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CRAS – pathophysiology. CRAS is a Vicious Cycle Deteriorating kidney function worsens anaemia and heart function, which further impacts on kidney function.

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Presentation on theme: "CRAS – pathophysiology. CRAS is a Vicious Cycle Deteriorating kidney function worsens anaemia and heart function, which further impacts on kidney function."— Presentation transcript:

1 CRAS – pathophysiology

2 CRAS is a Vicious Cycle Deteriorating kidney function worsens anaemia and heart function, which further impacts on kidney function – The same is true of worsening anaemia and deteriorating heart function

3 The Pathophysiology of CRAS Mak G et al. Curr Treat Options Cardiovasc Med 2008;10:455–464; Murphy CL & McMurray JJV. Heart Fail Rev 2008;13:431–438; Felker GM et al. J Am Coll Cardiol 2004;44:959–966; van der Meer P et al. Eur Heart J 2004;25:285–291; Malyszko J & Mysliwiec M. Kidney Blood Press Res 2007;30:15–30 Hct Renal ischaemia Vasoconstriction Reduced haematopoiesis Sympathetic nervous system Renin-angiotensin system Ischaemia Haemodilution EPO Cytokines

4 Heart and Kidney Failure are Linked through the Sympathetic Nervous System The heart and kidney can directly interact through: 1–3 – The sympathetic nervous system – The renin-angiotensin system – Inflammation – Reactive oxygen species – Nitric oxide balance 1. Efstratiadis G et al. Hippokratia 2008;12:11–16; 2. Jie KE et al. Am J Physiol Renal Physiol 2006;291:F932–F944; 3. Ronco C et al. Blood Purif 2009;27:114–126 Reduced haematopoiesis Sympathetic nervous system Renin-angiotensin system EPO Cytokines

5 Pathophysiology of CRAS Mak G et al. Curr Treat Options Cardiovasc Med 2008;10:455–464; Murphy CL & McMurray JJV. Heart Fail Rev 2008;13:431–438; Felker GM et al. J Am Coll Cardiol 2004;44:959–966; van der Meer P et al. Eur Heart J 2004;25:285–291; Malyszko J & Mysliwiec M. Kidney Blood Press Res 2007;30:15–30 Reduced haematopoiesis Sympathetic nervous system Renin-angiotensin system

6 EPO and Iron Deficiency can Cause Anaemia in Patients with CKD Causes of anaemia in CKD 1–4 – Erythropoietin (EPO) deficiency/resistance – Iron deficiency Anaemia can worsen kidney function through: – Renal ischemia – Vasoconstriction 1. Kazory A & Ross EA. J Am Coll Cardiol 2009;53:639–647; 2. Akram K & Pearlman BL. Int J Cardiol 2007;117:296– Elliot J et al. Adv Chronic Kidney Dis 2009;16:94–100; 4. Fishbane S et al. Clin J Am Soc Nephrol 2009;4:57–61 Hct=haematocrit Hct Renal ischaemia Vasoconstriction Reduced haematopoiesis Sympathetic nervous system Renin-angiotensin system EPO

7 Pathophysiology of CRAS Mak G et al. Curr Treat Options Cardiovasc Med 2008;10:455–464; Murphy CL & McMurray JJV. Heart Fail Rev 2008;13:431–438; Felker GM et al. J Am Coll Cardiol 2004;44:959–966; van der Meer P et al. Eur Heart J 2004;25:285–291; Malyszko J & Mysliwiec M. Kidney Blood Press Res 2007;30:15–30 Hct Renal ischaemia Vasoconstriction Reduced haematopoiesis Sympathetic nervous system Renin-angiotensin system EPO

8 Mechanisms of Anaemia in CHF Haemodilution – Plasma Volume Forward failure – BM dysfunction Iron deficiency – Fe 2+ uptake – Malabsorption – Chronic bleeding (e.g., aspirin) Chronic immune activation – TNF Production of EPO EPO activity in BM Drugs – ACEi: EPO synthesis – EPO activity in BM Chronic kidney failure – Production of EPO – Loss in urine Silverberg DS et al. J Am Coll Cardiol 2000;35:1737–1744 BM=bone marrow; EPO=erythropoietin; ACEi=angiotensin- converting enzyme inhibitor

9 Nanas JN et al. J Am Coll Cardiol 2006;48:2485–2489 Iron deficiency Anaemia of chronic disease Haemodilution Drug induced Patients (%) 73.0% 18.9% 5.4% 2.7% Distribution of Aetiologies of Anaemia: Patients with Advanced CHF

10 Increased Levels of Inflammatory Cytokines and Iron Deficiency can cause Anaemia in Patients with CHF Causes of anaemia in CHF 1–5 – Increased cytokine levels – Iron deficiency Anaemia can worsen heart function through: – Ischaemia – Haemodilution 1. Akram K & Pearlman BL. Int J Cardiol 2007;117:296–305; 2. Morelli S et al. Acta Cardiol 2008;63:565–570; 3. Kazory A & Ross EA. J Am Coll Cardiol 2009;53:639–647; 4. Anand IS. J Am Coll Cardiol 2008;52:501–511; 5. Caramelo C et al. Rev Esp Cardiol 2007;60:848–860 Hct Reduced haematopoiesis Ischaemia Haemodilution Cytokines

11 Pathophysiology of CRAS Mak G et al. Curr Treat Options Cardiovasc Med 2008;10:455–464; Murphy CL & McMurray JJV. Heart Fail Rev 2008;13:431–438; Felker GM et al. J Am Coll Cardiol 2004;44:959–966; van der Meer P et al. Eur Heart J 2004;25:285–291; Malyszko J & Mysliwiec M. Kidney Blood Press Res 2007;30:15–30 Hct Renal ischaemia Vasoconstriction Reduced haematopoiesis Sympathetic nervous system Renin-angiotensin system EPO Ischaemia Haemodilution Cytokines


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