527908
research-article2014
AOPXXX10.1177/1060028014527908Annals of PharmacotherapyAlford et al
Research Reports
Glomerular Filtration Rate Equations Do Not Accurately Predict Vancomycin Trough Concentrations in Pediatric Patients
Annals of Pharmacotherapy 1–6 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1060028014527908 aop.sagepub.com
Elizabeth L. Alford, PharmD1,2,3, Rebecca F. Chhim, PharmD1,3, Catherine M. Crill, PharmD1,3, M. Colleen Hastings, MD1,3, Bettina H. Ault, MD1,3, and Chasity M. Shelton, PharmD1,3
Abstract Background: The Bedside Chronic Kidney Disease in Children (CKiD) equation was developed using data from children with chronic kidney disease. Some institutions are using this equation in all pediatric patients, regardless of renal function, to adjust medications. No data have shown that the Bedside CKiD equation is equivalent or better than the Schwartz equation in estimating glomerular filtration rate (GFR) in pediatric patients with normal renal function. Objective: To compare GFR estimates using the Bedside CKiD and Schwartz equations and determine if either offers sufficient vancomycin dosing guidance in hospitalized pediatric patients. Methods: This retrospective review at a single-center, academic, pediatric hospital included patients 2 to 12 years old with a steady-state vancomycin trough collected between January 1, 2010 and December 31, 2011. Patients with acute kidney injury or lacking essential data (e.g., height and serum creatinine), were excluded. An estimated GFR (eGFR) was calculated using the Schwartz and Bedside CKiD equations. Pearson correlations and linear regressions compared the eGFR values and vancomycin troughs. Results: A total of 50 vancomycin troughs were analyzed. There was a weak relationship between the eGFR and troughs for the Schwartz equation (r2 = 0.028) and Bedside CKiD equation (r2 = 0.028). A weak relationship between serum creatinine and troughs was observed (r2 = 0.132). Limitations include small sample size and retrospective design. Conclusions: Neither equation correlates well with vancomycin troughs, suggesting that therapeutic monitoring remains important. Better GFR estimation methods are needed in pediatrics to aid appropriate dosing of renally eliminated medications. Keywords pediatrics, serum creatinine–based glomerular filtration rate estimation, Schwartz equation, Bedside Chronic Kidney Disease in Children equation, vancomycin Glomerular filtration rate (GFR) is the best measure of kidney function and can be applied reliably to pediatric patients who are at least 1 year old because GFR is known to mature by the age of one.1 There are important clinical uses of estimated GFR (eGFR) because it is used to stage chronic kidney disease (CKD), so that complications of renal dysfunction may be anticipated and treated. In the hospital setting, eGFR is used to adjust dosing regimens of renally cleared medications in patients with an elevated serum creatinine (SCr). Some medications that require dose adjustments in patients with renal dysfunction include acyclovir, vancomycin, enoxaparin, ranitidine, gentamicin, morphine, and select cephalosporins and β-lactams. The gold standard for measuring GFR is inulin clearance. Alternative methods for measuring GFR include iothalamate clearance, 99mTc-DTPA clearance, iohexol clearance,
or 51Cr-EDTA clearance.2 It is not feasible to measure GFR directly in clinical practice because all these methods require a prolonged time period for collection, consequently delaying the time to results. SCr is a readily available bedside lab test used to estimate GFR, but there are different normal ranges depending on age, gender, and size. Various SCr-based, GFR 1
Le Bonheur Children’s Hospital, Memphis, TN, USA The Center for Pediatric Pharmacokinetics and Therapeutics, Memphis, TN, USA 3 The University of Tennessee Health Science Center, Memphis, TN, USA 2
Corresponding Author: Chasity M. Shelton, Department of Clinical Pharmacy, The University of Tennessee Health Science Center, 881 Madison Ave, Suite 343, Memphis, TN 38163, USA. Email: [email protected]
Downloaded from aop.sagepub.com at NORTHEASTERN UNIV LIBRARY on April 6, 2014
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Annals of Pharmacotherapy
Table 1. Equations for Estimating Glomerular Filtration Rate in Pediatric Patients. Equation Name Schwartz equation Bedside CKiD Equation
Equation eGFR (mL/min/1.73 m2) = k × Length ÷ SCr (mg/dL)3,4 k = 0.33 In preterm infants 90 mL/min/1.73 m2 showed an even greater underestimation (mean = 9.1 mL/min/1.73 m2). More recently, Lee et al11 investigated the Bedside CKiD equation, along with 3 other GFR estimation methods, in a retrospective, observational, cross-sectional study of 53 pediatric patients with CKD stages 2 to 5 and found that the Bedside CKiD equation provided accurate GFR estimates for patients with moderate to severe CKD but less accurate estimates for
Downloaded from aop.sagepub.com at NORTHEASTERN UNIV LIBRARY on April 6, 2014
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Annals of Pharmacotherapy
Table 2. Patient Demographics and Clinical Characteristics. Characteristic
Mean ± SD (Range)
Age, years Weight, kg Height, cm SCr, mg/dL BUN, mg/dL Urinary output, mL/kg/hra Vancomycin trough, µg/mL Schwartz eGFR, mL/min/1.73 m2 CKiD eGFR, mL/min/1.73 m2
6.5 ± 3.3 (2-12) 24.2 ± 11.3 (8.5-59) 116.2 ± 21.6 (74-165) 0.38 ± 0.1 (0.16-0.65) 10.4 ± 4.1 (2-22) 2.6 ± 1.2 (0.7-6) 10.7 ± 3.8 (5.2-19.6) 177 ± 46 (94-392) 133 ± 34 (71-294)
Number of Patientsb (%)
Gender Female Male Race Caucasian African American Asian Hispanic Other Vancomycin indication Abscess or cellulitis CNS infection Pneumonia or empyema CF exacerbation Hardware infection Osteomyelitis or septic joint Empirical therapy Other indicationc
26 (52%) 24 (48%) 25 (50%) 20 (40%) 2 (4%) 1 (2%) 2 (4%) 8 (16%) 8 (16%) 8 (16%) 5 (10%) 5 (10%) 5 (10%) 4 (8%) 7 (14%)
Abbreviations: SCr, serum creatinine; BUN, blood urea nitrogen; eGFR, estimated glomerular filtration rate; CKiD, Chronic Kidney Disease in Children; CNS, central nervous system; CF, cystic fibrosis. a Urinary output within 24 hours before the vancomycin trough assessment was reported for 44 of the 50 included assessments. b A total of 46 different patients with 50 trough assessments were included. One patient was admitted 3 times within the study time period, and 2 patients were admitted twice. c Other indications for vancomycin therapy were sinusitis (n = 3; 6%), central-line-associated bloodstream infection (n = 2; 4%), ruptured appendix (n = 1; 2%), and urinary tract infection (n = 1; 2%).
those with mild CKD.11 These studies show overall that the Bedside CKiD equation may provide less accurate estimates of GFR in patients with mild CKD or normal kidney function. The results of the present study are consistent with these previously reported findings because both the Bedside CKiD equation and Schwartz equation were not predictive of vancomycin trough concentrations in a pediatric population with normal renal function. Thus, the clinical use of these equations for drug dosing in hospitalized children is questionable and suggests that further studies are warranted. Therapeutic drug monitoring has an important role in ensuring optimal therapy for patients but also has its disadvantages.
Obtaining a blood sample from a patient can be difficult, especially in pediatrics, and does not come without a financial burden. In addition, the drug concentration must be drawn within a narrow time frame after the drug has been given. A routinely assessed patient parameter, such as GFR, would be ideal to assess the efficacy of the patient’s treatment. Monitoring concentrations of renally eliminated medications, such as vancomycin, could almost become obsolete if a GFR-estimating equation for pediatric patients could accurately predict medication clearance. Another advantage to having a GFRestimating equation that more accurately predicts clearance in pediatric patients would be the possible development of an empirical dosing algorithm for vancomycin based on eGFR, similar to those used in the adult population. There are a few limitations of this study that must be considered. First, this was a single-center study that included a relatively small sample. Because of the retrospective nature of this study, there is some variability of documentation noted within the electronic medical record. The amount of time between the last SCr reported and the patient’s subsequent vancomycin trough concentration was not consistent. In addition, urinary output was not always recorded in the electronic medical records for all patients included in the study, which could have provided another method to assess the patient’s renal function and determine whether the patient had undiagnosed acute kidney injury. The use of vancomycin troughs as a surrogate marker for renal function is not ideal because up to 30% of vancomycin clearance is nonrenal.12 However, previous studies in adults have reported the use of vancomycin-dosing nomograms based on creatinine clearance.6,7 Another limitation to this study is that patient groups known to have altered vancomycin pharmacokinetics were included in this study, including those with traumatic brain injury (n = 2) and cystic fibrosis (n =7). Although including those patients with potentially altered vancomycin pharmacokinetics may affect the relationship between eGFR and vancomycin trough concentrations, the wide variety of patients included increases the external validity of this study. Finally, although the inclusion criteria of this study were designed to include patients with normal renal function and mild CKD, only 3 patients with abnormal renal function (all stage 2 CKD) were included in the study cohort. Therefore, the data presented reflect the predictability of the SCr-based GFR equations in patients with normal, stable renal function. The Schwartz equation has been validated in both pediatric patients with normal renal function and those with CKD, but the CKiD equation has only been validated in CKD patients. The role of the Schwartz equation and Bedside CKiD equation in clinical practice, especially regarding the use of these estimates for dosage adjustments of renally eliminated
Downloaded from aop.sagepub.com at NORTHEASTERN UNIV LIBRARY on April 6, 2014
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Alford et al
Figure 2. Linear regressions for the Schwartz eGFR (A), Bedside CKiD eGFR (B), and SCr (C) versus vancomycin trough concentrations. Abbreviations: eGFR, estimated glomerular filtration rate; CKiD, Chronic Kidney Disease in Children; SCr, serum creatinine.
Table 3. Most Common Concurrent Nephrotoxic Drug Exposures. Medication NSAIDs Contrast agent Loop diuretics Aminoglycosides Acyclovir SMX/TMPb
Number of Patientsa 14 13 10 7 4 3
Abbreviations: NSAIDs, nonsteroidal anti-inflammatory drugs; SMX/ TMP, sulfamethoxazole/trimethoprim. a Number of patients may total more than 50 because patients could be exposed to more than 1 concomitant nephrotoxic drug. b Treatment dosing (n = 2) and prophylactic dosing (n = 1).
medications, needs to be further investigated. These equations should be validated for their use in dose adjustments of many different renally eliminated medications, not just vancomycin. A multicenter, prospective study that includes patients with both normal and abnormal renal function is warranted to determine the clinical utility of these equations. Neither the Schwartz equation nor the Bedside CKiD equation can reliably predict vancomycin trough concentrations in pediatric patients. These findings suggest that better GFR estimation methods are needed in pediatric patients to ensure appropriate dosing of vancomycin. Furthermore, additional studies are needed to validate the use of these GFR-estimating equations for adjusting doses of other renally eliminated medications.
Downloaded from aop.sagepub.com at NORTHEASTERN UNIV LIBRARY on April 6, 2014
6
Annals of Pharmacotherapy
Author Note The preliminary background and methods for this article were presented as a poster at the American Society of Health-System Pharmacists Midyear Clinical Meeting in Las Vegas, Nevada, December 2-6, 2012. The background, methods, results, and conclusion for this article were presented as a platform presentation at the Mid-South Regional Pharmacy Residents Conference in Memphis, Tennessee, April 25-26, 2013, and the 22nd Annual Pediatric Pharmacy Advocacy Group Meeting in Indianapolis, Indiana, May 1-5, 2013. The background, methods, results, and conclusion for this article were presented as a poster presentation at the local 6th Annual Pediatrics Research Day at Le Bonheur Children’s Hospital in Memphis, Tennessee on November 20, 2013.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Arant BS Jr. Developmental patterns of renal functional maturation compared in the human neonate. J Pediatr. 1978;92:705-712. 2. National Kidney Foundation. KDOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39:S1-S266. 3. Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics. 1976;58:259-263. 4. Schwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate
in infants, children, and adolescents. Pediatr Clin North Am. 1987;34:571-590. 5. Schwartz GJ, Muñoz A, Schneider MF, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009;20:629-637. doi:10.1681/ASN.2008030287. 6. Matzke GR, McGory RW, Halstenson CE, Keane WF. Pharmacokinetics of vancomycin in patients with various degrees of renal function. Antimicrob Agents Chemother. 1984;25:433-437. 7. Pea F, Porreca L, Baraldo M, Furlanut M. High vancomycin dosage regiments required by intensive care unit patients cotreated with drugs to improve haemodynamics following cardiac surgical procedures. J Antimicrob Chemother. 2000;45:329-335. 8. Chicella M, Adkins J, Mancao MY, Estrada B, Hoff C. Impact of pediatric specific guidelines for vancomycin serum concentration monitoring on patient care. J Pediatr Pharmacol Ther. 1999;4:146-151. doi:10.5863/1551-6776-4.3.146. 9. Bellomo R, Ronco C, Kellum JA, et al. Acute renal failure: definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8:R204-R212. doi:10.1186/ cc2872. 10. Staples A, LeBlond R, Watkins S, Wong C, Brandt J. Validation of the revised Schwartz estimating equation in a predominantly non-CKD population. Pediatr Nephrol. 2010;25:2321-2326. doi:10.1007/s00467-010-1598-7. 11. Lee CK, Swinford RD, Cerda RD, Portman RJ, Hwang W, Furth SL. Evaluation of serum creatinine concentration-based glomerular filtration rate equations in pediatric patients with chronic kidney disease. Pharmacotherapy. 2012;32:624-628. doi:10.1002/j.1875-9114.2012.01095.x. 12. Golper TA, Noonan HM, Elzinga L, et al. Vancomycin pharmacokinetics, renal handling, and nonrenal clearances in normal human subjects. Clin Pharmacol Ther. 1988;43: 565-570.
Downloaded from aop.sagepub.com at NORTHEASTERN UNIV LIBRARY on April 6, 2014
research-article2014
AOPXXX10.1177/1060028014527908Annals of PharmacotherapyAlford et al
Research Reports
Glomerular Filtration Rate Equations Do Not Accurately Predict Vancomycin Trough Concentrations in Pediatric Patients
Annals of Pharmacotherapy 1–6 © The Author(s) 2014 Reprints and permissions: sagepub.com/journalsPermissions.nav DOI: 10.1177/1060028014527908 aop.sagepub.com
Elizabeth L. Alford, PharmD1,2,3, Rebecca F. Chhim, PharmD1,3, Catherine M. Crill, PharmD1,3, M. Colleen Hastings, MD1,3, Bettina H. Ault, MD1,3, and Chasity M. Shelton, PharmD1,3
Abstract Background: The Bedside Chronic Kidney Disease in Children (CKiD) equation was developed using data from children with chronic kidney disease. Some institutions are using this equation in all pediatric patients, regardless of renal function, to adjust medications. No data have shown that the Bedside CKiD equation is equivalent or better than the Schwartz equation in estimating glomerular filtration rate (GFR) in pediatric patients with normal renal function. Objective: To compare GFR estimates using the Bedside CKiD and Schwartz equations and determine if either offers sufficient vancomycin dosing guidance in hospitalized pediatric patients. Methods: This retrospective review at a single-center, academic, pediatric hospital included patients 2 to 12 years old with a steady-state vancomycin trough collected between January 1, 2010 and December 31, 2011. Patients with acute kidney injury or lacking essential data (e.g., height and serum creatinine), were excluded. An estimated GFR (eGFR) was calculated using the Schwartz and Bedside CKiD equations. Pearson correlations and linear regressions compared the eGFR values and vancomycin troughs. Results: A total of 50 vancomycin troughs were analyzed. There was a weak relationship between the eGFR and troughs for the Schwartz equation (r2 = 0.028) and Bedside CKiD equation (r2 = 0.028). A weak relationship between serum creatinine and troughs was observed (r2 = 0.132). Limitations include small sample size and retrospective design. Conclusions: Neither equation correlates well with vancomycin troughs, suggesting that therapeutic monitoring remains important. Better GFR estimation methods are needed in pediatrics to aid appropriate dosing of renally eliminated medications. Keywords pediatrics, serum creatinine–based glomerular filtration rate estimation, Schwartz equation, Bedside Chronic Kidney Disease in Children equation, vancomycin Glomerular filtration rate (GFR) is the best measure of kidney function and can be applied reliably to pediatric patients who are at least 1 year old because GFR is known to mature by the age of one.1 There are important clinical uses of estimated GFR (eGFR) because it is used to stage chronic kidney disease (CKD), so that complications of renal dysfunction may be anticipated and treated. In the hospital setting, eGFR is used to adjust dosing regimens of renally cleared medications in patients with an elevated serum creatinine (SCr). Some medications that require dose adjustments in patients with renal dysfunction include acyclovir, vancomycin, enoxaparin, ranitidine, gentamicin, morphine, and select cephalosporins and β-lactams. The gold standard for measuring GFR is inulin clearance. Alternative methods for measuring GFR include iothalamate clearance, 99mTc-DTPA clearance, iohexol clearance,
or 51Cr-EDTA clearance.2 It is not feasible to measure GFR directly in clinical practice because all these methods require a prolonged time period for collection, consequently delaying the time to results. SCr is a readily available bedside lab test used to estimate GFR, but there are different normal ranges depending on age, gender, and size. Various SCr-based, GFR 1
Le Bonheur Children’s Hospital, Memphis, TN, USA The Center for Pediatric Pharmacokinetics and Therapeutics, Memphis, TN, USA 3 The University of Tennessee Health Science Center, Memphis, TN, USA 2
Corresponding Author: Chasity M. Shelton, Department of Clinical Pharmacy, The University of Tennessee Health Science Center, 881 Madison Ave, Suite 343, Memphis, TN 38163, USA. Email: [email protected]
Downloaded from aop.sagepub.com at NORTHEASTERN UNIV LIBRARY on April 6, 2014
2
Annals of Pharmacotherapy
Table 1. Equations for Estimating Glomerular Filtration Rate in Pediatric Patients. Equation Name Schwartz equation Bedside CKiD Equation
Equation eGFR (mL/min/1.73 m2) = k × Length ÷ SCr (mg/dL)3,4 k = 0.33 In preterm infants 90 mL/min/1.73 m2 showed an even greater underestimation (mean = 9.1 mL/min/1.73 m2). More recently, Lee et al11 investigated the Bedside CKiD equation, along with 3 other GFR estimation methods, in a retrospective, observational, cross-sectional study of 53 pediatric patients with CKD stages 2 to 5 and found that the Bedside CKiD equation provided accurate GFR estimates for patients with moderate to severe CKD but less accurate estimates for
Downloaded from aop.sagepub.com at NORTHEASTERN UNIV LIBRARY on April 6, 2014
4
Annals of Pharmacotherapy
Table 2. Patient Demographics and Clinical Characteristics. Characteristic
Mean ± SD (Range)
Age, years Weight, kg Height, cm SCr, mg/dL BUN, mg/dL Urinary output, mL/kg/hra Vancomycin trough, µg/mL Schwartz eGFR, mL/min/1.73 m2 CKiD eGFR, mL/min/1.73 m2
6.5 ± 3.3 (2-12) 24.2 ± 11.3 (8.5-59) 116.2 ± 21.6 (74-165) 0.38 ± 0.1 (0.16-0.65) 10.4 ± 4.1 (2-22) 2.6 ± 1.2 (0.7-6) 10.7 ± 3.8 (5.2-19.6) 177 ± 46 (94-392) 133 ± 34 (71-294)
Number of Patientsb (%)
Gender Female Male Race Caucasian African American Asian Hispanic Other Vancomycin indication Abscess or cellulitis CNS infection Pneumonia or empyema CF exacerbation Hardware infection Osteomyelitis or septic joint Empirical therapy Other indicationc
26 (52%) 24 (48%) 25 (50%) 20 (40%) 2 (4%) 1 (2%) 2 (4%) 8 (16%) 8 (16%) 8 (16%) 5 (10%) 5 (10%) 5 (10%) 4 (8%) 7 (14%)
Abbreviations: SCr, serum creatinine; BUN, blood urea nitrogen; eGFR, estimated glomerular filtration rate; CKiD, Chronic Kidney Disease in Children; CNS, central nervous system; CF, cystic fibrosis. a Urinary output within 24 hours before the vancomycin trough assessment was reported for 44 of the 50 included assessments. b A total of 46 different patients with 50 trough assessments were included. One patient was admitted 3 times within the study time period, and 2 patients were admitted twice. c Other indications for vancomycin therapy were sinusitis (n = 3; 6%), central-line-associated bloodstream infection (n = 2; 4%), ruptured appendix (n = 1; 2%), and urinary tract infection (n = 1; 2%).
those with mild CKD.11 These studies show overall that the Bedside CKiD equation may provide less accurate estimates of GFR in patients with mild CKD or normal kidney function. The results of the present study are consistent with these previously reported findings because both the Bedside CKiD equation and Schwartz equation were not predictive of vancomycin trough concentrations in a pediatric population with normal renal function. Thus, the clinical use of these equations for drug dosing in hospitalized children is questionable and suggests that further studies are warranted. Therapeutic drug monitoring has an important role in ensuring optimal therapy for patients but also has its disadvantages.
Obtaining a blood sample from a patient can be difficult, especially in pediatrics, and does not come without a financial burden. In addition, the drug concentration must be drawn within a narrow time frame after the drug has been given. A routinely assessed patient parameter, such as GFR, would be ideal to assess the efficacy of the patient’s treatment. Monitoring concentrations of renally eliminated medications, such as vancomycin, could almost become obsolete if a GFR-estimating equation for pediatric patients could accurately predict medication clearance. Another advantage to having a GFRestimating equation that more accurately predicts clearance in pediatric patients would be the possible development of an empirical dosing algorithm for vancomycin based on eGFR, similar to those used in the adult population. There are a few limitations of this study that must be considered. First, this was a single-center study that included a relatively small sample. Because of the retrospective nature of this study, there is some variability of documentation noted within the electronic medical record. The amount of time between the last SCr reported and the patient’s subsequent vancomycin trough concentration was not consistent. In addition, urinary output was not always recorded in the electronic medical records for all patients included in the study, which could have provided another method to assess the patient’s renal function and determine whether the patient had undiagnosed acute kidney injury. The use of vancomycin troughs as a surrogate marker for renal function is not ideal because up to 30% of vancomycin clearance is nonrenal.12 However, previous studies in adults have reported the use of vancomycin-dosing nomograms based on creatinine clearance.6,7 Another limitation to this study is that patient groups known to have altered vancomycin pharmacokinetics were included in this study, including those with traumatic brain injury (n = 2) and cystic fibrosis (n =7). Although including those patients with potentially altered vancomycin pharmacokinetics may affect the relationship between eGFR and vancomycin trough concentrations, the wide variety of patients included increases the external validity of this study. Finally, although the inclusion criteria of this study were designed to include patients with normal renal function and mild CKD, only 3 patients with abnormal renal function (all stage 2 CKD) were included in the study cohort. Therefore, the data presented reflect the predictability of the SCr-based GFR equations in patients with normal, stable renal function. The Schwartz equation has been validated in both pediatric patients with normal renal function and those with CKD, but the CKiD equation has only been validated in CKD patients. The role of the Schwartz equation and Bedside CKiD equation in clinical practice, especially regarding the use of these estimates for dosage adjustments of renally eliminated
Downloaded from aop.sagepub.com at NORTHEASTERN UNIV LIBRARY on April 6, 2014
5
Alford et al
Figure 2. Linear regressions for the Schwartz eGFR (A), Bedside CKiD eGFR (B), and SCr (C) versus vancomycin trough concentrations. Abbreviations: eGFR, estimated glomerular filtration rate; CKiD, Chronic Kidney Disease in Children; SCr, serum creatinine.
Table 3. Most Common Concurrent Nephrotoxic Drug Exposures. Medication NSAIDs Contrast agent Loop diuretics Aminoglycosides Acyclovir SMX/TMPb
Number of Patientsa 14 13 10 7 4 3
Abbreviations: NSAIDs, nonsteroidal anti-inflammatory drugs; SMX/ TMP, sulfamethoxazole/trimethoprim. a Number of patients may total more than 50 because patients could be exposed to more than 1 concomitant nephrotoxic drug. b Treatment dosing (n = 2) and prophylactic dosing (n = 1).
medications, needs to be further investigated. These equations should be validated for their use in dose adjustments of many different renally eliminated medications, not just vancomycin. A multicenter, prospective study that includes patients with both normal and abnormal renal function is warranted to determine the clinical utility of these equations. Neither the Schwartz equation nor the Bedside CKiD equation can reliably predict vancomycin trough concentrations in pediatric patients. These findings suggest that better GFR estimation methods are needed in pediatric patients to ensure appropriate dosing of vancomycin. Furthermore, additional studies are needed to validate the use of these GFR-estimating equations for adjusting doses of other renally eliminated medications.
Downloaded from aop.sagepub.com at NORTHEASTERN UNIV LIBRARY on April 6, 2014
6
Annals of Pharmacotherapy
Author Note The preliminary background and methods for this article were presented as a poster at the American Society of Health-System Pharmacists Midyear Clinical Meeting in Las Vegas, Nevada, December 2-6, 2012. The background, methods, results, and conclusion for this article were presented as a platform presentation at the Mid-South Regional Pharmacy Residents Conference in Memphis, Tennessee, April 25-26, 2013, and the 22nd Annual Pediatric Pharmacy Advocacy Group Meeting in Indianapolis, Indiana, May 1-5, 2013. The background, methods, results, and conclusion for this article were presented as a poster presentation at the local 6th Annual Pediatrics Research Day at Le Bonheur Children’s Hospital in Memphis, Tennessee on November 20, 2013.
Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Arant BS Jr. Developmental patterns of renal functional maturation compared in the human neonate. J Pediatr. 1978;92:705-712. 2. National Kidney Foundation. KDOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002;39:S1-S266. 3. Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A. A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics. 1976;58:259-263. 4. Schwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate
in infants, children, and adolescents. Pediatr Clin North Am. 1987;34:571-590. 5. Schwartz GJ, Muñoz A, Schneider MF, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol. 2009;20:629-637. doi:10.1681/ASN.2008030287. 6. Matzke GR, McGory RW, Halstenson CE, Keane WF. Pharmacokinetics of vancomycin in patients with various degrees of renal function. Antimicrob Agents Chemother. 1984;25:433-437. 7. Pea F, Porreca L, Baraldo M, Furlanut M. High vancomycin dosage regiments required by intensive care unit patients cotreated with drugs to improve haemodynamics following cardiac surgical procedures. J Antimicrob Chemother. 2000;45:329-335. 8. Chicella M, Adkins J, Mancao MY, Estrada B, Hoff C. Impact of pediatric specific guidelines for vancomycin serum concentration monitoring on patient care. J Pediatr Pharmacol Ther. 1999;4:146-151. doi:10.5863/1551-6776-4.3.146. 9. Bellomo R, Ronco C, Kellum JA, et al. Acute renal failure: definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8:R204-R212. doi:10.1186/ cc2872. 10. Staples A, LeBlond R, Watkins S, Wong C, Brandt J. Validation of the revised Schwartz estimating equation in a predominantly non-CKD population. Pediatr Nephrol. 2010;25:2321-2326. doi:10.1007/s00467-010-1598-7. 11. Lee CK, Swinford RD, Cerda RD, Portman RJ, Hwang W, Furth SL. Evaluation of serum creatinine concentration-based glomerular filtration rate equations in pediatric patients with chronic kidney disease. Pharmacotherapy. 2012;32:624-628. doi:10.1002/j.1875-9114.2012.01095.x. 12. Golper TA, Noonan HM, Elzinga L, et al. Vancomycin pharmacokinetics, renal handling, and nonrenal clearances in normal human subjects. Clin Pharmacol Ther. 1988;43: 565-570.
Downloaded from aop.sagepub.com at NORTHEASTERN UNIV LIBRARY on April 6, 2014
