- Email: [email protected]
Implementing GFR Estimation Guidelines Using Cystatin C: A Quality Improvement Project
Correspondence
Supplementary Material Item S1. Misclassification data and multivariable logistic regression analysis. Note: The supplementary material accompanying this article (http://dx.doi.org/10.1053/j.ajkd.2015.09.028) is available at www.ajkd.org.
References 1. Agarwal R, Bills JE, Light RP. Diagnosing obesity by body mass index in chronic kidney disease: an explanation for the “obesity paradox?”. Hypertension. 2010;56(5):893-900. 2. Furstenberg A, Davenport A. Comparison of multifrequency bioelectrical impedance analysis and dual-energy x-ray absorptiometry assessments in outpatient hemodialysis patients. Am J Kidney Dis. 2011;57(1):123-129. 3. Collins AJ, Foley RN, Herzog C, et al. US Renal Data System 2010 annual data report. Am J Kidney Dis. 2011;57(1)(suppl 1):e1-e526. 4. Okorodudu DO, Jumean MF, Montori VM, et al. Diagnostic performance of body mass index to identify obesity as defined by body adiposity: a systematic review and meta-analysis. Int J Obes (Lond). 2010;34(5):791-799. 5. World Health Organization. Obesity preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 2000;894:1-253. 6. National Cholesterol Education Program. Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III Final Report). National Institutes of Health: Bethesda, Maryland; 2002. 7. Romero-Corral A, Somers VK, Sierra-Johnson J, et al. Accuracy of body mass index in diagnosing obesity in the adult general population. Int J Obes (Lond). 2008;32(6):959-966. 8. Janssen I, Katzmarzyk PT, Ross R. Waist circumference and not body mass index explains obesity-related health risk. Am J Clin Nutr. 2004;79(3):379-384. 9. Guallar-Castillon P, Balboa-Castillo T, Lopez-Garcia E, et al. BMI, waist circumference, and mortality according to health status in the older adult population of Spain. Obesity (Silver Spring). 2009;17(12):2232-2238. 10. Postorino M, Marino C, Tripepi G, Zoccali C. Abdominal obesity and all-cause and cardiovascular mortality in end-stage renal disease. J Am Coll Cardiol. 2009;53(15):1265-1272. Received June 12, 2015. Accepted in revised form August 28, 2015. Originally published online November 21, 2015. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. http://dx.doi.org/10.1053/j.ajkd.2015.09.028
Implementing GFR Estimation Guidelines Using Cystatin C: A Quality Improvement Project To the Editor: eGFRcr-cys is more precise than eGFRcr.1 The KDIGO CKD clinical practice guideline suggests determining eGFRcr-cys for patients with eGFRcr of 45 to 59 mL/min/1.73 m2 without markers of kidney damage, such as albuminuria. In the United States, 3.6% of adults overall and 31% of those classified as having CKD based on eGFRcr and urine albumin-creatinine ratio (UACR) have eGFRcr of 45 to 59 mL/min/1.73 m2 and UACR , 30 mg/g.2 Ongoing investigation is recommended when nephrology Am J Kidney Dis. 2016;67(4):709-712
guidelines are based on low-quality evidence,3 but the clinical effectiveness of this level 2C recommendation has not been reported and some disagree with it.4,5 We performed a quality improvement project aimed at increasing implementation of the eGFRcr-cys recommendation and investigating the outcomes of implementation. Because many of our patients are current or former military personnel with large lean body weight, we hypothesized that many would be reclassified to eGFR $ 60 mL/min/1.73 m2. All new outpatient nephrology clinic encounters in the 3 months prior to the intervention were reviewed. eGFRcr-cys was considered indicated for patients referred for eGFRcr of 45 to 59 mL/min/ 1.73 m2, with urinalysis negative for protein, urine proteincreatinine ratio , 150 mg/g, or UACR , 30 mg/g. Amputees,6 patients taking corticosteroids,7 and those with urinary sediment, electrolyte, or structural abnormalities were excluded.2 A 6-month intervention followed. Lectures were administered on GFR estimation principles and eGFR literature and to review CKD guidelines. Flyers summarizing eGFRcr-cys testing criteria were posted in examination rooms, “Cystatin C: Just Check It” T-shirts were offered to nephrology providers, and the consult review process was modified to facilitate preordered laboratory testing coinciding with the initial outpatient encounter. A 6-month postintervention chart review was performed, using identical criteria to determine eligibility for eGFRcr-cys. eGFRs and demographic and comorbid condition data were recorded for patients who underwent eGFRcr-cys testing. eGFRcr and eGFRcr-cys values were compared by paired t test. Scr and Scys were quantified by standardized assays traceable to international references; eGFR was calculated by CKD-EPI equations. Proportions of indicated cases in which eGFRcr-cys was performed pre- and postintervention were compared by c2. Statistics were analyzed with GraphPad QuickCalcs. Fourteen providers saw patients during both pre- and postintervention periods, whereas 3 and 2 were present during only pre- or postintervention periods, respectively. eGFRcr-cys was obtained in 38 of 58 (66%) versus 12 of 32 (38%) indicated cases post- and preintervention, respectively (P 5 0.02). Table 1 shows demographic and clinical information for these 50 participants. Although all 50 patients entered had eGFRcr of 45 to 59 mL/min/ Table 1. Characteristics of Participants for Whom eGFRcr-cys Was Obtained eGFRcr and eGFRcr-cys , 60 (n 5 6)
eGFRcr , 60 and eGFRcr-cys $ 60 (n 5 20)
eGFRcr $ 60 and eGFRcr-cys $ 60 (n 5 24)
Median (range) Male sex Black race BMI category 18.5-24.9 kg/m2 25.0-29.9 kg/m2 $30.0 kg/m2
62 (32-80) 2 (33) 0 (0)
57 (33-68) 15 (75) 9 (45)
51 (41-66) 22 (92) 11 (46)
2 (33) 1 (17) 3 (50)
3 (15) 6 (30) 11 (55)
1 (4) 9 (38) 14 (58)
Diabetes mellitus Hypertension Scr at referral, mg/dL Scr at retest, mg/dL Scys, mg/dL
1 (17) 2 (33) 1.29 6 0.20
4 (20) 11 (55) 1.47 6 0.18
3 (13) 17 (71) 1.50 6 0.15
1.33 6 0.18
1.41 6 0.21
1.32 6 0.16
1.09 6 0.09
0.84 6 0.13
0.77 6 0.11
Note: N 5 50. eGFRs given in mL/min/1.73 m2. Classification based on eGFRcr at time of eGFRcr-cys. Categorical data given as number (percentage); continuous data as mean (range) or mean 6 standard deviation. Abbreviations: BMI, body mass index; eGFR, estimated glomerular filtration rate; eGFRcr-cys, eGFR calculated using the Scr-Scys-based CKD-EPI equation; eGFRcys, eGFR calculated using the Scr-based CKD-EPI equation; Scr, serum creatinine; Scys, serum cystatin C.
711
Correspondence 1
Walter Reed National Military Medical Center, Bethesda, Maryland 2 Eisenhower Army Medical Center, Augusta, Georgia 3 Madigan Army Medical Center, Tacoma, Washington Corresponding author: [email protected]
Acknowledgements
Figure 1. Comparison of eGFRcr and eGFRcr-cys in individual patients. Dashed and solid lines are those with eGFRcr , 60 and $60 mL/min/1.73 m2, respectively. One participant is not shown (eGFRcr and eGFRcr-cys of 86 and 106 mL/min/1.73 m2, respectively).
1.73 m2 on referral, 24 (48%) had eGFRcr $ 60 mL/min/1.73 m2 on repeat testing, concurrent with eGFRcr-cys determination. Mean eGFRcr-cys was significantly higher than eGFRcr (77.0 6 12.3 vs 58.8 6 7.9 mL/min/1.73 m2; P , 0.001). eGFRcr-cys was greater than eGFRcr in all cases and was $60 mL/min/1.73 m2 in 88% overall (44 of 50) and in 20 of 26 (77%) in the subgroup with eGFRcr , 60 mL/min/1.73 m2 (Fig 1). This is the first report of implementation of the KDIGO CKD guideline recommending eGFRcr-cys in select patients to confirm CKD diagnosis. Our simple methods could be duplicated in many clinical environments, including primary care, where increased use of eGFRcr-cys could reduce nephrology referrals. In our study, patients with eGFRcr of 45 to 59 mL/min/1.73 m2 were more than twice as likely as those in larger population-based studies to have eGFRcr-cys $ 60 mL/min/1.73 m2.1,8 One possible explanation is that prior studies have not limited analysis to participants with UACR , 30 mg/g.1,8 Possibly people with UACR . 30 mg/g are more likely to have low eGFRcr-cys than people with UACR , 30 mg/g. Second, 88% and 56% of our participants had BMI . 25 and .30 kg/m2, respectively, versus 66% and 31% and 48% and 13% of participants in the CKD-EPI Scr-Scys development and internal validation data sets, respectively.1 Scr is more affected by lean body weight than Scys,9 so eGFRcr may have been more biased (larger underestimate of measured GFR) in our patients. Third, regression to the mean in eGFRcr was common (eGFRcr was $60 mL/min/1.73 m2 in 48% on repeat testing) and may have affected eGFRcr-cys too. Reclassification from eGFRcr of 45 to 59 mL/min/1.73 m2 to eGFRcr-cys $ 60 mL/min/1.73 m2 associates with decreased risk for all-cause and cardiovascular mortality and ESRD.8 Implementation of recommended eGFRcr-cys testing in our clinic led predominately to reclassification of patients into the lower risk group. Because these patients may require less frequent clinic visits and laboratory monitoring,2 our results support the need for formal cost-utility analysis of targeted eGFRcr-cys testing. In conclusion, we successfully implemented KDIGOrecommended eGFRcr-cys testing, and a large fraction of patients were reclassified to eGFRcr-cys $ 60 mL/min/1.73 m2. Further study is needed to determine whether our report of a small number of patients from a single center is generalizable to the broader population and to determine the appropriate frequency of clinical and laboratory monitoring of patients reclassified to eGFRcr-cys $ 60 mL/min/1.73 m2. Dustin J. Little, MD,1 Heather M. Mascio, Ryan J. Altenburg, DO,2 Deepti S. Moon, Wondaye T. Deressa, NP,1 Stephen Wong, Christina M. Yuan, 712
MD1 MD1 MD3 MD1
The views expressed in this paper are those of the authors and do not reflect the official policy of the US Departments of the Army, Navy, or Defense or the US government. Support: None. Financial Disclosure: The authors declare that they have no relevant financial interests. Contributions: Idea and design: DJL, HMM, RJA, DSM, CMY; data acquisition: DJL, HMM, RJA, DSM, WTD, SW; data analysis/interpretation: DJL, HMM, RJA, DSM; statistical analysis: DJL; supervision or mentorship: CMY. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. DJL takes responsibility that this project has been reported honestly, accurately, and transparently; that no important aspects have been omitted; and that any discrepancies from the project as planned have been explained. Peer Review: Evaluated by 2 external peer reviewers, a Statistical Editor, and the Editor-in-Chief.
References 1. Inker LA, Schmid CH, Tighiouart H, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med. 2012;367(1):20-29. 2. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:S1-S150. 3. Levin A, Wheeler C. A fine balance: developing clinical practice guidelines in areas where evidence is lacking. Semin Dial. 2015;28(6):654-656. 4. Akbari A, Clase CM, Acott P, et al. Canadian Society of Nephrology commentary on the KDIGO clinical practice guideline for CKD evaluation and management. Am J Kidney Dis. 2015;65(2):177-205. 5. Inker LA, Astor BC, Fox CH, et al. KDOQI commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis. 2014;63(5):713-735. 6. Thurlow JS, Abbott KC, Linberg A, Little D, Fenderson J, Olson SW. SCr and SCysC concentrations before and after traumatic amputation in male soldiers: a case-control study. Am J Kidney Dis. 2014;63(1):167-170. 7. Cimerman N, Brguljan PM, Krasovec M, Suskovic S, Kos J. Serum cystatin C, a potent inhibitor of cysteine proteinases, is elevated in asthmatic patients. Clin Chim Acta. 2000;300(1-2):83-95. 8. Shlipak MG, Matsushita K, Ärnlöv J, et al. Cystatin C versus creatinine in determining risk based on kidney function. N Engl J Med. 2013;369(10):932-943. 9. Baxmann AC, Ahmed MS, Marques NC, et al. Influence of muscle mass and physical activity on serum and urinary creatinine and serum cystatin C. Clin J Am Soc Nephrol. 2008;3(2):348-354. Received August 15, 2015. Accepted in revised form October 8, 2015. Originally published online November 23, 2015. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. http://dx.doi.org/10.1053/j.ajkd.2015.10.014 Am J Kidney Dis. 2016;67(4):709-712
Supplementary Material Item S1. Misclassification data and multivariable logistic regression analysis. Note: The supplementary material accompanying this article (http://dx.doi.org/10.1053/j.ajkd.2015.09.028) is available at www.ajkd.org.
References 1. Agarwal R, Bills JE, Light RP. Diagnosing obesity by body mass index in chronic kidney disease: an explanation for the “obesity paradox?”. Hypertension. 2010;56(5):893-900. 2. Furstenberg A, Davenport A. Comparison of multifrequency bioelectrical impedance analysis and dual-energy x-ray absorptiometry assessments in outpatient hemodialysis patients. Am J Kidney Dis. 2011;57(1):123-129. 3. Collins AJ, Foley RN, Herzog C, et al. US Renal Data System 2010 annual data report. Am J Kidney Dis. 2011;57(1)(suppl 1):e1-e526. 4. Okorodudu DO, Jumean MF, Montori VM, et al. Diagnostic performance of body mass index to identify obesity as defined by body adiposity: a systematic review and meta-analysis. Int J Obes (Lond). 2010;34(5):791-799. 5. World Health Organization. Obesity preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser. 2000;894:1-253. 6. National Cholesterol Education Program. Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III Final Report). National Institutes of Health: Bethesda, Maryland; 2002. 7. Romero-Corral A, Somers VK, Sierra-Johnson J, et al. Accuracy of body mass index in diagnosing obesity in the adult general population. Int J Obes (Lond). 2008;32(6):959-966. 8. Janssen I, Katzmarzyk PT, Ross R. Waist circumference and not body mass index explains obesity-related health risk. Am J Clin Nutr. 2004;79(3):379-384. 9. Guallar-Castillon P, Balboa-Castillo T, Lopez-Garcia E, et al. BMI, waist circumference, and mortality according to health status in the older adult population of Spain. Obesity (Silver Spring). 2009;17(12):2232-2238. 10. Postorino M, Marino C, Tripepi G, Zoccali C. Abdominal obesity and all-cause and cardiovascular mortality in end-stage renal disease. J Am Coll Cardiol. 2009;53(15):1265-1272. Received June 12, 2015. Accepted in revised form August 28, 2015. Originally published online November 21, 2015. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. http://dx.doi.org/10.1053/j.ajkd.2015.09.028
Implementing GFR Estimation Guidelines Using Cystatin C: A Quality Improvement Project To the Editor: eGFRcr-cys is more precise than eGFRcr.1 The KDIGO CKD clinical practice guideline suggests determining eGFRcr-cys for patients with eGFRcr of 45 to 59 mL/min/1.73 m2 without markers of kidney damage, such as albuminuria. In the United States, 3.6% of adults overall and 31% of those classified as having CKD based on eGFRcr and urine albumin-creatinine ratio (UACR) have eGFRcr of 45 to 59 mL/min/1.73 m2 and UACR , 30 mg/g.2 Ongoing investigation is recommended when nephrology Am J Kidney Dis. 2016;67(4):709-712
guidelines are based on low-quality evidence,3 but the clinical effectiveness of this level 2C recommendation has not been reported and some disagree with it.4,5 We performed a quality improvement project aimed at increasing implementation of the eGFRcr-cys recommendation and investigating the outcomes of implementation. Because many of our patients are current or former military personnel with large lean body weight, we hypothesized that many would be reclassified to eGFR $ 60 mL/min/1.73 m2. All new outpatient nephrology clinic encounters in the 3 months prior to the intervention were reviewed. eGFRcr-cys was considered indicated for patients referred for eGFRcr of 45 to 59 mL/min/ 1.73 m2, with urinalysis negative for protein, urine proteincreatinine ratio , 150 mg/g, or UACR , 30 mg/g. Amputees,6 patients taking corticosteroids,7 and those with urinary sediment, electrolyte, or structural abnormalities were excluded.2 A 6-month intervention followed. Lectures were administered on GFR estimation principles and eGFR literature and to review CKD guidelines. Flyers summarizing eGFRcr-cys testing criteria were posted in examination rooms, “Cystatin C: Just Check It” T-shirts were offered to nephrology providers, and the consult review process was modified to facilitate preordered laboratory testing coinciding with the initial outpatient encounter. A 6-month postintervention chart review was performed, using identical criteria to determine eligibility for eGFRcr-cys. eGFRs and demographic and comorbid condition data were recorded for patients who underwent eGFRcr-cys testing. eGFRcr and eGFRcr-cys values were compared by paired t test. Scr and Scys were quantified by standardized assays traceable to international references; eGFR was calculated by CKD-EPI equations. Proportions of indicated cases in which eGFRcr-cys was performed pre- and postintervention were compared by c2. Statistics were analyzed with GraphPad QuickCalcs. Fourteen providers saw patients during both pre- and postintervention periods, whereas 3 and 2 were present during only pre- or postintervention periods, respectively. eGFRcr-cys was obtained in 38 of 58 (66%) versus 12 of 32 (38%) indicated cases post- and preintervention, respectively (P 5 0.02). Table 1 shows demographic and clinical information for these 50 participants. Although all 50 patients entered had eGFRcr of 45 to 59 mL/min/ Table 1. Characteristics of Participants for Whom eGFRcr-cys Was Obtained eGFRcr and eGFRcr-cys , 60 (n 5 6)
eGFRcr , 60 and eGFRcr-cys $ 60 (n 5 20)
eGFRcr $ 60 and eGFRcr-cys $ 60 (n 5 24)
Median (range) Male sex Black race BMI category 18.5-24.9 kg/m2 25.0-29.9 kg/m2 $30.0 kg/m2
62 (32-80) 2 (33) 0 (0)
57 (33-68) 15 (75) 9 (45)
51 (41-66) 22 (92) 11 (46)
2 (33) 1 (17) 3 (50)
3 (15) 6 (30) 11 (55)
1 (4) 9 (38) 14 (58)
Diabetes mellitus Hypertension Scr at referral, mg/dL Scr at retest, mg/dL Scys, mg/dL
1 (17) 2 (33) 1.29 6 0.20
4 (20) 11 (55) 1.47 6 0.18
3 (13) 17 (71) 1.50 6 0.15
1.33 6 0.18
1.41 6 0.21
1.32 6 0.16
1.09 6 0.09
0.84 6 0.13
0.77 6 0.11
Note: N 5 50. eGFRs given in mL/min/1.73 m2. Classification based on eGFRcr at time of eGFRcr-cys. Categorical data given as number (percentage); continuous data as mean (range) or mean 6 standard deviation. Abbreviations: BMI, body mass index; eGFR, estimated glomerular filtration rate; eGFRcr-cys, eGFR calculated using the Scr-Scys-based CKD-EPI equation; eGFRcys, eGFR calculated using the Scr-based CKD-EPI equation; Scr, serum creatinine; Scys, serum cystatin C.
711
Correspondence 1
Walter Reed National Military Medical Center, Bethesda, Maryland 2 Eisenhower Army Medical Center, Augusta, Georgia 3 Madigan Army Medical Center, Tacoma, Washington Corresponding author: [email protected]
Acknowledgements
Figure 1. Comparison of eGFRcr and eGFRcr-cys in individual patients. Dashed and solid lines are those with eGFRcr , 60 and $60 mL/min/1.73 m2, respectively. One participant is not shown (eGFRcr and eGFRcr-cys of 86 and 106 mL/min/1.73 m2, respectively).
1.73 m2 on referral, 24 (48%) had eGFRcr $ 60 mL/min/1.73 m2 on repeat testing, concurrent with eGFRcr-cys determination. Mean eGFRcr-cys was significantly higher than eGFRcr (77.0 6 12.3 vs 58.8 6 7.9 mL/min/1.73 m2; P , 0.001). eGFRcr-cys was greater than eGFRcr in all cases and was $60 mL/min/1.73 m2 in 88% overall (44 of 50) and in 20 of 26 (77%) in the subgroup with eGFRcr , 60 mL/min/1.73 m2 (Fig 1). This is the first report of implementation of the KDIGO CKD guideline recommending eGFRcr-cys in select patients to confirm CKD diagnosis. Our simple methods could be duplicated in many clinical environments, including primary care, where increased use of eGFRcr-cys could reduce nephrology referrals. In our study, patients with eGFRcr of 45 to 59 mL/min/1.73 m2 were more than twice as likely as those in larger population-based studies to have eGFRcr-cys $ 60 mL/min/1.73 m2.1,8 One possible explanation is that prior studies have not limited analysis to participants with UACR , 30 mg/g.1,8 Possibly people with UACR . 30 mg/g are more likely to have low eGFRcr-cys than people with UACR , 30 mg/g. Second, 88% and 56% of our participants had BMI . 25 and .30 kg/m2, respectively, versus 66% and 31% and 48% and 13% of participants in the CKD-EPI Scr-Scys development and internal validation data sets, respectively.1 Scr is more affected by lean body weight than Scys,9 so eGFRcr may have been more biased (larger underestimate of measured GFR) in our patients. Third, regression to the mean in eGFRcr was common (eGFRcr was $60 mL/min/1.73 m2 in 48% on repeat testing) and may have affected eGFRcr-cys too. Reclassification from eGFRcr of 45 to 59 mL/min/1.73 m2 to eGFRcr-cys $ 60 mL/min/1.73 m2 associates with decreased risk for all-cause and cardiovascular mortality and ESRD.8 Implementation of recommended eGFRcr-cys testing in our clinic led predominately to reclassification of patients into the lower risk group. Because these patients may require less frequent clinic visits and laboratory monitoring,2 our results support the need for formal cost-utility analysis of targeted eGFRcr-cys testing. In conclusion, we successfully implemented KDIGOrecommended eGFRcr-cys testing, and a large fraction of patients were reclassified to eGFRcr-cys $ 60 mL/min/1.73 m2. Further study is needed to determine whether our report of a small number of patients from a single center is generalizable to the broader population and to determine the appropriate frequency of clinical and laboratory monitoring of patients reclassified to eGFRcr-cys $ 60 mL/min/1.73 m2. Dustin J. Little, MD,1 Heather M. Mascio, Ryan J. Altenburg, DO,2 Deepti S. Moon, Wondaye T. Deressa, NP,1 Stephen Wong, Christina M. Yuan, 712
MD1 MD1 MD3 MD1
The views expressed in this paper are those of the authors and do not reflect the official policy of the US Departments of the Army, Navy, or Defense or the US government. Support: None. Financial Disclosure: The authors declare that they have no relevant financial interests. Contributions: Idea and design: DJL, HMM, RJA, DSM, CMY; data acquisition: DJL, HMM, RJA, DSM, WTD, SW; data analysis/interpretation: DJL, HMM, RJA, DSM; statistical analysis: DJL; supervision or mentorship: CMY. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved. DJL takes responsibility that this project has been reported honestly, accurately, and transparently; that no important aspects have been omitted; and that any discrepancies from the project as planned have been explained. Peer Review: Evaluated by 2 external peer reviewers, a Statistical Editor, and the Editor-in-Chief.
References 1. Inker LA, Schmid CH, Tighiouart H, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med. 2012;367(1):20-29. 2. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl. 2013;3:S1-S150. 3. Levin A, Wheeler C. A fine balance: developing clinical practice guidelines in areas where evidence is lacking. Semin Dial. 2015;28(6):654-656. 4. Akbari A, Clase CM, Acott P, et al. Canadian Society of Nephrology commentary on the KDIGO clinical practice guideline for CKD evaluation and management. Am J Kidney Dis. 2015;65(2):177-205. 5. Inker LA, Astor BC, Fox CH, et al. KDOQI commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis. 2014;63(5):713-735. 6. Thurlow JS, Abbott KC, Linberg A, Little D, Fenderson J, Olson SW. SCr and SCysC concentrations before and after traumatic amputation in male soldiers: a case-control study. Am J Kidney Dis. 2014;63(1):167-170. 7. Cimerman N, Brguljan PM, Krasovec M, Suskovic S, Kos J. Serum cystatin C, a potent inhibitor of cysteine proteinases, is elevated in asthmatic patients. Clin Chim Acta. 2000;300(1-2):83-95. 8. Shlipak MG, Matsushita K, Ärnlöv J, et al. Cystatin C versus creatinine in determining risk based on kidney function. N Engl J Med. 2013;369(10):932-943. 9. Baxmann AC, Ahmed MS, Marques NC, et al. Influence of muscle mass and physical activity on serum and urinary creatinine and serum cystatin C. Clin J Am Soc Nephrol. 2008;3(2):348-354. Received August 15, 2015. Accepted in revised form October 8, 2015. Originally published online November 23, 2015. Published by Elsevier Inc. on behalf of the National Kidney Foundation, Inc. This is a US Government Work. There are no restrictions on its use. http://dx.doi.org/10.1053/j.ajkd.2015.10.014 Am J Kidney Dis. 2016;67(4):709-712