Cardiorenal Syndrome Prof. Dr. Bülent ALTUN Hacettepe University Faculty of Medicine Department of Internal Medicine Division of Nephrology

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1 Cardiorenal Syndrome Prof. Dr. Bülent ALTUN Hacettepe University Faculty of Medicine Department of Internal Medicine Division of Nephrology

2 Heart and Kidney The kidney yin dominates water, The heart yang dominates fire. When the kidney fails to evaporate fluid which then floods and ascends to depress to function of heart yang Ancient Chinese Medicine

3 Heart and Kidney When kidneys get smaller,the heart gets bigger Dr. R. Bright

Heart and Kidney When this combination of symptoms is of such character that the observer cannot readily assign to either the cardiovascular system or to the kidneys the

4 Heart and Kidney When this combination of symptoms is of such character that the observer cannot readily assign to either the cardiovascular system or to the kidneys the preponderance of responsibility, the term "cardio-renal disease" is often employed. Alfred Stengel 1914 L. G. Bongartz.et.al. DOI: /25350

5 Cardiorenal Syndrome Heart Diseases Kidney Diseases Coronary artery disease Heart Failure Acute decompansated heart failure Chronic Kidney Disease Acute Kidney Disease Acute Kidney Injury

6 Cardiorenal Syndrome (CRS) Pathophysiologic disorder of the heart and kidneys whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction in the other organ.

7 Cardiorenal Syndrome (CRS) CRS Type 1: Acute Cardiorenal Syndrome Abrupt worsening of cardiac function (e.g. Acutely decompensated congestive heart failure) leading to acute kidney injury. CRS Type 2: Chronic Cardiorenal Syndrome Chronic abnormalities in cardiac function (e.g. chronic congestive heart failure) causing progressive and permanent chronic kidney disease. Ronco C. et.al. J Am Coll Cardiol 2008;52:

8 Cardiorenal Syndrome (CRS) CRS Type 3: Acute Renocardiac Syndrome Abrupt worsening of renal function (e.g. acute kidney injury) causing acute cardiac disorder (acute heart failure) CRS Type 4: Chronic Renocardiac Syndrome Chronic kidney disease (diabetic nephropathy) contributing to decreased cardiac function,cardiac hypertrophy, fibrosis, and/or increased risk of adverse cardiovascular events Ronco C. et.al. J Am Coll Cardiol 2008;52:

9 Cardiorenal Syndrome (CRS) CRS Type 5: Secondary Cardiorenal Syndrome Systemic condition (e.g. sepsis) causing both acute cardiac and renal injury and dysfunction events Ronco C. et.al. J Am Coll Cardiol 2008;52:

10 Cardiorenal Syndrome Type 1 CRS Type 1: Acute Cardiorenal Syndrome Abrupt worsening of cardiac function (e.g. Acutely decompensated congestive heart failure) leading to acute kidney injury.

11 Cardiorenal Syndrome Type 1 Breidthardt T. et. al. Crit Care 2012; 16:R2.

12 HR 95% CI Change in Screatinine During Hospitalization of Patients with HF and Prognosis Change in Serum Creatinine mg/dl Smith GL et. al. February Prof Dr. volbülent 9, Altun

13 Cardiorenal Syndrome Type 1

14 Cardiorenal Syndrome Type 1 Sympathetic Activity Angiotensin II Afferent Arteriole Dilatation Renin Efferent Arteriole Constriction Myogenic stimulus Tubuloglomerular feedback

15 Prostaglandins and Heart Failure Abassi Z. et.al. Am J Physiology Reanl Physiol 2001 Jan: 280(1);F43-F53

16 Cardiorenal Syndrome Type 1 Angiotensin II Endothelin Sympathetic activity Prostaglandins Nitric Oxide Renal Perfusion

Sympathetic Activity Renin Angiotensin system Water

17 Cardiorenal Syndrome Type 1 Cardiac Output Decrease in arterial volume Non osmotic ADH secretion Sympathetic Activity Renin Angiotensin system Water retention Peripheral renal vascular resistance Salt retention

18 Cardiorenal Syndrome Type 1 Myocardial Injury Ventricular Dysfunction Increase Preload /afterload Decrease CO Systemic vasoconstriction Salt /water retention Sympathetic activity RAAS activation ADH secretion

19 Cardiorenal Syndrome Type 1 Angiotensin II Sympathetic activity Aldosterone Escape Phenomen Aldosterone Angiotensin II ADH Prostoglandins Natriuretic peptides

20 Natriuretic Peptides Atrial /ventriculer strain Shear stress ANP BNP CNP Vasodilatation Baroreflex activ. GFR NatriUresis Diüresis Renin, Ang II, Aldo Mezangial contraction ADH secretion Sympathetic aktiv. Thirst

21 Collecting Duct Principal Cell Bazolateral Aldosterone Mineralocorticoid receptor sgk K-ras Apical Na ENaC - a ENaC - b ENaC - g Epithelial sodium channel

22 Cardiorenal Syndrome Type 1 Decrease in cardiac output Renal vasocoonstriction Renal perfusison pressure Adrenergic activity Angiotensin activity GFR Sodium / water reabsorbtion in proximal tubulus Sodium /water in distal tubulus Resistance to natriueretic peptides Impaired escape phenomen of aldosterone

23 Cardiorenal Syndrome Type 1 Na /H 2 O Balance

24 Cardiorenal Syndrome Type 1

25 Cardiorenal Syndrome Type 1: Acute Decompansated Heart Failure (ADHF)

26 Cardiorenal Syndrome Type 1 Haase M. et.al. Contrib Nephrol 2013;183:91-116

27 Cardiorenal Syndrome Type 1 1. Blockade of renin angiotensin system (ACE/ARB) 2. Blockade of SNS activity (Beta blockers 3. Restriction of salt and water 4. Diüretics (High Dose /Infusion/Combination) 5. Ultrafiltration 6. Aquaretics, Nesiritide, Adenosine Receptor Antagonist

28 Cardiorenal Syndrome Type 1 Patients' Global Assessment of Symptoms during the 72-Hour Study-Treatment Period. Felker GM et al. N Engl J Med 2011;364: Felker et al. NEJM 2011

29 Cardiorenal Syndrome Type 1 Haase M.ve ark. Contrib Nephrol 2013;183:91-116

30 Cardiorenal Syndrome Type 1

31 Cardiorenal Syndrome Type 2 CRS Type 2: Chronic Cardiorenal Syndrome Chronic abnormalities in cardiac function (e.g. chronic congestive heart failure) causing progressive and permanent chronic kidney disease.

32 Relative Risk Prognosis of Patients with Heart Failure and GFR 2,4 >90 ml/min 2 1,6 N:6493 patient year ml/min ml/min ml/min <45 ml/min 1,2 0,8 0,4 0 CV death/ Hospitalization All death Hillige HL..et. al..circulation Feb 7;113(5):671-8

33 Cardiorenal Syndrome Type 2 Cruz D..et.al. Contrib Nephrol 2013;183:

34 Cardiorenal Syndrome Type 2 Cruz D.. et.al Contrib Nephrol 2013;183:

35 Cardiorenal Syndrome Type 2

36 Cardiorenal Syndrome Type 2

37 Cardiorenal Syndrome Type 1 1. Blockade of renin angiotensin system (ACE/ARB) 2. Blockade of SNS activity (Beta blockers 3. Restriction of salt and water 4. Diüretics (High Dose /Infusion/Combination) 5. Ultrafiltration 6. Aquaretics, Nesiritide, Adenosine Receptor Antagonist

38 Cardiorenal Syndrome Type 2

39 Sacubitril/valsartan in heart failure Kaplinsky E. Ther Adv Chronic Dis 2016, Vol. 7(6)

40 Sacubitril/valsartan in heart failure Kaplinsky E. Ther Adv Chronic Dis 2016, Vol. 7(6)

41 Cardiorenal Syndrome Type 3 CRS Type 3: Acute Renocardiac Syndrome Abrupt worsening of renal function (e.g. acute kidney injury) causing acute cardiac disorder (acute heart failure)

42 Cardiorenal Syndrome Type 3 Acute Kidney Injury Increase in SCr by 0.3 mg/dl (26.5 l mol/l) within 48 hours; OR Increase in SCr to 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days OR Urine volume <0.5 ml/kg/h for 6 hours.

43 Cardiorenal Syndrome Type 3

44 Cardiorenal Syndrome Type 3 Bagshav S. Et.al.. Contrib Nephrol 2013;183:

45 Treatment: AKI -STAGES Serum Creatinine times baseline OR 0.3 mg/dl (26.5 mmol/l) increase Urine output < 0.5 ml/kg/h for 6 12 hours times baseline < 0.5 ml/kg/h for 12 hours times baseline OR Increase in serum creatinine to 4.0 mg/dl (353.6 mmol/l) OR Initiation of renal replacement therapy OR, In patients <18 years, decrease in egfr to < 35 ml/min per 1.73 m2 < 0.3 ml/kg/h for 24 hours OR Anuria for 12 hours

46 Cardiorenal Syndrome Type 4 CRS Type 4: Chronic Renocardiac Syndrome Chronic kidney disease (diabetic nephropathy) contributing to decreased cardiac function,cardiac hypertrophy, fibrosis, and/or increased risk of adverse cardiovascular events

47 Cardiorenal Syndrome Type 4 Ronco C. et. al.kidney Dis 2016;2:

48 Cardiorenal Syndrome Type 4 Tumlin JA.. et.al. Contrib Nephrol 2013;183:

49 Cardiorenal Syndrome Type 4 Tumlin JA.. et.al. Contrib Nephrol 2013;183:

50 Cardiorenal Syndrome Type 4 Guo J,et.al. Am J Physiol Heart Circ Physiol 313: H1 H13, 2017.

51 Cardiorenal Syndrome Type 5 CRS Type 5: Secondary Cardiorenal Syndrome Systemic condition (e.g. sepsis) causing both acute cardiac and renal injury and dysfunction events

52 Cardiorenal Syndrome Type 5: L. Di Lullo et al. Indian Heart Journal 69 (2017)

53 Cardiorenal Syndrome Type 5: Sepsis L. Di Lullo et al. Indian Heart Journal 69 (2017)

54 Cardiorenal Syndrome Type 5: Cirrhosis Kotecha et al. Journal of Critical Care 43 (2018)

55 Cardiorenal Syndrome Type 5: Cirrhosis L. Di Lullo et al. Indian Heart Journal 69 (2017)

56 Cardiorenal Syndrome (CRS)

The Cardiorenal Syndrome in Heart Failure

The Cardiorenal Syndrome in Heart Failure Van N Selby, MD Assistant Professor of Medicine Advanced Heart Failure Program, UCSF October 9, 2015 Disclosures None 1 Cardiorenal Syndrome (CRS) A pathophysiologic