for AMI and stroke was increased by 31% and 29%, respectively. After adjusting for the last eGFR at the end of the accrual period, the observed association remained significantly higher for CHF but diminished for AMI and stroke. A similar pattern was observed when change in eGFR was quantified as annual percentage change., Conclusion: In this large community-based cohort, we observed that a declining eGFR was associated with an increased risk of CHF, AMI, and stroke. However, when the risk of CVD events was adjusted for the last eGFR measurement, decline in eGFR per se was no longer associated with increased risk of AMI or stroke, and the association with CHF remained significant but was attenuated. These results demonstrate the importance of monitoring change in eGFR over time to improve cardiovascular risk prognostication., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Diabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain., Study Design: Meta-analysis of cohort studies., Setting & Population: 8 general-population (1,285,045 participants) and 5 chronic kidney disease (CKD; 79,519 participants) cohorts., Selection Criteria for Studies: Cohorts participating in the CKD Prognosis Consortium., Predictors: Diabetes and hypertension status, eGFR by the 2009 CKD Epidemiology Collaboration creatinine equation, urine ACR, and interactions., Outcome: Hospitalization with AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results., Results: During a mean follow-up of 4 years, there were 16,480 episodes of AKI in the general-population and 2,087 episodes in the CKD cohorts. Low eGFRs and high ACRs were associated with higher risks of AKI in individuals with or without diabetes and with or without hypertension. When compared to a common reference of eGFR of 80mL/min/1.73m(2) in nondiabetic patients, HRs for AKI were generally higher in diabetic patients at any level of eGFR. The same was true for diabetic patients at all levels of ACR compared with nondiabetic patients. The risk gradient for AKI with lower eGFRs was greater in those without diabetes than with diabetes, but similar with higher ACRs in those without versus with diabetes. Those with hypertension had a higher risk of AKI at eGFRs>60mL/min/1.73m(2) than those without hypertension. However, risk gradients for AKI with both lower eGFRs and higher ACRs were greater for those without than with hypertension., Limitations: AKI identified by diagnostic code., Conclusions: Lower eGFRs and higher ACRs are associated with higher risks of AKI among individuals with or without either diabetes or hypertension., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Lower estimated glomerular filtration rate (eGFR) on a single occasion is associated with risk of cardiovascular events; whether the degree of change in eGFR during a 1-year period adds prognostic information is unknown., Methods and Results: We included adults who had ≥2 outpatient eGFR measurements (≥6 months apart) during a 1-year accrual period in Alberta, Canada. According to recent guidelines, we used a change in eGFR category (≥90, 60 to 89, 45 to 59, 30 to 44, 15 to 29, and <15 mL/min per 1.73 m(2)), and the presence/absence of a ≥25% change from baseline to classify participants into 5 groups: certain drop, uncertain drop, stable (no change), uncertain rise, and certain rise. We calculated adjusted rates of cardiovascular events (per 10 000 person-years) for each group. We estimated the adjusted risks of cardiovascular events associated with each category of change in eGFR, in reference to stable kidney function. Among the 526 388 participants, 76.1% (n=400 560) had stable, 2.6% (n=13 668) had a certain drop, and 3.3% (n=17 499) had a certain rise in eGFR. Compared with participants with stable kidney function, adjusted risks of myocardial infarction, heart failure, and stroke were 27%, 51%, and 20% higher, respectively, for those with a certain drop in kidney function. After adjusting for the last eGFR at the end of the accrual period, the observed association diminished., Conclusion: Clinically relevant changes in eGFR are associated with increased risk of cardiovascular events. However, most of the apparent increase in risk can be accounted for by assessing comorbidity and baseline kidney function., (© 2014 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background and Objectives: Although patients with ESRD have a higher fracture risk than the general population, there is conflicting evidence regarding fracture incidence in those with CKD. This study sought to determine the association between estimated GFR (eGFR) and fracture rates., Design, Setting, Participants, & Measurements: This study identified 1,815,943 community-dwelling adults who had at least one outpatient serum creatinine measurement between 2002 and 2008. Patients with eGFR <15 ml/min per 1.73 m(2) and those who required dialysis were excluded. Incident fractures of the hip, wrist, and vertebrae were identified using diagnostic and procedure codes. Poisson regression was used to determine adjusted rates of each fracture type by eGFR, age, and sex., Results: The median age of the cohort was 47 years (interquartile range, 24), and 7.1% had eGFR <60 ml/min per 1.73 m(2). Over a median follow-up of 4.4 years, fracture rates increased with age at all sites. Within each age stratum, unadjusted rates increased with declining eGFR; however, adjusted rates were similar across eGFR categories. For example, among women aged 65-74 years, adjusted hip fracture rates were 3.41 per 1000 person-years (95% confidence interval, 2.30 to 4.53) and 4.58 per 1000 person-years (95% confidence interval, 0.02 to 9.14) in those with eGFR ≥90 and 15-29 ml/min per 1.73 m(2), respectively. Similar results were observed for wrist and vertebral fractures., Conclusions: In contrast to earlier studies, patients with eGFR<60 ml/min per 1.73 m(2) do not appear to have increased rates of hip, wrist, and vertebral fractures independent of age and sex.

The estimated glomerular filtration rate (eGFR) is a powerful predictor of adverse outcomes, but most attention has focused on studies in the setting of reduced eGFR. Here we tested whether patients with an eGFR higher than 60-89.9 ml/min per 1.73 m(2) could also be at elevated risk of adverse outcomes. Further, we tested whether concomitant proteinuria further increases the risk of outcomes among individuals with an eGFR equal to or above 90 ml/min per 1.73 m(2), as it does for those with reduced eGFR. Using data from a population-based outpatient laboratory data set of 1,526,437 patients, we measured adjusted associations between eGFR calculated by the modification of diet in renal disease equation, urine dipstick proteinuria, and adverse clinical outcomes. The adjusted risk of all-cause mortality was lowest at an eGFR of 60-74.9 ml/min per 1.73 m(2) (referent) and increased at both lower and higher levels of eGFR. Specifically, the hazard ratio of death was 3.7 and 1.8 among patients with an eGFR equal to or above 105 and 90-104.9 ml/min per 1.73 m(2), respectively, compared to the referent group. Similar results were seen when the CKD-EPI equation (sensitivity analyses) was used to assess eGFR. Higher levels of eGFR were not associated with the risk of kidney failure or myocardial infarction. Thus, the presence and severity of proteinuria was significantly associated with graded increases in the risk of clinical outcomes for both lower and higher eGFR. We do not know, however, whether the finding at higher eGFR could be due to inadequacies of the eGFR formula at low serum creatinine levels.

Background and Objectives: Most studies of chronic kidney disease (CKD) and outcomes focus on mortality and ESRD, with limited data on other adverse outcomes. This study examined the associations among proteinuria, eGFR, and adverse cardiovascular (CV) events., Design, Setting, Participants, & Measurements: This was a population-based longitudinal study with patients identified from province-wide laboratory data from Alberta, Canada, between 2002 and 2007. Selected for this study from a total of 1,526,437 patients were 920,985 (60.3%) patients with at least one urine dipstick measurement and 102,701 patients (6.7%) with at least one albumin-creatinine ratio (ACR) measurement. Time to hospitalization was considered for one of four indications: congestive heart failure (CHF), coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI), peripheral vascular disease (PVD), and stroke/transient ischemic attacks [TIAs] (cerebrovascular accident [CVA]/TIA)., Results: After a median follow-up of 35 months, in fully adjusted models and compared with patients with estimated GFR (eGFR) of 45 to 59 ml/min per 1.73 m(2) and no proteinuria, patients with heavy proteinuria by dipstick and eGFR ≥ 60 ml/min per 1.73 m(2) had higher rates of CABG/PCI and CVA/TIA. Similar results were obtained in patients with proteinuria measured by ACR., Conclusions: Risks of major CV events at a given level of eGFR increased with higher levels of proteinuria. The findings extend current data on risk of mortality and ESRD. Measurement of proteinuria is of incremental prognostic benefit at every level of eGFR. The data support use of proteinuria measurement with eGFR for definition and risk stratification in CKD.

Background: The staging system for chronic kidney disease relies almost exclusively on estimated glomerular filtration rate (eGFR), although proteinuria is also associated with adverse outcomes., Objective: To validate a 5-category system for risk stratification based on the combination of eGFR and proteinuria., Design: Retrospective cohort study., Setting: A provincial laboratory registry in Alberta, Canada, and a representative sample of noninstitutionalized U.S. adults., Patients: A derivation data set of 474 521 adult outpatients, 2 independent internal validation cohorts with 51 356 and 460 623 patients, and an external validation cohort of 14 358 patients., Measurements: Glomerular filtration rate, estimated by using the Modification of Diet in Renal Disease Study equation, and proteinuria, measured by using urine albumin-to-creatinine ratio or dipstick urinalysis. Outcomes included all-cause mortality and a composite renal outcome of kidney failure or doubling of serum creatinine level., Results: Over a median follow-up of 38 months in the internal validation cohorts, higher risk categories (indicating lower eGFR or more proteinuria) were associated with a graded increase in the risk for the composite renal outcome. The projected number of U.S. adults assigned to risk categories 3 and 4 in the alternate system was 3.9 million, compared with 16.3 million assigned to stage 3 and 4 in the current staging system. The alternate system was more likely to correctly reclassify persons who did not develop the renal outcome than those who did, although some persons developed the renal outcome despite reclassification to a lower category. However, all analyses of patients reclassified to a lower category showed that substantially fewer such patients developed the renal outcome than did not. Correct reclassification by the alternate system was more likely when proteinuria was measured by using albumin-to-creatinine ratio than with dipstick testing, and also more likely for the composite renal outcome than for mortality., Limitation: The study had a short follow-up time., Conclusion: Using proteinuria in combination with eGFR may reduce unnecessary referrals for care at the cost of not referring or delaying referral for some patients who go on to develop kidney failure., Primary Funding Source: Alberta Heritage Foundation for Medical Research interdisciplinary research team grant.

Background: Low values of estimated glomerular filtration rate (eGFR) predispose to acute kidney injury, and proteinuria is a marker of kidney disease. We aimed to investigate how eGFR and proteinuria jointly modified the risks of acute kidney injury and subsequent adverse clinical outcomes., Methods: We did a cohort study of 920,985 adults residing in Alberta, Canada, between 2002 and 2007. Participants not needing chronic dialysis at baseline and with at least one outpatient measurement of both serum creatinine concentration and proteinuria (urine dipstick or albumin-creatinine ratio) were included. We assessed hospital admission with acute kidney injury with validated administrative codes; other outcomes were all-cause mortality and a composite renal outcome of end-stage renal disease or doubling of serum creatinine concentration., Findings: During median follow-up of 35 months (range 0-59 months), 6520 (0·7%) participants were admitted with acute kidney injury. In those with eGFR 60 mL/min per 1·73 m(2) or greater, the adjusted risk of admission with this disorder was about 4 times higher in those with heavy proteinuria measured by dipstick (rate ratio 4·4 vs no proteinuria, 95% CI 3·7-5·2). The adjusted rates of admission with acute kidney injury and kidney injury needing dialysis remained high in participants with heavy dipstick proteinuria for all values of eGFR. The adjusted rates of death and the composite renal outcome were also high in participants admitted with acute kidney injury, although the rise associated with this injury was attenuated in those with low baseline eGFR and heavy proteinuria., Interpretation: These findings suggest that information on proteinuria and eGFR should be used together when identifying people at risk of acute kidney injury, and that an episode of acute kidney injury provides further long-term prognostic information in addition to eGFR and proteinuria., Funding: The study was funded by an interdisciplinary team grant from Alberta Heritage Foundation for Medical Research., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Context: Laboratory reporting of estimated glomerular filtration rate (GFR) has been widely implemented, with limited evaluation., Objective: To examine trends in nephrologist visits and health care resource use before and after estimated GFR reporting., Design, Setting, and Patients: Community-based cohort study (N = 1,135,968) with time-series analysis. Participants were identified from a laboratory registry in Alberta, Canada, and followed up from May 15, 2003, to March 14, 2007 (with estimated GFR reporting implemented October 15, 2004)., Main Outcome Measure: Nephrologist visits and patient management., Results: Following estimated GFR reporting, the rate of first outpatient visits to a nephrologist for patients with chronic kidney disease (CKD; estimated GFR <60 mL/min/1.73 m(2)) increased by 17.5 (95% confidence interval [CI], 16.5-18.6) visits per 10,000 CKD patients per month, corresponding to a relative increase from baseline of 68.4% (95% CI, 65.7%-71.2%). There was no association between estimated GFR reporting and rate of first nephrologist visit among patients without CKD. Among patients with an estimated GFR of less than 30 mL/min/1.73 m(2), the rate of first nephrologist visits increased by 134.4 (95% CI, 60.0-208.7) visits per 10,000 patients per month. This increase was predominantly seen in women, patients aged 46 to 65 years as well as those aged 86 years or older, and those with hypertension, diabetes, and comorbidity. Reporting of estimated GFR was not associated with increased rates of internal medicine or general practitioner visits or increased use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers among patients with CKD and proteinuria or the subgroup limited to patients with diabetes., Conclusions: Reporting of estimated GFR was associated with an increase in first nephrologist visits, particularly among patients with more severe kidney dysfunction, women, middle-aged and very elderly patients, and those with comorbidities. Any effect on outcomes remains to be shown.

Context: The current staging system for chronic kidney disease is based primarily on estimated glomerular filtration rate (eGFR) with lower eGFR associated with higher risk of adverse outcomes. Although proteinuria is also associated with adverse outcomes, it is not used to refine risk estimates of adverse events in this current system., Objective: To determine the association between reduced GFR, proteinuria, and adverse clinical outcomes., Design, Setting, and Participants: Community-based cohort study with participants identified from a province-wide laboratory registry that includes eGFR and proteinuria measurements from Alberta, Canada, between 2002 and 2007. There were 920 985 adults who had at least 1 outpatient serum creatinine measurement and who did not require renal replacement treatment at baseline. Proteinuria was assessed by urine dipstick or albumin-creatinine ratio (ACR)., Main Outcome Measures: All-cause mortality, myocardial infarction, and progression to kidney failure., Results: The majority of individuals (89.1%) had an eGFR of 60 mL/min/1.73 m(2) or greater. Over median follow-up of 35 months (range, 0-59 months), 27 959 participants (3.0%) died. The fully adjusted rate of all-cause mortality was higher in study participants with lower eGFRs or heavier proteinuria. Adjusted mortality rates were more than 2-fold higher among individuals with heavy proteinuria measured by urine dipstick and eGFR of 60 mL/min/1.73 m(2) or greater, as compared with those with eGFR of 45 to 59.9 mL/min/1.73 m(2) and normal protein excretion (rate, 7.2 [95% CI, 6.6-7.8] vs 2.9 [95% CI, 2.7-3.0] per 1000 person-years, respectively; rate ratio, 2.5 [95% CI, 2.3-2.7]). Similar results were observed when proteinuria was measured by ACR (15.9 [95% CI, 14.0-18.1] and 7.0 [95% CI, 6.4-7.6] per 1000 person-years for heavy and absent proteinuria, respectively; rate ratio, 2.3 [95% CI, 2.0-2.6]) and for the outcomes of hospitalization with acute myocardial infarction, end-stage renal disease, and doubling of serum creatinine level., Conclusion: The risks of mortality, myocardial infarction, and progression to kidney failure associated with a given level of eGFR are independently increased in patients with higher levels of proteinuria.

BackgroundAcute kidney injury (AKI) is a serious global public health problem. We aimed to quantify the risk of AKI associated with estimated glomerular filtration rate (eGFR), albuminuria (albumin-creatinine ratio [ACR]), age, sex, and race (African American and white).Study designCollaborative meta-analysis.Setting & population8 general-population cohorts (1,285,049 participants) and 5 chronic kidney disease (CKD) cohorts (79,519 participants).Selection criteria for studiesAvailable eGFR, ACR, and 50 or more AKI events.PredictorsAge, sex, race, eGFR, urine ACR, and interactions.OutcomeHospitalized with or for AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results.Results16,480 (1.3%) general-population cohort participants had AKI over a mean follow-up of 4 years; 2,087 (2.6%) CKD participants had AKI over a mean follow-up of 1 year. Lower eGFR and higher ACR were strongly associated with AKI. Compared with eGFR of 80mL/min/1.73m(2), the adjusted HR of AKI at eGFR of 45mL/min/1.73m(2) was 3.35 (95% CI, 2.75-4.07). Compared with ACR of 5mg/g, the risk of AKI at ACR of 300mg/g was 2.73 (95% CI, 2.18-3.43). Older age was associated with higher risk of AKI, but this effect was attenuated with lower eGFR or higher ACR. Male sex was associated with higher risk of AKI, with a slight attenuation in lower eGFR but not in higher ACR. African Americans had higher AKI risk at higher levels of eGFR and most levels of ACR.LimitationsOnly 2 general-population cohorts could contribute to analyses by race; AKI identified by diagnostic code.ConclusionsReduced eGFR and increased ACR are consistent strong risk factors for AKI, whereas associations of AKI with age, sex, and race may be weaker in more advanced stages of CKD.

Background: People with kidney failure have a high incidence of major surgery, though the risk of perioperative outcomes at a population-level is unknown. Our objective was to estimate the proportion of people with kidney failure that experience acute myocardial infarction (AMI) or death within 30 days of major non-cardiac surgery, based on surgery type. Methods: In this retrospective population-based cohort study, we used administrative health data to identify adults from Alberta, Canada with major surgery between April 12,005 and February 282,017 that had preoperative estimated glomerular filtration rates (eGFRs) < 15 mL/min/1.73m2 or received chronic dialysis. The index surgical procedure for each participant was categorized within one of fourteen surgical groupings based on Canadian Classification of Health Interventions (CCI) codes applied to hospitalization administrative datasets. We estimated the proportion of people that had AMI or died within 30 days of the index surgical procedure (with 95% confidence intervals [CIs]) following logistic regression, stratified by surgery type. Results: Overall, 3398 people had a major surgery (1905 hemodialysis; 590 peritoneal dialysis; 903 non-dialysis). Participants were more likely male (61.0%) with a median age of 61.5 years (IQR 50.0–72.7). Within 30 days of surgery, 272 people (8.0%) had an AMI or died. The probability was lowest following ophthalmologic surgery at 1.9% (95%CI: 0.5, 7.3) and kidney transplantation at 2.1% (95%CI: 1.3, 3.2). Several types of surgery were associated with greater than one in ten risk of AMI or death, including retroperitoneal (10.0% [95%CI: 2.5, 32.4]), intra-abdominal (11.7% [8.7, 15.5]), skin and soft tissue (12.1% [7.4, 19.1]), musculoskeletal (MSK) (12.3% [9.9, 15.5]), vascular (12.6% [10.2, 15.4]), anorectal (14.7% [6.3, 30.8]), and neurosurgical procedures (38.1% [20.3, 59.8]). Urgent or emergent procedures had the highest risk, with 12.1% experiencing AMI or death (95%CI: 10.7, 13.6) compared with 2.6% (1.9, 3.5) following elective surgery. Conclusions: After major non-cardiac surgery, the risk of death or AMI for people with kidney failure varies significantly based on surgery type. This study informs our understanding of surgery type and risk for people with kidney failure. Future research should focus on identifying high risk patients and strategies to reduce these risks. [ABSTRACT FROM AUTHOR]

Background: We developed and validated laboratory test--based risk scores (i.e., lab risk scores) to reclassify mortality risk among patients undergoing their first coronary catheterization. Methods: Patients were catheterized between 2009 and 2015 in Calgary, Alberta, Canada (n=14 135, derivation cohort), and in Edmonton, Alberta, Canada (n=12 143, validation cohort). Logistic regression with group LASSO (least absolute shrinkage and selection operator) penalty was used to select quintiles of the last laboratory tests (red blood cell count, mean corpuscular hemoglobin concentration, mean corpuscular hemoglobin, mean corpuscular volume, red cell distribution width, platelet count, total white blood cell count, plasma sodium, potassium, chloride, CO2, international normalized ratio, estimated glomerular filtration rate) performed <30 days before catheterization and by age and sex that were significantly associated with death ≤60 and >60 days after catheterization. Follow-up was until 2016. Risk scores were developed from significant tests, internally validated in Calgary among bootstrap samples and externally validated in Edmonton after recalibration using coefficients developed in Calgary. Interaction tests were performed, and net reclassification improvement vs conventional demographic and clinical risk factors was determined. Results: Lab risk scores were strongly associated with mortality (29-40x for top vs bottom quintile, P for trends <0.01), had good discrimination and were well calibrated in Calgary (C=0.80-0.85, slope=0.99-1.01) and Edmonton (C=0.80-0.82; slope=1.02-1.05)--similar to demographic and clinical risk factors alone. Associations were attenuated by several comorbidities; however, scores appropriately reclassified 11%-20% of deaths (both follow-up periods) and 6%-9% of survivors (>60 days) after catheterization vs demographic and clinical risk factors. [ABSTRACT FROM AUTHOR]

Background Improving recognition of patients at increased risk of acute kidney injury (AKI) in the community may facilitate earlier detection and implementation of proactive prevention measures that mitigate the impact of AKI. The aim of this study was to develop and externally validate a practical risk score to predict the risk of AKI in either hospital or community settings using routinely collected data. Methods Routinely collected linked datasets from Tayside, Scotland, were used to develop the risk score and datasets from Kent in the UK and Alberta in Canada were used to externally validate it. AKI was defined using the Kidney Disease: Improving Global Outcomes serum creatinine–based criteria. Multivariable logistic regression analysis was performed with occurrence of AKI within 1 year as the dependent variable. Model performance was determined by assessing discrimination (C-statistic) and calibration. Results The risk score was developed in 273 450 patients from the Tayside region of Scotland and externally validated into two populations: 218 091 individuals from Kent, UK and 1 173 607 individuals from Alberta, Canada. Four variables were independent predictors for AKI by logistic regression: older age, lower baseline estimated glomerular filtration rate, diabetes and heart failure. A risk score including these four variables had good predictive performance, with a C-statistic of 0.80 [95% confidence interval (CI) 0.80–0.81] in the development cohort and 0.71 (95% CI 0.70–0.72) in the Kent, UK external validation cohort and 0.76 (95% CI 0.75–0.76) in the Canadian validation cohort. Conclusion We have devised and externally validated a simple risk score from routinely collected data that can aid both primary and secondary care physicians in identifying patients at high risk of AKI. [ABSTRACT FROM AUTHOR]

Importance: Some patients will develop chronic kidney disease after a hospitalization with acute kidney injury; however, no risk-prediction tools have been developed to identify high-risk patients requiring follow-up.Objective: To derive and validate predictive models for progression of acute kidney injury to advanced chronic kidney disease.Design, Setting, and Participants: Data from 2 population-based cohorts of patients with a prehospitalization estimated glomerular filtration rate (eGFR) of more than 45 mL/min/1.73 m2 and who had survived hospitalization with acute kidney injury (defined by a serum creatinine increase during hospitalization > 0.3 mg/dL or > 50% of their prehospitalization baseline), were used to derive and validate multivariable prediction models. The risk models were derived from 9973 patients hospitalized in Alberta, Canada (April 2004-March 2014, with follow-up to March 2015). The risk models were externally validated with data from a cohort of 2761 patients hospitalized in Ontario, Canada (June 2004-March 2012, with follow-up to March 2013).Exposures: Demographic, laboratory, and comorbidity variables measured prior to discharge.Main Outcomes and Measures: Advanced chronic kidney disease was defined by a sustained reduction in eGFR less than 30 mL/min/1.73 m2 for at least 3 months during the year after discharge. All participants were followed up for up to 1 year.Results: The participants (mean [SD] age, 66 [15] years in the derivation and internal validation cohorts and 69 [11] years in the external validation cohort; 40%-43% women per cohort) had a mean (SD) baseline serum creatinine level of 1.0 (0.2) mg/dL and more than 20% had stage 2 or 3 acute kidney injury. Advanced chronic kidney disease developed in 408 (2.7%) of 9973 patients in the derivation cohort and 62 (2.2%) of 2761 patients in the external validation cohort. In the derivation cohort, 6 variables were independently associated with the outcome: older age, female sex, higher baseline serum creatinine value, albuminuria, greater severity of acute kidney injury, and higher serum creatinine value at discharge. In the external validation cohort, a multivariable model including these 6 variables had a C statistic of 0.81 (95% CI, 0.75-0.86) and improved discrimination and reclassification compared with reduced models that included age, sex, and discharge serum creatinine value alone (integrated discrimination improvement, 2.6%; 95% CI, 1.1%-4.0%; categorical net reclassification index, 13.5%; 95% CI, 1.9%-25.1%) or included age, sex, and acute kidney injury stage alone (integrated discrimination improvement, 8.0%; 95% CI, 5.1%-11.0%; categorical net reclassification index, 79.9%; 95% CI, 60.9%-98.9%).Conclusions and Relevance: A multivariable model using routine laboratory data was able to predict advanced chronic kidney disease following hospitalization with acute kidney injury. The utility of this model in clinical care requires further research. [ABSTRACT FROM AUTHOR]

The article focuses on a study to determine the association of age with the likelihood of treatment of kidney failure. A community-based cohort study of adults in Alberta, Canada, who had outpatient estimated glomerular filtration rate measured between May 1, 2002 and March 31, 2008 and who did not require renal replacement therapy at baseline, was conducted. Main outcomes included adjusted rates of treated kidney failure, untreated kidney failure and death. The study concluded that in Alberta, Canada, rates of untreated kidney failure are significantly higher in older compared with younger individuals.

Background. Administrative data are commonly used for surveillance of chronic medical conditions. The purpose of this study was to determine the validity of an algorithm derived from administrative data for identifying chronic kidney disease (CKD) compared to the reference standard of estimated glomerular filtration rate (eGFR). Methods. We identified adults from the province of Alberta with at least two outpatient serum creatinine measurements within a 1-year time period. Validity indices were estimated for CKD using up to 3 years of administrative data (physician billing claims and hospital discharge abstracts) for various case–definition combinations. For each algorithm, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated against two reference standard definitions of CKD (two eGFR measurements <60 mL/min/1.73m2 or mean eGFR < 30 mL/min/1.73m2). Results. A total of 321 293 eligible subjects were identified. Irrespective of the algorithm, sensitivities for defining CKD (eGFR < 60 mL/min/1.73m2) using administrative codes were low. A case–definition algorithm employing two physician claims or one hospitalization within a 2-year period had sensitivity of 19.4%, specificity of 97.2%, PPV of 60.1% and NPV of 84.8% for detecting CKD. Estimates of sensitivity were higher when <30 mL/min/1.73m2 was used as the reference standard, although PPVs were lower and consistently less than 50%. Conclusion. These results, using eGFR as a reference standard, suggest that administrative data have insufficient sensitivity and PPV for CKD surveillance, although they may be useful when highly specific algorithms are required for research purposes. [ABSTRACT FROM PUBLISHER]

To determine whether acute kidney injury results in later long-term decline in kidney function we measured changes in kidney function over a 3-year period in adults undergoing coronary angiography who had serum creatinine measurements as part of their clinical care. Acute kidney injury was categorized by the magnitude of increase in serum creatinine (mild (50-99% or 0.3 mg/dl) and moderate or severe (100%)) within 7 days of coronary angiography. Compared to patients without acute kidney injury, the adjusted odds of a sustained decline in kidney function at 3 months following angiography increased more than 4-fold for patients with mild to more than 17-fold for those with moderate or severe acute kidney injury. Among those with an estimated glomerular filtration rate after angiography less than 90 ml/min per 1.73 m2, the subsequent adjusted mean rate of decline in estimated glomerular filtration rate during long-term follow-up (all normalized to 1.73 m2 per year) was 0.2 ml/min in patients without acute kidney injury, 0.8 ml/min following mild injury, and 2.8 ml/min following moderate to severe acute kidney injury. Thus, acute kidney injury following coronary angiography is associated with a sustained loss and a larger rate of future decline in kidney function. [ABSTRACT FROM AUTHOR]

The article discusses possible techniques that can be applied for the early diagnosis and treatment of high-risk patients in order to reduce morbidity and mortality in chronic kidney disease. Chronic kidney disease is a condition characterized with sustained reduction in glomerular filtration rate or abnormalities in urinalysis, biopsy or imaging. It is found to be prevalent in developed countries but is unknown in developing countries. Early detection of chronic kidney disease can be done through population-based screening, screening for proteinuria and screening to detect glomerulonephritis. The prevention and therapeutic management of chronic kidney diseases are also explained.

The article presents information on a cohort study to undermine the risk of coronary heart disease in patients with chronic kidney disease compared to diabetes. It informs that the study was undertaken in Alberta, Canada and highlights that the population-based cohort included the measurement of glomerular filtration rate (eGFR) and proteinuria. The findings of the study suggest that chronic kidney disease can be regarded as one of the factors for future coronary disease. INSET: Panel: Research in context.

Many patients with non-dialysis dependent chronic kidney disease (CKD) live far from the closest nephrologist; although reversible, this might constitute a barrier to optimal care. In order to evaluate outcomes, we selected 31,452 outpatients older than 18 years with an estimated glomerular filtration rate (eGFR) less than 45 ml/min per 1.73 m2 who had serum creatinine measured at least once during 2005 in Alberta, Canada. We then used logistic regression to examine the association between outcomes of 6545 patients who lived more than 50 km from the nearest nephrologist. Over a median follow-up of 27 months, 7684 participants died and 15,075 were hospitalized at least once. Compared with those living within 50 km, those further away were significantly less likely to visit a nephrologist or a multidisciplinary CKD clinic within 18 months of the index measurement of the eGFR. Similarly, remote dwellers with diabetes were significantly less likely to have hemoglobin A1c evaluated within 1 year of the index eGFR measurement, to have urinary albumin assessed biannually, or to receive an angiotensin converting enzyme inhibitor or receptor blocker in the setting of diabetes or proteinuria. Remote-dwelling participants were also significantly more likely to die or be hospitalized during follow-up than those living closer. Thus, among people with CKD, remote dwellers were less likely to receive specialist care, recommended laboratory testing, and appropriate medications, and were more likely to die or be hospitalized compared with those living closer to a nephrologist. [ABSTRACT FROM AUTHOR]