Hospital Readmission After Acute Kidney Injury—Why?* Christian Fynbo Christiansen, MD, PhD Department of Clinical Epidemiology Aarhus University Hospital Aarhus, Denmark
A
cute kidney injury (AKI) is a common condition in critically ill patients and associated with increased mortality not only during hospitalization but also after hospital discharge (1, 2). Despite the increasing number of studies on AKI outcome, information on nonfatal outcome occurring after hospital discharge remains limited. Such information could improve our understanding of the clinical pathways leading to an increased long-term mortality in AKI survivors. The close relationship between AKI and chronic kidney disease (CKD) may be an important link (3, 4). Like in patients with CKD, there is growing evidence of an increased risk of myocardial infarction and heart failure in patients surviving AKI, in particular, in AKI patients without renal recovery at hospital discharge (5–8). AKI is associated with increased length of hospital stay and increased costs, but given the potential postdischarge complications, patients with AKI are also likely to require considerable healthcare resources after hospital discharge. In this issue of Critical Care Medicine, Horkan et al (9) report a two-center study from Brigham and Women’s Hospital and Massachusetts General Hospital examining the impact of AKI on outcome after hospital discharge among survivors of critical illness during 1997–2012. The study included 62,096 adult survivors of critical illness and confirmed previous findings by showing an increased 30-day postdischarge mortality and an increased 1-year risk of end-stage renal disease in patients with AKI compared with non-AKI patients (1, 4). The study also contributes to the field with novel data by examining 30-day hospital readmission rate in survivors of critical illness as the main outcome. Patients without AKI had a 30-day readmission risk of 12%, while patients with AKI had an admission risk of 19–21% depending on severity of AKI. After adjustment for age, race, gender, comorbidity, patient type, and sepsis, the odds were still 39–46% increased in patients with AKI compared with non-AKI patients. The association was confirmed in analyses stratified by subgroups of patients according to comorbidity level, age group, and CKD stage, which is a clinical
*See also p. 354. Key Words: acute kidney injury; chronic kidney failure; critical care; mortality; patient readmission Dr. Christiansen is an employee of Aarhus University. His institution received grant support from various companies. Copyright © 2015 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/CCM.0000000000000778
490
www.ccmjournal.org
meaningful way to address any different effect across a heterogeneous cohort of critically ill patients. To my knowledge, this is the first study examining the association between AKI and readmission rate in survivors of critical care. There are, however, a few studies of AKI and readmission from other settings with similar findings. In a cohort of all hospitalized patients at Brigham and Women’s Hospital, AKI was associated with a 16% readmission rate within 30 days after discharge compared with 9% in patients without AKI (10). Patients with AKI after cardiac surgery were also at increased risk of readmission (16–29% according to severity of AKI vs 9% in non-AKI patients) (11). Also in patients hospitalized with heart failure, AKI was associated with an increased rate of 30-day readmission for heart failure (21% vs 14%) (12). The study by Horkan et al (9) is well-designed, and study strengths include, among others, a large number of patients included in the cohort and the assessment of AKI using creatinine measurements rather than diagnostic coding. However, the definition of AKI is crucial when comparing study findings. Horkan et al (9) used the original Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) criteria instead of the newer and slightly more sensitive Kidney Disease Improving Global Outcome criteria, but the differences are minimal and unlikely to influence the study findings (10, 13). Nevertheless, the reported AKI prevalence of 13% (8,189/62,096) within 3 days before and 7 days after critical care initiation is rather low compared with previous studies reporting prevalence of AKI at ICU admission between 15.6% and 36.1% using the RIFLE criteria (14–16) and much lower than studies including AKI during the entire hospitalization with reported period prevalence as high as 60% in patients receiving critical care (10). It is reasonable to use creatinine measurements around critical care initiation in order to avoid immortal time in studies with start of followup shortly after critical care initiation. However, in this study of postdischarge outcome, it would have been appropriate to include all measurements before hospital discharge. This was done in a sensitivity analysis that confirmed the overall findings. Importantly, the definition of baseline creatinine has major impact on assessment of AKI. Horkan et al (9) used the most recent creatinine measurement within 7–365 days before hospital admission. If unavailable, they used first creatinine at hospital admission. It is reasonable to use measured instead of estimated baseline creatinine, but the algorithm potentially includes creatinine during previous or current hospital admission that are influenced by acute illness thereby not reflecting the true outpatient baseline value (17). This could explain the low prevalence of AKI in the current study. Measuring and interpreting readmission rates are not straightforward. The current study included unplanned readmission to the same hospitals only and thereby potentially February 2015 • Volume 43 • Number 2
Editorials
underestimated the true readmission rate. But why is the readmission rate increased in patients with AKI? One explanation could be that patients with AKI are more fragile or ill than non-AKI patients as reflected by more organ dysfunctions and longer hospital stay; on the contrary, the most severely ill patients with AKI may have died during hospitalization and are thus not included in the analysis. Severity of illness, including renal recovery, at hospital discharge may be important predictors of postdischarge complications and readmission not addressed in the current study. In addition, the study may also be confounded by potential differences in the patients’ socioeconomic status and their access to the healthcare system, which are important predictors of readmission and should be considered in future studies (18). What can we conclude from this study? First, the study confirmed that patients with AKI are at increased risk of death and end-stage renal disease after hospital discharge. Second, complications leading to hospital readmission may be a pathway explaining the increased mortality. Nonetheless, the study raises several questions that need to be addressed in future studies on the outcome of AKI after hospital discharge, including the timing and reason for readmission. The study provides important information for healthcare planners, but we need to know why patients are readmitted before we can answer whether and how the number could be reduced.
REFERENCES
1. Ricci Z, Cruz D, Ronco C: The RIFLE criteria and mortality in acute kidney injury: A systematic review. Kidney Int 2008; 73:538–546 2. Coca SG, Yusuf B, Shlipak MG, et al: Long-term risk of mortality and other adverse outcomes after acute kidney injury: A systematic review and meta-analysis. Am J Kidney Dis 2009; 53:961–973 3. Chawla LS, Eggers PW, Star RA, et al: Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med 2014; 371:58–66 4. Coca SG, Singanamala S, Parikh CR: Chronic kidney disease after acute kidney injury: A systematic review and meta-analysis. Kidney Int 2012; 81:442–448
Critical Care Medicine
5. Hansen MK, Gammelager H, Mikkelsen MM, et al: Post-operative acute kidney injury and five-year risk of death, myocardial infarction, and stroke among elective cardiac surgical patients: A cohort study. Crit Care 2013; 17:R292 6. Gammelager H, Christiansen CF, Johansen MB, et al: Three-year risk of cardiovascular disease among intensive care patients with acute kidney injury: A population-based cohort study. Crit Care 2014; 18:492 7. Olsson D, Sartipy U, Braunschweig F, et al: Acute kidney injury following coronary artery bypass surgery and long-term risk of heart failure. Circ Heart Fail 2013; 6:83–90 8. Rydén L, Ahnve S, Bell M, et al: Acute kidney injury after coronary artery bypass grafting and long-term risk of myocardial infarction and death. Int J Cardiol 2014; 172:190–195 9. Horkan CM, Purtle SW, Mendu ML, et al: The Association of Acute Kidney Injury in the Critically Ill and Postdischarge Outcomes: A Cohort Study. Crit Care Med 2015; 43:354–364 10. Zeng X, McMahon GM, Brunelli SM, et al: Incidence, outcomes, and comparisons across definitions of AKI in hospitalized individuals. Clin J Am Soc Nephrol 2014; 9:12–20 11. Brown JR, Parikh CR, Ross CS, et al; Northern New England Cardiovascular Disease Study Group: Impact of perioperative acute kidney injury as a severity index for thirty-day readmission after cardiac surgery. Ann Thorac Surg 2014; 97:111–117 12. Thakar CV, Parikh PJ, Liu Y: Acute kidney injury (AKI) and risk of readmissions in patients with heart failure. Am J Cardiol 2012; 109:1482–1486 13. Fujii T, Uchino S, Takinami M, et al: Validation of the Kidney Disease Improving Global Outcomes criteria for AKI and comparison of three criteria in hospitalized patients. Clin J Am Soc Nephrol 2014; 9:848–854 14. Gammelager H, Christiansen CF, Johansen MB, et al: One-year mortality among Danish intensive care patients with acute kidney injury: A cohort study. Crit Care 2012; 16:R124 15. Bagshaw SM, George C, Dinu I, et al: A multi-centre evaluation of the RIFLE criteria for early acute kidney injury in critically ill patients. Nephrol Dial Transplant 2008; 23:1203–1210 16. Joannidis M, Metnitz B, Bauer P, et al: Acute kidney injury in critically ill patients classified by AKIN versus RIFLE using the SAPS 3 database. Intensive Care Med 2009; 35:1692–1702 17. Siew ED, Ikizler TA, Matheny ME, et al: Estimating baseline kidney function in hospitalized patients with impaired kidney function. Clin J Am Soc Nephrol 2012; 7:712–719 18. Kangovi S, Grande D: Hospital readmissions–not just a measure of quality. JAMA 2011; 306:1796–1797
www.ccmjournal.org
491
Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
A
cute kidney injury (AKI) is a common condition in critically ill patients and associated with increased mortality not only during hospitalization but also after hospital discharge (1, 2). Despite the increasing number of studies on AKI outcome, information on nonfatal outcome occurring after hospital discharge remains limited. Such information could improve our understanding of the clinical pathways leading to an increased long-term mortality in AKI survivors. The close relationship between AKI and chronic kidney disease (CKD) may be an important link (3, 4). Like in patients with CKD, there is growing evidence of an increased risk of myocardial infarction and heart failure in patients surviving AKI, in particular, in AKI patients without renal recovery at hospital discharge (5–8). AKI is associated with increased length of hospital stay and increased costs, but given the potential postdischarge complications, patients with AKI are also likely to require considerable healthcare resources after hospital discharge. In this issue of Critical Care Medicine, Horkan et al (9) report a two-center study from Brigham and Women’s Hospital and Massachusetts General Hospital examining the impact of AKI on outcome after hospital discharge among survivors of critical illness during 1997–2012. The study included 62,096 adult survivors of critical illness and confirmed previous findings by showing an increased 30-day postdischarge mortality and an increased 1-year risk of end-stage renal disease in patients with AKI compared with non-AKI patients (1, 4). The study also contributes to the field with novel data by examining 30-day hospital readmission rate in survivors of critical illness as the main outcome. Patients without AKI had a 30-day readmission risk of 12%, while patients with AKI had an admission risk of 19–21% depending on severity of AKI. After adjustment for age, race, gender, comorbidity, patient type, and sepsis, the odds were still 39–46% increased in patients with AKI compared with non-AKI patients. The association was confirmed in analyses stratified by subgroups of patients according to comorbidity level, age group, and CKD stage, which is a clinical
*See also p. 354. Key Words: acute kidney injury; chronic kidney failure; critical care; mortality; patient readmission Dr. Christiansen is an employee of Aarhus University. His institution received grant support from various companies. Copyright © 2015 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins DOI: 10.1097/CCM.0000000000000778
490
www.ccmjournal.org
meaningful way to address any different effect across a heterogeneous cohort of critically ill patients. To my knowledge, this is the first study examining the association between AKI and readmission rate in survivors of critical care. There are, however, a few studies of AKI and readmission from other settings with similar findings. In a cohort of all hospitalized patients at Brigham and Women’s Hospital, AKI was associated with a 16% readmission rate within 30 days after discharge compared with 9% in patients without AKI (10). Patients with AKI after cardiac surgery were also at increased risk of readmission (16–29% according to severity of AKI vs 9% in non-AKI patients) (11). Also in patients hospitalized with heart failure, AKI was associated with an increased rate of 30-day readmission for heart failure (21% vs 14%) (12). The study by Horkan et al (9) is well-designed, and study strengths include, among others, a large number of patients included in the cohort and the assessment of AKI using creatinine measurements rather than diagnostic coding. However, the definition of AKI is crucial when comparing study findings. Horkan et al (9) used the original Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) criteria instead of the newer and slightly more sensitive Kidney Disease Improving Global Outcome criteria, but the differences are minimal and unlikely to influence the study findings (10, 13). Nevertheless, the reported AKI prevalence of 13% (8,189/62,096) within 3 days before and 7 days after critical care initiation is rather low compared with previous studies reporting prevalence of AKI at ICU admission between 15.6% and 36.1% using the RIFLE criteria (14–16) and much lower than studies including AKI during the entire hospitalization with reported period prevalence as high as 60% in patients receiving critical care (10). It is reasonable to use creatinine measurements around critical care initiation in order to avoid immortal time in studies with start of followup shortly after critical care initiation. However, in this study of postdischarge outcome, it would have been appropriate to include all measurements before hospital discharge. This was done in a sensitivity analysis that confirmed the overall findings. Importantly, the definition of baseline creatinine has major impact on assessment of AKI. Horkan et al (9) used the most recent creatinine measurement within 7–365 days before hospital admission. If unavailable, they used first creatinine at hospital admission. It is reasonable to use measured instead of estimated baseline creatinine, but the algorithm potentially includes creatinine during previous or current hospital admission that are influenced by acute illness thereby not reflecting the true outpatient baseline value (17). This could explain the low prevalence of AKI in the current study. Measuring and interpreting readmission rates are not straightforward. The current study included unplanned readmission to the same hospitals only and thereby potentially February 2015 • Volume 43 • Number 2
Editorials
underestimated the true readmission rate. But why is the readmission rate increased in patients with AKI? One explanation could be that patients with AKI are more fragile or ill than non-AKI patients as reflected by more organ dysfunctions and longer hospital stay; on the contrary, the most severely ill patients with AKI may have died during hospitalization and are thus not included in the analysis. Severity of illness, including renal recovery, at hospital discharge may be important predictors of postdischarge complications and readmission not addressed in the current study. In addition, the study may also be confounded by potential differences in the patients’ socioeconomic status and their access to the healthcare system, which are important predictors of readmission and should be considered in future studies (18). What can we conclude from this study? First, the study confirmed that patients with AKI are at increased risk of death and end-stage renal disease after hospital discharge. Second, complications leading to hospital readmission may be a pathway explaining the increased mortality. Nonetheless, the study raises several questions that need to be addressed in future studies on the outcome of AKI after hospital discharge, including the timing and reason for readmission. The study provides important information for healthcare planners, but we need to know why patients are readmitted before we can answer whether and how the number could be reduced.
REFERENCES
1. Ricci Z, Cruz D, Ronco C: The RIFLE criteria and mortality in acute kidney injury: A systematic review. Kidney Int 2008; 73:538–546 2. Coca SG, Yusuf B, Shlipak MG, et al: Long-term risk of mortality and other adverse outcomes after acute kidney injury: A systematic review and meta-analysis. Am J Kidney Dis 2009; 53:961–973 3. Chawla LS, Eggers PW, Star RA, et al: Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med 2014; 371:58–66 4. Coca SG, Singanamala S, Parikh CR: Chronic kidney disease after acute kidney injury: A systematic review and meta-analysis. Kidney Int 2012; 81:442–448
Critical Care Medicine
5. Hansen MK, Gammelager H, Mikkelsen MM, et al: Post-operative acute kidney injury and five-year risk of death, myocardial infarction, and stroke among elective cardiac surgical patients: A cohort study. Crit Care 2013; 17:R292 6. Gammelager H, Christiansen CF, Johansen MB, et al: Three-year risk of cardiovascular disease among intensive care patients with acute kidney injury: A population-based cohort study. Crit Care 2014; 18:492 7. Olsson D, Sartipy U, Braunschweig F, et al: Acute kidney injury following coronary artery bypass surgery and long-term risk of heart failure. Circ Heart Fail 2013; 6:83–90 8. Rydén L, Ahnve S, Bell M, et al: Acute kidney injury after coronary artery bypass grafting and long-term risk of myocardial infarction and death. Int J Cardiol 2014; 172:190–195 9. Horkan CM, Purtle SW, Mendu ML, et al: The Association of Acute Kidney Injury in the Critically Ill and Postdischarge Outcomes: A Cohort Study. Crit Care Med 2015; 43:354–364 10. Zeng X, McMahon GM, Brunelli SM, et al: Incidence, outcomes, and comparisons across definitions of AKI in hospitalized individuals. Clin J Am Soc Nephrol 2014; 9:12–20 11. Brown JR, Parikh CR, Ross CS, et al; Northern New England Cardiovascular Disease Study Group: Impact of perioperative acute kidney injury as a severity index for thirty-day readmission after cardiac surgery. Ann Thorac Surg 2014; 97:111–117 12. Thakar CV, Parikh PJ, Liu Y: Acute kidney injury (AKI) and risk of readmissions in patients with heart failure. Am J Cardiol 2012; 109:1482–1486 13. Fujii T, Uchino S, Takinami M, et al: Validation of the Kidney Disease Improving Global Outcomes criteria for AKI and comparison of three criteria in hospitalized patients. Clin J Am Soc Nephrol 2014; 9:848–854 14. Gammelager H, Christiansen CF, Johansen MB, et al: One-year mortality among Danish intensive care patients with acute kidney injury: A cohort study. Crit Care 2012; 16:R124 15. Bagshaw SM, George C, Dinu I, et al: A multi-centre evaluation of the RIFLE criteria for early acute kidney injury in critically ill patients. Nephrol Dial Transplant 2008; 23:1203–1210 16. Joannidis M, Metnitz B, Bauer P, et al: Acute kidney injury in critically ill patients classified by AKIN versus RIFLE using the SAPS 3 database. Intensive Care Med 2009; 35:1692–1702 17. Siew ED, Ikizler TA, Matheny ME, et al: Estimating baseline kidney function in hospitalized patients with impaired kidney function. Clin J Am Soc Nephrol 2012; 7:712–719 18. Kangovi S, Grande D: Hospital readmissions–not just a measure of quality. JAMA 2011; 306:1796–1797
www.ccmjournal.org
491
Copyright of Critical Care Medicine is the property of Lippincott Williams & Wilkins and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
