- Email: [email protected]
Assessing Kidney Function in Transplant Recipients: Time to Work Together and Address the Most Relevant Questions
Correspondence
Creatinine-Based GFR Estimating Equations in Kidney Transplant Recipients To the Editor: Shaffi et al1 conclude that the MDRD (Modification of Diet in Renal Disease) Study and CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations perform better in kidney transplant recipients than all other proposed glomerular filtration rate (GFR) estimating equations, confirming data from White et al2 in 2008. We have 4 comments regarding this conclusion. First, it is not surprising that equations developed with standardized serum creatinine level and validated against a “true” reference method (not creatinine clearance) perform better than others. Second, we believe that the most important question in clinical practice is which of the 2 equations performs better in kidney transplant recipients. This question is examined only partially in the article, though a recent study3 showed that the MDRD Study equation outperforms the CKD-EPI equation in these patients. Third, the authors evaluated the Berlin Initiative Study (BIS) equation in a cohort with a mean age of 54 years. This is questionable and unfair because the BIS equation was explicitly designed to estimate GFR in patients 70 years or older. These patients are poorly represented in the 5 cohorts studied; thus, the results of Shaffi et al1 unjustly discredit the BIS equation, which was developed with highquality methodology.4 Fourth, the authors conclude that the MDRD Study and CKD-EPI equations can be used for clinical management. However, we must keep in mind that these equations misestimate true GFR by .30% in 1 of 5 patients. It is time to focus on these individuals. Further, in the context of kidney transplantation, we believe that measuring GFR is useful in both clinical practice and research.5
Renal Disease) Study and CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations over other glomerular filtration rate (GFR) estimating equations in transplant recipients.2,3 The continued emphasis on demonstrating the superiority of particular creatinine-based equations over others, including immaterial comparisons with equations designed for use in very different populations (ie, individuals of Japanese ancestry or advanced age)4,5 fails to address the most clinically relevant issues related to kidney function assessment in transplantation. Immune and nonimmune transplant injuries often occur without a change in serum creatinine level or estimated GFR. Creatininebased equations have never been shown to improve the clinical recognition of acute or long-term changes in transplant function compared to the use of serum creatinine concentration alone. Further, improvements in immunosuppression have reduced the relevance of acute rejection, and there is a pressing need to identify novel surrogates of long-term transplant survival for use in the next generation of clinical trials. Without this advance, desperately needed trials to improve long-term transplant survival are economically and logistically unattractive; thus, they will not be conducted. Whether longitudinal changes in creatinine-based estimates of transplant function or the combined use of these estimates with measures of proteinuria (as proposed for use in the setting of nontransplant CKD) may be targets for clinical transplantation trials is an open question of paramount importance. The shared need for a durable surrogate outcome for use in interventional studies in native6 and transplant CKD populations is an opportunity for all researchers to work together on addressing the most relevant questions. John S. Gill, MD, MS University of British Columbia–St Paul’s Hospital Vancouver, Canada
Pierre Delanaye, MD, PhD University of Liège Liège, Belgium
Randall Morris, MD Stanford University School of Medicine Stanford, California
Acknowledgements Financial Disclosure: The author declares that he has no relevant financial interests.
References
Acknowledgements
1. Shaffi K, Uhlig K, Perrone RD, et al. Performance of creatinine-based GFR estimating equations in solid-organ transplant recipients. Am J Kidney Dis. 2014;63(6):1007-1018. 2. White CA, Huang D, Akbari A, Garland J, Knoll GA. Performance of creatinine-based estimates of GFR in kidney transplant recipients: a systematic review. Am J Kidney Dis. 2008;51(6):1005-1015. 3. Masson I, Flamant M, Maillard N, et al. MDRD versus CKD-EPI equation to estimate glomerular filtration rate in kidney transplant recipients. Transplantation. 2013;95(10):1211-1217. 4. Schaeffner ES, Ebert N, Delanaye P, et al. Two novel equations to estimate kidney function in persons aged 70 years or older. Ann Intern Med. 2012;157(7):471-481. 5. Delanaye P, Mariat C. The applicability of eGFR equations to different populations. Nat Rev Nephrol. 2013;9(9):513-522.
Financial Disclosure: The authors declare that they have no relevant financial interests.
Ó 2014 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2014.05.027
Assessing Kidney Function in Transplant Recipients: Time to Work Together and Address the Most Relevant Questions To the Editor: The study by Shaffi et al1 validates previous work demonstrating the superiority of the MDRD (Modification of Diet in 818
References 1. Shaffi K, Uhlig K, Perrone R, et al. Performance of creatinine based GFR estimating equations in solid organ transplant recipients. Am J Kidney Dis. 2014;63(6):1007-1018. 2. White CA, Huang D, Akbari A, Garland J, Knoll GA. Performance of creatinine-based estimates of GFR in kidney transplant recipients: a systematic review. Am J Kidney Dis. 2008;51(6):1005-1015. 3. White CA, Akbari A, Doucette S, Fergusson D, Knoll GA. Estimating glomerular filtration rate in kidney transplantation: is the new Chronic Kidney Disease Epidemiology Collaboration equation any better? Clin Chem. 2010;56(3):474-477. 4. Matsuo S, Imai E, Horio M, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53(6):982-992. 5. Schaeffner ES, Ebert N, Delanaye P, et al. Two novel equations to estimate kidney function in persons aged 70 years or older. Ann Intern Med. 2012;157(7):471-481. 6. Rosansky SJ, Glassock RJ. Is a decline in estimated GFR an appropriate surrogate end point for renoprotection drug trials. Kidney Int. 2014;85:723-727. Ó 2014 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2014.06.034
Am J Kidney Dis. 2014;64(5):817-820
Creatinine-Based GFR Estimating Equations in Kidney Transplant Recipients To the Editor: Shaffi et al1 conclude that the MDRD (Modification of Diet in Renal Disease) Study and CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations perform better in kidney transplant recipients than all other proposed glomerular filtration rate (GFR) estimating equations, confirming data from White et al2 in 2008. We have 4 comments regarding this conclusion. First, it is not surprising that equations developed with standardized serum creatinine level and validated against a “true” reference method (not creatinine clearance) perform better than others. Second, we believe that the most important question in clinical practice is which of the 2 equations performs better in kidney transplant recipients. This question is examined only partially in the article, though a recent study3 showed that the MDRD Study equation outperforms the CKD-EPI equation in these patients. Third, the authors evaluated the Berlin Initiative Study (BIS) equation in a cohort with a mean age of 54 years. This is questionable and unfair because the BIS equation was explicitly designed to estimate GFR in patients 70 years or older. These patients are poorly represented in the 5 cohorts studied; thus, the results of Shaffi et al1 unjustly discredit the BIS equation, which was developed with highquality methodology.4 Fourth, the authors conclude that the MDRD Study and CKD-EPI equations can be used for clinical management. However, we must keep in mind that these equations misestimate true GFR by .30% in 1 of 5 patients. It is time to focus on these individuals. Further, in the context of kidney transplantation, we believe that measuring GFR is useful in both clinical practice and research.5
Renal Disease) Study and CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations over other glomerular filtration rate (GFR) estimating equations in transplant recipients.2,3 The continued emphasis on demonstrating the superiority of particular creatinine-based equations over others, including immaterial comparisons with equations designed for use in very different populations (ie, individuals of Japanese ancestry or advanced age)4,5 fails to address the most clinically relevant issues related to kidney function assessment in transplantation. Immune and nonimmune transplant injuries often occur without a change in serum creatinine level or estimated GFR. Creatininebased equations have never been shown to improve the clinical recognition of acute or long-term changes in transplant function compared to the use of serum creatinine concentration alone. Further, improvements in immunosuppression have reduced the relevance of acute rejection, and there is a pressing need to identify novel surrogates of long-term transplant survival for use in the next generation of clinical trials. Without this advance, desperately needed trials to improve long-term transplant survival are economically and logistically unattractive; thus, they will not be conducted. Whether longitudinal changes in creatinine-based estimates of transplant function or the combined use of these estimates with measures of proteinuria (as proposed for use in the setting of nontransplant CKD) may be targets for clinical transplantation trials is an open question of paramount importance. The shared need for a durable surrogate outcome for use in interventional studies in native6 and transplant CKD populations is an opportunity for all researchers to work together on addressing the most relevant questions. John S. Gill, MD, MS University of British Columbia–St Paul’s Hospital Vancouver, Canada
Pierre Delanaye, MD, PhD University of Liège Liège, Belgium
Randall Morris, MD Stanford University School of Medicine Stanford, California
Acknowledgements Financial Disclosure: The author declares that he has no relevant financial interests.
References
Acknowledgements
1. Shaffi K, Uhlig K, Perrone RD, et al. Performance of creatinine-based GFR estimating equations in solid-organ transplant recipients. Am J Kidney Dis. 2014;63(6):1007-1018. 2. White CA, Huang D, Akbari A, Garland J, Knoll GA. Performance of creatinine-based estimates of GFR in kidney transplant recipients: a systematic review. Am J Kidney Dis. 2008;51(6):1005-1015. 3. Masson I, Flamant M, Maillard N, et al. MDRD versus CKD-EPI equation to estimate glomerular filtration rate in kidney transplant recipients. Transplantation. 2013;95(10):1211-1217. 4. Schaeffner ES, Ebert N, Delanaye P, et al. Two novel equations to estimate kidney function in persons aged 70 years or older. Ann Intern Med. 2012;157(7):471-481. 5. Delanaye P, Mariat C. The applicability of eGFR equations to different populations. Nat Rev Nephrol. 2013;9(9):513-522.
Financial Disclosure: The authors declare that they have no relevant financial interests.
Ó 2014 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2014.05.027
Assessing Kidney Function in Transplant Recipients: Time to Work Together and Address the Most Relevant Questions To the Editor: The study by Shaffi et al1 validates previous work demonstrating the superiority of the MDRD (Modification of Diet in 818
References 1. Shaffi K, Uhlig K, Perrone R, et al. Performance of creatinine based GFR estimating equations in solid organ transplant recipients. Am J Kidney Dis. 2014;63(6):1007-1018. 2. White CA, Huang D, Akbari A, Garland J, Knoll GA. Performance of creatinine-based estimates of GFR in kidney transplant recipients: a systematic review. Am J Kidney Dis. 2008;51(6):1005-1015. 3. White CA, Akbari A, Doucette S, Fergusson D, Knoll GA. Estimating glomerular filtration rate in kidney transplantation: is the new Chronic Kidney Disease Epidemiology Collaboration equation any better? Clin Chem. 2010;56(3):474-477. 4. Matsuo S, Imai E, Horio M, et al. Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis. 2009;53(6):982-992. 5. Schaeffner ES, Ebert N, Delanaye P, et al. Two novel equations to estimate kidney function in persons aged 70 years or older. Ann Intern Med. 2012;157(7):471-481. 6. Rosansky SJ, Glassock RJ. Is a decline in estimated GFR an appropriate surrogate end point for renoprotection drug trials. Kidney Int. 2014;85:723-727. Ó 2014 by the National Kidney Foundation, Inc. http://dx.doi.org/10.1053/j.ajkd.2014.06.034
Am J Kidney Dis. 2014;64(5):817-820