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Source Citation: Vazquez MA, Oliver G, Amarasingham R, et al; ICD-Pieces Study Group. Pragmatic trial of hospitalization rate in chronic kidney disease. N Engl J Med. 2024;390:1196-1206. 38598574., Competing Interests: Disclosures: Disclosure forms are available with the article online.

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.)

Rationale & Objective: Survivors of acute kidney injury (AKI) are at high risk of adverse outcomes. Monitoring of kidney function, screening for proteinuria, use of statins and renin-angiotensin-aldosterone system (RAAS) inhibitors, and nephrology follow-up among survivors have not been fully characterized. We examined these processes of care after discharge in survivors of hospitalized AKI., Study Design: Population-based retrospective cohort study., Setting & Participants: Adults in Alberta, Canada, admitted to the hospital between 2009 and 2017, then followed from their discharge date until 2019 for a median follow-up of 2.7 years., Exposure: Hospital-acquired AKI diagnostically conforming to Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria for stage 2 or stage 3 disease, or the need for acute dialysis., Outcome: Outcomes after hospital discharge included the proportion of participants who had evaluation of kidney function, were seen by a specialist or general practitioner, and received postdischarge prescriptions for recommended medications for chronic kidney disease (CKD)., Analytical Approach: Cumulative incidence curves to characterize the proportion of participants who received each process of care outcome within the first 90 days and subsequent 1-year follow-up period after hospital discharge. To avoid risks associated with multiple hypothesis testing, differences were not statistically compared across groups., Results: The cohort (n=23,921) included 50.2% men (n=12,015) with a median age of 68.1 [IQR, 56.9-78.8] years. Within 90 days after discharge, 21.2% and 8.6% of patients with and without pre-existing CKD, respectively, were seen by a nephrologist; 60.1% of AKI survivors had at least 1 serum creatinine measured, but only 25.5% had an assessment for albuminuria within 90 days after discharge; 52.7% of AKI survivors with pre-existing CKD, and 51.6% with de novo CKD were prescribed a RAAS inhibitor within 4-15 months after discharge., Limitations: Retrospective data were collected as part of routine clinical care., Conclusions: The proportion of patients receiving optimal care after an episode of AKI in Alberta was low and may represent a target for improving long-term outcomes for this population., Plain-Language Summary: A study in Alberta, Canada, examined the care received by patients with acute kidney disease (AKI) during hospitalization and after discharge between 2007 and 2019. The results showed that a low proportion of patients with moderate to severe AKI were seen by a kidney specialist during hospitalization or within 90 days after discharge. Fewer than 25% of AKI patients had their kidney function monitored with both blood and urine tests within 90 days of discharge. Additionally, about half of AKI survivors with chronic kidney disease (CKD) were prescribed guideline recommended medications for CKD within 15 months after discharge. There is potential to improve health care delivery to these patients both in hospital and after hospital discharge., (Copyright © 2023 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Early interventions in CKD have been shown to improve health outcomes; however, gaps in access to nephrology care remain common. Nurse practitioners can improve access to care; however, the quality and outcomes of nurse practitioner care for CKD are uncertain., Methods: In this propensity score-matched cohort study, patients with CKD meeting criteria for nurse practitioner care were matched 1:1 on their propensity scores for ( 1 ) nurse practitioner care versus primary care alone and ( 2 ) nurse practitioner versus nephrologist care. Processes of care were measured within 1 year after cohort entry, and clinical outcomes were measured over 5 years of follow-up and compared between propensity score-matched groups., Results: A total of 961 (99%) patients from the nurse practitioner clinic were matched on their propensity score to 961 (1%) patients receiving primary care only while 969 (100%) patients from the nurse practitioner clinic were matched to 969 (7%) patients receiving nephrologist care. After matching to patients receiving primary care alone, those receiving nurse practitioner care had greater use of angiotensin-converting enzyme inhibitors/angiotensin receptor blocker (82% versus 79%; absolute differences [ADs] 3.4% [95% confidence interval, 0.0% to 6.9%]) and statins (75% versus 66%; AD 9.7% [5.8% to 13.6%]), fewer prescriptions of nonsteroidal anti-inflammatory drugs (10% versus 17%; AD -7.2% [-10.4% to -4.2%]), greater eGFR and albuminuria monitoring, and lower rates of all-cause hospitalization (34.1 versus 43.3; rate difference -9.2 [-14.7 to -3.8] per 100 person-years) and all-cause mortality (3.3 versus 6.0; rate difference -2.7 [-3.6 to -1.7] per 100 person-years). When matched to patients receiving nephrologist care, those receiving nurse practitioner care were also more likely to be prescribed angiotensin-converting enzyme inhibitors/angiotensin receptor blockers and statins, with no difference in the risks of experiencing adverse clinical outcomes., Conclusions: Nurse practitioner care for patients with CKD was associated with better guideline-concordant care than primary care alone or nephrologist care, with clinical outcomes that were better than or equivalent to primary care alone and similar to those with care by nephrologists., Podcast: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/CJASN/2023&#95;12&#95;08&#95;CJN0000000000000305.mp3., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.)

Background Patients with chronic kidney disease (CKD) can experience acute coronary syndromes (ACS) with high morbidity and mortality. Early invasive management of ACS is recommended for most high-risk patients; however, choosing between an early invasive versus conservative management approach may be influenced by the unique risk of kidney failure for patients with CKD. Methods and Results This discrete choice experiment measured the preferences of patients with CKD for future cardiovascular events versus acute kidney injury and kidney failure following invasive heart procedures for ACS. The discrete choice experiment, consisting of 8 choice tasks, was administered to adult patients attending 2 CKD clinics in Calgary, Alberta. The part-worth utilities of each attribute were determined using multinomial logit models, and preference heterogeneity was explored using latent class analysis. A total of 140 patients completed the discrete choice experiment. The mean age of patients was 64 years, 52% were male, and mean estimated glomerular filtration rate was 37 mL/min per 1.73 m 2 . Across the range of levels, risk of mortality was the most important attribute, followed by risk of end-stage kidney disease and risk of recurrent myocardial infarction. Latent class analysis identified 2 distinct preference groups. The largest group included 115 (83%) patients, who placed the greatest value on treatment benefits and expressed the strongest preference for reducing mortality. A second group of 25 (17%) patients was identified who were procedure averse and had a strong preference toward conservative management of ACS and avoiding acute kidney injury requiring dialysis. Conclusions The preferences of most patients with CKD for management of ACS were most influenced by lowering mortality. However, a distinct subgroup of patients was strongly averse to invasive management. This highlights the importance of clarifying patient preferences to ensure treatment decisions are aligned with patient values.

Objective: The aim of this study was to estimate the association between estimated glomerular filtration rate (eGFR) and acute myocardial infarction (AMI) or death after ambulatory noncardiac surgery., Summary Background Data: People with chronic kidney disease (CKD) commonly undergo surgical procedures. Although most are performed in an ambulatory setting, the risk of major perioperative outcomes after ambulatory surgery for people with CKD is unknown., Methods: In this retrospective population-based cohort study using administrative health data from Alberta, Canada, we included adults with measured preoperative kidney function undergoing ambulatory noncardiac surgery between April 1, 2005 and February 28, 2017. Participants were categorized into 6 eGFR categories (in mL/min/1.73m 2 )of ≥60 (G1-2), 45 to 59 (G3a), 30 to 44 (G3b), 15 to 29 (G4), <15 not receiving dialysis (G5ND), and those receiving chronic dialysis (G5D). The odds of AMI or death within 30 days of surgery were estimated using multivariable generalized estimating equation models., Results: We identified 543,160 procedures in 323,521 people with a median age of 66 years (IQR 56-76); 52% were female. Overall, 2338 people (0.7%) died or had an AMI within 30 days of surgery. Compared with the G1-2 category, the adjusted odds ratio of death or AMI increased from 1.1 (95% confidence interval: 1.0-1.3) for G3a to 3.1 (2.6-3.6) for G5D. Emergency Department and Urgent Care Center visits within 30 days were frequent (17%), though similar across eGFR categories., Conclusions: Ambulatory surgery was associated with a low risk of major postoperative events. This risk was higher for people with CKD, which may inform their perioperative shared decision-making and management., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: People with kidney failure receiving dialysis (CKD-G5D) are more likely to undergo surgery and experience poorer postoperative outcomes than those without kidney failure. In this scoping review, we aimed to systematically identify and summarize perioperative strategies, protocols, pathways, and interventions that have been studied or implemented for people with CKD-G5D., Methods: We searched MEDLINE, EMBASE, CINAHL Plus, Cochrane Database of Systematic Reviews, and Cochrane Controlled Trials registry (inception to February 2020), in addition to an extensive grey literature search, for sources that reported on a perioperative strategy to guide management for people with CKD-G5D. We summarized the overall study characteristics and perioperative management strategies and identified evidence gaps based on surgery type and perioperative domain. Publication trends over time were assessed, stratified by surgery type and study design., Results: We included 183 studies; the most common study design was a randomized controlled trial (27%), with 67% of publications focused on either kidney transplantation or dialysis vascular access. Transplant-related studies often focused on fluid and volume management strategies and risk stratification, whereas dialysis vascular access studies focused most often on imaging. The number of publications increased over time, across all surgery types, though driven by non-randomized study designs., Conclusions: Despite many current gaps in perioperative research for patients with CKD-G5D, evidence generation supporting perioperative management is increasing, with recent growth driven primarily by non-randomized studies. Our review may inform organization of evidence-based strategies into perioperative care pathways where evidence is available while also highlighting gaps that future perioperative research can address., (© 2022 Wiley Periodicals LLC.)

Background: There is limited research of electronic tools for self-management for patients with chronic kidney disease (CKD). We sought to evaluate participant engagement, perceived self-efficacy and website usage in a preliminary evaluation of My Kidneys My Health, a patient-facing eHealth tool in Canada., Methods: We conducted an explanatory sequential mixed-methods study of adults with CKD who were not on kidney replacement therapy and who had access to My Kidneys My Health for 8 weeks. Outcomes included acceptance (measured by the Technology Acceptance Model), self-efficacy (measured by the Chronic Disease Self-Efficacy Scale [CDSES]) and website usage patterns (captured using Google Analytics). We analyzed participant interviews using qualitative content analysis., Results: Twenty-nine participants with CKD completed baseline questionnaires, of whom 22 completed end-of-study questionnaires; data saturation was achieved with 15 telephone interviews. Acceptance was high, with more than 70% of participants agreeing or strongly agreeing that the website was easy to use and useful. Of the 22 who completed end-of-study questionnaires, 18 (82%) indicated they would recommend its use to others and 16 (73%) stated they would use the website in the future. Average scores for website satisfaction and look and feel were 7.7 (standard deviation [SD] 2.0) and 8.2 (SD 2.0) out of 10, respectively. The CDSES indicated that participants gained an increase in CKD information. Interviewed participants reported that the website offered valuable information and interactive tools for patients with early or newly diagnosed CKD, or for those experiencing changes in health status. Popular website pages and interactive features included Food and Diet, What is CKD, My Question List and the Depression Screener., Interpretation: Participants indicated that the My Kidneys My Health website provided accessible content and tools that may improve self-efficacy and support in CKD self-management. Further evaluation of the website's effectiveness in supporting self-management among a larger, more heterogenous population is warranted., Competing Interests: Competing interests: None declared., (© 2022 CMA Impact Inc. or its licensors.)

Introduction: Information on early, guideline discordant referrals in nephrology is limited. Our objective was to investigate trends in referral patterns to nephrology for patients with chronic kidney disease (CKD)., Methods: Retrospective cohort study of adults with ≥1 visits to a nephrologist from primary care with ≥1 serum creatinine and/or urine protein measurement <180 days before index nephrology visit, from 2006 and 2019 in Alberta, Canada. Guideline discordant referrals were those that did not meet ≥1 of: Estimated glomerular filtration rate (eGFR) ˂ 30 mL/min/1.73m2, persistent albuminuria (ACR ≥ 300 mg/g, PCR ≥ 500 mg/g, or Udip ≥ 2+), or progressive and persistent decline in eGFR until index nephrology visit (≥ 5 mL/min/1.73m2)., Results: Of 69,372 patients with CKD, 28,518 (41%) were referred in a guideline concordant manner. The overall rate of first outpatient visits to nephrology increased from 2006 to 2019, although guideline discordant referrals showed a greater increase (trend 21.9 per million population/year, 95% confidence interval 4.3, 39.4) versus guideline concordant referrals (trend 12.4 per million population/year, 95% confidence interval 5.7, 19.0). The guideline concordant cohort were more likely to be on renin-angiotensin system blockers or beta blockers (hazard ratio 1.14, 95% confidence interval 1.12, 1.16), and had a higher risk of CKD progression (hazard ratio 1.09, 95% confidence interval 1.06, 1.13), kidney failure (hazard ratio 7.65, 95% confidence interval 6.83, 8.56), cardiovascular event (hazard ratio 1.40, 95% confidence interval 1.35,1.45) and mortality (hazard ratio 1.58, 95% confidence interval 1.52, 1.63)., Conclusions: A significant proportion nephrology referrals from primary care were not consistent with current guideline-recommended criteria for referral. Further work is needed to identify quality improvement initiatives aimed at enhancing referral patterns of patients with CKD., Competing Interests: The authors have declared that no competing interests exist.

Rationale & Objective: The KDIGO (Kidney Disease: Improving Global Outcomes) definition of acute kidney injury (AKI) is frequently used in studies to examine the epidemiology of AKI. This definition is variably interpreted and applied to routinely collected health care data. The aim of this study was to examine this variation and to achieve consensus in how AKI should be defined for research using routinely collected health care data., Sources of Evidence and Study Design: Scoping review via searching Medline and EMBASE for studies using health care data to examine AKI by using the KDIGO creatinine-based definition. An international panel of experts formed to participate in a modified Delphi process to attempt to generate consensus about how AKI should be defined when using routinely collected laboratory data., Charting Methods and Analytical Approach: The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) extension for scoping reviews was followed. For the Delphi process, 2 rounds of questions were distributed via internet-based questionnaires to all participants with a prespecified cutoff of 75% agreement used to define consensus., Results: The scoping review found 174 studies that met the inclusion criteria. The KDIGO definition was inconsistently applied, and the methods for application were poorly described. We found 58 (33%) of papers did not provide a definition of how the baseline creatinine value was determined, and only 34 (20%) defined recovery of kidney function. Of 55 invitees to the Delphi process, 35 respondents participated in round 1, and 25 participated in round 2. Some consensus was achieved in areas related to how to define the baseline creatinine value, which patients should be excluded from analysis of routinely collected laboratory data, and how persistent chronic kidney disease or nonrecovery of AKI should be defined., Limitations: The Delphi panel members predominantly came from the United Kingdom, the United States, and Canada, and there were low response rates for some questions in round 1., Conclusions: The current methods for defining AKI using routinely collected data are inconsistent and poorly described in the available literature. Experts could not achieve consensus for many aspects of defining AKI and describing its sequelae. The KDIGO guidelines should be extended to include a standardized definition for how AKI should be defined when using routinely collected data., (Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Importance: Although the public is aware that cancer is associated with excess mortality and adverse outcomes, the clinical consequences of chronic kidney disease (CKD) are not well understood., Objective: To compare the clinical consequences of incident severe CKD and the first diagnosis with a malignant tumor, focusing on the 10 leading causes of cancer in men and women residing in Canada., Design, Setting, and Participants: This population-based cohort study enrolled individuals aged 19 years and older with severe CKD or certain types of cancer between 2004 and 2015 in Alberta, Canada. Data were analyzed in November 2021., Exposures: Individuals were categorized as having severe CKD (based on estimated glomerular filtration rate <30 mL/min/1.73 m2 or nephrotic albuminuria without dialysis or kidney transplantation) or nonmetastatic or metastatic cancer (defined by a diagnosis of lung, breast, colorectal, prostate, bladder, thyroid, kidney or renal pelvis, uterus, pancreas, or oral cancer)., Main Outcomes and Measures: All-cause mortality, number of hospitalizations, total number of hospital days, and placement into long-term care were calculated after diagnosis., Results: Of 200 494 individuals in the cohort (104 559 women [52.2%]; median [IQR] age, 66.8 [55.9-77.7] years), 51 159 (25.5%) had incident severe CKD, 115 504 (57.6%) had nonmetastatic cancer, and 33 831 (16.9%) had metastatic cancer. Kaplan-Meier 1-year survival was 83.3% (95% CI, 83.0%-83.6%) for patients with CKD, 91.2% (95% CI, 91.0%-91.4%) for patients with nonmetastatic cancer, and 52.8% (95% CI, 52.2%-53.3%) for patients with metastatic cancer. Kaplan-Meier 5-year survival was 54.6% (95% CI, 54.2%-55.1%) for patients with CKD, 76.6% (95% CI, 76.3%-76.8%) for patients with nonmetastatic cancer, and 33.9% (95% CI, 33.3%-34.4%) for patients with metastatic cancer. Compared with nonmetastatic cancer, the age-, sex-, and comorbidity-adjusted relative rate of death was similar for CKD (adjusted relative rate, 1.00; 95% CI, 0.97-1.03; P = .92) during the first year of follow-up and was higher for CKD at years 1 to 5 (adjusted relative rate 1.23; 95% CI, 1.19-1.26). During the first year of follow-up, for patients with CKD, adjusted rates of placement in long-term care (adjusted relative rate, 0.88; 95% CI, 0.82-0.94) and hospitalization (adjusted relative rate, 0.65; 95% CI, 0.64-0.66) were lower than rates for patients with nonmetastatic cancer; however, those rates were higher for the CKD group than for the nonmetastatic cancer group during years 1 to 5 (long-term care placement, adjusted relative rate, 1.36; 95% CI, 1.29-1.43; hospitalization, adjusted relative rate, 1.55; 95% CI, 1.52-1.58). As expected, adjusted rates of long-term care placement and hospitalization were higher for patients with metastatic cancer than for the other 2 groups., Conclusions and Relevance: In this study, mortality, hospitalization, and likelihood of placement into long-term care were similar for CKD and nonmetastatic cancer. These data highlight the importance of CKD as a public health problem.

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.

Background: Guidelines recommend referral for nephrology consultation for people with severe chronic kidney disease (CKD) to improve care and renal outcomes, yet the advocated benefits of nephrology referral on CKD progression in this patient population are unclear., Methods: We linked laboratory and administrative data in Alberta, Canada to identify adults with stage 4 CKD between 2002 and 2014 (follow-up end on March 31, 2017). We studied the association between time-varying receipt of outpatient nephrology consultation and kidney failure (the earlier of renal replacement initiation or eGFR < 10 mL/min/1.73 m 2 for more than 3 months), accounting for the competing risk of death., Results: Of the 14,382 participants, 41% were ≥ 85 years old, 33% saw a nephrologist as an outpatient, 9% developed kidney failure, and 53% died over a median of 2.6 years. Compared with people who did not see a nephrologist before or at 7 months (median time to consultation), those who did were more likely to develop kidney failure [5-year risk (95% CI) 0.23 (0.21-0.24) vs 0.07 (0.065-0.075)]. With increasing age or higher eGFR, the 5-year risk of kidney failure became progressively smaller, from 0.24 (0.18-0.29) at age < 65 to 0.01 (0.006-0.015) at age ≥ 85 years and from 0.21 (0.18-0.23) at eGFR 15-19 to 0.066 (0.060-0.072) at eGFR 25-29 mL/min/1.73 m 2 ; yet, the hazard ratio of kidney failure (1.6-4.3) increased following nephrology consultation in people who were older or had higher eGFR., Conclusions: Adults with stage 4 CKD who see a nephrologist are more likely to develop kidney failure than those who don't, especially within lower absolute risk categories. Although selective referral may explain these findings, there is no evidence of an association between nephrology care and reduced risk of kidney failure in people with severe CKD. Studies are needed to assess the benefits of nephrology consultation in people with moderate CKD., (© 2020. Italian Society of Nephrology.)

Objective: The aim of this study was to examine relationships between ileostomy formation and subsequent kidney disease., Summary and Background Data: Colonic absorptive capacity loss from ileostomy formation can cause volume depletion and could result in kidney disease., Methods: We conducted a population-based cohort study comparing patients who underwent ileostomy formation with or without bowel resection (ileostomy group) to patients who underwent bowel resection without ileostomy formation (reference group). Adjusted odds ratios (aORs) for community-onset acute kidney injury (AKI) within 3 months and new-onset chronic kidney disease (CKD) within 1 year following hospital discharge were determined., Results: Among 19,889 patients, 4136 comprised the ileostomy group and 15,753 comprised the reference group; 1350 patients experienced community-onset AKI and 464 developed new-onset CKD. The aOR for community-onset AKI with ileostomy formation was 4.08 [95% confidence interval (CI) = 3.62-4.61] for any stage AKI, 7.08 (95% CI = 5.66-8.85) for stage ≥2 injury, and 7.67 (95% CI = 5.06-11.63) for stage 3 injuries. Community-onset AKI modified associations between ileostomy formation and new-onset CKD (P = 0.002). Odds of new-onset CKD were increased in the ileostomy group relative to the reference group for patients both with (aOR = 4.99; 95% CI = 3.42-7.28) and without (aOR = 2.45; 95% CI = 1.85-2.23) previous community-onset AKI episodes. In analyses comparing patients that underwent ileostomy formation and subsequent reversal within 1 year to the reference group without ileostomy, the relationship with new-onset CKD was attenuated for patients both with (aOR = 2.49; 95% CI = 1.50-4.12) and without (aOR = 0.97; 95% CI = 0.67-1.40) previous community-onset AKI episodes., Conclusions: Ileostomy formation is strongly associated with subsequent kidney disease. Vigilance for this complication and new strategies for prevention and treatment are necessary., Competing Interests: The authors report no conflict of interests., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Patients with chronic kidney disease (CKD) and heart disease face challenging treatment decisions. We sought to explore the perceptions of patients and physicians about shared decision-making for coronary procedures for people with CKD, as well as opinions about strategies and tools to improve these decisions., Methods: We partnered with 4 patients with CKD and 1 caregiver to design and conduct a qualitative descriptive study using semi-structured interviews and content analysis. Patient participants with CKD and either acute coronary syndrome or cardiac catheterization in the preceding year were recruited from a provincial cardiac registry, cardiology wards and clinics in Calgary between March and September 2018. Cardiologists from the region also participated in the study. Data analysis emphasized identifying, organizing and describing themes found within the data., Results: Twenty patients with CKD and 10 cardiologists identified several complexities related to bidirectional information exchange needed for shared decision-making. Themes identified by both patients and physicians included challenges synthesizing best evidence, variable patient knowledge seeking, timeliness in the acute care setting and influence of roles on decision-making. Themes identified by physicians related to processes and tools to help support shared decision-making in this setting included personalization to reflect the variability of risks and heterogeneity of patient preferences as well as allowing for physicians to share their clinical judgment., Interpretation: There are complexities related to bidirectional information exchange between patients with CKD and their physicians for shared decision-making about coronary procedures. Processes and tools to facilitate shared decision-making in this setting require personalization and need to be time sensitive., Competing Interests: Competing interests: Matthew James has received investigator-initiated research grant funding for unrelated work from Amgen Canada. No other competing interests were declared., (Copyright 2020, Joule Inc. or its licensors.)

Importance: With population aging, the burden of many age-related chronic conditions, including kidney failure, is increasing globally., Objective: To investigate the risks of kidney failure and death in adults with incident stage IV chronic kidney disease (CKD)., Design, Setting, and Participants: This population-based cohort study obtained data recorded between July 30, 2002, and March 31, 2014, from the linked laboratory and administrative data set of Alberta Health in Alberta, Canada. All adults of the province of Alberta with stage IV CKD (estimated glomerular filtration rate [eGFR] of 15-30 mL/min/1.73 m2) were eligible for inclusion. Included individuals were followed up from study entry until the date of kidney failure, death, or censoring, whichever occurred first. Observations were censored at the date of emigration from the province, the study end date (March 31, 2017), or at 10 years after study entry. Data analyses were performed from January 2020 to June 2020., Main Outcomes and Measures: The primary outcome was kidney failure, defined as the earlier of either renal replacement (dialysis or kidney transplant) initiation or severe kidney impairment (eGFR <10 mL/min/1.73 m2). Incidence of stage IV CKD in Alberta was examined over time, along with the association between age at study entry and the competing risks of kidney failure and death. Cumulative incidence functions (95% CIs) were estimated to summarize absolute risks over time across categories of age, accounting for sex, diabetes, cardiovascular disease, eGFR, and albuminuria., Results: The study included 30 801 adults (mean [SD] age, 76.8 [13.3] years; 17 294 women [56.1%]) with stage IV CKD. Of these, 5511 developed kidney failure (17.9%) and 16 285 died (52.9%). The incidence rate of stage IV CKD increased sharply with advancing age; the absolute risk of kidney failure decreased with advancing age, and the risk of death increased, especially in those aged 85 years or older. Compared with the 5-year risk of death, the 5-year risk of kidney failure was higher in people younger than 65 years, similar in people aged 65 to 74 years, and lower for older age groups. For those aged 75 years or older, the risk of death was much higher than the risk of kidney failure: 6-fold higher among those aged 75 to 84 years (0.51 [95% CI, 0.5-0.52] vs 0.09 [95% CI, 0.08-0.09]) and 25-fold higher among those aged 85 years or older (0.75 [95% CI, 0.74-0.76] vs 0.03 [95% CI, 0.02-0.03]). The risk of death was higher than the risk of kidney failure by 24-fold among those aged 85 to 94 years (0.73 [95% CI, 0.72-0.74] vs 0.03 [95% CI, 0.02-0.03]) and by 149-fold among those aged 95 years or older (0.89 [95% CI, 0.87-0.92] vs <0.01 [95% CI, <0.01 to 0.01])., Conclusions and Relevance: This study found that, although the incidence rate of stage IV CKD increased with advancing age, the absolute risk of kidney failure decreased. Unlike other age-related conditions, the expected increase in the burden of kidney failure in the older adults may be less dramatic than expected.

Acute kidney injury (AKI), once viewed predominantly as a self-limited and reversible condition, is now recognized as a growing problem associated with significant risks of adverse long-term health outcomes. Many cohort studies have established important relationships between AKI and subsequent risks of recurrent AKI, hospital re-admission, morbidity and mortality from cardiovascular disease and cancer, as well as the development of chronic kidney disease and end-stage kidney disease. In both high-income countries (HICs) and low-income or middle-income countries (LMICs), several challenges exist in providing high-quality, patient-centered care following AKI. Despite advances in our understanding about the long-term risks following AKI, large gaps in knowledge remain about effective interventions that can improve the outcomes of patients. Therapies for high blood pressure, glycaemic control (for patients with diabetes), renin-angiotensin inhibition and statins might be important in improving long-term cardiovascular and kidney outcomes after AKI. Novel strategies that incorporate risk stratification approaches, educational interventions and new models of ambulatory care following AKI have been described, and some of these are now being implemented and evaluated in clinical studies in HICs. Care for AKI in LMICs must overcome additional barriers due to limited resources for diagnosis and management.

Background: Urine albumin-to-creatinine ratio (ACR) and protein-to-creatinine ratio (PCR) are used to measure urine protein. Recent guidelines endorse ACR use, and equations have been developed incorporating ACR to predict risk of kidney failure. For situations in which PCR only is available, having a method to estimate ACR from PCR as accurately as possible would be useful., Methods: We used data from a population-based cohort of 47,714 adults in Alberta, Canada, who had simultaneous assessments of urine ACR and PCR. After log-transforming ACR and PCR, we used cubic splines and quantile regression to estimate the median ACR from a PCR, allowing for modification by specified covariates. On the basis of the cubic splines, we created models using linear splines to develop equations to estimate ACR from PCR. In a subcohort with eGFR<60 ml/min per 1.73 m 2 , we then used the kidney failure risk equation to compare kidney failure risk using measured ACR as well as estimated ACR that had been derived from PCR., Results: We found a nonlinear association between log(ACR) and log(PCR), with the implied albumin-to-protein ratio increasing from <30% in normal to mild proteinuria to about 70% in severe proteinuria, and with wider prediction intervals at lower levels. Sex was the most important modifier of the relationship between ACR and PCR, with men generally having a higher albumin-to-protein ratio. Estimates of kidney failure risk were similar using measured ACR and ACR estimated from PCR., Conclusions: We developed equations to estimate the median ACR from a PCR, optionally including specified covariates. These equations may prove useful in certain retrospective clinical or research applications where only PCR is available., (Copyright © 2020 by the American Society of Nephrology.)

Rationale & Objective: Fostering the ability of patients to self-manage their chronic kidney disease (CKD), with support from caregivers and providers, may slow disease progression and improve health outcomes. However, little is known about such patients' needs for self-management interventions. We aimed to identify and describe the needs of adults with CKD and informal caregivers for CKD self-management support., Study Design: Descriptive qualitative study using semi-structured interviews and focus groups., Setting & Participants: 6 focus groups (37 participants) and 11 telephone interviews with adults with CKD (stages 1-5, not on renal replacement therapy) and informal caregivers from across Canada., Analytic Approach: Thematic analysis., Results: 3 major themes were identified: (1) empowerment through knowledge (awareness and understanding of CKD, diet challenges, medication and alternative treatments, attuning to the body, financial implications, mental and physical health consequences, travel and transportation restrictions, and maintaining work and education), (2) activation through information sharing (access, meaningful and relevant, timing, and amount), and (3) tangible supports for the health journey (family, community, and professionals)., Limitations: Participants were primarily white, educated, married, and English speaking, which limits generalizability., Conclusions: There are opportunities to enhance CKD self-management support by addressing knowledge pertinent to living well with CKD and priority areas for sharing information and providing tangible support. Future efforts may consider the development of innovative CKD self-management support interventions based on the diverse patient and caregiver needs identified in this study., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Despite the interrelationships between obesity, eGFR and albuminuria, few large studies examine how obesity modifies the association between these markers of kidney function and adverse clinical outcomes., Methods: We examined the joint associations between obesity, eGFR and albuminuria on four clinical outcomes (death, end-stage renal disease [ESRD], myocardial infarction [MI], and placement in a long-term care facility) using a population-based cohort with procedures from Alberta. Obesity was defined by body mass index ≥35 kg/m 2 as defined by a fee modifier applied to an eligible procedure., Results: We studied 1,293,362 participants, of whom 171,650 (13.3%) had documented obesity (BMI ≥ 35 kg/m 2 based on claims data) and 1,121,712 (86.7%) did not. The association between eGFR and death was J-shaped for participants with and without documented obesity. After full adjustment, obesity tended to be associated with slightly lower odds of mortality (OR range 0.71-1.02; p for interaction between obesity and eGFR 0.008). For participants with and without obesity, the adjusted odds of ESRD were lowest for participants with eGFR > 90 mL/min*1.73m 2 and increased with lower eGFR, with no evidence of an interaction with obesity (p = 0.37). Although albuminuria and obesity were both associated with higher odds of ESRD, the excess risk associated with obesity was substantially attenuated at higher levels of albuminuria (p for interaction 0.0006). The excess risk of MI associated with obesity was observed at eGFR > 60 mL/min*1.73m 2 but not at lower eGFR (p for interaction < 0.0001). Participants with obesity had a higher adjusted likelihood of placement in long-term care than those without, and the likelihood of such placement was higher at lower eGFR for those with and without obesity (p for interaction = 0.57)., Conclusions: We found significant interactions between obesity and eGFR and/or albuminuria on the likelihood of adverse outcomes including death and ESRD. Since obesity is common, risk prediction tools for people with CKD might be improved by adding information on BMI or other proxies for body size in addition to eGFR and albuminuria.

Importance: Abnormal measurements of kidney function or structure may be identified that do not meet criteria for acute kidney injury (AKI) or chronic kidney disease (CKD) but nonetheless may require medical attention. The Kidney Disease: Improving Global Outcomes Clinical Practice Guideline for AKI proposed criteria for the definition of acute kidney diseases and disorders (AKD), which include AKI; however, the incidence and prognosis of AKD without AKI remain unknown., Objective: To characterize the incidence and outcomes of AKD without AKI, with or without CKD., Design, Setting, and Participants: Retrospective cohort study including all adult residents in a universal health care system in Alberta, Canada, without end-stage kidney disease (ESKD) and with at least 1 serum creatinine measurement between January 1 and December 31, 2008, in a community or hospital setting. Data analysis took place in 2018., Main Outcomes and Measures: The Kidney Disease: Improving Global Outcomes guideline definitions for CKD, AKI, and AKD based on serum creatinine, estimated glomerular filtration rate, and albuminuria criteria were applied to estimate the proportion of patients with CKD, AKI, and AKD without AKI, and combinations of the conditions. Patients were followed up for up to 8 years (study end date, June 31, 2016) to characterize their risks of mortality, development of new CKD, progression of preexisting CKD, and ESKD., Results: Among 1 109 099 Alberta residents included in the cohort, the mean (SD) age was 52.3 (17.6) years, and 43.0% were male. Findings showed that AKD without AKI was common (3.8 individuals without preexisting CKD and 0.6 with preexisting CKD per 100 population tested). In Cox proportional hazards and competing risks models over a median (interquartile range) of 6.0 (5.7-6.3) years of follow-up, AKD without AKI (compared with no kidney disease) was associated with higher risks of developing new CKD (37.4% vs 7.4%%; adjusted sub-hazard ratio [sHR], 3.17; 95% CI, 3.10-3.23), progression of preexisting CKD (49.5% vs 34.6%; adjusted sHR, 1.38; 95% CI, 1.33-1.44), ESKD (0.6% vs 0.1%; adjusted sHR, 8.56; 95% CI, 7.32-10.01), and death (25.8% vs 7.3%; adjusted hazard ratio, 1.42; 95% CI, 1.39-1.45)., Conclusions and Relevance: Criteria for AKD identified many patients who did not meet the criteria for CKD or AKI but had overall modestly increased risks of incident and progressive CKD, ESKD, and death. The clinical importance of AKD remains to be determined.

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.)

In older people with chronic kidney disease (CKD) and comorbidities, the risk of death or disability may overshadow the risk of kidney failure. To help refine this we did a retrospective population-based cohort study to evaluate the relative likelihood of adverse outcomes as functions of age and comorbidity burden among 47,228 adults with severe non-dialysis dependent CKD. We identified comorbidities using 29 validated algorithms applied to administrative data and assessed death, end-stage renal disease (ESRD), cardiovascular disease (CVD) events, and long-term care. Over five years of follow-up, 53.4% of participants died, 24.1% had a CVD event, 14.3% were placed into long-term care and 5.3% developed ESRD. Death was 145 times more likely and 11 times more likely than ESRD for participants aged 80 years or more and 60-79 years, respectively; long-term care was 30 times more likely and 1.7 times as likely as ESRD for participants aged 80 years or more and 60-79 years, respectively. Increasing comorbidity burden was similarly associated with increased risk of death and long-term care placement but reduced the likelihood of ESRD, and the risks of increasing age were similarly incremental. Thus, among patients with severe CKD, older age and/or higher comorbidity burden, death and long-term care placement are markedly more likely than ESRD. Hence, clinicians, patients and families should all consider the relative magnitude of these risks when making decisions about renal replacement., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Objective: To systematically identify and describe self-management interventions for adult patients with chronic kidney disease (CKD)., Setting: Community-based., Participants: Adults with CKD stages 1-5 (not requiring kidney replacement therapy)., Interventions: Self-management strategies for adults with CKD., Primary and Secondary Outcome Measures: Using a scoping review, electronic databases and grey literature were searched in October 2016 to identify self-management interventions for adults with CKD stages 1-5 (not requiring kidney replacement therapy). Randomised controlled trials (RCTs), non-RCTs, qualitative and mixed method studies were included and study selection and data extraction were independently performed by two reviewers. Outcomes included behaviours, cognitions, physiological measures, symptoms, health status and healthcare., Results: Fifty studies (19 RCTs, 7 quasi-experimental, 5 observational, 13 pre-post intervention, 1 mixed method and 5 qualitative) reporting 45 interventions were included. The most common intervention topic was diet/nutrition and interventions were regularly delivered face to face. Interventions were administered by a variety of providers, with nursing professionals the most common health professional group. Cognitions (ie, changes in general CKD knowledge, perceived self-management and motivation) were the most frequently reported outcome domain that showed improvement. Less than 1% of the interventions were co-developed with patients and 20% were based on a theory or framework., Conclusions: There was a wide range of self-management interventions with considerable variability in outcomes for adults with CKD. Major gaps in the literature include lack of patient engagement in the design of the interventions, with the majority of interventions not applying a behavioural change theory to inform their development. This work highlights the need to involve patients to co-developed and evaluate a self-management intervention based on sound theories and clinical evidence., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

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.

Background: The prevalence of menopause in women with or at risk of chronic kidney disease is increasing globally. Although international guidelines on menopause recommend the use of postmenopausal hormone therapy with or without selective estrogen receptor modulators for control of vasomotor symptoms, the effects of these treatments on kidney function and albuminuria are unclear. Furthermore, women with chronic kidney disease are at significantly increased risk of venous thromboembolism and malignancy, well-documented adverse effects of postmenopausal hormone therapy. Our study aims to establish the effect of these treatments on kidney function and albuminuria in women, as well as determine the safety of these treatments in the chronic kidney disease population., Methods: We will conduct a systematic review and meta-analysis addressing the effect and safety of postmenopausal hormone therapy and selective estrogen receptor modulators on kidney outcomes in women. We plan to search for published (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), tables of contents of relevant journals) and unpublished (ongoing studies, conference proceedings) studies in all languages examining the effect of postmenopausal hormone therapy, including selective estrogen receptor modulators, on kidney function and albuminuria, as well as the risk of adverse outcomes of these treatments in women with chronic kidney disease. Two independent investigators will screen identified abstracts and select studies that examine the effect of postmenopausal hormone therapy and selective estrogen receptor modulators on kidney outcomes in the general population or adverse outcomes in the chronic kidney disease population. Data on study population, intervention, outcomes, as well as study quality and risk of bias will be independently extracted from each eligible study. Along with descriptive presentation of data, outcome measures will be presented as meta-analyses using a random effects model. Planned subgroup analyses will be completed, and meta-regression will be performed if significant heterogeneity is noted., Discussion: By examining the effects of postmenopausal hormone therapy and selective estrogen receptor modulators on kidney function and albuminuria, the results of this systematic review and meta-analysis will inform management of postmenopausal women in the general population. Furthermore, it will evaluate the safety, including the risks of known adverse outcomes of postmenopausal hormone therapy and selective estrogen receptor modulators, in the already vulnerable chronic kidney disease population., Systematic Review Registration: PROSPERO CRD42016050651.

Canadian indigenous (First Nations) have rates of kidney failure that are 2- to 4-fold higher than the non-indigenous general Canadian population. As such, a strategy of targeted screening and treatment for CKD may be cost-effective in this population. Our objective was to assess the cost utility of screening and subsequent treatment for CKD in rural Canadian indigenous adults by both estimated glomerular filtration rate and the urine albumin-to-creatinine ratio. A decision analytic Markov model was constructed comparing the screening and treatment strategy to usual care. Primary outcomes were presented as incremental cost-effectiveness ratios (ICERs) presented as a cost per quality-adjusted life-year (QALY). Screening for CKD was associated with an ICER of $23,700/QALY in comparison to usual care. Restricting the model to screening in communities accessed only by air travel (CKD prevalence 34.4%), this ratio fell to $7,790/QALY. In road accessible communities (CKD prevalence 17.6%) the ICER was $52,480/QALY. The model was robust to changes in influential variables when tested in univariate sensitivity analyses. Probabilistic sensitivity analysis found 72% of simulations to be cost-effective at a $50,000/QALY threshold and 93% of simulations to be cost-effective at a $100,000/QALY threshold. Thus, targeted screening and treatment for CKD using point-of-care testing equipment in rural Canadian indigenous populations is cost-effective, particularly in remote air access-only communities with the highest risk of CKD and kidney failure. Evaluation of targeted screening initiatives with cluster randomized controlled trials and integration of screening into routine clinical visits in communities with the highest risk is recommended., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background: The effectiveness and safety of warfarin use among patients with atrial fibrillation (AF) and reduced kidney function are uncertain., Study Design: Community-based retrospective cohort study (May 1, 2003, to March 31, 2012) using province-wide laboratory and administrative data in Alberta, Canada., Setting & Participants: 14,892 adults 66 years or older with new AF and a measurement of kidney function. Long-term dialysis patients or kidney transplant recipients were excluded., Predictor: Propensity scores were used to construct a matched-pairs cohort of patients with AF who did and did not have a warfarin prescription within a 60-day period surrounding their AF diagnosis., Outcomes: Within 1 year of initiating warfarin therapy (or the matched date for nonusers): (1) the composite of all-cause death, ischemic stroke, or transient ischemic attack (also assessed as separate end points) and (2) first hospitalization or emergency department visit for a major bleeding episode defined as an intracranial, upper or lower gastrointestinal, or other bleeding., Measurements: Baseline glomerular filtration rate (GFR) was estimated using the CKD-EPI creatinine equation. Patients were matched within estimated GFR (eGFR) categories: ≥90, 60 to 89, 45 to 59, 30 to 44, and <30mL/min/1.73m 2 . Information for baseline characteristics (sociodemographics, comorbid conditions, and prescription drug use) was obtained., Results: Across eGFR categories, warfarin therapy initiation was associated with lower risk for the composite outcome compared to nonuse (adjusted HRs [95% CI] for eGFR categories ≥ 90, 60-89, 45-59, 30-44, and <30mL/min/1.73m 2 : 0.59 [0.35-1.01], 0.61 [0.54-0.70], 0.55 [0.47-0.65], 0.54 [0.44-0.67], and 0.64 [0.47-0.87] mL/min/1.73m 2 , respectively). Compared to nonuse, warfarin therapy was not associated with higher risk for major bleeding except for those with eGFRs of 60 to 89mL/min/1.73m 2 (HR, 1.36; 95% CI, 1.13-1.64)., Limitations: Selection bias., Conclusions: Among older adults with AF, warfarin therapy initiation was associated with a significantly lower 1-year risk for the composite outcome across all strata of kidney function. The risk for major bleeding associated with warfarin use was increased only among those with eGFRs of 60 to 89mL/min/1.73m 2 ., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Although prior studies have observed high resource use among patients with CKD, there is limited exploration of emergency department use in this population and the proportion of encounters related to CKD care specifically., Design, Setting, Participants, & Measurements: We identified all adults (≥18 years old) with eGFR<60 ml/min per 1.73 m 2 (including dialysis-dependent patients) in Alberta, Canada between April 1, 2010 and March 31, 2011. Patients with CKD were linked to administrative data to capture clinical characteristics and frequency of emergency department encounters and followed until death or end of study (March 31, 2013). Within each CKD category, we calculated adjusted rates of overall emergency department use as well as rates of potentially preventable emergency department encounters (defined by four CKD-specific ambulatory care-sensitive conditions: heart failure, hyperkalemia, volume overload, and malignant hypertension)., Results: During mean follow-up of 2.4 years, 111,087 patients had 294,113 emergency department encounters; 64.2% of patients had category G3A CKD, and 1.6% were dialysis dependent. Adjusted rates of overall emergency department use were highest among patients with more advanced CKD; 5.8% of all emergency department encounters were for CKD-specific ambulatory care-sensitive conditions, with approximately one third resulting in hospital admission. Heart failure accounted for over 80% of all potentially preventable emergency department events among patients with categories G3A, G3B, and G4 CKD, whereas hyperkalemia accounted for almost one half (48%) of all ambulatory care-sensitive conditions among patients on dialysis. Adjusted rates of emergency department events for heart failure showed a U-shaped relationship, with the highest rates among patients with category G4 CKD. In contrast, there was a graded association between rates of emergency department use for hyperkalemia and CKD category., Conclusions: Emergency department use is high among patients with CKD, although only a small proportion of these encounters is for potentially preventable CKD-related care. Strategies to reduce emergency department use among patients with CKD will, therefore, need to target conditions other than CKD-specific ambulatory care-sensitive conditions., (Copyright © 2017 by the American Society of Nephrology.)

Background: Comparative effectiveness studies are common in patients with nonvalvular atrial fibrillation (NVAF) and chronic kidney disease (CKD), but the accuracy of current thromboembolic (n = 4) and bleeding (n = 3) prediction scores used for risk adjustment are uncertain in these patients because previous studies have included few CKD patients., Methods: This was a retrospective cohort study, using Cox models adjusted for time-varying coefficients, of nonanticoagulated adults with incident NVAF and kidney function (defined into Kidney Disease: Improving Global Outcomes [KDIGO] CKD categories) between 2002 and 2013., Results: Of 58,451 patients (mean age 66 years, 31.3% with CKD) followed for a median of 31 months, 21.3% died, 12.6% had a thromboembolic event (4.2 per 100 patient-years), and 7.8% had a major bleed (2.6 per 100 patient-years). There were graded associations between kidney function and all-cause mortality (adjusted hazard ratio [aHR], 1.88 [95% confidence interval (CI), 1.79-1.98] for very high vs low risk KDIGO category), major bleeding (aHR, 1.61 [95% CI, 1.47-1.76]), and thromboembolic events (aHR, 1.13 [95% CI, 1.04-1.23]). All 7 prediction scores had significantly poorer c statistics in patients with CKD: 0.50-0.59; all P < 0.0001 compared with those with normal kidney function (c statistics 0.69-0.70 for the 4 thromboembolic risk scores and 0.60-0.68 for the 3 bleeding risk scores). Inclusion of KDIGO category did not improve calibration or discrimination statistics for current prediction scores., Conclusions: Existing NVAF risk scores exhibit poor discrimination in patients with CKD, limiting their utility for clinical decision-making or for risk adjustment in comparative effectiveness studies. Although CKD is an independent risk factor for adverse events, adding KDIGO class to current risk scores did not improve their performance., (Copyright © 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Although patients with CKD are commonly hospitalized, little is known about those with frequent hospitalization and/or longer lengths of stay (high inpatient use). The objective of this study was to explore clinical characteristics, patterns of hospital use, and potentially preventable acute care encounters among patients with CKD with at least one hospitalization., Design, Setting, Participants, & Measurements: We identified all adults with nondialysis CKD (eGFR<60 ml/min per 1.73 m 2 ) in Alberta, Canada between January 1 and December 31, 2009, excluding those with prior kidney failure. Patients with CKD were linked to administrative data to capture clinical characteristics and frequency of hospital encounters, and they were followed until death or end of study (December 31, 2012). Patients with one or more hospital encounters were categorized into three groups: persistent high inpatient use (upper 5% of inpatient use in 2 or more years), episodic high use (upper 5% in 1 year only), or nonhigh use (lower 95% in all years). Within each group, we calculated the proportion of potentially preventable hospitalizations as defined by four CKD-specific ambulatory care sensitive conditions: heart failure, hyperkalemia, volume overload, and malignant hypertension., Results: During a median follow-up of 3 years, 57,007 patients with CKD not on dialysis had 118,671 hospitalizations, of which 1.7% of patients were persistent high users, 12.3% were episodic high users, and 86.0% were nonhigh users of hospital services. Overall, 24,804 (20.9%) CKD-related ambulatory care sensitive condition encounters were observed in the cohort. The persistent and episodic high users combined (14% of the cohort) accounted for almost one half (45.5%) of the total ambulatory care sensitive condition hospitalizations, most of which were attributed to heart failure and hyperkalemia. Risk of hospitalization for any CKD-specific ambulatory care sensitive condition was higher among older patients, higher CKD stage, lower income, registered First Nations status, and those with poor attachment to primary care., Conclusions: Many hospitalizations among patients with CKD and high inpatient use are ambulatory care sensitive condition related, suggesting opportunities to improve outcomes and reduce cost by focusing on better community-based care for this population., (Copyright © 2016 by the American Society of Nephrology.)

Objective: Women with chronic kidney disease (CKD) experience kidney dysfunction-mediated premature menopause. The role of postmenopausal hormone therapy (HT) in this population is unclear. We sought to summarize current knowledge regarding use of postmenopausal HT and cardiovascular (CV) outcomes, and established surrogate measures of CV risk in women with CKD., Methods: This is a systematic review and meta-analysis of adult women with CKD. We searched electronic bibliographic databases (MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials) (inception to 2014 December), relevant conference proceedings, tables of contents of journals, and review articles. Randomized controlled trials and observational studies examining postmenopausal HT compared with either placebo or untreated control groups were included. The intervention of interest was postmenopausal HT, and the outcome measures were all-cause and CV mortality, nonfatal CV event (myocardial infarction, stroke), and surrogate measures of CV risk (serum lipids, blood pressure)., Results: Of 12,482 references retrieved, four randomized controlled trials and two cohort studies (N = 1,666 participants) were identified. No studies reported on CV outcomes or mortality. Compared with placebo, postmenopausal HT was associated with decreased low-density lipoprotein cholesterol (-13.2 mg/dL [95% CI, -23.32 to -3.00 mg/dL]), and increased high-density lipoprotein (8.73 mg/dL [95% CI, 4.72-12.73 mg/dL]) and total cholesterol (7.96 mg/dL [95% CI, 0.07-15.84 mg/dL]). No associations were observed between postmenopausal HT triglyceride levels and blood pressure., Conclusions: Studies examining the effect of postmenopausal HT on CV outcomes in women with CKD are lacking. Further prospective study of the role of postmenopausal HT in this high-risk group is required.

Background: Although patients with kidney disease have potential to benefit from revascularization, they are also at higher risk of complications, which may affect quality of life., Methods and Results: We studied a cohort of 8198 adults who underwent coronary angiography in Alberta, between 2004 and 2008, and completed health-related quality-of-life (HR-QOL) surveys. Changes in HR-QOL measures were most favorable among patients who received coronary artery bypass graft (CABG), but did not significantly differ by kidney function within groups of patients who received CABG, percutaneous coronary intervention (PCI), or medical therapy (P value for interaction between estimated glomerular filtration rate [eGFR] and revascularization status >0.10 for all outcomes). Among those who received CABG, the adjusted mean EuroQol 5 dimensions (EQ-5D) utility score for those with eGFR >90 mL/min per 1.73 m(2) increased by 0.11 (95% CI, 0.09-0.14) and for those with eGFR <30 mL/min per 1.73m(2) by 0.13 (95% CI, 0.05-0.21). The adjusted mean EQ-5D utility score also increased similarly at all levels of eGFR for those who received PCI and for those who received medical management. Mean changes in Seattle Angina Questionnaire (SAQ) scores were also similar across all levels of eGFR within each treatment group for the quality of life, angina frequency, angina stability, physical limitations, and treatment satisfaction domains of the SAQ. Among those who received CABG, the adjusted mean SAQ quality of life score for those with eGFR >90 mL/min per 1.73m(2) increased by 22.1 (95% CI, 18.5-25.7) and for those with eGFR <30 mL/min per 1.73m(2) by 14.0 (95% CI, 2.31-25.63)., Conclusions: Changes in HR-QOL do not vary by kidney function among patients selected for CABG, PCI, or medical management of coronary disease., (© 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

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.)

Chronic kidney disease (CKD) is associated with poor outcomes, perhaps due to a high burden of comorbidity. Most studies of CKD populations focus on concordant comorbidities, which cause CKD (such as hypertension and diabetes) or often accompany CKD (such as heart failure or coronary disease). Less is known about the burden of mental health conditions and discordant conditions (those not concordant but still clinically relevant, like dementia or cancer). Here we did a retrospective population-based cohort study of 530,771 adults with CKD residing in Alberta, Canada between 2003 and 2011. Validated algorithms were applied to data from the provincial health ministry to assess the presence/absence of 29 chronic comorbidities. Linkage between comorbidity burden and adverse clinical outcomes (mortality, hospitalization or myocardial infarction) was examined over median follow-up of 48 months. Comorbidities were classified into three categories: concordant, mental health/chronic pain, and discordant. The median number of comorbidities was 1 (range 0-15) but a substantial proportion of participants had 3 and more, or 5 and more comorbidities (25 and 7%, respectively). Concordant comorbidities were associated with excess risk of hospitalization, but so were discordant comorbidities and mental health conditions. Thus, discordant comorbidities and mental health conditions as well as concordant comorbidities are important independent drivers of the adverse outcomes associated with CKD.

Background: Chronic kidney disease affects approximately one in ten North Americans and is associated with a high risk of cardiovascular disease. Chronic kidney disease in women is characterized by an abnormal sex hormone profile and low estradiol levels. Since low estradiol levels are associated with an increased cardiovascular risk in healthy women, our objective is to determine the effect of hormone therapy on all-cause mortality, cardiovascular mortality, and cardiovascular morbidity in women with chronic kidney disease., Methods/design: Studies examining hormone therapy for adult women with chronic kidney disease will be included. The primary outcome is all-cause or cardiovascular mortality and morbidity. We will search electronic bibliographic databases (MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL)) along with relevant conference proceedings, table of contents of journals, and review articles. Two investigators will independently screen identified abstracts and select observational cohort studies, case-control studies, and randomized controlled trials examining hormone therapy in women with chronic kidney disease. These investigators will also independently abstract data from relevant full-text journal articles and assess risk of bias. Where possible, these data will be summarized using pooled or combined estimates for the risk ratio or hazard ratio of all-cause mortality, cardiovascular mortality, and cardiovascular morbidity in women with chronic kidney disease with and without hormone therapy. A random effects model will be used, and meta-regression and subgroup analyses will be used to explore potential source of heterogeneity., Discussion: Given the high burden of cardiovascular disease in women with chronic kidney disease, this study will help guide clinical practice by summarizing current evidence on the use of hormone therapy for prevention of all-cause mortality, cardiovascular mortality, and cardiovascular morbidity in this population., Systematic Review Registration: The final protocol was registered with PROSPERO ( CRD42014014566) .

Objective: To determine rates of major bleeding by level of kidney function for older adults with atrial fibrillation starting warfarin., Design: Retrospective cohort study., Setting: Community based, using province wide laboratory and administrative data in Alberta, Canada., Participants: 12,403 adults aged 66 years or more, with atrial fibrillation who started warfarin treatment between 1 May 2003 and 31 March 2010 and had a measure of kidney function at baseline. Kidney function was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation and participants were categorised based on estimated glomerular filtration rate (eGFR): ≥ 90, 60-89, 45-59, 30-44, 15-29, <15 mL/min/1.73 m(2). We excluded participants with end stage renal disease (dialysis or renal transplant) at baseline., Main Outcome Measures: Admission to hospital or visit to an emergency department for major bleeding (intracranial, upper and lower gastrointestinal, or other)., Results: Of 12,403 participants, 45% had an eGFR <60 mL/min/1.73 m(2). Overall, 1443 (11.6%) experienced a major bleeding episode over a median follow-up of 2.1 (interquartile range: 1.0-3.8) years. During the first 30 days of warfarin treatment, unadjusted and adjusted rates of major bleeding were higher at lower eGFR (P for trend <0.001 and 0.001, respectively). Adjusted bleeding rates per 100 person years were 63.4 (95% confidence interval 24.9 to 161.6) in participants with eGFR <15 mL/min/1.73 m(2) compared with 6.1 (1.9 to 19.4) among those with eGFR >90 mL/min/1.73 m(2) (adjusted incidence rate ratio 10.3, 95% confidence interval 2.3 to 45.5). Similar associations were observed at more than 30 days after starting warfarin, although the magnitude of the increase in rates across eGFR categories was attenuated. Across all eGFR categories, adjusted rates of major bleeding were consistently higher during the first 30 days of warfarin treatment compared with the remainder of follow-up. Increases in major bleeding rates were largely due to gastrointestinal bleeding (3.5-fold greater in eGFR <15 mL/min/1.73 m(2) compared with ≥ 90 mL/min/1.73 m(2)). Intracranial bleeding was not increased with worsening kidney function., Conclusions: Reduced kidney function was associated with an increased risk of major bleeding among older adults with atrial fibrillation starting warfarin; excess risks from reduced eGFR were most pronounced during the first 30 days of treatment. Our results support the need for careful consideration of the bleeding risk relative to kidney function when assessing the risk-benefit ratio of warfarin treatment in people with chronic kidney disease and atrial fibrillation, particularly in the first 30 days of treatment., (© Jun et al 2015.)

Background: Ambulatory care-sensitive conditions have been described as those that (if appropriately managed in an outpatient setting) generally do not require subsequent hospitalization. Our goal was to identify clinical populations of people who are at the highest risk of ambulatory care-sensitive conditions related to chronic kidney disease (CKD)., Study Design: Retrospective cohort study., Setting & Participants: 2,003,054 adults (including 238,747 adults with CKD) residing in Alberta, Canada, with at least one serum creatinine measurement between 2002 and 2009., Predictors: Estimated glomerular filtration rate and albuminuria categories, CKD status, demographics, and clinical characteristics., Outcomes: Hospitalization with heart failure, hyperkalemia, volume overload, or malignant hypertension., Measurements: We used the Alberta Kidney Disease Network database, which incorporates data from Alberta Health, the Northern and Southern Alberta Renal Programs, and clinical laboratories in Alberta., Results: During a median follow-up of 4.1 years, 43,863 participants were hospitalized for heart failure; 6,274 participants, for hyperkalemia; 2,035 participants, for volume overload; and 481 participants, for malignant hypertension. All 4 conditions were more common at lower estimated glomerular filtration rates and in the presence of albuminuria. In the subset of participants with CKD, heart failure, hyperkalemia, and volume overload were associated most strongly with older age, diabetes, chronic liver disease, and prior heart failure. Malignant hypertension was associated with prior hypertension, aboriginal status, and peripheral vascular disease. Remote-dwelling participants were more likely to experience heart failure and malignant hypertension than those living closer to providers., Limitations: No data for medication use or potentially important process-based outcomes for study participants., Conclusions: Our findings suggest that future studies seeking to determine how to prevent ambulatory care-sensitive conditions in people with CKD should target remote dwellers and those with comorbid conditions such as concomitant heart failure and liver disease., (Copyright © 2014 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Survivors of acute kidney injury are at an increased risk of developing irreversible deterioration in kidney function and in some cases, the need for chronic dialysis. We aimed to determine predictors of chronic dialysis and death among survivors of dialysis-requiring acute kidney injury., Methods: We used linked administrative databases in Ontario, Canada, to identify patients who were discharged from hospital after an episode of acute kidney injury requiring dialysis and remained free of further dialysis for at least 90 days after discharge between 1996 and 2009. Follow-up extended until March 31, 2011. The primary outcome was progression to chronic dialysis. Predictors for this outcome were evaluated using cause-specific Cox proportional hazards models, and a competing risk approach was used to calculate absolute risk., Results: We identified 4 383 patients with acute kidney injury requiring temporary in-hospital dialysis who survived to discharge. After a mean follow-up of 2.4 years, 356 (8%) patients initiated chronic dialysis and 1475 (34%) died. The cumulative risk of chronic dialysis was 13.5% by the Kaplan-Meier method, and 10.3% using a competing risk approach. After accounting for the competing risk of death, previous nephrology consultation (subdistribution hazard ratio (sHR) 2.03; 95% confidence interval (CI) 1.61-2.58), a history of chronic kidney disease (sHR3.86; 95% CI 2.99-4.98), a higher Charlson comorbidity index score (sHR 1.10; 95% CI 1.05-1.15/per unit) and pre-existing hypertension (sHR 1.82; 95% CI 1.28-2.58) were significantly associated with an increased risk of progression to chronic dialysis., Conclusions: Among survivors of dialysis-requiring acute kidney injury who initially become dialysis independent, the subsequent need for chronic dialysis is predicted by pre-existing kidney disease, hypertension and global comorbidity. This information can identify patients at high risk of progressive kidney disease who may benefit from closer surveillance after cessation of the acute phase of illness.

Purpose of Review: People with chronic kidney disease (CKD) are less likely to receive early-invasive management of acute coronary syndrome (ACS). The purpose of this article is to review the risks and outcomes of early-invasive versus conservative strategies, and to consider how contrast-induced acute kidney injury (CI-AKI) should factor in treatment decisions for people with CKD., Recent Findings: Numerous observational studies have characterized the prognostic importance of CI-AKI. However, recent studies illustrate that compared to the risk of AKI in individuals treated conservatively, the additional risk of kidney injury associated with invasive coronary procedures is relatively modest. Despite the risk of CI-AKI, early-invasive management of ACS has been associated with important long-term benefits., Summary: These findings illustrate that the additional short-term risk of AKI associated with invasive management should be considered alongside long-term treatment effects on other clinical outcomes and should not act as a deterrent to their use. Strategies to increase the uptake of an invasive management approach, accompanied by the use of CI-AKI prevention strategies, could benefit high-risk individuals with CKD.

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.

In the past two decades, a substantial increase in the incidence of acute kidney injury (AKI) and kidney injury requiring dialysis has occurred in North America. This increase has coincided with an increase in the incidence of end-stage renal disease (ESRD), which has exceeded that expected based upon the prevalence of chronic kidney disease (CKD). In order to better understand the association between these conditions, there has been a proliferation of studies that have examined the risks of incident and progressive CKD following AKI. Animal studies have shown that failed differentiation of epithelial cells following renal ischaemia-reperfusion injury might lead to tubulointerstitial fibrosis, supporting a biological mechanism linking AKI and CKD. Strong and consistent associations between AKI and incident CKD, progression of CKD and incident ESRD have also been shown in epidemiological studies. In this Review, we summarize the wealth of available data on the relationship between AKI and CKD, and discuss the implications of these findings for the long-term clinical management of patients following AKI. We also identify areas of active investigation and future directions for research.

Background: Diabetes is regarded as a coronary heart disease risk equivalent-ie, people with the disorder have a risk of coronary events similar to those with previous myocardial infarction. We assessed whether chronic kidney disease should be regarded as a coronary heart disease risk equivalent., Methods: We studied a population-based cohort with measures of estimated glomerular filtration rate (eGFR) and proteinuria from Alberta, Canada. We used validated algorithms based on hospital admission and medical-claim data to classify participants with baseline history of myocardial infarction or diabetes and to ascertain which patients were admitted to hospital for myocardial infarction during follow-up (the primary outcome). For our primary analysis, we defined baseline chronic kidney disease as eGFR 15-59·9 mL/min per 1·73 m(2) (stage 3 or 4 disease). We used Poisson regression to calculate unadjusted rates and relative rates of myocardial infarction during follow-up for five risk groups: people with previous myocardial infarction (with or without diabetes or chronic kidney disease), and (of those without previous myocardial infarction), four mutually exclusive groups defined by the presence or absence of diabetes and chronic kidney disease., Findings: During a median follow-up of 48 months (IQR 25-65), 11,340 of 1,268,029 participants (1%) were admitted to hospital with myocardial infarction. The unadjusted rate of myocardial infarction was highest in people with previous myocardial infarction (18·5 per 1000 person-years, 95% CI 17·4-19·8). In people without previous myocardial infarction, the rate of myocardial infarction was lower in those with diabetes (without chronic kidney disease) than in those with chronic kidney disease (without diabetes; 5·4 per 1000 person-years, 5·2-5·7, vs 6·9 per 1000 person-years, 6·6-7·2; p<0·0001). The rate of incident myocardial infarction in people with diabetes was substantially lower than for those with chronic kidney disease when defined by eGFR of less than 45 mL/min per 1·73 m(2) and severely increased proteinuria (6·6 per 1000 person-years, 6·4-6·9 vs 12·4 per 1000 person-years, 9·7-15·9)., Interpretation: Our findings suggest that chronic kidney disease could be added to the list of criteria defining people at highest risk of future coronary events., Funding: Alberta Heritage Foundation for Medical Research., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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.

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.