B-Type Natriuretic Peptide and Acute Kidney Injury: Not Yet Ready for Prime Time* Jean-Sebastien Rachoin, MD Division of Critical Care Medicine Department of Medicine Cooper Medical School of Rowan University Camden, NJ
Current accepted practice relies on temporal changes in serum creatinine or urine output. Clinical criteria such as Risk, Injury, Failure, Loss and End-stage renal disease. Acute Kidney Injury Network, and Kidney Disease: Improving Global Outcomes have been developed and validated based on small changes in serum creatinine that occur within a time frame of 48 hours. Unfortunately, such a window may still be too long Jason Kline, MD for effective early management, and the search for biomarkers Division cf Nephrology that detect earlier renal injury remains an active area of great Department cf Medicine interest. Cooper Medical School of Rowan University Camden, NJ What would an ideal biomarker look like? Naturally, an ideal biomarker would need to be highly sensitive (in order to avoid underdiagnosis) and specific (in order to avoid unneccute myocardial infarction (AMI) is a common medical event that can result in dire clinical complications. essary additional testing or treatments). Because of the wide Although the prevalence of coronary artery disease has heterogeneity of mechanisms underlying causes of AKI, no single reliable biomarker has emerged. It may be that a panel declined, the prevalence of AMI still remains unchanged. More concerning is that after decades of improvements in mortality, of biomarkers, and perhaps more importantly, their variawe seem to have reached a plateau with respect to survival (1). tions over time and in proper clinical scenarios would be most useful (5,6). One report recently published has demonstrated that mortalThe study by Moltraso et al (7) published in this issue of ity is unchanged despite improvement in processes of care, as Critical Care Medicine adds some thoughtful findings. Moltraso defined by lower door to balloon time (2). et al (7) analyzed 639 patients with ACS (non-ST-elevation One less well-described consequence of AMI is the occurmyocardial infarction and ST-elevation myocardial infarction rence of acute kidney injury (AKI). In a recent study. Fox et al [STEMI] ) and analyzed the relationship between B-type natri(3) analyzed the prevalence and outcome of AKI in more than uretic peptide (BNP) levels at admission and development of 59,000 patients presenting with AMI in 383 hospitals in the AKI. They found that of the 13% of patients in whom AKI was United States. The authors found that the prevalence of AKI developed, BNP was not only significantly associated with AKI was around 16% and its presence greatly increased the likelibut also the degree of AKI risk increased in parallel with the hood of death. These findings were confirmed by other reports absolute BNP level. In a previous study on patients present(4). It is conceivable that timely appropriate prevention of AKI ing with STEMI, Jarai et al (8) showed that measuring BNP could reduce mortality, and for this reason, great efforts have at admission enhanced the ability to identify patients at risk been devoted to the prevention and medical treatment of AKI for developing AKI after percutaneous coronary intervention. in patients presenting with acute coronary syndrome (ACS). Also in another study of patients undergoing elective cardiac However, currently there are no universally accepted effective surgery, preoperative BNP marginally improved classification preventative strategies. for risk of AKI (9). Clearly, a correlation between admission Why is that the case? An essential part of any successful inter- BNP levels and risk of AKI has been previously established and confirmed by Moltraso et al (7). However, in terms of vention strategy starts with proper and accurate identification the capacity of BNP alone to predict AKI, the authors of the of AKI early enough in the course of the acute event in order to take measures to minimize and even potentially reverse kid- current study failed to demonstrate any improvement in risk prediction with BNP over other variables (age, left ventricular ney injury. Another important consideration is the ability to ejection fraction, estimated glomerular filtration rate, and type identify patients who are at greatest risk of developing severe of ACS) previously shown to predict AKI risk. AKI such that closer monitoring and swift intervention might The question remains as to whether BNP represents a relibe implemented. able early marker for AKI or simply a surrogate for other underlying cardiac or renal issues. Compared with clinical models, in 'See also p. 619. both the study by Patel et al (9) and Moltraso et al (7), the appliKey Words: acute kidney injury; biomarker; B-type natriuretic peptide cation of BNP did not increase the area under the curve. FurThe authors have disclosed that they do not have any potential conflicts thermore, patients with high BNP levels also had baseline lower of interest. ejection fraction, a variable that has already been shown to be Copyright © 2013 by the Society of Critical Care Medicine and Lippincott associated with AKI. Also, the present study did not identify Williams & Wilkins early treatment strategies used to manage the subjects on initial
A
DOI:10.1097/CCM.0000000000000082 March 2014 • Volume 42 • Number 3 746
www.ccmjournal.org
Editorials
presentation. AKI had been defined by RIELE classification using serum creatinine levels and urine output. Consider the observation that serum creatinine can he spuriously depressed in the setting of intravascular volume expansion (precisely the condition where elevated BNP levels are detected) and that perhaps appropriate diuresis on presentation may have resulted in an expected rise of creatinine in the absence of true renal injury. There are several limitations to this study, some of which have been acknowledged by the authors: first, as a single-center study, the universal relevance remains unanswered; second, the absence of serial measurement of BNP prevents us from studying the utility of the trajectory rather than the absolute value of BNP in predicting AKI; third, volume management was not reported in this study. Although appropriate use of diuretics may have explained an elevated serum creatinine not necessarily related to true renal injury, inappropriate administration of TVfiuidsin patients presenting with shock may have precipitated AKI fi-om worsening of cardiorenal syndrome. Indeed, imhalances in the gradient of arterial to venous pressure can significantly impact renal perfusion pressure (10). Lastly, despite the practical use of serum creatinine in defining AKI, there are real limitations in its utility as a surrogate marker of renal function, particularly in the setting of intravascular volume shifts. In conclusion, the results of this article add some interesting findings despite some of its limitations. Like many other earlier biomarkers, BNP may eventually find its role in predicting AKI, and future work studying clinical settings and its utility in coordination with other biomarkers may prove to be fruitful. However, at this time, it would he premature to suggest that
BNP measurement is ready for the spotlight in prime time use with respect to predicting AKI.
REFERENCES 1. Roger VL, Wesfon SA, Gerber Y, et al; Trends in incidence, severity, and outcome of hospifalized myocardial infarcfion. Circulation 2010; 121;863-869 2. Menees DS, Peterson ED, Wang Y, ef al: Door-to-balloon fime and mortality among patients undergoing primary PCI. N EngI J Med 2013;369;901-909 3. Fox CS, Muntner P, Chen AY, et al: Shorf-term outcomes of acufe myocardial infarcfion in patients wifh acufe kidney injury: A reporf from fhe national cardiovascular dafa registry. Circulation 2012; 125:497-504 4. Parikh CR, Coca SG, Wang Y, ef al: Long-ferm prognosis of acufe kidney injury after acufe myocardial infarcfion. Arch Intern Med 2008; 168:987-995 5. Heviiift SM, Dear J, Sfar RA: Discovery of profein biomarkers for renal diseases, i / I m Soc Nephrol 2004; 15;1677-1 689 6. Parikh CR, Devarajan P: Nevi biomarkers of acute kidney injury. Crit Care Med 2008; 36;S159-S165 7 Moltraso M, Cabiafi A, Milazzo V, ef al; B-Type Nafriurefic Peptide and Risk of Acufe Kidney Injury in Patients Hospitalized With Acute Coronary Syndromes. Crit Care Med 2014; 42:619-624 8. Jarai R, Dangas G, Huber K, ef al: B-type nafriuretic pepfide and risk of contrast-induced acufe kidney injury in acute ST-segment-elevation myocardial infarction: A subsfudy from the HORIZCNS-AMI trial. Circ Cardiovasc Interv 201 2; 5:813-820 9. Patel UD, Garg AX, Krumholz HM, ef al; Translafional Research Investigating Biomarker Endpoints in Acufe Kidney Injury (TRIBEAKI) Consorfium; Preoperafive serum brain nafriuretic pepfide and risk of acute kidney injury affer cardiac surgery. Circulation 2012; 125;1347-1355 10. Schrier RW; Fluid administrafion in critically ill patienfs with acufe kidney injury. Clin J Am Soc Nephrol 2010; 5:733-739
Can Administrative Data Be Used to Consistently IVIeasure the Burden of Sepsis?* Olaf L Cremer, MD, PhD Department of Intensive Care Medicine University Medical Center Utrecht Utrecht, The Netherlands
*See also p. 625. Key Words: diagnosis; epidemiology; morfalify; septic shock; severe sepsis Dr. Cremer's instifufion received granf supporf from fhe Cenfer for Translational Molecular Medicine (Projecf MARS [molecular diagnosis and risk stratificafion of sepsis], granf 041-201). Copyright © 2013 by fhe Society of Crifical Care Medicine and Lippincoff Williams & Wilkins DOI: 10.1097/CCM.0000000000000075
Critical Care Medicine
M
ore than a decade has passed since the launch of the first Surviving Sepsis Campaign initiative in 2002, and issued guidelines have now reached their third version (1). In parallel with this collaborative effort to raise awareness and improve the treatment of sepsis by introducing care bundles, published case fatality rates have been slowly declining (2). At the same time, numerous authors have reported that—due to an aging population—the prevalence of sepsis in the United States is rising (2-4). The majority of these reports have used administrative databases to retrospectively assess the prevalence, variations in care, and outcomes of sepsis over time. This approach is attractive, because administrative data are readily available at low cost and are able to span multiple years and healthcare settings. Presumably, administrative data also better reñect real-world treatment than data collected in prospective trials. However, to avoid erroneous conclusions, users must be aware of the vvww.ccmjournal.org
747
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.
Current accepted practice relies on temporal changes in serum creatinine or urine output. Clinical criteria such as Risk, Injury, Failure, Loss and End-stage renal disease. Acute Kidney Injury Network, and Kidney Disease: Improving Global Outcomes have been developed and validated based on small changes in serum creatinine that occur within a time frame of 48 hours. Unfortunately, such a window may still be too long Jason Kline, MD for effective early management, and the search for biomarkers Division cf Nephrology that detect earlier renal injury remains an active area of great Department cf Medicine interest. Cooper Medical School of Rowan University Camden, NJ What would an ideal biomarker look like? Naturally, an ideal biomarker would need to be highly sensitive (in order to avoid underdiagnosis) and specific (in order to avoid unneccute myocardial infarction (AMI) is a common medical event that can result in dire clinical complications. essary additional testing or treatments). Because of the wide Although the prevalence of coronary artery disease has heterogeneity of mechanisms underlying causes of AKI, no single reliable biomarker has emerged. It may be that a panel declined, the prevalence of AMI still remains unchanged. More concerning is that after decades of improvements in mortality, of biomarkers, and perhaps more importantly, their variawe seem to have reached a plateau with respect to survival (1). tions over time and in proper clinical scenarios would be most useful (5,6). One report recently published has demonstrated that mortalThe study by Moltraso et al (7) published in this issue of ity is unchanged despite improvement in processes of care, as Critical Care Medicine adds some thoughtful findings. Moltraso defined by lower door to balloon time (2). et al (7) analyzed 639 patients with ACS (non-ST-elevation One less well-described consequence of AMI is the occurmyocardial infarction and ST-elevation myocardial infarction rence of acute kidney injury (AKI). In a recent study. Fox et al [STEMI] ) and analyzed the relationship between B-type natri(3) analyzed the prevalence and outcome of AKI in more than uretic peptide (BNP) levels at admission and development of 59,000 patients presenting with AMI in 383 hospitals in the AKI. They found that of the 13% of patients in whom AKI was United States. The authors found that the prevalence of AKI developed, BNP was not only significantly associated with AKI was around 16% and its presence greatly increased the likelibut also the degree of AKI risk increased in parallel with the hood of death. These findings were confirmed by other reports absolute BNP level. In a previous study on patients present(4). It is conceivable that timely appropriate prevention of AKI ing with STEMI, Jarai et al (8) showed that measuring BNP could reduce mortality, and for this reason, great efforts have at admission enhanced the ability to identify patients at risk been devoted to the prevention and medical treatment of AKI for developing AKI after percutaneous coronary intervention. in patients presenting with acute coronary syndrome (ACS). Also in another study of patients undergoing elective cardiac However, currently there are no universally accepted effective surgery, preoperative BNP marginally improved classification preventative strategies. for risk of AKI (9). Clearly, a correlation between admission Why is that the case? An essential part of any successful inter- BNP levels and risk of AKI has been previously established and confirmed by Moltraso et al (7). However, in terms of vention strategy starts with proper and accurate identification the capacity of BNP alone to predict AKI, the authors of the of AKI early enough in the course of the acute event in order to take measures to minimize and even potentially reverse kid- current study failed to demonstrate any improvement in risk prediction with BNP over other variables (age, left ventricular ney injury. Another important consideration is the ability to ejection fraction, estimated glomerular filtration rate, and type identify patients who are at greatest risk of developing severe of ACS) previously shown to predict AKI risk. AKI such that closer monitoring and swift intervention might The question remains as to whether BNP represents a relibe implemented. able early marker for AKI or simply a surrogate for other underlying cardiac or renal issues. Compared with clinical models, in 'See also p. 619. both the study by Patel et al (9) and Moltraso et al (7), the appliKey Words: acute kidney injury; biomarker; B-type natriuretic peptide cation of BNP did not increase the area under the curve. FurThe authors have disclosed that they do not have any potential conflicts thermore, patients with high BNP levels also had baseline lower of interest. ejection fraction, a variable that has already been shown to be Copyright © 2013 by the Society of Critical Care Medicine and Lippincott associated with AKI. Also, the present study did not identify Williams & Wilkins early treatment strategies used to manage the subjects on initial
A
DOI:10.1097/CCM.0000000000000082 March 2014 • Volume 42 • Number 3 746
www.ccmjournal.org
Editorials
presentation. AKI had been defined by RIELE classification using serum creatinine levels and urine output. Consider the observation that serum creatinine can he spuriously depressed in the setting of intravascular volume expansion (precisely the condition where elevated BNP levels are detected) and that perhaps appropriate diuresis on presentation may have resulted in an expected rise of creatinine in the absence of true renal injury. There are several limitations to this study, some of which have been acknowledged by the authors: first, as a single-center study, the universal relevance remains unanswered; second, the absence of serial measurement of BNP prevents us from studying the utility of the trajectory rather than the absolute value of BNP in predicting AKI; third, volume management was not reported in this study. Although appropriate use of diuretics may have explained an elevated serum creatinine not necessarily related to true renal injury, inappropriate administration of TVfiuidsin patients presenting with shock may have precipitated AKI fi-om worsening of cardiorenal syndrome. Indeed, imhalances in the gradient of arterial to venous pressure can significantly impact renal perfusion pressure (10). Lastly, despite the practical use of serum creatinine in defining AKI, there are real limitations in its utility as a surrogate marker of renal function, particularly in the setting of intravascular volume shifts. In conclusion, the results of this article add some interesting findings despite some of its limitations. Like many other earlier biomarkers, BNP may eventually find its role in predicting AKI, and future work studying clinical settings and its utility in coordination with other biomarkers may prove to be fruitful. However, at this time, it would he premature to suggest that
BNP measurement is ready for the spotlight in prime time use with respect to predicting AKI.
REFERENCES 1. Roger VL, Wesfon SA, Gerber Y, et al; Trends in incidence, severity, and outcome of hospifalized myocardial infarcfion. Circulation 2010; 121;863-869 2. Menees DS, Peterson ED, Wang Y, ef al: Door-to-balloon fime and mortality among patients undergoing primary PCI. N EngI J Med 2013;369;901-909 3. Fox CS, Muntner P, Chen AY, et al: Shorf-term outcomes of acufe myocardial infarcfion in patients wifh acufe kidney injury: A reporf from fhe national cardiovascular dafa registry. Circulation 2012; 125:497-504 4. Parikh CR, Coca SG, Wang Y, ef al: Long-ferm prognosis of acufe kidney injury after acufe myocardial infarcfion. Arch Intern Med 2008; 168:987-995 5. Heviiift SM, Dear J, Sfar RA: Discovery of profein biomarkers for renal diseases, i / I m Soc Nephrol 2004; 15;1677-1 689 6. Parikh CR, Devarajan P: Nevi biomarkers of acute kidney injury. Crit Care Med 2008; 36;S159-S165 7 Moltraso M, Cabiafi A, Milazzo V, ef al; B-Type Nafriurefic Peptide and Risk of Acufe Kidney Injury in Patients Hospitalized With Acute Coronary Syndromes. Crit Care Med 2014; 42:619-624 8. Jarai R, Dangas G, Huber K, ef al: B-type nafriuretic pepfide and risk of contrast-induced acufe kidney injury in acute ST-segment-elevation myocardial infarction: A subsfudy from the HORIZCNS-AMI trial. Circ Cardiovasc Interv 201 2; 5:813-820 9. Patel UD, Garg AX, Krumholz HM, ef al; Translafional Research Investigating Biomarker Endpoints in Acufe Kidney Injury (TRIBEAKI) Consorfium; Preoperafive serum brain nafriuretic pepfide and risk of acute kidney injury affer cardiac surgery. Circulation 2012; 125;1347-1355 10. Schrier RW; Fluid administrafion in critically ill patienfs with acufe kidney injury. Clin J Am Soc Nephrol 2010; 5:733-739
Can Administrative Data Be Used to Consistently IVIeasure the Burden of Sepsis?* Olaf L Cremer, MD, PhD Department of Intensive Care Medicine University Medical Center Utrecht Utrecht, The Netherlands
*See also p. 625. Key Words: diagnosis; epidemiology; morfalify; septic shock; severe sepsis Dr. Cremer's instifufion received granf supporf from fhe Cenfer for Translational Molecular Medicine (Projecf MARS [molecular diagnosis and risk stratificafion of sepsis], granf 041-201). Copyright © 2013 by fhe Society of Crifical Care Medicine and Lippincoff Williams & Wilkins DOI: 10.1097/CCM.0000000000000075
Critical Care Medicine
M
ore than a decade has passed since the launch of the first Surviving Sepsis Campaign initiative in 2002, and issued guidelines have now reached their third version (1). In parallel with this collaborative effort to raise awareness and improve the treatment of sepsis by introducing care bundles, published case fatality rates have been slowly declining (2). At the same time, numerous authors have reported that—due to an aging population—the prevalence of sepsis in the United States is rising (2-4). The majority of these reports have used administrative databases to retrospectively assess the prevalence, variations in care, and outcomes of sepsis over time. This approach is attractive, because administrative data are readily available at low cost and are able to span multiple years and healthcare settings. Presumably, administrative data also better reñect real-world treatment than data collected in prospective trials. However, to avoid erroneous conclusions, users must be aware of the vvww.ccmjournal.org
747
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.
