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Rationale & Objective: Acute kidney injury (AKI) is common among hospitalized children and is associated with increased hospital length of stay and costs. However, there are limited data on postdischarge health care utilization after AKI hospitalization. Our objectives were to evaluate health care utilization and physician follow-up patterns after dialysis-treated AKI in a pediatric population., Study Design: Retrospective cohort study, using provincial health administrative databases., Setting & Participants: All children (0-18 years) hospitalized between 1996 and 2017 in Ontario, Canada. Excluded individuals comprised non-Ontario residents; those with metabolic disorders or poisoning; and those who received dialysis or kidney transplant before admission, a kidney transplant by 104 days after discharge, or were receiving dialysis 76-104 days from dialysis start date., Exposure: Episodes of dialysis-treated AKI, identified using validated health administrative codes. AKI survivors were matched to 4 hospitalized controls without dialysis-treated AKI by age, sex, and admission year., Outcome: Our primary outcome was postdischarge hospitalizations, emergency department visits, and outpatient physician visits. Secondary outcomes included outpatient visits by physician type and composite health care costs., Analytical Approach: Proportions with≥1 event and rates (per 1,000 person-years). Total and median composite health care costs. Adjusted rate ratios using negative binomial regression models., Results: We included 1,688 pediatric dialysis-treated AKI survivors and 6,752 matched controls. Dialysis-treated AKI survivors had higher rehospitalization and emergency department visit rates during the analyzed follow-up periods (0-1, 0-5, and 0-10 years postdischarge, and throughout follow-up), and higher outpatient visit rates in the 0-1-year follow-up period. The overall adjusted rate ratio for rehospitalization was 1.46 (95% CI, 1.25-1.69; P<0.0001) and for outpatient visits was 1.16 (95% CI, 1.09-1.23; P=0.01). Dialysis-treated AKI survivors also had higher health care costs. Nephrologist follow-up was infrequent among dialysis-treated AKI survivors (18.6% by 1 year postdischarge)., Limitations: Potential miscoding of study exposures or outcomes. Residual uncontrolled confounding. Data for health care costs and emergency department visits was unavailable before 2006 and 2001, respectively., Conclusions: Dialysis-treated AKI survivors had greater postdischarge health care utilization and costs versus hospitalized controls. Strategies are needed to improve follow-up care for children after dialysis-treated AKI to prevent long-term complications., (Copyright © 2022 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: AKI is common during pediatric hospitalizations and associated with adverse short-term outcomes. However, long-term outcomes among survivors of pediatric AKI who received dialysis remain uncertain., Methods: To determine the long-term risk of kidney failure (defined as receipt of chronic dialysis or kidney transplant) or death over a 22-year period for pediatric survivors of dialysis-treated AKI, we used province-wide health administrative databases to perform a retrospective cohort study of all neonates and children (aged 0-18 years) hospitalized in Ontario, Canada, from April 1, 1996, to March 31, 2017, who survived a dialysis-treated AKI episode. Each AKI survivor was matched to four hospitalized pediatric comparators without dialysis-treated AKI, on the basis of age, sex, and admission year. We reported the incidence of each outcome and performed Cox proportional hazards regression analyses, adjusting for relevant covariates., Results: We identified 1688 pediatric dialysis-treated AKI survivors (median age 5 years) and 6752 matched comparators. Among AKI survivors, 53.7% underwent mechanical ventilation and 33.6% had cardiac surgery. During a median 9.6-year follow-up, AKI survivors were at significantly increased risk of a composite outcome of kidney failure or death versus comparators. Death occurred in 113 (6.7%) AKI survivors, 44 (2.6%) developed kidney failure, 174 (12.1%) developed hypertension, 213 (13.1%) developed CKD, and 237 (14.0%) had subsequent AKI. AKI survivors had significantly higher risks of developing CKD and hypertension versus comparators. Risks were greatest in the first year after discharge and gradually decreased over time., Conclusions: Survivors of pediatric dialysis-treated AKI are at higher long-term risks of kidney failure, death, CKD, and hypertension, compared with a matched hospitalized cohort., (Copyright © 2021 by the American Society of Nephrology.)

Background: Sustained low efficiency dialysis (SLED) has emerged as an alternative to continuous renal replacement therapy (CRRT) for the treatment of acute kidney injury (AKI) in critically ill patients. However, there is limited information on the short- and long-term outcomes of SLED compared to CRRT., Methods: We conducted a retrospective cohort study of patients with AKI who commenced either SLED or CRRT in ICUs at a tertiary care hospital in Toronto, Canada. The primary outcome was 90-day all-cause mortality. Secondary outcomes included mortality at one year, and dialysis dependence at 90 days and one year. All outcomes were ascertained by linkage to provincial datasets., Results: We identified 284 patients, of whom 95 and 189 commenced SLED and CRRT, respectively. Compared to SLED recipients, more CRRT recipients were mechanically ventilated (96% vs 86%, p = 0.002) and receiving vasopressors (94% vs 84%, p = 0.01) at the time of RRT initiation. At 90 days following RRT initiation, 52 (55%) and 126 (67%) SLED and CRRT recipients, respectively, died (adjusted risk ratio (RR) 0.91, 95% CI 0.75-1.11). There was no inter-modality difference in time to death through 90 days (adjusted hazard ratio 0.90, 95% CI 0.64-1.27). Among patients surviving to Day 90, a higher proportion of SLED recipients remained RRT dependent (10 (23%) vs 6 (10%) CRRT recipients, adjusted RR 2.82, 95% CI 1.02-7.81). At one year, there was no difference in mortality or dialysis dependence., Conclusions: Among critically ill patients with acute kidney injury, mortality at 90 days and one year was not different among patients initiating SLED as compared to CRRT., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Clinical practice guidelines recommend routine kidney function and serum potassium testing within 30 days of initiating ACE (angiotensin-converting enzyme) inhibitor or angiotensin II receptor blocker therapy. However, evidence is lacking about whether follow-up testing reduces therapy-related adverse outcomes., Methods and Results: We conducted 2 population-based retrospective cohort studies in Kaiser Permanente Northern California and Ontario, Canada. Patients with outpatient serum creatinine and potassium tests in the 30 days after starting ACE inhibitor or angiotensin II receptor blocker therapy were matched 1:1 to patients without follow-up tests. We evaluated the association of follow-up testing with 30-day all-cause mortality and hospitalization with acute kidney injury or hyperkalemia using Cox regression. We also developed and externally validated a risk score to identify patients at risk of having abnormally high serum creatinine and potassium values in follow-up. We identified 75 251 matched pairs initiating ACE inhibitor or angiotensin II receptor blocker therapy between January 1, 2007, and December 31, 2017, in Kaiser Permanente Northern California. Follow-up testing was not significantly associated with 30-day all-cause mortality in Kaiser Permanente Northern California (hazard ratio, 0.75 [95% CI, 0.54-1.06]) and was associated with higher mortality in 84 905 matched pairs in Ontario (hazard ratio, 1.32 [95% CI, 1.07-1.62]). In Kaiser Permanente Northern California, follow-up testing was significantly associated with higher rates of hospitalization with acute kidney injury (hazard ratio, 1.66 [95% CI, 1.10-2.22]) and hyperkalemia (hazard ratio, 3.36 [95% CI, 1.08-10.41]), as was observed in Ontario. The risk score for abnormal potassium provided good discrimination (area under the curve [AUC], 0.75) and excellent calibration of predicted risks, while the risk score for abnormal serum creatinine provided moderate discrimination (AUC, 0.62) but excellent calibration., Conclusions: Routine laboratory monitoring after ACE inhibitor or angiotensin II receptor blocker initiation was not associated with a lower risk of 30-day mortality. We identified patient subgroups in which targeted testing may be effective in identifying therapy-related changes in serum potassium or kidney function.

Purpose: Severe acute kidney injury (AKI) is associated with a significant risk of mortality and persistent renal replacement therapy (RRT) dependence. The objective of this study was to develop prediction models for mortality at 90-day and 1-year following RRT initiation in critically ill patients with AKI., Methods: All patients who commenced RRT in the intensive care unit for AKI at a tertiary care hospital between 2007 and 2014 constituted the development cohort. We evaluated the external validity of our mortality models using data from the multicentre OPTIMAL-AKI study., Results: The development cohort consisted of 594 patients, of whom 320(54%) died and 40 (15% of surviving patients) remained RRT-dependent at 90-day Eleven variables were included in the model to predict 90-day mortality (AUC:0.79, 95%CI:0.76-0.82). The performance of the 90-day mortality model declined upon validation in the OPTIMAL-AKI cohort (AUC:0.61, 95%CI:0.54-0.69) and showed modest calibration. Similar results were obtained for mortality model at 1-year., Conclusions: Routinely collected variables at the time of RRT initiation have limited ability to predict mortality in critically ill patients with AKI who commence RRT., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests, (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Patients undergoing treatment for cancer are at increased risk of acute kidney injury (AKI). There are few data on AKI incidence and risk factors in the current era of cancer treatment., Methods: We conducted a population-based study of all patients initiating systemic therapy (chemotherapy or targeted agents) for a new cancer diagnosis in Ontario, Canada (2007-2014). The primary outcome was hospitalization with AKI or acute dialysis. We estimated the cumulative incidence of AKI and fitted Fine and Gray models, adjusting for demographics, cancer characteristics, comorbidities, and coprescriptions. We modeled exposure to systemic therapy (the 90-day period following treatments) as a time-varying covariate. We also assessed temporal trends in annual AKI incidence., Results: We identified 163 071 patients initiating systemic therapy of whom 10 880 experienced AKI. The rate of AKI was 27 per 1000 person-years, with overall cumulative incidence of 9.3% (95% CI = 9.1% to 9.6%). Malignancies with the highest 5-year AKI incidence were myeloma (26.0%, 95% CI = 24.4% to 27.7%), bladder (19.0%, 95% CI = 17.6% to 20.5%), and leukemia (15.4%, 95% CI = 14.3% to 16.5%). Advanced cancer stage, chronic kidney disease, and diabetes were associated with increased risk of AKI (adjusted hazard ratios [aHR] = 1.41, 95% CI = 1.28 to 1.54; 1.80, 95% CI = 1.67 to 1.93; and 1.43, 95% CI = 1.37 to 1.50, respectively). In patients aged 66 years or older with universal drug benefits, diuretic, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker coprescription was associated with higher AKI risk (aHR = 1.20, 95% CI = 1.14 to 1.28; 1.30, 95% CI = 1.23 to 1.38). AKI risk was further accentuated during the 90-day period following systemic therapy (aHR = 2.34, 95% CI = 2.24 to 2.45). The annual incidence of AKI increased from 18 to 52 per 1000 person-years between 2007 and 2014., Conclusion: Cancer-related AKI is common and associated with advanced stage, chronic kidney disease, diabetes, and concomitant receipt of diuretics or angiotensin-converting enzyme inhibitors/angiotensin receptor blockers. Risk is heightened in the 90 days after systemic therapy. Preventive strategies are needed to address the increasing burden of AKI in this population., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Clinical guidelines caution against nonsteroidal anti-inflammatory drug (NSAID) use in older adults. The study objective was to quantify the 30-day risk of acute kidney injury (AKI) and hyperkalemia in older adults after NSAID initiation and to develop a model to predict these outcomes., Methods: We conducted a population-based retrospective cohort study in Ontario, Canada from 2007 to 2015 of patients ≥66 years. We matched 46 107 new NSAID users with 46 107 nonusers with similar baseline health. The primary outcome was 30-day risk of AKI and secondary outcomes were hyperkalemia and all-cause mortality., Results: NSAID use versus nonuse was associated with a higher 30-day risk of AKI {380 [0.82%] versus 272 [0.59%]; odds ratio (OR) 1.41 [95% confidence interval (CI) 1.20-1.65]} and hyperkalemia [184 (0.40%) versus 123 (0.27%); OR 1.50 (95% CI 1.20-1.89); risk difference 0.23% (95% CI 0.13-0.34)]. There was no association between NSAID use and all-cause mortality. A prediction model incorporated six predictors of AKI or hyperkalemia: older age, male gender, lower baseline estimated glomerular filtration rate, higher baseline serum potassium, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use or diuretic use. This model had moderate discrimination [C-statistic 0.72 (95% CI 0.70-0.74)] and good calibration., Conclusions: In older adults, new NSAID use compared with nonuse was associated with a higher 30-day risk of AKI and hyperkalemia but not all-cause mortality. Prescription NSAID use among many older adults may be safe, but providers should use caution and assess individual risk., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.)

Purpose: To determine whether patients with severe acute kidney injury who receive dialysis (AKI-D) experience better outcomes at centres that care for more patients with AKI-D., Materials and Methods: Linked administrative datasets where used to perform a retrospective cohort study of all critically ill patients in Ontario, Canada, who had a first episode of AKI-D between 2002 and 2011. Centre volume for a given year, was designated by calculating the mean number of patients treated with acute dialysis at that centre during that year and the one preceding it. Patients treated at that centre were then assigned to a centre volume quartile for that year., Results: We identified 19,658 critically ill patients with AKI-D treated at 54 Ontario hospitals. Mortality and dialysis dependence at 90-days were 46% and 31%, respectively. Centre volume was not associated with mortality at 90 days (with quartile 1 as the reference, adjusted odds ratio (aOR) 1.16 (95% CI, 0.87 - 1.54) in quartile 2, aOR 1.17 (95% CI, 0.91 - 1.50) in quartile 3, and aOR 1.06 (95% CI, 0.81 - 1.41) in quartile 4)., Conclusions: There are no Centre volume survival associations in the management of AKI-D despite high mortality and dependence rate., (Copyright © 2018. Published by Elsevier Inc.)

Mortality after AKI is high, but the causes of death are not well described. To better understand causes of death in patients after a hospitalization with AKI and to determine patient and hospital factors associated with mortality, we conducted a population-based study of residents in Ontario, Canada, who survived a hospitalization with AKI from 2003 to 2013. Using linked administrative databases, we categorized cause of death in the year after hospital discharge as cardiovascular, cancer, infection-related, or other. We calculated standardized mortality ratios to compare the causes of death in survivors of AKI with those in the general adult population and used Cox proportional hazards modeling to estimate determinants of death. Of the 156,690 patients included, 43,422 (28%) died in the subsequent year. The most common causes of death were cardiovascular disease (28%) and cancer (28%), with respective standardized mortality ratios nearly six-fold (5.81; 95% confidence interval [95% CI], 5.70 to 5.92) and eight-fold (7.87; 95% CI, 7.72 to 8.02) higher than those in the general population. The highest standardized mortality ratios were for bladder cancer (18.24; 95% CI, 17.10 to 19.41), gynecologic cancer (16.83; 95% CI, 15.63 to 18.07), and leukemia (14.99; 95% CI, 14.16 to 15.85). Along with older age and nursing home residence, cancer and chemotherapy strongly associated with 1-year mortality. In conclusion, cancer-related death was as common as cardiovascular death in these patients; moreover, cancer-related deaths occurred at substantially higher rates than in the general population. Strategies are needed to care for and counsel patients with cancer who experience AKI., (Copyright © 2018 by the American Society of Nephrology.)

Purpose: To compare clinical outcomes among critically ill adults with acute kidney injury (AKI) treated with continuous renal replacement therapy (CRRT), intermittent hemodialysis (IHD) or sustained low efficiency dialysis (SLED)., Materials and Methods: We completed a systematic review and meta-analysis of studies published in 2015 or earlier using MEDLINE®, EMBASE®, Cochrane databases and grey literature. Eligible studies included randomized clinical trials (RCTs) or prospective cohort studies comparing outcomes of mortality, dialysis dependence or length of stay among critically ill adults receiving CRRT, IHD or SLED to treat AKI. Mortality and dialysis dependence from RCTs were pooled using meta-analytic techniques. Length of stay from RCTs and results from prospective cohort studies were described qualitatively., Results: Twenty-one studies were eligible. RRT modality was not associated with in-hospital mortality (CRRT vs IHD: RR 1.00 [95% CI, 0.92-1.09], CRRT vs SLED: RR 1.23 [95% CI, 1.00-1.51]) or dialysis dependence (CRRT vs IHD: RR 0.90 [95% CI, 0.59-1.38], CRRT vs SLED: RR 1.15 [95% CI, 0.67-1.99])., Conclusions: We did not find a definitive advantage for any RRT modality on short-term patient or kidney survival. Well-designed, adequately-powered trials are needed to better define the role of RRT modalities for treatment of critically ill patients with AKI., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: The risk of hospital readmission in acute kidney injury survivors is not well understood. We estimated the proportion of acute kidney injury patients who were rehospitalized within 30 days and identified characteristics associated with hospital readmission., Methods: We conducted a population-based study of patients who survived a hospitalization complicated by acute kidney injury from 2003-2013 in Ontario, Canada. The primary outcome was 30-day hospital readmission. We used a propensity score model to match patients with and without acute kidney injury, and a Cox proportional hazards model with death as a competing risk to identify predictors of 30-day readmission., Results: We identified 156,690 patients who were discharged from 197 hospitals after an episode of acute kidney injury. In the subsequent 30 days, 27,457 (18%) patients were readmitted; 15,988 (10%) visited the emergency department and 7480 (5%) died. We successfully matched 111,778 patients with acute kidney injury 1:1 to patients without acute kidney injury. The likelihood of 30-day readmission was higher in acute kidney injury patients than those without acute kidney injury (hazard ratio [HR] 1.53; 95% confidence interval [CI], 1.50-1.57). Factors most strongly associated with 30-day rehospitalization were the number of hospitalizations in the preceding year (adjusted HR 1.45 for ≥2 hospitalizations; 95% CI, 1.40-1.51) and receipt of inpatient chemotherapy (adjusted HR 1.44; 95% CI, 1.32-1.58)., Conclusions: One in 5 patients who survive a hospitalization complicated by acute kidney injury is readmitted in the next 30 days. Better strategies are needed to identify and care for acute kidney injury survivors in the community., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Dialysis-requiring acute kidney injury (AKI) is common among critically ill patients, but little is known about trends in the incidence and outcomes of this condition over time., Study Design: Population-based cohort study., Setting & Participants: All adult patients admitted to an intensive care unit in Ontario, Canada, 1996 to 2010., Predictor: Year and era (1996-2000, 2001-2005, and 2006-2010) of cohort entry., Outcomes: Mortality and dialysis dependence, each evaluated at 90 and 365 days after initiation of dialysis therapy for AKI., Measurements: The annual incidence proportion of dialysis-requiring AKI was evaluated and patients with this condition were characterized by era. Associations between era and the outcomes of interest were evaluated with Cox proportional hazards (for time to death) and logistic regression (for dialysis dependence), with adjustment for relevant demographic and clinical variables., Results: The annual incidence of dialysis-requiring AKI among critically ill patients increased from 0.8% in 1996 to 3.0% in 2010 (P for trend < 0.001). 90-day mortality declined from 50% in 1996 to 2000 to 45% in 2006 to 2010 (adjusted HR, 0.83 [95% CI, 0.79-0.87] compared to 1996-2000). Dialysis dependence among surviving patients at 90 days was marginally lower in 2006 to 2010 (25.1%) compared to 1996 to 2000 (27.2%), but after adjustment for confounding factors, was not significantly different (adjusted OR, 0.91; 95% CI, 0.80-1.03)., Limitations: Unmeasured confounding by factors that may have changed in patients with dialysis-requiring AKI during the different eras; data set does not allow for mechanistic explanation for the findings; and lack of access to laboratory investigations after hospital discharge., Conclusions: The incidence proportion of dialysis-requiring AKI among critically ill patients increased by almost 4-fold between 1996 and 2010. This was accompanied by a significant decline in mortality, but the risk of long-term dialysis dependence continues to affect a substantial minority of surviving patients with no clear evidence of improvement over time., (Copyright © 2015 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Several adverse outcomes attributed to atypical antipsychotic drugs, specifically quetiapine, risperidone, and olanzapine, are known to cause acute kidney injury (AKI). Such outcomes include hypotension, acute urinary retention, and the neuroleptic malignant syndrome or rhabdomyolysis., Objective: To investigate the risk for AKI and other adverse outcomes associated with use of atypical antipsychotic drugs versus nonuse., Design: Population-based cohort study., Setting: Ontario, Canada, from 2003 to 2012., Patients: Adults aged 65 years or older who received a new outpatient prescription for an oral atypical antipsychotic drug (n=97,777) matched 1:1 with those who did not receive such a prescription., Measurements: The primary outcome was hospitalization with AKI (assessed by using a hospital diagnosis code and, in a subpopulation, serum creatinine levels) within 90 days of prescription for atypical antipsychotic drugs., Results: Atypical antipsychotic drug use versus nonuse was associated with a higher risk for hospitalization with AKI (relative risk [RR], 1.73 [95% CI, 1.55 to 1.92]). This association was consistent when AKI was assessed in a subpopulation for which information on serum creatinine levels was available (5.46% vs. 3.34%; RR, 1.70 [CI, 1.22 to 2.38]; absolute risk increase, 2.12% [CI, 0.80% to 3.43%]). Drug use was also associated with hypotension (RR, 1.91 [CI, 1.60 to 2.28]), acute urinary retention (RR, 1.98 [CI, 1.63 to 2.40]), and all-cause mortality (RR, 2.39 [CI, 2.28 to 2.50])., Limitation: Only older adults were included in the study., Conclusion: Atypical antipsychotic drug use is associated with an increased risk for AKI and other adverse outcomes that may explain the observed association with AKI. The findings support current safety concerns about the use of these drugs in older adults., Primary Funding Source: Academic Medical Organization of Southwestern Ontario.