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Acute Kidney Injury Recovery Pattern and Subsequent Risk of CKD: An Analysis of Veterans Health Administration Data.

ABSTRACT: BACKGROUND:Studies suggest an association between acute kidney injury (AKI) and long-term risk for chronic kidney disease (CKD), even following apparent renal recovery. Whether the pattern of renal recovery predicts kidney risk following AKI is unknown. STUDY DESIGN:Retrospective cohort. SETTING & PARTICIPANTS:Patients in the Veterans Health Administration in 2011 hospitalized (> 24 hours) with at least 2 inpatient serum creatinine measurements, baseline estimated glomerular filtration rate > 60 mL/min/1.73 m², and no diagnosis of end-stage renal disease or non-dialysis-dependent CKD: 17,049 (16.3%) with and 87,715 without AKI. PREDICTOR:Pattern of recovery to creatinine level within 0.3 mg/dL of baseline after AKI: within 2 days (fast), in 3 to 10 days (intermediate), and no recovery by 10 days (slow or unknown). OUTCOME:CKD stage 3 or higher, defined as 2 outpatient estimated glomerular filtration rates < 60 mL/min/1.73m² at least 90 days apart or CKD diagnosis, dialysis therapy, or transplantation. MEASUREMENTS:Risk for CKD was modeled using modified Poisson regression and time to death-censored CKD was modeled using Cox proportional hazards regression, both stratified by AKI stage. RESULTS:Most patients' AKI episodes were stage 1 (91%) and 71% recovered within 2 days. At 1 year, 18.2% had developed CKD (AKI, 31.8%; non-AKI, 15.5%; P < 0.001). In stage 1, the adjusted relative risk ratios for CKD stage 3 or higher were 1.43 (95% CI, 1.39-1.48), 2.00 (95% CI, 1.88-2.12), and 2.65 (95% CI, 2.51-2.80) for fast, intermediate, and slow/unknown recovery. A similar pattern was observed in subgroup analyses incorporating albuminuria and sensitivity analysis of death-censored time to CKD. LIMITATIONS:Variable timing of follow-up and mostly male veteran cohort may limit generalizability. CONCLUSIONS:Patients who develop AKI during a hospitalization are at substantial risk for the development of CKD by 1 year following hospitalization and timing of AKI recovery is a strong predictor, even for the mildest forms of AKI.

SUBMITTER: Heung M

PROVIDER: S-EPMC6837804 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Acute Kidney Injury Recovery Pattern and Subsequent Risk of CKD: An Analysis of Veterans Health Administration Data.

Heung Michael M Steffick Diane E DE Zivin Kara K Gillespie Brenda W BW Banerjee Tanushree T Hsu Chi-Yuan CY Powe Neil R NR Pavkov Meda E ME Williams Desmond E DE Saran Rajiv R Shahinian Vahakn B VB

American journal of kidney diseases : the official journal of the National Kidney Foundation 20151212 5

<h4>Background</h4>Studies suggest an association between acute kidney injury (AKI) and long-term risk for chronic kidney disease (CKD), even following apparent renal recovery. Whether the pattern of renal recovery predicts kidney risk following AKI is unknown.<h4>Study design</h4>Retrospective cohort.<h4>Setting & participants</h4>Patients in the Veterans Health Administration in 2011 hospitalized (> 24 hours) with at least 2 inpatient serum creatinine measurements, baseline estimated glomerula ...[more]

PMID: 26690912

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Project description:Few trials of acute kidney injury (AKI) prevention after surgery have been conducted, and most observational studies focus on AKI following cardiac surgery. The frequency of, risk factors for, and outcomes after AKI following other types of major surgery have not been well characterized and may present additional opportunities for trials in AKI.Observational cohort study.3.6 million US veterans followed up from 2004 to 2011 for the receipt of major surgery (cardiac; general; ear, nose, and throat; thoracic; vascular; urologic; and orthopedic) and postoperative outcomes.Demographics, health characteristics, and type of surgery.Postoperative AKI defined by the KDIGO creatinine criteria, postoperative length of stay, end-stage renal disease, and mortality.Postoperative AKI occurred in 11.8% of the 161,185 major surgery hospitalizations (stage 1, 76%; stage 2, 15%, stage 3 [without dialysis], 7%; and AKI requiring dialysis, 2%). Cardiac surgery had the highest postoperative AKI risk (relative risk [RR], 1.22; 95% CI, 1.17-1.27), followed by general (reference), thoracic (RR, 0.92; 95% CI, 0.87-0.98), orthopedic (RR, 0.70; 95% CI, 0.67-0.73), vascular (RR, 0.68; 95% CI, 0.64-0.71), urologic (RR, 0.65; 95% CI, 0.61-0.69), and ear, nose, and throat (RR, 0.32; 95% CI, 0.28-0.37) surgery. Risk factors for postoperative AKI included older age, African American race, hypertension, diabetes mellitus, and, for estimated glomerular filtration rate < 90mL/min/1.73m(2), lower estimated glomerular filtration rate. Participants with postoperative AKI had longer lengths of stay (15.8 vs 8.6 days) and higher rates of 30-day hospital readmission (21% vs 13%), 1-year end-stage renal disease (0.94% vs 0.05%), and mortality (19% vs 8%), with similar associations by type of surgery and more severe stage of AKI relating to poorer outcomes.Urine output was not available to classify AKI; cohort included mostly men.AKI was common after major surgery, with similar risk factor and outcome associations across surgery type. These results can inform the design of clinical trials in postoperative AKI to the noncardiac surgery setting.

Project description:Rationale: Acute kidney injury (AKI) has substantial rates of mortality and morbidity, coupled with an absence of efficacious treatment options. AKI commonly transits into chronic kidney disease (CKD) and ultimately culminates in end-stage renal failure. The interferon-stimulated gene 15 (ISG15) level was upregulated in the kidneys of mice injured by ischemia-reperfusion injury (IRI), cisplatin, or unilateral ureteral obstruction (UUO), however, its role in AKI development and subsequent AKI-to-CKD transition remains unknown. Methods: Isg15 knockout (Isg15 KO) mice challenged with bilateral or unilateral IRI, cisplatin, or UUO were used to investigate its role in AKI. We established cellular models with overexpression or knockout of ISG15 and subjected them to hypoxia-reoxygenation, cisplatin, or transforming growth factor- β1 (TGF-β1) stimulation. Renal RNA-seq data obtained from AKI models sourced from public databases and our studies, were utilized to examine the expression profiles of ISG15 and its associated genes. Additionally, published single cell RNA-seq data from human kidney allograft biopsies and mouse IRI model were analyzed to investigate the expression patterns of ISG15 and the type I TGF-β receptor (TGFβR1). Western blotting, qPCR, co-immunoprecipitation, and immunohistochemical staining assays were performed to validate our findings. Results: Alleviated pathological injury and renal function were observed in Isg15 KO mice with IRI-, cisplatin-, or UUO-induced AKI and the following AKI-to-CKD transition. In hypoxia-reoxygenation, cisplatin or TGF-β1 treated HK-2 cells, knockout ISG15 reduced stimulus-induced cell fibrosis, while overexpression of ISG15 with modification capacity exacerbated cell fibrosis. Immunoprecipitation assays demonstrated that ISG15 promoted ISGylation of TGFβR1, and inhibited its ubiquitination. Moreover, knockout of TGFβR1 blocked ISG15's fibrosis-exacerbating effect in HK-2 cells, while overexpression of TGFβR1 abolished the renal protective effect of ISG15 knockout during IRI-induced kidney injury. Conclusions: ISG15 plays an important role in the development of AKI and subsequent AKI-to-CKD transition by promoting TGFβR1 ISGylation.

Project description:ImportanceAmong patients who had acute kidney injury (AKI) during hospitalization, there is a need to improve risk prediction such that those at highest risk for subsequent loss of kidney function are identified for appropriate follow-up.ObjectiveTo evaluate the association of post-AKI proteinuria with increased risk of future loss of renal function.Design, setting, and participantsThe Assessment, Serial Evaluation, and Subsequent Sequelae in Acute Kidney Injury (ASSESS-AKI) Study was a multicenter prospective cohort study including 4 clinical centers in North America included 1538 patients enrolled 3 months after hospital discharge between December 2009 and February 2015.ExposuresUrine albumin-to-creatinine ratio (ACR) quantified 3 months after hospital discharge.Main outcomes and measuresKidney disease progression defined as halving of estimated glomerular filtration rate (eGFR) or end-stage renal disease.ResultsOf the 1538 participants, 769 (50%) had AKI durring hospitalization. The baseline study visit took place at a mean (SD) 91 (23) days after discharge. The mean (SD) age was 65 (13) years; the median eGFR was 68 mL/min/1.73 m2; and the median urine ACR was 15 mg/g. Overall, 547 (37%) study participants were women and 195 (13%) were black. After a median follow-up of 4.7 years, 138 (9%) participants had kidney disease progression. Higher post-AKI urine ACR level was associated with increased risk of kidney disease progression (hazard ratio [HR], 1.53 for each doubling; 95% CI, 1.45-1.62), and urine ACR measurement was a strong discriminator for future kidney disease progression (C statistic, 0.82). The performance of urine ACR was stronger in patients who had had AKI than in those who had not (C statistic, 0.70). A comprehensive model of clinical risk factors (eGFR, blood pressure, and demographics) including ACR provided better discrimination for predicting kidney disease progression after hospital discharge among those who had had AKI (C statistic, 0.85) vs those who had not (C statistic, 0.76). In the entire matched cohort, after taking into account urine ACR, eGFR, demographics, and traditional chronic kidney risk factors determined 3 months after discharge, AKI (HR, 1.46; 95% CI, 0.51-4.13 for AKI vs non-AKI) or severity of AKI (HR, 1.54; 95% CI, 0.50-4.72 for AKI stage 1 vs non-AKI; HR, 0.56; 95% CI, 0.07-4.84 for AKI stage 2 vs non-AKI; HR, 2.24; 95% CI, 0.33-15.29 for AKI stage 3 vs non-AKI) was not independently associated with more rapid kidney disease progression.Conclusions and relevanceProteinuria level is a valuable risk-stratification tool in the post-AKI period. These results suggest there should be more widespread and routine quantification of proteinuria after hospitalized AKI.

Project description:Rationale & objectiveCommunity-acquired acute kidney injury (CA-AKI) develops outside of the hospital and is the most common form of AKI globally. National estimates of CA-AKI in the United States are absent due to limited availability of laboratory data. This study leverages national data from the Veterans Health Administration (VA) to estimate incidence and risk factors of CA-AKI.Study designRetrospective cohort study using national VA administrative and laboratory data to assess cumulative CA-AKI incidence.Setting & participantsVA primary care patients in 2013-2017 with recorded outpatient serum creatinine (Scr) and no history of chronic kidney disease≥stage 5.PredictorSociodemographics, comorbidities, medication use, and health care utilization.OutcomeAnnual incidence of CA-AKI defined as a≥1.5-fold relative increase in Scr on either a subsequent outpatient Scr or inpatient Scr obtained within ≤24 hours of admission.Analytical approachWe calculated the relative change in Scr within 12 months of an outpatient Scr value. A Cox model was used to estimate the association between CA-AKI and baseline characteristics, accounting for repeated measurements.ResultsOf approximately 2.5 million eligible veterans each year, the cumulative incidence of CA-AKI was approximately 2% annually. Only 27% of CA-AKI was detected at hospital admission. In adjusted analyses, high health care utilization, chronic illness, cancer, rural location, female sex, and use of renin-angiotensin aldosterone system inhibitors or diuretics were associated with increased CA-AKI risk (all, HR>1.20).LimitationsLimited generalizability of results outside a veteran population, lack of a standardized definition for CA-AKI, and possibility of surveillance bias and misclassification.ConclusionsCA-AKI affects 1 of every 50 US veterans annually. With less than a third of CA-AKI observed in the inpatient hospital setting, reliance on inpatient evaluation of AKI suggests significant underrecognition and missed opportunities to prevent and manage the long-term consequences of AKI.

Project description:BackgroundThe progression from acute kidney injury (AKI) to chronic kidney disease (CKD) is not well understood in children.ObjectivesWe aimed to develop a pediatric CKD definition using administrative data and use it to evaluate the association between AKI in critically ill children and CKD 5 years after hospital discharge.DesignRetrospective cohort study using chart collection and administrative data.SettingTwo-center study in Montreal, Canada.PatientsChildren (?18 years old) admitted to two pediatric intensive care units (ICUs) between 2003 and 2005. We a priori excluded patients with end-stage renal disease or no health care number. Only the first admission during the study period was included. We excluded patients who could not be linked to administrative data, did not survive hospitalization, or had preexisting renal disease.MeasurementsAcute kidney injury was defined using Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Patients were defined as having CKD 5 years post-discharge if they had ?1 CKD diagnostic code or ?1 CKD-specific medication prescription.MethodsChart data used to define the exposure (AKI) were merged with provincial administrative data used to define the outcome (CKD). Cox regression was used to evaluate the AKI-CKD association.ResultsA total of 2235 (56% male) patients were included, and the median admission age was 3.7 years. A total of 464 (21%) patients developed AKI during pediatric ICU admission. At 5 years post-discharge, 43 (2%) patients had a CKD diagnosis. Patients with both stage 1 and stage 2-3 AKI had increased risk of a CKD diagnosis, with the adjusted hazard ratios (95% confidence intervals) of 2.2 (1.1-4.5) and 2.5 (1.1-5.7), respectively (P < .001).LimitationsResults may not be generalizable to non-ICU patients. We were not able to control for post-discharge variables; future research should try to explore these additional potential risk factors further.ConclusionsAcute kidney injury is associated with 5-year post-discharge CKD diagnosis defined by administrative health care data.

Dataset Information

Acute Kidney Injury Recovery Pattern and Subsequent Risk of CKD: An Analysis of Veterans Health Administration Data.

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Acute Kidney Injury Recovery Pattern and Subsequent Risk of CKD: An Analysis of Veterans Health Administration Data.

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