Editorial Recovery From Acute Kidney Injury: Predicting Outcomes Related Article, p. 592
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n the era of evidence-based medicine, there is a growing demand to extract information from clinical and research databases that may positively affect aspects of health care such as patient mortality and quality of life, as well as cost containment. Acute kidney injury (AKI) remains an important health care burden, as it is associated with high morbidity and mortality.1 It represents an ominous diagnosis complicating a patient’s hospital course. AKI may result from many causes (eg, ischemia, nephrotoxins, or sepsis) and is associated with immune dysfunction, sepsis, and multi-organ dysfunction, which lead to poor and often catastrophic outcomes. The US Renal Data System recently released epidemiologic data that showed continued growth in the incidence of AKI from 2003 through 2012.2 According to a conceptual framework on the natural history of AKI, possible outcomes for patients with AKI include death; complete recovery of kidney function; or development of progressive chronic kidney disease (CKD), AKI on CKD, or irreversible loss of kidney function leading to end-stage renal disease (ESRD).3 One crucial question in the management of severe AKI requiring dialysis is if and when a patient will recover kidney function. This question is important to patients, their families, and their health care team, as predicting a patient’s outcome can guide therapy: nephrologists can meticulously follow kidney function, avoid conditions that may lead to hypotension and ischemic episodes, and arrange for timely hemodialysis (HD) vascular access placement if the need for renal replacement therapy (RRT) is imminent. In this issue of AJKD, Hickson et al4 provide a timely study with valuable insight into this major problem of predicting which patients will require continued dialysis treatment following in-hospital initiation of RRT. Hickson et al examined incident outpatient HD patients treated at Mayo Clinic Dialysis Services from January 1, 2006 to December 31, 2009. All patients aged 18 years or older who initiated RRT in the hospital before transitioning to outpatient in-center HD were included in the study. The primary outcome of interest Address correspondence to Emaad M. Abdel-Rahman, MD, PhD, Division of Nephrology, University of Virginia Health System, Box 800133, Charlottesville, VA 22908. E-mail: ea6n@ virginia.edu Ó 2015 by the National Kidney Foundation, Inc. 0272-6386 http://dx.doi.org/10.1053/j.ajkd.2015.02.316 528
was recovery of sufficient kidney function to discontinue outpatient HD therapy. Of note, close to 60% of the outpatient HD cohort started dialysis treatment in the hospital setting. Furthermore, while 20% of the population started in-hospital HD as a consequence of progression to CKD stage 5, 70% of patients started inhospital HD due to AKI. These facts should serve to alert the nephrology community about AKI’s importance as a source of incident outpatients who require in-center HD, and the value of early diagnosis of AKI and accurate identification of prognostic predictors. Nephrologists have recognized that the unfavorable outcome of postdischarge RRT might be linked to the late detection of AKI when using serum creatinine as a marker of AKI. Hence, research has focused on identifying earlier markers to help accelerate diagnosis as well as aid in prognosis of patients with AKI. The demand for such markers has prompted the discovery of several candidates.5-7 Even so, predicting outcomes of patients with AKI using basic clinical parameters remains a viable approach, and one of the strengths of the study by Hickson et al is the ability to predict outcomes by using readily available clinical parameters. Most of the patients who recovered enough kidney function to discontinue dialysis did so by 3 months (73%) and 6 months (94%) after RRT initiation. The remainder of the patients recovered kidney function by 12 months. Hickson et al also identified specific independent predictors of kidney function recovery: higher baseline estimated glomerular filtration rate (eGFR), sepsis/postoperative acute tubular necrosis, and absence of heart failure. Another important finding was that none of the patients with CKD stage 5 recovered kidney function. This is not surprising; at that advanced stage of kidney disease, the possibility of recovery is negligible, and priority should be placed on discussing RRT modalities and arranging for a permanent vascular access. Another notable finding of the study was that in patients with baseline eGFR . 30 mL/min/1.73 m2, recovery of kidney function was not uncommon. The study demonstrates that recovery remains a function of baseline eGFR: of patients with a baseline eGFR . 60 mL/min/1.73 m2, more than half regained enough kidney function to discontinue dialysis, compared with only 17% of patients with CKD stages 3 and 4 at baseline.4 A very important point to highlight is the need for meticulous oversight of the medical management of patients with AKI who continue to require outpatient dialysis treatment. Such an approach would allow for the best chance of kidney function recovery. This Am J Kidney Dis. 2015;65(4):528-529
Editorial
careful approach includes several measures. Often medications need to be adjusted as blood pressure, volume status, and GFR may change. Nephrotoxic drugs (eg, nonsteroidal anti-inflammatory agents, aminoglycosides, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers) and intravenous radiocontrast agents for radiographic procedures should be avoided. Residual kidney function, electrolytes, and urine output should be monitored and recorded once weekly. Dialysis prescription should avoid excessive ultrafiltration and hypotensive episodes. This approach should be extended for a minimum of 6 months. Beyond this time period, recovery is less likely: in the study by Hickson et al, only 6% patients recovered kidney function after 6 months of dialysis.4 In spite of recovery in a subset of the population studied by Hickson et al who started dialysis in the hospital setting, mortality remained significant. More than one third of the study population died during the follow-up period. Follow-up care during outpatient dialysis treatment is critical and could potentially affect kidney function recovery and mortality. In our institution, we operate a provider-based dialysis facility in which physicians see patients 3 times per week, reviewing medications and assessing volume status at each visit. In addition, each week we assess each patient’s kidney function and collect a 24-hour urine specimen to measure urea and creatinine clearance. It should be noted that the current study by Hickson et al was conducted well before 2012. The Centers for Medicare and Medicaid Services (CMS) have since provided clarification of their policy, which states that certified dialysis facilities cannot provide outpatient dialysis for the treatment of AKI. Thus, currently, the options for these patients are limited. Either patients must remain hospitalized, or, alternatively, outpatient dialysis for patients with AKI can be delivered in locations that qualify as provider-based departments of the hospital. Another option entails the potential use of CMS-certified dialysis facilities, which offers convenience and expertise but would necessitate new algorithms and treatment protocols tailored to AKI patients that are different from the standards of care for patients with ESRD.
Am J Kidney Dis. 2015;65(4):528-529
The article from Hickson et al sheds considerable light on conditions associated with long-term recovery of kidney function and mortality in patients who initiate dialysis in the hospital setting. It also highlights the importance of using clinical parameters to predict prognosis while awaiting the ideal biomarker: one that serves both diagnostic and prognostic functions with the ultimate goal of improving outcomes of patients with AKI. Lastly, optimizing recovery of kidney function in this vulnerable population should occur in a setting that is practical yet incorporates personalized medical management. Emaad M. Abdel-Rahman, MD, PhD Mark D. Okusa, MD University of Virginia Health System Charlottesville, Virginia
ACKNOWLEDGEMENTS Support: None. Financial Disclosure: The authors declare that they have no relevant financial interests.
REFERENCES 1. Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294:813-818. 2. US Renal Data System. USRDS 2014 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2014. 3. Cerdá J, Lameire N, Eggers P, et al. Epidemiology of acute kidney injury. Clin J Am Soc Nephrol. 2008;3:881-886. 4. Hickson LJ, Chadhary S, Williams AW, et al. Predictors of outpatient kidney function recovery among patients who initiate hemodialysis in the hospital. Am J Kidney Dis. 2015;65(4): 592-602. 5. Schmitt R, Coca S, Kanbay M, Tinetti ME, Cantley LG, Parikh CR. Recovery of kidney function after acute kidney injury in the elderly: a systematic review and meta-analysis. Am J Kidney Dis. 2008;52:262-271. 6. Murray PT, Mehta RL, Shaw A, et al. Potential use of biomarkers in acute kidney injury: report and summary of recommendations from the 10th Acute Dialysis Quality Initiative consensus conference. Kidney Int. 2014;85:513-521. 7. Kashani K, Al-Khafaji A, Ardiles T, et al. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care. 2013;17:R25.
529
I
n the era of evidence-based medicine, there is a growing demand to extract information from clinical and research databases that may positively affect aspects of health care such as patient mortality and quality of life, as well as cost containment. Acute kidney injury (AKI) remains an important health care burden, as it is associated with high morbidity and mortality.1 It represents an ominous diagnosis complicating a patient’s hospital course. AKI may result from many causes (eg, ischemia, nephrotoxins, or sepsis) and is associated with immune dysfunction, sepsis, and multi-organ dysfunction, which lead to poor and often catastrophic outcomes. The US Renal Data System recently released epidemiologic data that showed continued growth in the incidence of AKI from 2003 through 2012.2 According to a conceptual framework on the natural history of AKI, possible outcomes for patients with AKI include death; complete recovery of kidney function; or development of progressive chronic kidney disease (CKD), AKI on CKD, or irreversible loss of kidney function leading to end-stage renal disease (ESRD).3 One crucial question in the management of severe AKI requiring dialysis is if and when a patient will recover kidney function. This question is important to patients, their families, and their health care team, as predicting a patient’s outcome can guide therapy: nephrologists can meticulously follow kidney function, avoid conditions that may lead to hypotension and ischemic episodes, and arrange for timely hemodialysis (HD) vascular access placement if the need for renal replacement therapy (RRT) is imminent. In this issue of AJKD, Hickson et al4 provide a timely study with valuable insight into this major problem of predicting which patients will require continued dialysis treatment following in-hospital initiation of RRT. Hickson et al examined incident outpatient HD patients treated at Mayo Clinic Dialysis Services from January 1, 2006 to December 31, 2009. All patients aged 18 years or older who initiated RRT in the hospital before transitioning to outpatient in-center HD were included in the study. The primary outcome of interest Address correspondence to Emaad M. Abdel-Rahman, MD, PhD, Division of Nephrology, University of Virginia Health System, Box 800133, Charlottesville, VA 22908. E-mail: ea6n@ virginia.edu Ó 2015 by the National Kidney Foundation, Inc. 0272-6386 http://dx.doi.org/10.1053/j.ajkd.2015.02.316 528
was recovery of sufficient kidney function to discontinue outpatient HD therapy. Of note, close to 60% of the outpatient HD cohort started dialysis treatment in the hospital setting. Furthermore, while 20% of the population started in-hospital HD as a consequence of progression to CKD stage 5, 70% of patients started inhospital HD due to AKI. These facts should serve to alert the nephrology community about AKI’s importance as a source of incident outpatients who require in-center HD, and the value of early diagnosis of AKI and accurate identification of prognostic predictors. Nephrologists have recognized that the unfavorable outcome of postdischarge RRT might be linked to the late detection of AKI when using serum creatinine as a marker of AKI. Hence, research has focused on identifying earlier markers to help accelerate diagnosis as well as aid in prognosis of patients with AKI. The demand for such markers has prompted the discovery of several candidates.5-7 Even so, predicting outcomes of patients with AKI using basic clinical parameters remains a viable approach, and one of the strengths of the study by Hickson et al is the ability to predict outcomes by using readily available clinical parameters. Most of the patients who recovered enough kidney function to discontinue dialysis did so by 3 months (73%) and 6 months (94%) after RRT initiation. The remainder of the patients recovered kidney function by 12 months. Hickson et al also identified specific independent predictors of kidney function recovery: higher baseline estimated glomerular filtration rate (eGFR), sepsis/postoperative acute tubular necrosis, and absence of heart failure. Another important finding was that none of the patients with CKD stage 5 recovered kidney function. This is not surprising; at that advanced stage of kidney disease, the possibility of recovery is negligible, and priority should be placed on discussing RRT modalities and arranging for a permanent vascular access. Another notable finding of the study was that in patients with baseline eGFR . 30 mL/min/1.73 m2, recovery of kidney function was not uncommon. The study demonstrates that recovery remains a function of baseline eGFR: of patients with a baseline eGFR . 60 mL/min/1.73 m2, more than half regained enough kidney function to discontinue dialysis, compared with only 17% of patients with CKD stages 3 and 4 at baseline.4 A very important point to highlight is the need for meticulous oversight of the medical management of patients with AKI who continue to require outpatient dialysis treatment. Such an approach would allow for the best chance of kidney function recovery. This Am J Kidney Dis. 2015;65(4):528-529
Editorial
careful approach includes several measures. Often medications need to be adjusted as blood pressure, volume status, and GFR may change. Nephrotoxic drugs (eg, nonsteroidal anti-inflammatory agents, aminoglycosides, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers) and intravenous radiocontrast agents for radiographic procedures should be avoided. Residual kidney function, electrolytes, and urine output should be monitored and recorded once weekly. Dialysis prescription should avoid excessive ultrafiltration and hypotensive episodes. This approach should be extended for a minimum of 6 months. Beyond this time period, recovery is less likely: in the study by Hickson et al, only 6% patients recovered kidney function after 6 months of dialysis.4 In spite of recovery in a subset of the population studied by Hickson et al who started dialysis in the hospital setting, mortality remained significant. More than one third of the study population died during the follow-up period. Follow-up care during outpatient dialysis treatment is critical and could potentially affect kidney function recovery and mortality. In our institution, we operate a provider-based dialysis facility in which physicians see patients 3 times per week, reviewing medications and assessing volume status at each visit. In addition, each week we assess each patient’s kidney function and collect a 24-hour urine specimen to measure urea and creatinine clearance. It should be noted that the current study by Hickson et al was conducted well before 2012. The Centers for Medicare and Medicaid Services (CMS) have since provided clarification of their policy, which states that certified dialysis facilities cannot provide outpatient dialysis for the treatment of AKI. Thus, currently, the options for these patients are limited. Either patients must remain hospitalized, or, alternatively, outpatient dialysis for patients with AKI can be delivered in locations that qualify as provider-based departments of the hospital. Another option entails the potential use of CMS-certified dialysis facilities, which offers convenience and expertise but would necessitate new algorithms and treatment protocols tailored to AKI patients that are different from the standards of care for patients with ESRD.
Am J Kidney Dis. 2015;65(4):528-529
The article from Hickson et al sheds considerable light on conditions associated with long-term recovery of kidney function and mortality in patients who initiate dialysis in the hospital setting. It also highlights the importance of using clinical parameters to predict prognosis while awaiting the ideal biomarker: one that serves both diagnostic and prognostic functions with the ultimate goal of improving outcomes of patients with AKI. Lastly, optimizing recovery of kidney function in this vulnerable population should occur in a setting that is practical yet incorporates personalized medical management. Emaad M. Abdel-Rahman, MD, PhD Mark D. Okusa, MD University of Virginia Health System Charlottesville, Virginia
ACKNOWLEDGEMENTS Support: None. Financial Disclosure: The authors declare that they have no relevant financial interests.
REFERENCES 1. Uchino S, Kellum JA, Bellomo R, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005;294:813-818. 2. US Renal Data System. USRDS 2014 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2014. 3. Cerdá J, Lameire N, Eggers P, et al. Epidemiology of acute kidney injury. Clin J Am Soc Nephrol. 2008;3:881-886. 4. Hickson LJ, Chadhary S, Williams AW, et al. Predictors of outpatient kidney function recovery among patients who initiate hemodialysis in the hospital. Am J Kidney Dis. 2015;65(4): 592-602. 5. Schmitt R, Coca S, Kanbay M, Tinetti ME, Cantley LG, Parikh CR. Recovery of kidney function after acute kidney injury in the elderly: a systematic review and meta-analysis. Am J Kidney Dis. 2008;52:262-271. 6. Murray PT, Mehta RL, Shaw A, et al. Potential use of biomarkers in acute kidney injury: report and summary of recommendations from the 10th Acute Dialysis Quality Initiative consensus conference. Kidney Int. 2014;85:513-521. 7. Kashani K, Al-Khafaji A, Ardiles T, et al. Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury. Crit Care. 2013;17:R25.
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