- Email: [email protected]
Target haemoglobin concentrations in chronic kidney disease
Correspondence
stress and impairs endothelial function, both of which could theoretically increase the risk of cardiovascular events in CKD patients.5 The independent contribution of this intervention to cardiovascular events and mortality in such patients warrants further investigation. HK has been on steering committees for the erythropoietin trials with Amgen and has been a consultant to Roche for anaemia in heart failure.
*Arintaya Phrommintikul, Steven Joseph Haas, Maros Elsik, Henry Krum [email protected] NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, Victoria, Australia (AP, SJH, ME, HK); and Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand (AP) 1
2
3
4
5
KDOQI clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease. Am J Kidney Dis 2006; 47 (5 suppl 3): S11–45. Besarab A, Bolton WK, Browne JK, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med 1998; 339: 584–90. Foley RN, Parfrey PS, Morgan J, et al. Effect of hemoglobin levels in hemodialysis patients with asymptomatic cardiomyopathy. Kidney Int 2000; 58: 1325–35. KDOQI clinical practice guidelines and clinical practice recommendations for hemodialysis adequacy: update 2000. Am J Kidney Dis 2001; 37(1 suppl 1): S7–64. Brewster UC. Intravenous iron therapy in end-stage renal disease. Semin Dial 2006; 19: 285–90.
Arintaya Phrommintikul and colleagues1 report that higher haemoglobin concentrations in patients with chronic kidney disease resulting from administration of recombinant human erythropoietin results in a higher risk of death. In the accompanying Comment,2 Giovanni Strippoli and colleagues recommend the cessation of the current clinical trials with erythropoietin that target normal haemoglobin concentrations. We agree with the suggestion of trial cessation put forward by Strippoli and colleagues. The progression of anaemia in patients www.thelancet.com Vol 369 May 5, 2007
with chronic kidney disease is one of the adaptations to reduced renal function. The decrease in the haematocrit causes a proportional increase in plasma, resulting in increased renal plasma flow with no changes in renal blood flow. Therefore, aggressive correction of anaemia would be expected to decrease glomerular filtration rate in predialysis patients. Normalisation of anaemia in predialysis patients will very probably accelerate the decline in renal function. In fact, such early induction of renal replacement therapy has been reported in patients with higher haemoglobin concentrations.3 In patients on dialysis, the blood test is done just before haemodialysis.4 The haemoglobin concentration, however, is increased by the haemoconcentration after haemodialysis. Thus, normalisation of the haemoglobin concentration in patients on haemodialysis could cause a further increase of the haemoglobin concentration after dialysis. Correction of the haemoglobin concentration should be based on postdialysis values, namely dry haemoglobin concentrations. Left ventricular function is different between the before and after haemodialysis conditions. The timing of examinations must be carefully considered. The adequate correction of anaemia should be examined differently in predialysis and postdialysis patients. We declare that we have no conflict of interest.
*Hiroshi Nonoguchi, Yushi Nakayama, Takeaki Inoue, Yukimasa Kohda, Kimio Tomita [email protected]
3
4
Arintaya Phrommintikul and colleagues1 report data from a large meta-analysis on the mortality of anaemic patients with chronic kidney disease treated with erythropoietin,1 which suggests increased overall mortality with higher haemoglobin targets. Major side-effects of erythropoietin treatment include induction or worsening of hypertension and profibrotic effects on the vascular system.2,3 Therefore the negative effects seen in the high haemoglobin group might not result from normalised haemoglobin concentrations, but from a deleterious effect of high-dose erythropoietin per se. Since nearly all studies included in the meta-analysis achieved the higher haemoglobin target concentrations by use of about two-fold higher doses of epoetin alfa or epoetin beta compared with the lower targets, additional analyses to investigate mortality dependent on the administered erythropoietin dose would be very interesting. We declare that we have no conflict of interest.
*Stephan W Reinhold, Bernhard K Krämer, Bernhard Banas [email protected] Klinik und Poliklinik für Innere Medizin II, University of Regensburg, Regensburg, Germany 1
Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto, Kumamoto 860-8556, Japan 1
2
Phrommintikul A, Haas SJ, Elsik M, et al. Mortality and target haemoglobin concentrations in anaemic patients with chronic kidney disease treated with erythropoietin: a meta-analysis. Lancet 2007; 369: 381–88. Strippoli GFM, Tognoni G, Navaneethan SD, Nicolucci A, Craig JC. Haemoglobin targets: we were wrong, time to move on. Lancet 2007; 369: 346–50.
Drueke TB, Locatelli F, Clyne N, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 2006; 355: 2071–84. Besarab A, Bolton K, Browne JK, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med 1998; 339: 584–90.
2
3
Phrommintikul A, Haas SJ, Elsik M, Krum H. Mortality and target haemoglobin concentrations in anemic patients with chronic kidney desease treated with erythropoietin: a meta-analysis. Lancet 2007; 369: 381–88. Lebel M, Rodrigue ME, Agharazii M, Lariviere R. Antihypertensive and renal protective effects of renin-angiotensin system blockade in uremic rats treated with erythropoietin. Am J Hypertens 2006; 19: 1286–92 Raine AE, Roger SD. Effects of erythropoietin on blood pressure. Am J Kidney Dis 1991; 18: 76–83.
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stress and impairs endothelial function, both of which could theoretically increase the risk of cardiovascular events in CKD patients.5 The independent contribution of this intervention to cardiovascular events and mortality in such patients warrants further investigation. HK has been on steering committees for the erythropoietin trials with Amgen and has been a consultant to Roche for anaemia in heart failure.
*Arintaya Phrommintikul, Steven Joseph Haas, Maros Elsik, Henry Krum [email protected] NHMRC Centre of Clinical Research Excellence in Therapeutics, Department of Epidemiology and Preventive Medicine, Monash University, Alfred Hospital, Melbourne, Victoria, Australia (AP, SJH, ME, HK); and Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand (AP) 1
2
3
4
5
KDOQI clinical practice guidelines and clinical practice recommendations for anemia in chronic kidney disease. Am J Kidney Dis 2006; 47 (5 suppl 3): S11–45. Besarab A, Bolton WK, Browne JK, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med 1998; 339: 584–90. Foley RN, Parfrey PS, Morgan J, et al. Effect of hemoglobin levels in hemodialysis patients with asymptomatic cardiomyopathy. Kidney Int 2000; 58: 1325–35. KDOQI clinical practice guidelines and clinical practice recommendations for hemodialysis adequacy: update 2000. Am J Kidney Dis 2001; 37(1 suppl 1): S7–64. Brewster UC. Intravenous iron therapy in end-stage renal disease. Semin Dial 2006; 19: 285–90.
Arintaya Phrommintikul and colleagues1 report that higher haemoglobin concentrations in patients with chronic kidney disease resulting from administration of recombinant human erythropoietin results in a higher risk of death. In the accompanying Comment,2 Giovanni Strippoli and colleagues recommend the cessation of the current clinical trials with erythropoietin that target normal haemoglobin concentrations. We agree with the suggestion of trial cessation put forward by Strippoli and colleagues. The progression of anaemia in patients www.thelancet.com Vol 369 May 5, 2007
with chronic kidney disease is one of the adaptations to reduced renal function. The decrease in the haematocrit causes a proportional increase in plasma, resulting in increased renal plasma flow with no changes in renal blood flow. Therefore, aggressive correction of anaemia would be expected to decrease glomerular filtration rate in predialysis patients. Normalisation of anaemia in predialysis patients will very probably accelerate the decline in renal function. In fact, such early induction of renal replacement therapy has been reported in patients with higher haemoglobin concentrations.3 In patients on dialysis, the blood test is done just before haemodialysis.4 The haemoglobin concentration, however, is increased by the haemoconcentration after haemodialysis. Thus, normalisation of the haemoglobin concentration in patients on haemodialysis could cause a further increase of the haemoglobin concentration after dialysis. Correction of the haemoglobin concentration should be based on postdialysis values, namely dry haemoglobin concentrations. Left ventricular function is different between the before and after haemodialysis conditions. The timing of examinations must be carefully considered. The adequate correction of anaemia should be examined differently in predialysis and postdialysis patients. We declare that we have no conflict of interest.
*Hiroshi Nonoguchi, Yushi Nakayama, Takeaki Inoue, Yukimasa Kohda, Kimio Tomita [email protected]
3
4
Arintaya Phrommintikul and colleagues1 report data from a large meta-analysis on the mortality of anaemic patients with chronic kidney disease treated with erythropoietin,1 which suggests increased overall mortality with higher haemoglobin targets. Major side-effects of erythropoietin treatment include induction or worsening of hypertension and profibrotic effects on the vascular system.2,3 Therefore the negative effects seen in the high haemoglobin group might not result from normalised haemoglobin concentrations, but from a deleterious effect of high-dose erythropoietin per se. Since nearly all studies included in the meta-analysis achieved the higher haemoglobin target concentrations by use of about two-fold higher doses of epoetin alfa or epoetin beta compared with the lower targets, additional analyses to investigate mortality dependent on the administered erythropoietin dose would be very interesting. We declare that we have no conflict of interest.
*Stephan W Reinhold, Bernhard K Krämer, Bernhard Banas [email protected] Klinik und Poliklinik für Innere Medizin II, University of Regensburg, Regensburg, Germany 1
Department of Nephrology, Kumamoto University Graduate School of Medical Sciences, 1-1-1 Honjo, Kumamoto, Kumamoto 860-8556, Japan 1
2
Phrommintikul A, Haas SJ, Elsik M, et al. Mortality and target haemoglobin concentrations in anaemic patients with chronic kidney disease treated with erythropoietin: a meta-analysis. Lancet 2007; 369: 381–88. Strippoli GFM, Tognoni G, Navaneethan SD, Nicolucci A, Craig JC. Haemoglobin targets: we were wrong, time to move on. Lancet 2007; 369: 346–50.
Drueke TB, Locatelli F, Clyne N, et al. Normalization of hemoglobin level in patients with chronic kidney disease and anemia. N Engl J Med 2006; 355: 2071–84. Besarab A, Bolton K, Browne JK, et al. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. N Engl J Med 1998; 339: 584–90.
2
3
Phrommintikul A, Haas SJ, Elsik M, Krum H. Mortality and target haemoglobin concentrations in anemic patients with chronic kidney desease treated with erythropoietin: a meta-analysis. Lancet 2007; 369: 381–88. Lebel M, Rodrigue ME, Agharazii M, Lariviere R. Antihypertensive and renal protective effects of renin-angiotensin system blockade in uremic rats treated with erythropoietin. Am J Hypertens 2006; 19: 1286–92 Raine AE, Roger SD. Effects of erythropoietin on blood pressure. Am J Kidney Dis 1991; 18: 76–83.
1517