Saturday, November 12, 2011

Dialysis Unplugged: Anemia and Humpty Dumpty

Humpty Dumpty sat on a wall, 

Humpty Dumpty had a great fall.

All the King's horses, And all the King's men

Couldn't put Humpty together again!

Why use this nursery rhyme in the context of anemia in dialysis patients? Has Singh finally gone mad? No, not yet. Many senior dialysis docs came up to me at the ASN and told me how confusing the FDA label is. Some comments: “There is no lower level of hemoglobin”. “There is no target range”. “We don’t know whether to hold or reduce the epo dose as the hemoglobin (Hb) level approaches 11 g/dL”.

Epo treatment became so big that we need time to build it up again with some cohesion and logic.

Back to Humpty Dumpty.  The latest information on Humpty Dumpty is that it was a huge cannon that sat on a wall of a castle in the town of Colchester, England around 1648. A shot from a Parliamentary cannon succeeded in damaging the wall beneath Humpty Dumpty, which caused the cannon to tumble to the ground. The Royalists, or Cavaliers, 'all the King's men' attempted to raise Humpty Dumpty on to another part of the wall, but because the cannon was so heavy ' All the King's horses and all the King's men couldn't put Humpty together again.'

It seems that most nephrologists are aiming for a Hb target of 9 to 11 g/dL. What might happen by aiming for a lower target?

I ran into David Goldfarb yesterday on my way to a session at the ASN.  David is a senior nephrologist at NYU. He told me that he examined this issue in a paper that he published this month in Nephron Extra – it’s available open access

Nguyen and colleagues hypothesized that reducing the target Hb would prevent levels >12 g/dl and lead to significant cost savings. Their target Hb range was reduced to 9–11 g/dl from 10–12 g/dl. 35 chronic hemodialysis patients received epo and intravenous iron from January to December 2009. EPO was administered via subcutaneous injection weekly or twice weekly. The mean monthly Hb level changed from 11.2 to 10.6 g/dl. The percentages of patients with mean Hb >10.0, 12.0 and 13.0 g/dl were 82 ± 6.5, 10 ± 5.6 and 1.8 ± 1.9%, respectively. Weekly EPO dose decreased from 9,500 to 5,600 units, a 40% reduction per dose per patient and costs. The savings exceeded USD 60,000 per year for 35 patients. More than 80% of patients had transferrin saturation >20% and ferritin >200 ng/ml throughout the entire period.

Nguyen and Goldfarb concluded: “Lowering the target Hb range to 9–11 g/dl in HD patients treated with EPO achieved quality anemia management with significantly fewer numbers of patients with a dangerous Hb rise >12 g/dl and at the same time resulted in cost savings”.

KDIGO will probably recommend a Hb target range of 9 to 11.5 g/dL. I don’t agree with 11.5 g/dL at the top end of the range. If one is using a target range for anemia management in a dialysis patient you should be guided by the Normal Hematorcrit study in which the lower Hb arm was 9 to 11 g/dL. Patients randomized to this target range had better outcomes than those patient’s randomized to 13 to 15 g/dL.

I suggest that individualization is important; one should establish the Hb trigger for the patient. For most, it will be a Hb of 9 g/dL, but for others it might be a bit higher (or even a little lower). The Hb trigger is the level of Hb at which you feel you have to intervene with either starting epo (or an increase in epo dose), iron, or a blood transfusion.

According to legend, Humpty Dumpty could not be put back together again. With treating anemia, we have to. And, it will result in lower cost and it will probably be safer.