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

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

Heart and Kidney When kidneys get smaller,the heart gets bigger Dr. R. Bright 1789-1858

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. https://www.researchgate.net/publication/221928884 DOI: 10.5772/25350

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

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.

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;52:1527 39

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;52:1527 39

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;52:1527 39

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.

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

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. 2003 Dr. volbülent 9, 13-25 Altun

Cardiorenal Syndrome Type 1

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

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

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

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

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

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

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

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

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

Cardiorenal Syndrome Type 1 Na /H 2 O Balance

Cardiorenal Syndrome Type 1

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

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

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

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;364:797-805 Felker et al. NEJM 2011

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

Cardiorenal Syndrome Type 1

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.

Relative Risk Prognosis of Patients with Heart Failure and GFR 2,4 >90 ml/min 2 1,6 N:6493 patient year 75-89 ml/min 60-74 ml/min 45-59 ml/min <45 ml/min 1,2 0,8 0,4 0 CV death/ Hospitalization All death Hillige HL..et. al..circulation. 2006 Feb 7;113(5):671-8

Cardiorenal Syndrome Type 2 Cruz D..et.al. Contrib Nephrol 2013;183:117-136

Cardiorenal Syndrome Type 2 Cruz D.. et.al Contrib Nephrol 2013;183:117-136

Cardiorenal Syndrome Type 2

Sacubitril/valsartan in heart failure Kaplinsky E. Ther Adv Chronic Dis 2016, Vol. 7(6) 278 290

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)

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.

Cardiorenal Syndrome Type 3

Cardiorenal Syndrome Type 3 Bagshav S. Et.al.. Contrib Nephrol 2013;183:137-157

Treatment: AKI -STAGES Serum Creatinine 1 1.5 1.9 times baseline OR 0.3 mg/dl (26.5 mmol/l) increase Urine output < 0.5 ml/kg/h for 6 12 hours 2 2.0 2.9 times baseline < 0.5 ml/kg/h for 12 hours 3 3.0 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

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

Cardiorenal Syndrome Type 4 Ronco C. et. al.kidney Dis 2016;2:151 163

Cardiorenal Syndrome Type 4 Tumlin JA.. et.al. Contrib Nephrol 2013;183:158-173

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

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

Cardiorenal Syndrome Type 5: L. Di Lullo et al. Indian Heart Journal 69 (2017) 255 265

Cardiorenal Syndrome Type 5: Sepsis L. Di Lullo et al. Indian Heart Journal 69 (2017) 255 265

Cardiorenal Syndrome Type 5: Cirrhosis Kotecha et al. Journal of Critical Care 43 (2018) 122 127

Cardiorenal Syndrome Type 5: Cirrhosis L. Di Lullo et al. Indian Heart Journal 69 (2017) 255 265

Cardiorenal Syndrome (CRS)