Hitting the Target But Missing the Goal? Hemoglobin Targets Versus Oxygen Delivery
2007; Elsevier BV; Volume: 50; Issue: 2 Linguagem: Inglês
10.1053/j.ajkd.2007.04.028
ISSN1523-6838
Autores Tópico(s)Neurological and metabolic disorders
ResumoI congratulate Dr Ritz for his work concerning higher hemoglobin (Hb) targets to reduce left ventricular hypertrophy1Ritz E. Laville M. Bilous R.W. et al.Anemia Correction in Diabetes Study Investigators Target level for hemoglobin correction in patients with diabetes and CKD: primary results of the Anemia Correction in Diabetes (ACORD) Study.Am J Kidney Dis. 2007; 49: 194-207Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar; however, even as his study reached publication, another meta-analysis concluded that higher Hb concentrations are associated with increased mortality.2Phrommintikul A. Haas S.J. Elsik M. Krum H. Mortality and target haemoglobin concentrations in anaemic patients with chronic kidney disease treated with erythropoietin: a meta-analysis.Lancet. 2007; 369: 381-388Abstract Full Text Full Text PDF PubMed Scopus (534) Google Scholar Perhaps the targeting of Hb levels might be the wrong approach. What we really should care about is oxygen delivery. Hb is merely a vehicle to achieve that delivery and the amount of vehicle necessary may change depending upon the clinical situation. It is usually tissue hypoxia that regulates Hb concentrations in normal subjects, but with exogenous administration of recombinant erythropoietin, that regulation is lost. For many years we have known that acidosis (Bohr effect) and hyperphosphatemia3Chanutin A. Hermann E. The interaction of organic and inorganic phosphates with hemoglobin.Arch Biochem Biophys. 1969; 131: 180-184Crossref PubMed Scopus (71) Google Scholar shift the oxygen-Hb dissociation curve to allow more oxygen delivery, yet we make no accommodation for these factors despite the fact that they are abnormal in the dialysis population. We recently found that acidosis and hyperphosphatemia independent of parathyroid hormone concentrations were the principal factors associated with erythropoietin resistance in our population.4Diskin C.J. Stokes T.J. Dansby L.M. Radcliff L. Carter T.B. Can acidosis and hyperphosphataemia result in increased erythropoietin dosing in haemodialysis patients?.Nephrology (Carlton). 2006; 11: 394-399Crossref PubMed Scopus (33) Google Scholar One possible explanation is that the increased oxygen delivery may be associated with down-regulation of erythropoietin receptors, since down-regulation of erythropoietin production is not possible. Perhaps it is time for a new paradigm. Perhaps we should look to create a new equation that accounts not only for the Hb concentration but also for the Hb P50 and all of the variables that affect oxygen delivery. While our present knowledge may be inadequate to account for all such variables, it may be time to shift our focus of research away from Hb levels to a more complex understanding of how Hb levels and other factors affect oxygen delivery in different situations.Letters to the Editor may be in response to an article that appeared in AJKD no more than 6 months previously, or may concern a topic of interest to current nephrology. The body of the letter should be as concise possible and in general should not exceed 250 words. Up to 10 references and 1 figure or table may be included. There is no guarantee that letters will be published. Letters are subject to editing and abridgment without notice.Letters should be submitted via AJKD’s online manuscript handling site, www.editorialmanager.com/ajkd. More information, including details about how to contact the editorial staff for assistance, is available in the journal’s Information for Authors. I congratulate Dr Ritz for his work concerning higher hemoglobin (Hb) targets to reduce left ventricular hypertrophy1Ritz E. Laville M. Bilous R.W. et al.Anemia Correction in Diabetes Study Investigators Target level for hemoglobin correction in patients with diabetes and CKD: primary results of the Anemia Correction in Diabetes (ACORD) Study.Am J Kidney Dis. 2007; 49: 194-207Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar; however, even as his study reached publication, another meta-analysis concluded that higher Hb concentrations are associated with increased mortality.2Phrommintikul A. Haas S.J. Elsik M. Krum H. Mortality and target haemoglobin concentrations in anaemic patients with chronic kidney disease treated with erythropoietin: a meta-analysis.Lancet. 2007; 369: 381-388Abstract Full Text Full Text PDF PubMed Scopus (534) Google Scholar Perhaps the targeting of Hb levels might be the wrong approach. What we really should care about is oxygen delivery. Hb is merely a vehicle to achieve that delivery and the amount of vehicle necessary may change depending upon the clinical situation. It is usually tissue hypoxia that regulates Hb concentrations in normal subjects, but with exogenous administration of recombinant erythropoietin, that regulation is lost. For many years we have known that acidosis (Bohr effect) and hyperphosphatemia3Chanutin A. Hermann E. The interaction of organic and inorganic phosphates with hemoglobin.Arch Biochem Biophys. 1969; 131: 180-184Crossref PubMed Scopus (71) Google Scholar shift the oxygen-Hb dissociation curve to allow more oxygen delivery, yet we make no accommodation for these factors despite the fact that they are abnormal in the dialysis population. We recently found that acidosis and hyperphosphatemia independent of parathyroid hormone concentrations were the principal factors associated with erythropoietin resistance in our population.4Diskin C.J. Stokes T.J. Dansby L.M. Radcliff L. Carter T.B. Can acidosis and hyperphosphataemia result in increased erythropoietin dosing in haemodialysis patients?.Nephrology (Carlton). 2006; 11: 394-399Crossref PubMed Scopus (33) Google Scholar One possible explanation is that the increased oxygen delivery may be associated with down-regulation of erythropoietin receptors, since down-regulation of erythropoietin production is not possible. Perhaps it is time for a new paradigm. Perhaps we should look to create a new equation that accounts not only for the Hb concentration but also for the Hb P50 and all of the variables that affect oxygen delivery. While our present knowledge may be inadequate to account for all such variables, it may be time to shift our focus of research away from Hb levels to a more complex understanding of how Hb levels and other factors affect oxygen delivery in different situations. Letters to the Editor may be in response to an article that appeared in AJKD no more than 6 months previously, or may concern a topic of interest to current nephrology. The body of the letter should be as concise possible and in general should not exceed 250 words. Up to 10 references and 1 figure or table may be included. There is no guarantee that letters will be published. Letters are subject to editing and abridgment without notice.Letters should be submitted via AJKD’s online manuscript handling site, www.editorialmanager.com/ajkd. More information, including details about how to contact the editorial staff for assistance, is available in the journal’s Information for Authors. Letters to the Editor may be in response to an article that appeared in AJKD no more than 6 months previously, or may concern a topic of interest to current nephrology. The body of the letter should be as concise possible and in general should not exceed 250 words. Up to 10 references and 1 figure or table may be included. There is no guarantee that letters will be published. Letters are subject to editing and abridgment without notice.Letters should be submitted via AJKD’s online manuscript handling site, www.editorialmanager.com/ajkd. More information, including details about how to contact the editorial staff for assistance, is available in the journal’s Information for Authors. Letters to the Editor may be in response to an article that appeared in AJKD no more than 6 months previously, or may concern a topic of interest to current nephrology. The body of the letter should be as concise possible and in general should not exceed 250 words. Up to 10 references and 1 figure or table may be included. There is no guarantee that letters will be published. Letters are subject to editing and abridgment without notice. Letters should be submitted via AJKD’s online manuscript handling site, www.editorialmanager.com/ajkd. More information, including details about how to contact the editorial staff for assistance, is available in the journal’s Information for Authors. Target Level for Hemoglobin Correction in Patients With Diabetes and CKD: Primary Results of the Anemia Correction in Diabetes (ACORD) StudyAmerican Journal of Kidney DiseasesVol. 49Issue 2PreviewPatients with diabetes and anemia are at high risk of cardiovascular disease. The Anemia CORrection in Diabetes (ACORD) Study aimed to investigate the effect of anemia correction on cardiac structure, function, and outcomes in patients with diabetes with anemia and early diabetic nephropathy. Full-Text PDF In ReplyAmerican Journal of Kidney DiseasesVol. 50Issue 2PreviewWe acknowledge the comments by Dr Diskin with respect to the complexity and confounding factors involved into the regulation of oxygen delivery such as acidosis, hyperphosphatemia, and maybe also the expression of erythropoietin receptors. Without any doubt, more preclinical and clinical research is needed here. It should, however, not be forgotten that the primary objective of the Anemia Correction in Diabetes (ACORD) study was to answer a clinical question raised by previously reported observational data, namely, whether higher Hb targets (Hb normalization) cause further reduction in left ventricular mass index as compared to the currently recommended lower Hb targets (partial Hb correction). Full-Text PDF
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