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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

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:

13.3 ± 0.9 g/dL 3000 2500 Hb distribution in men: 15.2 ± 0.9 g/dL 2000
13.3 ± 0.9 g/dL
3000
2500
Hb distribution in men: 15.2
± 0.9 g/dL
2000
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
Frequency

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 Males 15 13 11 9 7 0 10 20 30 40 50 Hb (g/dL)
17
Males
15
13
11
9
7
0
10
20
30
40
50
Hb (g/dL)

17

15

13

11

9

7

Females 0 10 20 30 40 50
Females
0
10
20
30
40
50

Creatinine clearance (mL/min/1.73m 2 )

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

Prevalence of Anemia

dependent on GFR

10% 40% 7%
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

for Hemoglobin • KDIGO 2012  CKD D Adult Patients  Hb 9-11.5 (not to exceed

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

Mr. AB; 56yo Male; ESKD x2yrs

Hb 14-15

on ESA 6000 / 4000 / 4000

Impact of Hemoglobin

Above Recommended Range

Impact of Hemoglobin Above Recommended Range • TREAT Trial • 101 patients (5%) developed CVA in

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

Mr. AB; 56yo Male; ESKD x2yrs

Hb 14-15

Not on ESA for 24months

Will he be at ‘Higher Risk’ ?

Will he be at ‘Higher Risk’ ? Hb around 13-14g/dL; mostly cystic kidney disease Goodkin et

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

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

patient’s 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

patient’s 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

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

Gliclazide 80mg BD Simvastatin 20mg ON Cardiprin 100mg OD FeSO4 400mg BD / Vit B / Folic Acid

PTH 256

Started on Cinacalcet

2 month later, PTH 142 and

Hb increased to > 9

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

THANK YOU