Optimizing the Treatment of

Renal Anemia
Dr Tan Li Ping
MD (Canada), MPH (Malaya), FASN (USA)
Board Certified, Internal Medicine and Nephrology (USA)
Fellowship, Transplant Nephrology (USA)
Consultant Nephrologist
Oriental Melaka Straits Medical Centre
 Agenda
Anemia in ESKD Population
** Part I
o Anemia and relation to Kidney Function
o Target Range for Hemoglobin in ESKD
o Risk when Hemoglobin range is exceeded
o Naturally occurring High Hemoglobin

** Part II
o Reasons for not reaching Hemoglobin target
KIDNEY FUNCTION AND ANEMIA
 Normal Range of Hemoglobin
Hb distribution in women:
3000 13.3 0.9 g/dL

Hb distribution in men: 15.2

2500 0.9 g/dL

2000
Frequency

1500

1000

500

0
10 10.5 11 11.5 12 12.5 13 13.5 14 14.5 15 15.5 16 16.5 17 17.5 18
Hb level (g/dL)
N=40,000 (NHANES III, 1988-1994)
Dallman et al. Iron Nutrition in health and disease. John Libbey & Co, London, 1996
 Hemoglobin Levels Correlate
with Renal Function

17 17
Males Females
15 15

13 13

11 11
Hb (g/dL)

9 9

7 7
0 10 20 30 40 50 0 10 20 30 40 50

Creatinine clearance (mL/min/1.73m2)

Jungers et al. Nephrol Dial Transplant 2002;17:1621-7

 Prevalence of Anemia
dependent on GFR

10%
40%

7%

Hyperparathyroidism = >60pg/mL; Anemia = < 110 g/L, Acidosis = <

22mmol/L, Hyperkalemia = > 5mmol/L, Hyperphosphatemia = > 1.38mmol/L
Moranne et al. J Am Soc Nephrol 2009
 Target Range for Hemoglobin
KDIGO 2012

CKD D Adult Patients

Hb 9-11.5 (not to exceed 13)
Check Hb monthly, esp. if on ESA

Kidney Disease: Improving Global Outcomes (KDIGO) Anemia Work Group. KDIGO Clinical Practice
Guideline for Anemia in Chronic Kidney Disease. Kidney inter., Suppl. 2012; 2: 279335.
Mr. AB; 56yo Male; ESKD x2yrs

Hb 14-15

on ESA 6000 / 4000 / 4000

 Impact of Hemoglobin
Above Recommended Range

TREAT Trial
101 patients (5%) developed CVA in the darbapoeitin arm as compared to 53
patients (2.6%) in the placebo arm
There were also more venous thromboembolic events in the darbapoeitin group
(2% vs 1.1%, p=0.02) amd more arterial thromboembolic events (8.9% vs 7.1%,
p=0.04)
Do All ESKD Patients have Anemia?
91% of ESKD patient (total number 28,898 in
2013) reported via the NRR are on ESA (2013
MDTR)

A small number of ESKD patients do not have

Anemia and are ESA independent
0.84% (1) to as high as 16% (2)
(1) Int Urol Nephrol. 2014 Aug;46(8):1651-4 Epub 2013 Oct 11.
Prevalence and related factors of the absence of anemia among Chinese chronic hemodialysis patients: a multicenter cross-sectional
study. Wan et al
(2) Blood Purif. 2011;32(1):69-74. Epub 2011 Feb 24.
Factors related to the absence of anemia in hemodialysis patients. Verdalles et al
Mr. AB; 56yo Male; ESKD x2yrs

Hb 14-15

Not on ESA for 24months

Will he be at Higher Risk ?

Hb around 13-14g/dL; mostly cystic kidney disease

Goodkin et al. J Am Soc Nephrol 2011; Feb 22(2)

 Agenda
Anemia in ESKD Population
** Part I
o Anemia and relation to Kidney Function
o Target Range for Hemoglobin in ESKD
o Risk when Hemoglobin range is exceeded
o Naturally occurring High Hemoglobin

** Part II
o Reasons for not reaching Hemoglobin target
WHAT ARE THE COMMON REASONS
FOR HEMOGLOBIN NOT TO BE IN THE
REQUIRED RANGE?
 Case Example
58yo M ESKD Patient; HD x 3 / week for 3 months via L
AVF. DM2 / HTN

HD stable; dry weight 80kg

HB persistently around 8-9

Iron studies on initiation: Fe Sat 28%, Ferritin 510

Recormon dose 2000units sc x2 /week

On monthly maintenance Venofer 100mg / month
 Suboptimal ESA Dosing
Starting ESA:
SC vs IV administration

Which Agent:
Epoetin alfa OR beta: 50-100IU/kg x3/week
Darbopoeitin alfa: 0.45ug/Kg x1/week
PEG epoetin beta: 0.6mcg/kg every 2 weeks (maintain
1x/month)

Target rise of Hb 1-2g/dL per month

 Case Example
39yo F ESKD Patient; HD x3/wk via tunneled catheter.

Labs indicate: Hb 9.8 (Jan) -> 8.9 (Feb) -> 7.8 (March)

Iron studies reveal Fe Sat 18%, Iron 4.5, Ferritin 80

What are the important things to do to optimize this

patients Hb?
 Iron Deficiency-Absolute
Causes:
Blood loss
GI Bleed
Bleed from other sources (e.g. heavy menses)
Dialyzer clotting
Bleeding during dialysis
 Case Example
39yo F ESKD Patient; HD x3/wk via tunneled catheter.

Labs indicate: Hb 9.8 (Jan) -> 8.9 (Feb) -> 8.8 (March)

Iron studies reveal Fe Sat 22%, Iron 8.9, Ferritin 480

What are the important things to do to optimize this

patients Hb?
 Iron Deficiency-Functional
KDIGO (2012) Guidelines
Oral iron has limited efficacy once patients have
reached dialysis stages (thus generally I/V iron used)

To achieve maximal ESA impact, Iron levels should be:

Transferrin Saturation (TSAT)
> 30%
Serum Ferritin
Dialysis CKD > 500ng/mL
 Case Example
42yo F ESKD, DM2/HTN. Patient; HD x3/wk via L AVF.

Labs indicate: Hb 9.8 (Jan) -> 9.5 (Feb) -> 9.3 (March)

Iron studies reveal Fe Sat 22%, Iron 8.9, Ferritin 480

Current Meds
EPO 2000u sc x3/wk
CaCO3 500mg TDS
Rocaltrol 0.25mcg EOD
Amlodipine 10mg OD
Gliclazide 80mg BD
Simvastatin 20mg ON
Cardiprin 100mg OD
 Details on Iron Administration
Oral iron
Fe sulphate 200mg 300mg tds (20% elemental iron)
Fe fumarate 200mg-400mg bd (33% elemental iron)
Recommended: 100mg elemental iron daily

Intravenous iron (Venofer [Iron Sucrose] /

Cosmofer [Iron Dextran]
1 course of Iron therapy is 1000mg
For Venofer, at 20mg/ml (max 200mg / dose)
For Cosmofer, at 50mg/ml (max 500mg/dose)
 Other Causes of Anemia
Inadequate Production of RBC
B12
Folate
Thalassemia
PRCA

Destruction of RBC
Hemolysis
 Case Example
56yo M ESKD, HTN; HD x3/wk via L AVF. 70kg dry weight.

Labs indicate: Hb 8.8 (Jan) -> 8.4(Feb) -> 8.8 (March)

Iron studies reveal Fe Sat 32%, Iron 14 Ferritin 880

Current Meds
EPO 6000/4000/4000u sc x3/wk (increasing trend)
CaCO3 500mg TDS
Rocaltrol 0.25mcg OD
Amlodipine 10mg OD
Gliclazide 80mg BD
Simvastatin 20mg ON
Cardiprin 100mg OD
FeSO4 400mg BD / Vit B / Folic Acid
ESA Resistance
 Case Example
56yo M ESKD, HTN; HD x3/wk via L AVF. 70kg dry weight.

Labs indicate: Hb 8.8 (Jan) -> 8.4(Feb) -> 8.8 (March)

Iron studies reveal Fe Sat 32%, Iron 14 Ferritin 880

Current Meds
EPO 6000/4000/4000u sc x3/wk (increasing trend)
CaCO3 500mg TDS
Rocaltrol 0.25mcg OD
Amlodipine 10mg OD PTH 256
Gliclazide 80mg BD Started on Cinacalcet
Simvastatin 20mg ON 2 month later, PTH 142 and
Cardiprin 100mg OD Hb increased to > 9
FeSO4 400mg BD / Vit B / Folic Acid
 Agenda
Anemia in ESKD Population
** Part I
o Anemia and relation to Kidney Function
o Target Range for Hemoglobin in ESKD
o Risk when Hemoglobin range is exceeded
o Naturally occurring High Hemoglobin

** Part II
o Reasons for not reaching Hemoglobin target
THANK YOU