Anemia in CKD

Hussein Sheashaa, MD, FACPProfessor of Nephrology, Urology and Nephrology Center and Director of

Medical E-Learning Unit, Mansoura University and Executive Director of ESNT-Virtual Academy: http://lms.mans.edu.eg/esnt/

Mansoura UNC, Feb 20th, 2017

1. Introduction

2. Iron

3. ESA

4. Adjuvants

5. ESA resistance

6. HIF Stabilizers

7. Special Issues

Corners

NCGC, AMCKD update, June 2015

Definition of Anemia

Impact of Anemia:2602 Japanese Patients

Clin Exp Nephrol (2016) 20:595–602

Quality-of-life Sexual function

Exercise capacity Endocrine function

cardiac output Immune function

Angina Muscle metabolism

LVH Hospitalizations

Bleeding tendency Transfusions

Brain / cognitive function Nutrition

Depression

Sleep patterns

Anemia Control:Benefits

Kidney International Supplements (2012), 299–310

CKD Associated Anemia:Potential Factors

ESA Deficiency

1. Introduction

2. Iron

3. ESA

4. Adjuvants

5. ESA resistance

6. HIF Stabilizers

7. Special Issues

Corners

NCGC, AMCKD update, June 2015

Diagnosis of Anemia:Iron Status

Am J Kidney Dis. 2016 March 2016 ;67(3):367-75.

Iron Therapy: Evolution

750 mg (IV)

NCGC, AMCKD update, June 2015

Oral Iron Preparations:Iron Contents

Parenteral Iron:

Doses

Am J Kidney Dis.November 2016;68(5):677-690

Iron Therapy:IV Versus Oral

Nephrol Dial Transplant (November 2016) 31: 1835–1845

IV Iron Therapy:Effects on Monocytes

Iron sucrose and sodium ferric gluconateFerric carboxymaltose and iron isomaltoside

IV Iron Therapy:Effects on Renal Function

BMC Nephrology (2017) 18:24

Phosphorus and Anemia

RCT 411 (FC: Active control), 52 W

Saving 2101 USD/P/Y

Nephrol Dial Transplant (December 2015) 30: 2019–2026

CRUISEContinuous Replacement Using Iron Soluble

Equivalents: Phase 3, RCT, n 599, 48 w

1. Introduction

2. Iron

3. ESA

4. Adjuvants

5. ESA resistance

6. HIF Stabilizers

7. Special Issues

Corners

Current ESAs

Am J Nephrol 2017;45:235–247 Published online: February 1, 2017

New Strategies:Stimulate Erythropoiesis

Am J Kidney Dis. 2016 Jan;67(1):133-42.

Refrigeration

Room Temperature Shelf Life

0

5

7

31

0 5 10 15 20 25 30 35

Darbepoetin alfa

Epoetin beta

Epoetin alfa

Days

C.E.R.A.

ESA Initiation

Conversion Among ESA

Short Acting ESA Therapy:Frequency

Cochrane Database of Systematic Reviews 2017, Issue 1. Art. No.: CD011690

The Cochrane Library 2014, Issue 12

Which ESA Therapy?

56 Studies, 15.596 Patients

The Cochrane Library 2014, Issue 12

Which ESA Therapy?

KDIGO 2012: ESA Strategy

VOLUME 2 | ISSUE 4 | AUGUST 2 2012

http://www.kidney-international.org

OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF NEPHROLOGY

KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease

KI_SuppCover_2.4.indd 1 7/11/12 12:00 PM

Transfusion and Apheresis Science 50 (2014) 16–19

ESA Therapy: Suggested Contraindications

Worsening of HTN

Seizure

Increased blood clotting

Slight decrease of Kt/ V

Impaired phosphorus balance

Hyperkalemia

Pure Red cell aplasia (PRCA)

Adverse Effects of ESA Therapy

ESA Route:Outcome

1. Introduction

2. Iron

3. ESA

4. Adjuvants

5. ESA resistance

6. HIF Stabilizers

7. Special Issues

Corners

Kidney International Supplements (2012), 299–310VOLUME 2 | ISSUE 4 | AUGUST 2 2012

http://www.kidney-international.org

OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF NEPHROLOGY

KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease

KI_SuppCover_2.4.indd 1 7/11/12 12:00 PM

KDIGO 2012: Adjuvant Therapy

1. Introduction

2. Iron

3. ESA

4. Adjuvants

5. ESA resistance

6. HIF Stabilizers

7. Special Issues

Corners

Am J Kidney Dis. November 2016;68(5):763-771

ESA Hyporesponsiveness

ESA Hypo-responsiveness:Effect of Hepcidin

Am J Nephrol 2017;45:187–199

Nephrol Dial Transplant (2015) 30: 682–689

ESA Hypo-responsiveness:Effect of Dialyzer Type

Seminars in Dialysis—Vol 28, No 5 (September–October) 2015 pp. 530–532

ESA Hypo-responsiveness:Effect of Graft Failure

1. Introduction

2. Iron

3. ESA

4. Adjuvants

5. ESA resistance

6. HIF Stabilizers

7. Special Issues

Corners

Nat. Rev. Nephrol. 11, 394–410 (2015); published online 9 June 2015

Anemia Control:Effect of Hypoxia

Am J Nephrol 2017;45:187–199

HIF Stabilizers

HIF Stabilizers

Clin J Am Soc Nephrol 11: 982–991, 2016

HIF Stabilizers: Roxadustat (Phase 2b)

J Am Soc Nephrol 27: 1225–1233, 2016

HIF Stabilizers: Roxadustat

1. Introduction

2. Iron

3. ESA

4. Adjuvants

5. ESA resistance

6. HIF Stabilizers

7. Special Issues

Corners

Nephrol Dial Transplant (Feb 2017) 32: 279–287

ESA Therapy:Reno-protection

Kidney International Supplements (2012), 299–310

Pure Red Cell Aplasia:2012 KDIGO Guidelines

VOLUME 2 | ISSUE 4 | AUGUST 2 2012

http://www.kidney-international.org

OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF NEPHROLOGY

KDIGO Clinical Practice Guideline for Anemia in Chronic Kidney Disease

KI_SuppCover_2.4.indd 1 7/11/12 12:00 PM

X

Critical Reviews in Oncology/Hematology 87 (2013) 132–139

ESA Therapy and Cancer Associated Anemia

ESA Therapy and Chemotherapy Induced Anemia

Onco Targets Ther. 2016 Oct 28;9:6689-6693

Nephrol Dial Transplant 2016, in press

ESA Therapy and Cancer

(n 4,983)

Br J Clin Pharmacol. 2012 Jul 16.

Hemoglobin Variability:Effect of Different ESA

Kidney International (2016) 90, 422–429

Anemia Control Model: ACM

J Am Soc Nephrol 27: 3129–3138, October 2016

Current Trends

15

14

10

11

12

13

9

Hb (

g/d

l)

2017 Target

Anemia Management:Hemoglobin Target