1. How to manage anaemia in HD patients
The Clinical Guide “A Guide to Implementing Renal Best Practice in Haemodialysis“
Chapter 7:
How to manage anaemia in HD patients
Compiled by Elizabeth Lindley with help from Lesley Bennett, Karen Jenkins, Digby Lund and Es Will

2. What does the chapter include?
Five sections
22 practice suggestions (bullet points)
Tables of characteristics for ESAs and IV irons
Two basic flow charts that can be adapted for local use
26 references, most with web link for free download

3. Section 7.1: Causes of anaemia in HD patients
Section 7.1 covers:
Erythropoetin (EPO) deficiency
Assessment for absolute and functional iron deficiency
Other causes of anaemia
Did you know that one ferritin molecule can store ~ 4500 iron atoms

4. Section 7.2: Treatment of renal anaemia
Section 7.2 covers:
Erythropoiesis stimulating agents’ (ESAs)
Intravenous and oral iron preparations
How the available products differ
They all work, so your unit should select an ESA and IV iron preparation based on cost, impact on workload and experience (local and published)

5. ESA’s for IV administration during haemodialysis
Information obtained from the SPC or manufacturer’s website in March 2013.

6. IV iron for maintenance and correction of deficiency in HD patients over several weeks
Information obtained from the SPC or manufacturer’s website in March 2013.

7. IV iron for maintenance and correction of deficiency in HD patients in one or two sessions
Information obtained from the SPC or manufacturer’s website in March 2013.

8. Section 7.3: Desired ranges for Hb and iron markers
Maintenance of Hb in the desired range is the ‘real’ outcome measure for anaemia management in an individual patient.
The ranges specified for iron markers are used to guide iron supplementation, but only when intervention is required to achieve or maintain an Hb in the desired range with minimal use of ESAs.
Anaemia management programmes are usually based on a protocol (algorithm) for starting and adjusting ESA and iron doses according to a set of rules (section 7.4).
The rules are usually based on six essential and two optional parameters which can be drawn from published guidance, national or local regulations and/or experience.

9. Your unit should decide on.....
a standard desired range for Hb, i.e. lowerHb to upperHb, and a policy covering how to adjust the range in individual cases.
a limit for ferritin, i.e. lowFer, below which therapy for absolute iron deficiency may be initiated.
a definition of functional iron deficiency, ‘functDef’, based on your unit’s standard test.
an upper limit for ferritin, i.e. highFer, above which iron therapy is normally withdrawn.
an upper limit for ESA dose, i.e. maxESA, above which above which a clinical review should be initiated.

10. Your unit may also decide on.....
a haemoglobin action level, actionHb, between lowerHb and upperHb, at which treatment for iron deficiency is initiated in patients not on an ESA.
an ESA action level, actionESA, below maxESA, above which treatment for iron deficiency is initiated in patients whose haemoglobin is in the desired range.

11. Changes in the recommended desired range for Hb
Beserab’s Normal vs Low Haematocrit Study
CREATE, CHOIR and TREAT confirmed higher mortality in patients randomised to treatment with ESA to a higher Hb (but these studies were not carried out in young active patients)

12. Legislation on target range
For patients not on dialysis
Consider starting ESA when Hb < 10 g/dl
Reduce or stop ESA when Hb > 10 g/dl
For patients on dialysis
Start ESA when Hb < 10 g/dl
Reduce or stop ESA when Hb approaches or exceeds 11 g/dl
Desired range 10 to 11 g/dL is low and narrow

13. Darren Cawley (patient advisor to the IQD work group)
“Would you want to run a marathon with a haemoglobin of 10.5?”

14. The KDIGO guidelines support individualisation of therapy in patients who may have improvements in quality of life with a higher desired range for Hb and who are prepared to accept the risks.

15. Respect the physiology!
Haemoglobin levels in most HD patients vary from day-to-day.
A narrow desired range can lead to dose changes based on normal fluctuations.
It takes about 3 months for the rate of production and loss of red blood cells to achieve a steady state after a change in ESA dose.
Repeated increases or decreases before steady state is achieved can lead to Hb cycling – especially if the desired range is narrow.

16. Section 7.4: Implementing an anaemia management programme
Section 7.4 covers:
Monitoring frequency for Hb, ferritin and measures of functional iron deficiency
When to provide maintenance iron therapy
When to treat functional iron deficiency
When to start ESA therapy
When to adjust ESA therapy
When to review for resistance to ESA therapy
Monthly is usually best
Not until the effective of the last dose change can be measured or estimated

17. Manufacturer’s instructions
NeoRecormon
At best, a waste of blood, at worst over-correction of Hb
Aranesp SPC
Mircera SPC

18. Manufacturer’s instructions
Could all lead to over- correction of Hb
NeoRecormon
Aranesp SPC
Mircera SPC

19. IV iron and ESA therapy for patients not already on ESA
Iron correction = treatment for deficiency (rather than maintenance)

20. IV iron and ESA treatment for patients who are on an ESA

21. Example: desired Hb range = 10 to 12 g/dL, lowFer = 200 ug/L, highFer = 500 ug/L functDef = Yes if RCH > 5% actionESA = 0 so iron deficiency is treated whenever Hb ≤ 12 g/dL X

22. Customised flow chart for patients who are on an ESA
Iron deficiency treated unless Hb > 12 g/dL

23. Section 7.5: Suggestions for audit
7.5.1 Audits of the proportion of patients in the (individualised) desired range for Hb, the ESA and iron doses and the number of dose changes per patient-month can be used to monitor the effectiveness of your anaemia management programme.
Ideally, audit before and after (e.g. at 3 to 6 month intervals after) introducing or changing a protocol or product

24. Conversion to predictive protocol
Proportion of patients with Hb > 12.5 g/dl
Conversion to predictive protocol
The proportion of patients with Hb above 12.5 g/dl decreased from 29% to 15%
The proportion of patients with Hb above 12.5 g/dl almost halved, going from 29 to 15%.
>14 g/dl
* Compared to Q4-2008, Fisher’s exact test

25. Conversion to predictive protocol
Patients prescribed a change in ESA/month
Conversion to predictive protocol
Rate of dose changes dropped from 1 per 2.5 patient-months to 1 per 6.1 patient-months
The most striking result of the audit was the decrease in frequency of dose changes. Dose changes dropped immediately from an average of 1 every 2.5 months to 1 every 3.9 months. It has stabilised at an average of one change every 6 months.
* Compared to Q4-2008, Fisher’s exact test