Creation/Revision Date: March 25, 2010
I am Alan Kliger, here for the Renal Physicians Association, the professional organization representing over 3,000 practicing nephrologists in the US. Since FDA approval in 1989, nephrologists have used ESAs to treat anemia in dialysis patients and in pre-dialysis patients with chronic kidney disease. While appropriate use of ESAs and iron have reduced substantially the numbers of patients with profound anemia, recent studies we’ve heard described this morning have raised substantial concern about the safety of ESAs when they are used to raise Hb concentrations to the normal or near normal range of Hb > 12 Gm/dL.
We asked a committee of experts in the treatment of anemia in CKD and dialysis to review the literature and to help give our members guidance in the safe and effective use of these agents
Concerning survival and cardiovascular risk:
We agree that the evidence is strong at high levels of Hb: targeting Hb at 13 Gm/dL and achieving Hb over 12 by use of ESAs for both dialysis and pre-dialysis CKD patients increases risk of death and cardiovascular complications like stroke. Furthermore, there is reasonably strong evidence that high ESA dose in patients with resistance to ESAs is a risk for these same complications.
The evidence is less clear at lower levels of Hb. In a study published this month in JAMA by Brookhart and colleagues, USRDS data were analyzed by examining ESA prescription patterns in dialysis facilities. Since patients do not select dialysis facilities according to their ESA prescribing patterns, the authors called this a “natural experiment,” subject to less confounding than other retrospective studies, and more similar to most of the major trials of ESAs. They found that when patients had Hct < 30%, centers using higher doses of ESAs and those using more frequent doses of Fe had lower mortality. Since a prospective trial of ESAs for patients with significant anemia will probably never be done, this study gives us reasonably strong evidence that ESA use and Fe use are associated with improved survival when Hb < 10.
Concerning patient-perceived QoL and Exercise Tolerance:
Two studies published this month in AJKD deserve attention. Gandra and colleagues performed a systematic literature review of prospective studies examining the impact of ESAs on energy and physical function in non-dialysis CKD patients. These 2 measures of QoL, rather than the less-specific general QoL tools, may be of more focused importance for CKD patients. They found in patients with Hb 8.8-11.9, ESA use correlated with higher energy or less fatigue, and with better physical function. In the second study, Johansen and co-authors did a systematic review and meta-analysis of exercise tolerance and physical functioning in dialysis patients treated with ESA. They also found a correlation between ESA treatment, higher Hb levels, and exercise capacity and physical functioning.
The evidence is excellent that ESA use in patients with Hb < 10 reduces transfusion requirements. This may be particularly important for patients awaiting kidney transplantation
We believe the evidence is reasonably strong that treating anemia in non-dialysis CKD patients and hemodialysis patients when Hb<10 improves survival, patient-perceived quality of life and exercise tolerance. We also believe that hemodialysis patients are different than non-dialysis CKD, and that it is prudent to follow the KDOQI guidelines to target Hb at 10 – 12 Gm/dL in those patients. It is important to remember that evidence-based medicine is designed for use at the individual patient level. As CMS examines the strength of the evidence and considers its coverage policies, we trust the agency will preserve the ability of doctors and patients together to consider risks and benefits, the particulars of each patient’s conditions and each patient’s preferences, and make decisions about ESA or other therapies one at a time at the bedside.
On behalf of the Renal Physicians Association, I thank you for this opportunity to speak today.