Author Interview: Dr. David Goodkin
Naturally Occurring Higher Hemoglobin Concentration Does Not Increase Mortality among Hemodialysis Patients
J Am Soc Nephrol 22: 2011.
David A. Goodkin,* Douglas S. Fuller,* Bruce M. Robinson,* Christian Combe,Richard Fluck, David Mendelssohn, Tadao Akizawa, Ronald L. Pisoni,* and Friedrich K. Port*
*Arbor Research Collaborative for Health, Ann Arbor, Michigan; Centre Hospitalier Universitaire de Bordeaux, University of Bordeaux, Bordeaux, France; Royal Derby Hospital, Derby, United Kingdom; University of Toronto, Weston, Ontario, Canada; and Showa University School of Medicine, Tokyo, Japan
Because uncertainty exists regarding the effects of higher hemoglobin concentration on mortality and quality of life among hemodialysis patients, studying this group of patients with sufficient endogenous erythropoietin may provide additional insights. The prospective, observational Dialysis Outcomes and Practice Patterns Study provides an opportunity to investigate this group.
Among 29,796 patients in 12 nations, 545 (1.8%) maintained hemoglobin concentrations >12 g/dl
for 4 months without erythropoietic support. This subset tended to be male, to have a longer duration
of end-stage renal disease, and to not dialyze via a catheter.
Cystic disease as the underlying cause of
renal failure was over-represented in this group but was present in only 25%. Lung disease, smoking, and
cardiovascular disease were associated with increased likelihood of naturally higher hemoglobin con- centration.
Quality-of-life scores were not higher among this subset compared with the other patients.
Unadjusted mortality risk for patients with hemoglobin >12 g/dl and no erythropoietic therapy was
lower than for the other patients, but after thorough adjustment for case mix, there was no difference
between groups (relative risk, 0.98; 95% CI 0.80 to 1.19).
These data show that naturally occurring
hemoglobin concentration >?12 g/dl does not associate with increased mortality among hemodialysis patients.
J Am Soc Nephrol 22: 2011.
What are the main findings of the study?
At entry into the Dialysis Outcomes and Practice Patterns Study (DOPPS), 483 out of 21,185 (2.3%) international hemodialysis patients maintained hemoglobin concentrations > 12 g/dL for 4 months without receiving ESA treatment.
Unadjusted mortality risk for these “Endogenous EPO” patients was lower than for the other patients, but after thorough adjustment for case mix, the relative risk was 0.98 (95% confidence interval 0.80 to 1.19) – ie, there was no significant difference between groups.
Quality-of-life scores among the Endogenous EPO group were not significantly higher than among the other patients.
The Endogenous EPO subset tended to be male, to have been on hemodialysis for more years, and to not dialyze with a catheter for hemoaccess. Polycystic kidney disease was the cause of ESRD among 25% of the Endogenous EPO patients, versus 5% of the other patients.
There was also an increased likelihood of being in the Endogenous EPO group for patients with conditions associated with hypoxemia (cardiovascular disease, pulmonary disease, smoking).
Were any of the findings unexpected?
Randomized, controlled studies of anemia correction with ESA in CKD patients have raised concerns regarding mortality and thrombotic complications when hemoglobin ranges above 12 g/dL have been targeted. Paradoxically, such studies have also suggested that the subsets of patients who actually attained higher hemoglobin concentrations survived longer. Hence, uncertainty exists regarding the effects of higher hemoglobin on dialysis patients.
If one expected that patients at higher hemoglobin levels would survive longer, as suggested by prior observational studies and post-hoc analyses of ESA interventional trials, then the present results showing no significant difference versus other patients was unexpected.
On the other hand, if one expected that higher hemoglobin levels would be associated with increased mortality based on the primary outcomes of the normal-hemoglobin CKD trials that found undesirable outcomes among patients assigned to higher-hemoglobin targets, then the present results showing no significant difference versus other patients was, again, unexpected.
The lack of quality-of-life score superiority among the Endogenous EPO group may have been surprising, although previous studies have not demonstrated unequivocal benefits in association with normalization of hemoglobin.
What should clinicians and patients take away from this study?
About 2% of hemodialysis patients maintain hemoglobin concentrations > 12 g/dL without ESA prescription.
Naturally-occurring higher hemoglobin concentration does not increase mortality among hemodialysis patients.
It is essentially to adjust thoroughly for case mix and other potentially confounding factors when studying associations between hemoglobin, ESA therapy, and mortality among hemodialysis patients.
Naturally-occurring higher hemoglobin concentration is not associated with improved quality-of-life scores.
The optimal hemoglobin target range and pharmacologic management strategy for dialysis patients has not been established and will require further study.
What recommendations do you have for nephrology health care providers as a result of your study?
These results indicate that What recommendations do you have for nephrology health care providers as a result of your study
These results indicate that there is no need to phlebotomize hemodialysis patients with naturally occurring hemoglobin concentrations in excess of 12 g/dL.
It is expected that 2% of prevalent hemodialysis patients will maintain hemoglobin concentration > 12 g/dL. Facilities should not be penalized for such patients when assessing anemia-management outcomes to a target range of 10 to 12 g/dL.