correspondence
The Authors Reply: Birzniece postulates that the decreased secretion of growth hormone was associated with an increase in fat mass in our participants with hypogonadism. As she notes, both estrogen deficiency and estrogen blockade reduce growth hormone secretion. Our study was not designed to examine mechanisms whereby estrogen deficiency increases body fat; however, we agree that diminished growth hormone secretion is a potential mechanism. Schooling et al. state that we implied that “boosting estrogen levels . . . may decrease cardiovascular risk.” We wrote that “the marked increase in intraabdominal fat with aromatase inhibition could portend an increase in cardiovascular disease with long-term estrogen deficiency,” not that estrogen administration would reduce such risk. Moreover, the studies they cited as evidence that estrogen administration increases the risk of cardiovascular disease among men1,2 used doses far higher than those needed for physiologic replacement. Schellhammer cites personal experience, published urologic literature, and our article as evidence that estrogen therapy is beneficial in men with prostate cancer who are receiving ADT. As noted above, we did not study the effects of estrogen administration in men receiving ADT. Nevertheless, the finding that estrogen deficiency is responsible for several of the undesirable consequences of ADT raises the possibility that the administration of low-dose estradiol might benefit men with prostate cancer who are receiving ADT. Randomized, controlled trials are needed to determine whether estradiol administration is effective and safe in such patients. Finally, Malnick et al. question the ethics of using a gonadotropin-releasing hormone agonist to investigate reproductive physiology. We3 and others4 have used this approach in studies for many years, and no safety issues have been observed. Our study was specifically designed to be
sufficiently brief so that clinically important bone loss, as assessed by means of dual-energy x-ray absorptiometry (DXA), would not occur. We measured bone mineral density (BMD) by means of DXA at baseline and study completion. As predicted, changes in the BMD of the spine and hip were 1% or less, and there were no significant differences between the hypogonadal group and the eugonadal (control) group. The major side effects of ADT, hot flashes and decreased sexual function, resolve with medication discontinuation and have no known residual effect on health. Moreover, because most of the men in our study received some testosterone, most participants did not report such ADT-related side effects. Participants were informed that if they had troubling side effects, they could withdraw from the study and receive testosterone replacement until the ADT wore off. Finally, ethical concerns were not raised by our institutional review board, our data and safety monitoring board, or the National Institutes of Health. Joel S. Finkelstein, M.D. Elaine W. Yu, M.D. Sherri-Ann M. Burnett-Bowie, M.D., M.P.H. Massachusetts General Hospital Boston, MA [email protected] Since publication of their article, the authors report no further potential conflict of interest. 1. The Coronary Drug Project Research Group. The Coronary
Drug Project: findings leading to discontinuation of the 2.5-mg/ day estrogen group. JAMA 1973;226:652-7. 2. Byar DP, Corle DK. Hormone therapy for prostate cancer: results of the Veterans Administration Cooperative Urological Research Group studies. NCI Monogr 1988;7:165-70. 3. Leder BZ, LeBlanc KM, Schoenfeld DA, Eastell R, Finkelstein JS. Differential effects of androgens and estrogens on bone turnover in normal men. J Clin Endocrinol Metab 2003;88:204-10. 4. Falahati-Nini A, Riggs BL, Atkinson EJ, O’Fallon WM, Eastell R, Khosla S. Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J Clin Invest 2000;106:1553-60. DOI: 10.1056/NEJMc1313169
Cystatin C versus Creatinine for Kidney Function–Based Risk To the Editor: The meta-analysis by Shlipak et al. (Sept. 5 issue)1 shows that a cystatin C–based estimated glomerular filtration rate (eGFR) offers improvements in predicting risks of death and end-stage renal disease across diverse populations.
In their editorial, Ingelfinger and Marsden2 caution that “results cannot be applied to Asian and Hispanic patients except by extrapolation.” Also, diabetes was underrepresented in the sample of patients with chronic kidney disease; it was pres-
n engl j med 369;25 nejm.org december 19, 2013
The New England Journal of Medicine Downloaded from nejm.org on April 21, 2015. For personal use only. No other uses without permission. Copyright © 2013 Massachusetts Medical Society. All rights reserved.
2457
The
n e w e ng l a n d j o u r na l
of
m e dic i n e
ent in only 9% of participants. Further, more information is still needed about the use of cystatin C in pregnant women, patients who have undergone renal transplantation, and children. Certain other issues would suggest other reasons for caution in adopting the measurement of cystatin C to assess the eGFR. In clinical hypothyroidism and hyperthyroidism, a change of 30% in the level of serum cystatin C has been observed, and in subclinical hypothyroidism and hyperthyroidism, a change of 15% in this level has been observed.3 Glucocorticoid therapy can modify cystatin C production.4 Changes in serum levels of cystatin C were also reported in colorectal cancer and melanoma and in association with Alzheimer’s disease and other neurodegenerative disorders.5 Enhanced cystatin C expression might be causing or exacerbating neurodegeneration or might be an endogenous neuroprotective response. Predictions of end-stage renal disease and death on the basis of cystatin C measurement would be better understood with further research about changes in this compound in aging and Alzheimer’s disease. Almir R. Tavares, Jr., M.D., Ph.D.
inulin clearance and the eGFR based on the measurement of cystatin C are influenced by plasma glucose levels because of intrarenal hemodynamic effects related to efferent vasoconstriction.2,3 As a result, even modest hyperglycemia can increase the GFR by as much as 20 ml per minute per 1.73 m2. Did the authors consider controlling for plasma glucose in their meta-analysis, since up to 32% of patients in the studies had diabetes? This may increase the “signal-to-noise” ratio, thereby improving the ability of the eGFR to detect important clinical outcomes. Moreover, current estimates of the GFR lack precision and accuracy before stage 3 chronic kidney disease.4 This is of particular concern in patients with diabetes, in whom early increased GFR (renal hyperfiltration) may promote kidney injury. Further refinement of GFR estimating equations could ultimately improve screening, detection, and prevention of early changes in the GFR, especially in high-risk populations such as adolescents and young adults with diabetes. David Cherney, M.D., Ph.D.
Federal University of Minas Gerais Belo Horizonte, Brazil [email protected] No potential conflict of interest relevant to this letter was reported.
David M. Maahs, M.D., Ph.D.
1. Shlipak MG, Matsushita K, Ärnlöv J, et al. Cystatin C versus
creatinine in determining risk based on kidney function. N Engl J Med 2013;369:932-43. 2. Ingelfinger JR, Marsden PA. Estimated GFR and risk of death — is cystatin C useful? N Engl J Med 2013;369:974-5. 3. Wiesli P, Schwegler B, Spinas GA, Schmid C. Serum cystatin C is sensitive to small changes in thyroid function. Clin Chim Acta 2003;338:87-90. 4. Pöge U, Gerhardt T, Bökenkamp A, Stoffel-Wagner B, Klehr HU, Sauerbruch T, et al. Time course of low molecular weight proteins in the early kidney transplantation period — influence of corticosteroids. Nephrol Dial Transplant 2004;19:2858-63. 5. Sundelöf J, Arnlöv J, Ingelsson E, et al. Serum cystatin C and the risk of Alzheimer disease in elderly men. Neurology 2008; 71:1072-9.
University Health Network Toronto, ON, Canada Barbara Davis Center for Childhood Diabetes Aurora, CO [email protected] No potential conflict of interest relevant to this letter was reported. 1. Odutayo A, Cherney D. Cystatin C and acute changes in glo-
merular filtration rate. Clin Nephrol 2012;78:64-75. 2. Miller JA. Impact of hyperglycemia on the renin angiotensin system in early human type 1 diabetes mellitus. J Am Soc Nephrol 1999;10:1778-85. 3. Cherney DZ, Reich HN, Miller JA, et al. Age is a determinant of acute hemodynamic responses to hyperglycemia and angiotensin II in humans with uncomplicated type 1 diabetes mellitus. Am J Physiol Regul Integr Comp Physiol 2010;299:R206-14. 4. Inker LA, Schmid CH, Tighiouart H, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 2012;367:20-9. [Errata, N Engl J Med 2012;367:681, 2060.] DOI: 10.1056/NEJMc1312801
DOI: 10.1056/NEJMc1312801
To the Editor: Shlipak et al. clarify the potential use of cystatin C as a measure of renal function to improve the prediction of health outcomes. Reduced confounding influences of nonrenal factors as compared with the eGFR calculated with the measurement of creatinine is one appeal of cystatin C.1 Nevertheless, the GFR based on
2458
To the Editor: Renal insufficiency strongly correlates with an excess of morbidity and mortality.1 This correlation is incremental with the degree of renal insufficiency, and — as indicated by Shlipak et al. — stronger when more precise estimations of renal function such as measurements of cystatin C are used. However, a more reliable identification of per-
n engl j med 369;25 nejm.org december 19, 2013
The New England Journal of Medicine Downloaded from nejm.org on April 21, 2015. For personal use only. No other uses without permission. Copyright © 2013 Massachusetts Medical Society. All rights reserved.
correspondence
sons at risk is of only limited value if it cannot be translated into better patient care. In patients at risk for progressive renal insufficiency, this implies a substantial risk modification deferring the development of end-stage renal disease, which often is not feasible. In patients with end-stage renal disease, this implies a more accurate identification of the ideal timing of initiation of renalreplacement therapy2 as well as a better selection of patients who truly benefit from renal-replacement therapy, even in subgroups with major coexisting conditions.3 The real value of a reliable estimation of renal risk would be integration of the estimation into an evidence-based selection of appropriate treatment strategies for various subpopulations, thus permitting the most appropriate individualized patient care.4 We need the right answers to the right questions. Stefaan J. Vandecasteele, M.D., Ph.D. An S. De Vriese, M.D., Ph.D. Sint-Jan Brugge General Hospital Brugge, Belgium [email protected] No potential conflict of interest relevant to this letter was reported. 1. Hallan SI, Orth SR. The KDOQI 2002 classification of
chronic kidney disease: for whom the bell tolls. Nephrol Dial Transplant 2010;25:2832-6. 2. Cooper BA, Branley P, Bulfone L, et al. A randomized, controlled trial of early versus late initiation of dialysis. N Engl J Med 2010;363:609-19. 3. Kurella Tamura M, Covinsky KE, Chertow GM, Yaffe K, Landefeld CS, McCulloch CE. Functional status of elderly adults before and after initiation of dialysis. N Engl J Med 2009;361: 1539-47. 4. Reuben DB, Tinetti ME. Goal-oriented patient care — an alternative health outcomes paradigm. N Engl J Med 2012;366: 777-9. DOI: 10.1056/NEJMc1312801
believe that the biologic roles of cystatin C within the brain are relevant to our study, since they are unlikely to influence the primary outcomes of death and end-stage renal disease. Cherney and Maahs question whether the plasma glucose concentration might have been an important missing bias of kidney function because of its vasoconstrictive effects. We did not adjust for glucose in this meta-analysis, and we agree that adjustment for glucose may have further improved the ability of GFR to detect important clinical outcomes. As to the point regarding the “signal-to-noise” ratio, we believe that the strong mortality risk gradient that we observed for the eGFR calculated with the measurement of cystatin C and the eGFR calculated with the measurement of both creatinine and cystatin C from 60 to 90 ml per minute per 1.73 m2 indicates that cystatin C offers a more useful GFR estimate for risk stratification among patients who have not yet reached the threshold for the diagnosis of chronic kidney disease of less than 60 ml per minute per 1.73 m2. We agree that this improved accuracy could be useful for the design of screening strategies for chronic kidney disease. Vandecasteele and De Vriese correctly point out that improved GFR estimation must be translated into actions that alter the disease course and improve patient care. Although there is a need for additional research, fortunately we can alter the course of decreasing kidney function by means of blood-pressure control and inhibition of the renin–angiotensin–aldosterone system, especially in the subgroup of patients with higher albuminuria, which is another important marker of chronic kidney disease. Patient care can be improved, moreover, by adjusting the medication dosage to the level of kidney function.
The Authors Reply: The first point by Tavares Michael G. Shlipak, M.D., M.P.H. raises valid issues regarding the generalizability San Francisco Veterans Affairs Medical Center of our participant population, since GFR esti- San Francisco, CA mates have not been validated among Hispanic Josef Coresh, M.D., Ph.D. populations. It is furthermore correct that some Johns Hopkins Bloomberg School of Public Health specific populations, such as kidney-transplant Baltimore, MD recipients, were underrepresented or excluded [email protected] from the cohort studies composing this meta- Ron T. Gansevoort, M.D., Ph.D. analysis. In addition, some non-GFR bias in cys- University Medical Center Groningen tatin C levels can occur in patients with untreated Groningen, the Netherlands thyroid disease or among those who receive glucoSince publication of their article, the authors report no furcorticoids; such patients would probably have been ther potential conflict of interest. uncommon in our study. In contrast, we do not DOI: 10.1056/NEJMc1312801
n engl j med 369;25 nejm.org december 19, 2013
The New England Journal of Medicine Downloaded from nejm.org on April 21, 2015. For personal use only. No other uses without permission. Copyright © 2013 Massachusetts Medical Society. All rights reserved.
2459
The Authors Reply: Birzniece postulates that the decreased secretion of growth hormone was associated with an increase in fat mass in our participants with hypogonadism. As she notes, both estrogen deficiency and estrogen blockade reduce growth hormone secretion. Our study was not designed to examine mechanisms whereby estrogen deficiency increases body fat; however, we agree that diminished growth hormone secretion is a potential mechanism. Schooling et al. state that we implied that “boosting estrogen levels . . . may decrease cardiovascular risk.” We wrote that “the marked increase in intraabdominal fat with aromatase inhibition could portend an increase in cardiovascular disease with long-term estrogen deficiency,” not that estrogen administration would reduce such risk. Moreover, the studies they cited as evidence that estrogen administration increases the risk of cardiovascular disease among men1,2 used doses far higher than those needed for physiologic replacement. Schellhammer cites personal experience, published urologic literature, and our article as evidence that estrogen therapy is beneficial in men with prostate cancer who are receiving ADT. As noted above, we did not study the effects of estrogen administration in men receiving ADT. Nevertheless, the finding that estrogen deficiency is responsible for several of the undesirable consequences of ADT raises the possibility that the administration of low-dose estradiol might benefit men with prostate cancer who are receiving ADT. Randomized, controlled trials are needed to determine whether estradiol administration is effective and safe in such patients. Finally, Malnick et al. question the ethics of using a gonadotropin-releasing hormone agonist to investigate reproductive physiology. We3 and others4 have used this approach in studies for many years, and no safety issues have been observed. Our study was specifically designed to be
sufficiently brief so that clinically important bone loss, as assessed by means of dual-energy x-ray absorptiometry (DXA), would not occur. We measured bone mineral density (BMD) by means of DXA at baseline and study completion. As predicted, changes in the BMD of the spine and hip were 1% or less, and there were no significant differences between the hypogonadal group and the eugonadal (control) group. The major side effects of ADT, hot flashes and decreased sexual function, resolve with medication discontinuation and have no known residual effect on health. Moreover, because most of the men in our study received some testosterone, most participants did not report such ADT-related side effects. Participants were informed that if they had troubling side effects, they could withdraw from the study and receive testosterone replacement until the ADT wore off. Finally, ethical concerns were not raised by our institutional review board, our data and safety monitoring board, or the National Institutes of Health. Joel S. Finkelstein, M.D. Elaine W. Yu, M.D. Sherri-Ann M. Burnett-Bowie, M.D., M.P.H. Massachusetts General Hospital Boston, MA [email protected] Since publication of their article, the authors report no further potential conflict of interest. 1. The Coronary Drug Project Research Group. The Coronary
Drug Project: findings leading to discontinuation of the 2.5-mg/ day estrogen group. JAMA 1973;226:652-7. 2. Byar DP, Corle DK. Hormone therapy for prostate cancer: results of the Veterans Administration Cooperative Urological Research Group studies. NCI Monogr 1988;7:165-70. 3. Leder BZ, LeBlanc KM, Schoenfeld DA, Eastell R, Finkelstein JS. Differential effects of androgens and estrogens on bone turnover in normal men. J Clin Endocrinol Metab 2003;88:204-10. 4. Falahati-Nini A, Riggs BL, Atkinson EJ, O’Fallon WM, Eastell R, Khosla S. Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J Clin Invest 2000;106:1553-60. DOI: 10.1056/NEJMc1313169
Cystatin C versus Creatinine for Kidney Function–Based Risk To the Editor: The meta-analysis by Shlipak et al. (Sept. 5 issue)1 shows that a cystatin C–based estimated glomerular filtration rate (eGFR) offers improvements in predicting risks of death and end-stage renal disease across diverse populations.
In their editorial, Ingelfinger and Marsden2 caution that “results cannot be applied to Asian and Hispanic patients except by extrapolation.” Also, diabetes was underrepresented in the sample of patients with chronic kidney disease; it was pres-
n engl j med 369;25 nejm.org december 19, 2013
The New England Journal of Medicine Downloaded from nejm.org on April 21, 2015. For personal use only. No other uses without permission. Copyright © 2013 Massachusetts Medical Society. All rights reserved.
2457
The
n e w e ng l a n d j o u r na l
of
m e dic i n e
ent in only 9% of participants. Further, more information is still needed about the use of cystatin C in pregnant women, patients who have undergone renal transplantation, and children. Certain other issues would suggest other reasons for caution in adopting the measurement of cystatin C to assess the eGFR. In clinical hypothyroidism and hyperthyroidism, a change of 30% in the level of serum cystatin C has been observed, and in subclinical hypothyroidism and hyperthyroidism, a change of 15% in this level has been observed.3 Glucocorticoid therapy can modify cystatin C production.4 Changes in serum levels of cystatin C were also reported in colorectal cancer and melanoma and in association with Alzheimer’s disease and other neurodegenerative disorders.5 Enhanced cystatin C expression might be causing or exacerbating neurodegeneration or might be an endogenous neuroprotective response. Predictions of end-stage renal disease and death on the basis of cystatin C measurement would be better understood with further research about changes in this compound in aging and Alzheimer’s disease. Almir R. Tavares, Jr., M.D., Ph.D.
inulin clearance and the eGFR based on the measurement of cystatin C are influenced by plasma glucose levels because of intrarenal hemodynamic effects related to efferent vasoconstriction.2,3 As a result, even modest hyperglycemia can increase the GFR by as much as 20 ml per minute per 1.73 m2. Did the authors consider controlling for plasma glucose in their meta-analysis, since up to 32% of patients in the studies had diabetes? This may increase the “signal-to-noise” ratio, thereby improving the ability of the eGFR to detect important clinical outcomes. Moreover, current estimates of the GFR lack precision and accuracy before stage 3 chronic kidney disease.4 This is of particular concern in patients with diabetes, in whom early increased GFR (renal hyperfiltration) may promote kidney injury. Further refinement of GFR estimating equations could ultimately improve screening, detection, and prevention of early changes in the GFR, especially in high-risk populations such as adolescents and young adults with diabetes. David Cherney, M.D., Ph.D.
Federal University of Minas Gerais Belo Horizonte, Brazil [email protected] No potential conflict of interest relevant to this letter was reported.
David M. Maahs, M.D., Ph.D.
1. Shlipak MG, Matsushita K, Ärnlöv J, et al. Cystatin C versus
creatinine in determining risk based on kidney function. N Engl J Med 2013;369:932-43. 2. Ingelfinger JR, Marsden PA. Estimated GFR and risk of death — is cystatin C useful? N Engl J Med 2013;369:974-5. 3. Wiesli P, Schwegler B, Spinas GA, Schmid C. Serum cystatin C is sensitive to small changes in thyroid function. Clin Chim Acta 2003;338:87-90. 4. Pöge U, Gerhardt T, Bökenkamp A, Stoffel-Wagner B, Klehr HU, Sauerbruch T, et al. Time course of low molecular weight proteins in the early kidney transplantation period — influence of corticosteroids. Nephrol Dial Transplant 2004;19:2858-63. 5. Sundelöf J, Arnlöv J, Ingelsson E, et al. Serum cystatin C and the risk of Alzheimer disease in elderly men. Neurology 2008; 71:1072-9.
University Health Network Toronto, ON, Canada Barbara Davis Center for Childhood Diabetes Aurora, CO [email protected] No potential conflict of interest relevant to this letter was reported. 1. Odutayo A, Cherney D. Cystatin C and acute changes in glo-
merular filtration rate. Clin Nephrol 2012;78:64-75. 2. Miller JA. Impact of hyperglycemia on the renin angiotensin system in early human type 1 diabetes mellitus. J Am Soc Nephrol 1999;10:1778-85. 3. Cherney DZ, Reich HN, Miller JA, et al. Age is a determinant of acute hemodynamic responses to hyperglycemia and angiotensin II in humans with uncomplicated type 1 diabetes mellitus. Am J Physiol Regul Integr Comp Physiol 2010;299:R206-14. 4. Inker LA, Schmid CH, Tighiouart H, et al. Estimating glomerular filtration rate from serum creatinine and cystatin C. N Engl J Med 2012;367:20-9. [Errata, N Engl J Med 2012;367:681, 2060.] DOI: 10.1056/NEJMc1312801
DOI: 10.1056/NEJMc1312801
To the Editor: Shlipak et al. clarify the potential use of cystatin C as a measure of renal function to improve the prediction of health outcomes. Reduced confounding influences of nonrenal factors as compared with the eGFR calculated with the measurement of creatinine is one appeal of cystatin C.1 Nevertheless, the GFR based on
2458
To the Editor: Renal insufficiency strongly correlates with an excess of morbidity and mortality.1 This correlation is incremental with the degree of renal insufficiency, and — as indicated by Shlipak et al. — stronger when more precise estimations of renal function such as measurements of cystatin C are used. However, a more reliable identification of per-
n engl j med 369;25 nejm.org december 19, 2013
The New England Journal of Medicine Downloaded from nejm.org on April 21, 2015. For personal use only. No other uses without permission. Copyright © 2013 Massachusetts Medical Society. All rights reserved.
correspondence
sons at risk is of only limited value if it cannot be translated into better patient care. In patients at risk for progressive renal insufficiency, this implies a substantial risk modification deferring the development of end-stage renal disease, which often is not feasible. In patients with end-stage renal disease, this implies a more accurate identification of the ideal timing of initiation of renalreplacement therapy2 as well as a better selection of patients who truly benefit from renal-replacement therapy, even in subgroups with major coexisting conditions.3 The real value of a reliable estimation of renal risk would be integration of the estimation into an evidence-based selection of appropriate treatment strategies for various subpopulations, thus permitting the most appropriate individualized patient care.4 We need the right answers to the right questions. Stefaan J. Vandecasteele, M.D., Ph.D. An S. De Vriese, M.D., Ph.D. Sint-Jan Brugge General Hospital Brugge, Belgium [email protected] No potential conflict of interest relevant to this letter was reported. 1. Hallan SI, Orth SR. The KDOQI 2002 classification of
chronic kidney disease: for whom the bell tolls. Nephrol Dial Transplant 2010;25:2832-6. 2. Cooper BA, Branley P, Bulfone L, et al. A randomized, controlled trial of early versus late initiation of dialysis. N Engl J Med 2010;363:609-19. 3. Kurella Tamura M, Covinsky KE, Chertow GM, Yaffe K, Landefeld CS, McCulloch CE. Functional status of elderly adults before and after initiation of dialysis. N Engl J Med 2009;361: 1539-47. 4. Reuben DB, Tinetti ME. Goal-oriented patient care — an alternative health outcomes paradigm. N Engl J Med 2012;366: 777-9. DOI: 10.1056/NEJMc1312801
believe that the biologic roles of cystatin C within the brain are relevant to our study, since they are unlikely to influence the primary outcomes of death and end-stage renal disease. Cherney and Maahs question whether the plasma glucose concentration might have been an important missing bias of kidney function because of its vasoconstrictive effects. We did not adjust for glucose in this meta-analysis, and we agree that adjustment for glucose may have further improved the ability of GFR to detect important clinical outcomes. As to the point regarding the “signal-to-noise” ratio, we believe that the strong mortality risk gradient that we observed for the eGFR calculated with the measurement of cystatin C and the eGFR calculated with the measurement of both creatinine and cystatin C from 60 to 90 ml per minute per 1.73 m2 indicates that cystatin C offers a more useful GFR estimate for risk stratification among patients who have not yet reached the threshold for the diagnosis of chronic kidney disease of less than 60 ml per minute per 1.73 m2. We agree that this improved accuracy could be useful for the design of screening strategies for chronic kidney disease. Vandecasteele and De Vriese correctly point out that improved GFR estimation must be translated into actions that alter the disease course and improve patient care. Although there is a need for additional research, fortunately we can alter the course of decreasing kidney function by means of blood-pressure control and inhibition of the renin–angiotensin–aldosterone system, especially in the subgroup of patients with higher albuminuria, which is another important marker of chronic kidney disease. Patient care can be improved, moreover, by adjusting the medication dosage to the level of kidney function.
The Authors Reply: The first point by Tavares Michael G. Shlipak, M.D., M.P.H. raises valid issues regarding the generalizability San Francisco Veterans Affairs Medical Center of our participant population, since GFR esti- San Francisco, CA mates have not been validated among Hispanic Josef Coresh, M.D., Ph.D. populations. It is furthermore correct that some Johns Hopkins Bloomberg School of Public Health specific populations, such as kidney-transplant Baltimore, MD recipients, were underrepresented or excluded [email protected] from the cohort studies composing this meta- Ron T. Gansevoort, M.D., Ph.D. analysis. In addition, some non-GFR bias in cys- University Medical Center Groningen tatin C levels can occur in patients with untreated Groningen, the Netherlands thyroid disease or among those who receive glucoSince publication of their article, the authors report no furcorticoids; such patients would probably have been ther potential conflict of interest. uncommon in our study. In contrast, we do not DOI: 10.1056/NEJMc1312801
n engl j med 369;25 nejm.org december 19, 2013
The New England Journal of Medicine Downloaded from nejm.org on April 21, 2015. For personal use only. No other uses without permission. Copyright © 2013 Massachusetts Medical Society. All rights reserved.
2459
