- Email: [email protected]
Lack of mortality benefit with sevelamer
letter to the editor
post-hemodialysis target blood pressure7 may therefore paradoxically decrease life expectancy rather than prolong it. 1. Agarwal R. Better blood pressure control is not causally linked to intradialytic hypotension. Kidney Int 2008; 73: 1092. 2. Tentori F, Hunt WC, Rohrscheib M et al. Which targets in clinical practice guidelines are associated with improved survival in a large dialysis organization? J Am Soc Nephrol 2007; 18: 2377–2384. 3. McIntyre CW, Burton JO, Selby NM et al. Hemodialysis-induced cardiac dysfunction is associated with an acute reduction in global and segmental myocardial blood flow. Clin J Am Soc Nephrol 2008; 3: 19–26. 4. Shoji T, Tsubakihara Y, Fujii M et al. Hemodialysis-associated hypotension as an independent risk factor for two-year mortality in hemodialysis patients. Kidney Int 2004; 66: 1212–1220. 5. Mitra S. The pathophysiology of fluid removal during hemodialysis: implications for blood volume monitoring and determination of dry weight. MD thesis, University of London, 2007. 6. Davenport A. Intradialytic complications during hemodialysis. Hemodial Int 2006; 10: 162–167. 7. Davenport A, Cox C, Thuraisingham R. Achieving blood pressure targets during dialysis improves control but increases intradialytic hypotension. Kidney Int 2007; 73: 759–764.
A Davenport1 1
Royal Free Hospital, UCL Center for Nephrology, London, UK Correspondence: A Davenport, Royal Free Hospital, UCL Center for Nephrology, Pond Street, London NW3 2QG, UK. E-mail: [email protected]
Lack of mortality benefit with sevelamer
of patient age on the results. A major case is made for a possible benefit on all-cause mortality in subjects aged over 65 years treated with sevelamer. This post hoc analysis will undoubtedly become fodder for pharmaceutical company marketing and quite possibly will be used to justify additional opinion-based recommendations for preferential use of sevelamer in the older dialysis patient population. However, we are quite concerned about incomplete reporting of the results of the DCOR study. The reported dropout rate (49%) is extremely high and unacceptable given the simplicity of the DCOR study design. DCOR is a mortality study that enrolled only Medicare-eligible dialysis patients. Although study subjects may withdraw consent for participation, an intentto-treat analysis of all enrolled subjects is feasible, as there are only three possible outcomes regarding mortality (alive on dialysis, alive after kidney transplant, or dead). Although data are not reported, the authors mention that an intentto-treat analysis of all-cause mortality employing the Centers for Medicare and Medicaid Services (CMS) database also showed no difference in all-cause mortality. Did the postulated age-related difference in mortality persist in this intent-to-treat data set? Full reporting of intent-to-treat data analysis should have been a prerequisite for publication and remains mandatory for any meaningful analysis of DCOR results. 1.
2.
Kidney International (2008) 73, 1093; doi:10.1038/ki.2008.46 3.
To the Editor: Hallelujah! The long anticipated results of the Dialysis Clinical Outcomes Revisited (DCOR) trial are finally published.1 To our surprise, despite triumphant press releases and hyperbolic pronouncements made in industry-sponsored symposia at nephrology meetings 2 years ago, the DCOR study actually found no mortality benefit among hemodialysis patients treated with sevelamer as compared with patients treated with CCPBs (calcium-containing phosphate binders). At once, the NKF-KDOQI/KDIGO opinion-based recommendations regarding the possible advantages of the non-calcium, non-aluminum resin-based phosphate binder, sevelamer become moot. In these guidelines, the postulated rationale for preferential use of non-calcium binders in certain clinical circumstances was based on observational studies showing an association between the use of CCPB and mortality risk or intervention trials employing surrogate end points such as cardiovascular calcification.2,3 These important results from DCOR imply that clinicians can now confidently prescribe effective and substantially less expensive CCPB therapy unburdened by prior expert ‘opinion’ suggesting that CCPBs represent arcane and potentially cardiotoxic therapy. Case closed, right? Well probably not. Although statistically invalid given the negative results for the primary outcomes (all-cause and cardiovascular mortality), the authors conducted a post hoc analysis to study the effect Kidney International (2008) 73, 1092–1096
Suki WN, Zabaneh R, Cangiano JL et al. Effect of sevelamer and calciumbased phosphate binders on mortality in hemodialysis patients. Kidney Int 2007; 72: 1130–1137. Chertow GM, Burke SK, Raggi P, et al., Treat to Goal Working Group. Sevelamer attenuated the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 2002; 62: 245–252. Block GA, Spiegel DM, Ehrlich J et al. Effect of sevelamer and calcium on coronary calcification in patients new to hemodialysis. Kidney Int 2005; 68: 1815–1824.
CR Nolan1 and DA McCarron2 1 Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA and 2Department of Nutrition, University of California, Davis, California, USA Correspondence: CR Nolan, Organ Transplant Center, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC 7882, San Antonio, Texas 78229-3900, USA. E-mail: [email protected]
Response to ‘Lack of mortality benefit with sevelamer’ Kidney International (2008) 73, 1093–1094; doi:10.1038/ki.2008.47
The case against calcium-based binders has been accumulating for years.1 The presence, and extent, of vascular calcifications are strong predictors of cardiovascular and all-cause mortality.2,3 The dose of calcium-based phosphate binders (acetate or carbonate) has been linked to the severity of vascular calcification.2,4 As a result of these observations, the US National Kidney Foundation had issued guidelines calling for lower serum phosphorus and calcium targets in dialysis patients, limitation of the dose 1093
post-hemodialysis target blood pressure7 may therefore paradoxically decrease life expectancy rather than prolong it. 1. Agarwal R. Better blood pressure control is not causally linked to intradialytic hypotension. Kidney Int 2008; 73: 1092. 2. Tentori F, Hunt WC, Rohrscheib M et al. Which targets in clinical practice guidelines are associated with improved survival in a large dialysis organization? J Am Soc Nephrol 2007; 18: 2377–2384. 3. McIntyre CW, Burton JO, Selby NM et al. Hemodialysis-induced cardiac dysfunction is associated with an acute reduction in global and segmental myocardial blood flow. Clin J Am Soc Nephrol 2008; 3: 19–26. 4. Shoji T, Tsubakihara Y, Fujii M et al. Hemodialysis-associated hypotension as an independent risk factor for two-year mortality in hemodialysis patients. Kidney Int 2004; 66: 1212–1220. 5. Mitra S. The pathophysiology of fluid removal during hemodialysis: implications for blood volume monitoring and determination of dry weight. MD thesis, University of London, 2007. 6. Davenport A. Intradialytic complications during hemodialysis. Hemodial Int 2006; 10: 162–167. 7. Davenport A, Cox C, Thuraisingham R. Achieving blood pressure targets during dialysis improves control but increases intradialytic hypotension. Kidney Int 2007; 73: 759–764.
A Davenport1 1
Royal Free Hospital, UCL Center for Nephrology, London, UK Correspondence: A Davenport, Royal Free Hospital, UCL Center for Nephrology, Pond Street, London NW3 2QG, UK. E-mail: [email protected]
Lack of mortality benefit with sevelamer
of patient age on the results. A major case is made for a possible benefit on all-cause mortality in subjects aged over 65 years treated with sevelamer. This post hoc analysis will undoubtedly become fodder for pharmaceutical company marketing and quite possibly will be used to justify additional opinion-based recommendations for preferential use of sevelamer in the older dialysis patient population. However, we are quite concerned about incomplete reporting of the results of the DCOR study. The reported dropout rate (49%) is extremely high and unacceptable given the simplicity of the DCOR study design. DCOR is a mortality study that enrolled only Medicare-eligible dialysis patients. Although study subjects may withdraw consent for participation, an intentto-treat analysis of all enrolled subjects is feasible, as there are only three possible outcomes regarding mortality (alive on dialysis, alive after kidney transplant, or dead). Although data are not reported, the authors mention that an intentto-treat analysis of all-cause mortality employing the Centers for Medicare and Medicaid Services (CMS) database also showed no difference in all-cause mortality. Did the postulated age-related difference in mortality persist in this intent-to-treat data set? Full reporting of intent-to-treat data analysis should have been a prerequisite for publication and remains mandatory for any meaningful analysis of DCOR results. 1.
2.
Kidney International (2008) 73, 1093; doi:10.1038/ki.2008.46 3.
To the Editor: Hallelujah! The long anticipated results of the Dialysis Clinical Outcomes Revisited (DCOR) trial are finally published.1 To our surprise, despite triumphant press releases and hyperbolic pronouncements made in industry-sponsored symposia at nephrology meetings 2 years ago, the DCOR study actually found no mortality benefit among hemodialysis patients treated with sevelamer as compared with patients treated with CCPBs (calcium-containing phosphate binders). At once, the NKF-KDOQI/KDIGO opinion-based recommendations regarding the possible advantages of the non-calcium, non-aluminum resin-based phosphate binder, sevelamer become moot. In these guidelines, the postulated rationale for preferential use of non-calcium binders in certain clinical circumstances was based on observational studies showing an association between the use of CCPB and mortality risk or intervention trials employing surrogate end points such as cardiovascular calcification.2,3 These important results from DCOR imply that clinicians can now confidently prescribe effective and substantially less expensive CCPB therapy unburdened by prior expert ‘opinion’ suggesting that CCPBs represent arcane and potentially cardiotoxic therapy. Case closed, right? Well probably not. Although statistically invalid given the negative results for the primary outcomes (all-cause and cardiovascular mortality), the authors conducted a post hoc analysis to study the effect Kidney International (2008) 73, 1092–1096
Suki WN, Zabaneh R, Cangiano JL et al. Effect of sevelamer and calciumbased phosphate binders on mortality in hemodialysis patients. Kidney Int 2007; 72: 1130–1137. Chertow GM, Burke SK, Raggi P, et al., Treat to Goal Working Group. Sevelamer attenuated the progression of coronary and aortic calcification in hemodialysis patients. Kidney Int 2002; 62: 245–252. Block GA, Spiegel DM, Ehrlich J et al. Effect of sevelamer and calcium on coronary calcification in patients new to hemodialysis. Kidney Int 2005; 68: 1815–1824.
CR Nolan1 and DA McCarron2 1 Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA and 2Department of Nutrition, University of California, Davis, California, USA Correspondence: CR Nolan, Organ Transplant Center, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, MC 7882, San Antonio, Texas 78229-3900, USA. E-mail: [email protected]
Response to ‘Lack of mortality benefit with sevelamer’ Kidney International (2008) 73, 1093–1094; doi:10.1038/ki.2008.47
The case against calcium-based binders has been accumulating for years.1 The presence, and extent, of vascular calcifications are strong predictors of cardiovascular and all-cause mortality.2,3 The dose of calcium-based phosphate binders (acetate or carbonate) has been linked to the severity of vascular calcification.2,4 As a result of these observations, the US National Kidney Foundation had issued guidelines calling for lower serum phosphorus and calcium targets in dialysis patients, limitation of the dose 1093