Abstract
Objective:
Postoperative acute kidney injury (AKI) is common after major surgery and is associated with increased morbidity, mortality and cost. Additionally, there are recent studies demonstrating that time to renal recovery may have a substantial impact on clinical outcomes. We hypothesized that patients with delayed renal recovery after major vascular surgery will have increased complications, mortality, and hospital cost.
Methods:
A single center retrospective cohort of patients undergoing non-emergent major vascular surgery between 6/1/2014–10/1/2020 was analyzed. Development of postoperative AKI (defined using Kidney Disease Improving Global Outcomes (KDIGO) criteria: > 50% or > 0.3 mg/dl absolute increase in serum creatinine relative to reference after surgery and before discharge) was evaluated. Patients were divided into three groups: no AKI, rapidly reversed AKI (< 48 hours), and persistent AKI (≥ 48 hours). Multivariable generalized linear models were used to evaluate the association between AKI groups and postoperative complications, 90-day mortality, and hospital cost.
Results:
A total of 1,881 patients undergoing 1,980 vascular procedures were included. Thirty five percent of patients developed postoperative AKI. Patients with persistent AKI had longer intensive care unit and hospital stays, as well as more mechanical ventilation days. In multivariable logistic regression analysis, persistent AKI was a major predictor of 90-day mortality (odds ratio 4.1, 95% confidence interval 2.4–7.1). Adjusted average cost was higher for patients with any type of AKI. The incremental cost of having any AKI ranged from $3,700 to $9,100, even after adjustment for comorbidities and other postoperative complications. The adjusted average cost for patients stratified by type of AKI was higher among patients with persistent AKI compared to those with no or rapidly reversed AKI.
Conclusions:
Persistent AKI after vascular surgery is associated with increased complications, mortality, and cost. Strategies to prevent and aggressively treat AKI, specifically persistent AKI, in the perioperative setting are imperative to optimize care for this population.
Keywords: acute kidney injury, vascular surgery, cost, mortality, outcomes
Introduction
Postoperative acute kidney injury (AKI) is a common complication in patients undergoing major surgery.1 It is particularly prevalent in the vascular surgical population, with an incidence of 20–70%, depending on the study cohort.2–4 Several high-quality studies have demonstrated the morbidity, mortality, and costs associated with postoperative AKI2, 5–8 However, the true effects of postoperative AKI remain underestimated given the lack of a consensus definition for postoperative AKI.
Until 2021, surgical literature and quality databases, including the National Surgical Quality Improvement Program (NSQIP), defined AKI as a creatinine >2 milligrams per deciliter (mg/dL) or as the acute need for renal replacement therapy (RRT).9 Multiple recent studies have shown that this definition is insensitive and overlooks important small rises in creatinine that reflect large changes in renal function.5, 10–12 Recognition of the impact of even small rises in creatinine on long-term patient outcomes has only recently led to the widespread adoption of the updated Kidney Disease Improving Global Outcomes (KDIGO) criteria (as at least a 50% or 0.3 mg/dL increase in serum creatinine relative to the reference creatinine) in quality databases such as NSQIP.12
Delayed or incomplete recovery of renal function increases patient risk for chronic critical illness, negatively impacting quality of life and long-term survival.13, 14 Recent studies have demonstrated that the course of renal function recovery after AKI has the potential to distinguish the risk of clinically important long-term outcomes.15–17 Despite the potential benefits of defining clinical AKI trajectory for patients described in the literature,16, 18 the financial and clinical impact of renal function recovery in vascular patients with postoperative AKI has yet to be elucidated. To address this knowledge gap, we performed a single-center retrospective review of patients undergoing non-emergent major vascular surgery to determine the impact of renal function recovery after postoperative AKI on clinical outcomes, resource utilization, and long-term survival.
Methods
Study Population and Design
The University of Florida Integrated Data Repository was used to assemble a single-center cohort for all patients admitted to the University of Florida Health who underwent major vascular surgery between June 1st, 2014 and October 1st, 2020 by integrating electronic health records (EHR) with other clinical, administrative and public databases, as previously described.4 Patients undergoing non-emergent major vascular surgery (lower extremity bypass, endovascular and open aortic surgery), as defined using current procedural terminology (CPT) codes listed in Supplemental Table 1, were included in the study. The University of Florida Institutional Review Board (#201600223) approved this study with a waiver of informed consent.
Assessment of Kidney Function and Medical Comorbidities
We utilized a previously validated computable phenotype algorithm to determine AKI status and classification during a patient’s hospital course.19 AKI was defined using the consensus Kidney Disease Improving Global Outcomes (KDIGO) criteria as at least a 50% or 0.3 mg/dL increase in serum creatinine relative to the reference creatinine.19 According to the KDIGO criteria, Stage 1 AKI is defined as an elevation in serum creatinine greater than 0.3 mg/dL within the past 48 hours or a 1.5 to 1.9-fold increase from baseline serum creatinine within seven days. Stage 2 AKI is defined as a 2 to 3-fold rise from the baseline serum creatinine within seven days. Stage 3 AKI is defined as an increase more than 3-fold from baseline serum creatinine within seven days. When patients need renal replacement therapy (RRT), it is defined as Stage 3 AKI with RRT. In our analysis, AKI was staged for severity (Stage 1–3), with mild AKI defined as Stage 1 and severe AKI defined as Stage 2 or Stage 3.20 The duration and evidence of renal recovery were used to define rapidly reversed and persistent AKI. Persistent AKI was defined as an AKI episode lasting beyond 48 hours. Rapid reversal of AKI was defined as complete reversal of AKI by KDIGO criteria within 48 hours of AKI onset and remaining without any additional episodes of AKI.20 We grouped each encounter based on worst trajectory group during hospitalization as persistent AKI, rapidly reversed AKI, or no AKI. Reference creatinine was determined using measurements prior to hospital admission, as previously described.19, 21
Charlson comorbidity index is a composite value that summarizes comorbidity burden with higher values indicating more additional frail conditions. We extracted preoperative medical comorbidities from electronic medical records by considering International Classification of Diseases (ICD) 9 and ICD 10 codes. Variables identifying patient comorbidities and Charlson comorbidity index were derived using previously validated methods.22–24
Outcomes
Primary outcomes included hospital cost, 90-day mortality, and three-year survival. Survival was assessed using hospital discharge and Social Security Death Index database. Total costs of health care expenses for a single admission incurred by hospital were obtained from hospital records. We transformed all the costs to 2021 dollars by using Consumer Price Index to adjust for inflation. In defining adverse hospital outcomes we considered the following eight major common postoperative complications, as previously described25: wound complications, mechanical ventilation (MV) and intensive care unit (ICU) admission for greater than 48 hours, cardiovascular (CV) complications, neurological complications, sepsis, venous thromboembolism (VTE) and AKI, occurring anytime during hospitalization after the index operation.
Statistical Methods
We followed the STROBE recommendations for reporting of observational studies.26 Patients were stratified into three groups: no AKI, rapidly reversed AKI (< 48 hours) and persistent AKI (≥ 48 hours). We analyzed the differences between groups with Kruskal-Wallis test or analysis of variance for continuous variables, and chi-square or Fisher’s exact test for categorical variables as appropriate. We considered two-sided significance tests with a p-value < 0.05 as statistically significant. While performing multiple comparisons, we adjusted tests with Bonferroni correction. We performed univariate model analyses by relating hospital cost and 90-day mortality with variables listed in Table 1 and 2 and included significant variables with a p-value < 0.05 in either of those models.
Table 1:
Clinical characteristics of the patients stratified by type of acute kidney injury.
| Variables | No AKI | Rapidly Reversed AKI | Persistent AKI |
|---|---|---|---|
| Demographics | |||
| Number of patients, n (%) | 1,225 (65) | 328 (17.5) | 328 (17.5) |
| Age, mean (SD) | 67 (13) | 68 (12) | 67 (13) |
| Female sex, n (%) | 458 (35) | 106 (32) | 117 (35) |
| Race, n (%) | |||
| Non-Hispanic Black | 131 (10) | 40 (12) | 48 (14) |
| Other | 45 (3) | 13 (4) | 15 (5) |
| White | 1,122 (85) | 276 (83) | 260 (78)* |
| Missing | 18 (1) | 3 (1) | 9 (3) |
| Rural area residency, n (%) | 331 (25) | 82 (25) | 66 (20) |
| Residence to hospital, miles, median (IQR) | 41 (25, 73) | 43 (27, 68) | 51 (34, 91)* |
| Prevalence of residents living below poverty at patient residential area, %, mean (SD) | 18.19 (8.56) | 18.72 (9.92) | 17.80 (8.37) |
| Area Deprivation Index, mean (SD) | |||
| National percentile | 62.03 (22.92) | 65.47 (22.43) | 62.86 (22.70) |
| State-specific decile | 6.51 (2.58) | 6.89 (2.50) | 6.62 (2.57) |
| Insurance, n (%) | |||
| Medicaid | 166 (13) | 40 (12) | 40 (12) |
| Medicare | 907 (69) | 240 (72) | 227 (68) |
| Private | 183 (14) | 37 (11) | 50 (15) |
| Uninsured | 60 (5) | 15 (5) | 15 (5) |
| Smoking Status, n (%) | |||
| Never | 159 (12) | 39 (12) | 46 (14) |
| Former | 686 (52) | 173 (52) | 151 (45) |
| Current | 379 (29) | 102 (31) | 98 (30) |
| Missing | 92 (7) | 18 (5) | 37 (11)* |
| Comorbidities | |||
| CCI, median (IQR) | 1 (0, 2) | 1 (0, 3)* | 1 (0, 3)* |
| Comorbidities present on admission, n (%) | |||
| Myocardial Infarction | 226 (17) | 73 (22) | 71 (21) |
| Congestive Heart Failure | 183 (14) | 70 (21)* | 79 (24)* |
| Peripheral Vascular Disease | 1,229 (93) | 318 (96) | 310 (93) |
| Cerebrovascular Disease | 95 (7) | 33 (10) | 34 (10) |
| Chronic Obstructive Pulmonary Disease | 521 (40) | 129 (39) | 126 (38) |
| Diabetes | 290 (22) | 85 (25) | 82 (25) |
| Chronic Kidney Disease | 289 (22) | 124 (37)* | 144 (43)* |
| Moderate/Severe (>= G-Stage 3), n (%) | 133 (46) | 85 (69)* | 87 (60)* |
| Preadmission eGFR, median (IQR) | 61 (49, 81) | 51 (41, 66)* | 54 (42, 71)* |
| Reference serum creatinine, mean (SD) | 0.89 (0.28) | 1.05 (0.44)* | 1.06 (0.49)* |
| Surgery groups | |||
| Lower extremity bypass surgeries | 466 (35) | 92 (28)* | 62 (19)* |
| Endovascular surgeries | 466 (35) | 98 (30) | 76 (23)* |
| Open aortic surgery surgeries | 384 (30) | 142 (42)* | 194 (58)* |
AKI, acute kidney injury; CCI, Charlson comorbidity index; eGFR, estimated glomerular filtration rate; IQR, interquartile range; SD, standard deviation.
p<0.05 compared with no acute kidney injury group.
Table 2:
Postoperative complications and hospital outcomes stratified by type of acute kidney injury.
| Variables | No AKI | Rapidly Reversed AKI | Persistent AKI |
|---|---|---|---|
| Resource Utilization | |||
| Days in hospital, median (IQR) | 7 (4, 10) | 11 (7, 16)* | 16 (10, 24)* |
| Days in intensive care unit, median (IQR) | 4 (2, 6) | 6 (3, 9)* | 10 (6, 19)* |
| Days on mechanical ventilation, median (IQR) | 1 (1, 2) | 2 (1, 3)* | 3 (2, 8)* |
| Postoperative Complications | |||
| AKI Stages, n (%) | |||
| No AKI | 1,316 (100) | 0 (0) | 0 (0) |
| AKI Stage 1 | 0 (0) | 316 (95) | 163 (49) |
| AKI Stage 2 | 0 (0) | 16 (5) | 79 (24) |
| AKI Stage 3 | 0 (0) | 0 (0) | 34 (10) |
| AKI Stage 3 with RRT | 0 (0) | 0 (0) | 56 (17) |
| Prolonged mechanical ventilation, n (%) | 44 (3) | 40 (12)* | 133 (40)* |
| Prolonged ICU stay, n (%) | 775 (59) | 244 (73)* | 303 (91)* |
| Wound complications, n (%) | 354 (27) | 125 (38)* | 164 (49)* |
| Neurological complications, n (%) | 180 (14) | 74 (22)* | 143 (43)* |
| Cardiovascular complications, n (%) | 263 (20) | 120 (36)* | 196 (59)* |
| Sepsis, n (%) | 66 (5) | 41 (12)* | 116 (35)* |
| Venous thromboembolism, n (%) | 95 (7) | 46 (14)* | 66 (20)* |
| Number of post-operative complications † | |||
| 0 | 351 (27) | 50 (15)* | 16 (5)* |
| 1 | 461 (35) | 94 (28)* | 47 (14)* |
| ≥ 2 | 504 (38) | 188 (57)* | 269 (81)* |
| In-hospital mortality, n (%) | 13 (1) | 1 (0) | 57 (17)* |
| 30-day mortality, n (%) | 21 (2) | 3 (1) | 56 (17)* |
| 90-day mortality, n (%) | 35 (3) | 13 (4)* | 77 (23)* |
AKI, acute kidney injury; IQR, interquartile range; RRT, renal replacement therapy; SD, standard deviation.
p<0.05 compared with no acute kidney injury group.
Postoperative complications include those listed in this table, except for acute kidney injury and mortality.
Multivariable generalized linear models (GLM) were constructed to evaluate 90-day mortality and hospital cost using occurrence and persistence of AKI as the main independent predictor. In modeling 90-day mortality we used logistic regression (GLM with logit link) and in modeling hospital cost we developed a GLM with log link function to alleviate the implications of skewed costs. Models were adjusted for age, ethnicity, Charlson comorbidity index, emergency admission, postoperative complications (prolonged MV, prolonged ICU stay, wound, neurological, cardiovascular, sepsis, VTE or AKI) and length of stay. Additionally, we assessed overall survival of each AKI group using log-rank and Kaplan-Meier estimations. Adjusted Kaplan-Meier survival curves were computed with propensity score based on inverse weighting. Here, we estimated propensity of being in a specific AKI group by using a multinomial logistic regression model for those patient groups. We included the variables used in derivation of primary outcomes’ models. Additionally, we utilized Cox proportional-hazards regression to evaluate the associations between the patient groups by incorporating the variables used in regression models built for primary outcomes. All statistical analyses were performed using R 4.1.2 and Python 3.8.8 software.
Results
Clinical characteristics of patient cohort
A total of 1,881 patients undergoing 1,980 vascular procedures were included in the study (Table 1). Thirty-five percent of patients developed AKI after surgery. Of patients with AKI, 17% had a rapidly reversed AKI and 17% had persistent AKI. Of the patients with persistent AKI, 45% had renal recovery. The mean age was 67 years with female and male sex almost equally distributed among the groups. There was a greater proportion of Caucasian patients in the no AKI as compared to the persistent AKI group (85% vs. 78%, p<0.05). Patients in the persistent AKI group had a higher median distance (in miles) of residence to the hospital as compared to the no AKI group (51 [interquartile range 34–91] vs. 41 [25–73], p<0.05). The area deprivation index and prevalence of patients living below the poverty line did not differ between groups. Comorbidities were similar among the three groups, however a greater proportion of patients with persistent AKI had congestive heart failure (CHF) (24% vs. 14%, p<0.05), chronic kidney disease (CKD) (43% vs. 22%, p<0.05), and a higher Charlson comorbidity index (1 [0,3] vs. 1 [0,2], p<0.05) compared to those without AKI. Additionally, patients in the persistent AKI group had lower median preadmission estimated glomerular filtration rate (eGFR) (54 [42–71] vs. 61 [49–80], p<0.05) and a higher average preadmission serum creatinine (1.06 [SD 0.49] vs. 0.89 [SD 0.28], p<0.05) compared to patients without AKI.
Postoperative complications and resource utilization
Table 2 depicts resource utilization and postoperative complications among patients stratified by occurrence and persistence of AKI. Patients with persistent AKI had increased hospital, ICU and mechanical ventilation days as compared to both the rapidly reversed AKI and no AKI groups. Patients with persistent AKI had more wound, neurologic, cardiovascular, sepsis, and VTE complications. Eighty-one percent of patients with persistent AKI had ≥2 postoperative complications compared to 38% of patients without AKI (p<0.05). Patients with persistent AKI had higher in-hospital, 30-day and 90-day mortality than those without AKI. There were few differences in outcomes between patients with persistent AKI with renal recovery and those with persistent AKI without renal recovery (Supplemental Table 2). The adjusted average cost of postoperative complications was higher in the persistent AKI group than the no AKI group (Figure 1). When stratified by age (18–64, 65–80 and >80 years old) and excluding patients who died within 90 days of admission, the adjusted average cost was greater in the persistent AKI group compared to the no AKI group across all age groups (Figure 2A). At all age groups, average adjusted costs were highest in the patients who did not survive within 90 days of admission and who had persistent AKI compared to those with rapidly reversed or no AKI (Figure 2B).
Figure 1:
Adjusted average cost of postoperative complications, stratified by acute kidney injury. AKI: acute kidney injury; RR-AKI: rapidly reversed acute kidney injury; P-AKI: persistent acute kidney injury; CV: cardiovascular complications; NC, neurological complications; Pro-ICU; prolonged ICU stay; Pro-MV, prolonged mechanical ventilation; VTE, venous thromboembolism; WC, wound complications.
Figure 2:
(A) Adjusted average cost for patients stratified by occurrence and persistence of acute kidney injury among patients who did not die within 90 days of admission. (B) Adjusted average cost for patients stratified by occurrence and persistence of acute kidney injury among patients who died within 90 days of admission.
In multivariable logistic regression models where 90-day mortality was set as the output, persistent AKI was independently associated with a four-fold increase in the odds of 90-day mortality (OR 4.11 95% CI 2.39–7.09), the average probability of 90-day mortality 12% (95% CI 8.8–15.1) as compared to 4% (95% CI 2.7–5.2) in the no AKI group (Table 3). The model resulted in an AUC value of 0.85 (95% CI 0.81–0.89), indicating reasonable model discrimination.
Table 3:
Adjusted association between type of acute kidney injury and 90-day mortality after major vascular surgery.
| 90-day Mortality | |||
|---|---|---|---|
| Unadjusted odds ratio (95% CI) | Adjusted odds ratio (95% CI) | Adjusted mean % (95% CI) | |
| No AKI | 1 (Reference) | 1 (Reference) | 4.0 (2.7, 5.2) |
| Rapidly Reversed AKI | 1.49 (0.77, 2.85) | 0.89 (0.43, 1.81) | 3.6 (1.8, 5.4) |
| Persistent AKI | 11.05 (7.25, 16.84)*† | 4.11 (2.39, 7.09)*† | 11.9 (8.8, 15.1) |
AKI, acute kidney injury; CI, confidence interval.
Adjusted risk ratios and means were calculated using a generalized linear model adjusted for age, ethnicity, Charlson comorbidity index, emergency admission, all postoperative complications and length of stay.
indicates statistical test with reference group set to no acute kidney injury as p<0.05.
Indicates rapidly reversed acute kidney injury is statistically different than persistent acute kidney injury with p <0.05.
In adjusted regression analysis, rapidly reversed and persistent AKI was a major predictor of hospital cost (OR 1.1 95% CI 1.0–1.1 vs OR 1.2, 95% CI 1.1–1.2, respectively). Adjusted incremental cost and average cost per patient was higher with any type of AKI. The incremental cost of having any AKI ranged from $3,700 to $9,100, even after adjustment for comorbidities and other postoperative complications. The adjusted average cost per patient stratified by type of AKI was higher among patients with persistent AKI ($67,461 95% CI 64,709–70,212) compared to those with rapidly reversed AKI ($62,037 95% CI 59,061–65,012) or no AKI ($58,000 95% CI 56,477–60,252) (Table 4).
Table 4:
Adjusted association between type of acute kidney injury and hospital cost after major vascular surgery.
| Hospital Cost | |||
|---|---|---|---|
| Adjusted relative cost ratio (95% CI) | Adjusted incremental cost per patient (95% CI) | Adjusted average cost per patient (95% CI) | |
| No AKI | 1 (Reference) | 0 (Reference) | $58,365 ($56,477, $60,252) |
| Rapidly Reversed AKI | 1.06 (1.00, 1.12)* | $3,671 ($117, $7,225)* | $62,037 ($59,061, $65,012) |
| Persistent AKI | 1.15 (1.09, 1.22)*† | $9,095 ($5,581, $12,609)*† | $67,461 ($64,709, $70,212) |
AKI, acute kidney injury; CI, confidence interval.
Adjusted risk ratios and means were calculated using a generalized linear model adjusted for age, ethnicity, Charlson comorbidity index, emergency admission, all postoperative complications and length of stay.
Indicates statistical test with reference group set to no acute kidney injury as p<0.05.
Indicates rapidly reversed acute kidney injury is statistically different than persistent acute kidney injury with p <0.05
We further examined the association between AKI status and long-term survival defined as three years after surgery. In both unadjusted and adjusted models, patients with persistent AKI had lower long-term survival probabilities (adjusted HR: 1.9 95% CI 1.4–2.5) compared to rapidly reversed AKI (adjusted HR: 1.1 95% CI 0.9–1.5) (Supplemental Figure 1). In weight adjusted survival curves, patients with persistent AKI again had lower survival probabilities at three years postoperatively. (Supplemental Figure 2).
Discussion
In a large single-center retrospective cohort of patients undergoing elective major vascular surgery we demonstrated that persistent AKI commonly occurs during a patient’s hospitalization and is associated with increased postoperative complications, resource utilization, hospital cost, 90-day mortality as well as decreased three-year survival. Even after adjustment for multiple variables, these findings suggest that persistent AKI after major vascular surgery is not just a marker for overall illness burden but is a complication that independently contributes to poor surgical outcomes and as well as resource utilization.
These findings are similar to those in a previous prospective, multicenter cohort study of 1,538 adults with or without AKI 90 days after hospital discharge which found a higher risk for major adverse kidney events (MAKE) among patients with resolving or non-resolving AKI compared to hospitalized patients without AKI.16 Even after adjusting for the magnitude of increased serum creatinine concentration, the authors found that the AKI recovery subgroups were still independently associated with long term risk of MAKE. In another retrospective longitudinal cohort study of 160,000 hospitalized patients, Ozrazgat-Baslanti et. al found that among ICU and non-ICU patients, persistent AKI and the absence of renal recovery was associated with reduced long-term survival independent of AKI severity.17 Additionally, among a cohort of 3,646 adult patients undergoing major vascular surgery from 2000–2010, Huber et. al, found that perioperative AKI was the most significant predictor of 90-day mortality. Authors from this study evaluated patients with no kidney disease, CKD with no AKI, AKI with no CKD and AKI with CKD and found increased postoperative complications as well as increased average costs of care for patients with any type of kidney disease.27
With the new adoption of the KDIGO guidelines by NSQIP, participating institutions will see an increase in the rate of reported postoperative AKIs.12 However, the KDIGO definition does not stratify patients based on differences in kidney function recovery. Combining patients with different AKI recovery patterns may hide patients at risk for certain clinical trajectories and may mask distinct pathophysiological diseases processes specific to patients with a kidney function recovery following AKI.16 To our knowledge, this is the first study to assess AKI recovery status with postoperative outcomes and resource utilization in patients undergoing elective major vascular surgery. Further study of these findings including how to optimize perioperative risk stratification as well as early AKI diagnosis and treatment are imperative.
Our study has limitations. Despite the large sample size and multivariate models, due to the retrospective nature of this study and potential for selection bias, there may be other unidentified variables that may contribute to the associations that we found. This cohort of patients was based on current procedural time codes and there is potential for misclassification and misrepresentation of patients in our cohort. Additionally, only the first surgery was used for patients that underwent multiple surgeries in the same admission, which may not reflect the true incidence of complications as the more procedures patients undergo, the more complications they are likely to incur. Values analyzed were total hospital cost incurred during hospitalization. Unfortunately, billing records provided by our institution’s Integrated Data Repository do not allow for cost breakdown analysis, therefore we could not directly access the hemodialysis related costs and isolate them to perform hemodialysis-specific analyses. We were only able to obtain survival curves up to three years due cohort study period and therefore are unable to comment on survival risk beyond this period. Additionally, as patient survival status was determined using hospital discharges and the Social Security Death Index information, we do not have access to cause of death. Future studies should seek to develop targeted preventative and therapeutic measures for vascular surgery patients at high risk for persistent AKI.
Conclusions
Persistent AKI after vascular surgery is associated with increased complications, mortality, and cost. Strategies to prevent and aggressively treat AKI, particularly persistent AKI, in the perioperative setting are imperative to optimize care for this population.
Supplementary Material
Sources of Funding
A.B. was supported R01 GM110240 from the National Institute of General Medical Sciences (NIH/NIGMS), R01 EB029699 and R21 EB027344 from the National Institute of Biomedical Imaging and Bioengineering (NIH/NIBIB), R01 NS120924 from the National Institute of Neurological Disorders and Stroke (NIH/NINDS), and by R01 DK121730 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK). T.O.B. was supported by K01 DK120784, R01 DK123078, and R01 DK121730 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIH/NIDDK), R01 GM110240 from the National Institute of General Medical Sciences (NIH/NIGMS), R01 EB029699 from the National Institute of Biomedical Imaging and Bioengineering (NIH/NIBIB), R01 NS120924 from the National Institute of Neurological Disorders and Stroke (NIH/NINDS), AGR DTD 12-02-20 from University of Florida Research, and UL1TR001427 from the National Center For Advancing Translational Sciences of the National Institutes of Health. This work was also supported in part by the NIH/NCATS Clinical and Translational Sciences Award to the University of Florida UL1 TR000064. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Footnotes
Presented as a poster presentation at the American Heart Association Scientific Sessions Annual Meeting, November 2022, Chicago, IL.
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