Primary Care Management of Cario-Renal Syndrome

1. Primary Care Management of Cario-Renal Syndrome R. Benjamin C. Grant, MS, PA-S OAPA CME Conference ‘13 October 25, 2013

2. Increasing Burden of Chronic Disease

3. Increasing Burden of Chronic Disease

4. Who is our population? • Obese • Diabetes • Inactive • Smokers • Hypertensive • Fixed Income • Fast Food • LOST!

5. Cardiorenal Syndrome • Objectives • Define Cardiorenal Syndrome • Classifications • Address pathophysiology • Discuss approach to treatment • Highlight Problems with management • Provide recommendations for screening and management • Generic term • Multiple combinations • Acute and Chronic dysfunction of Cardiovascular and Renal systems • Classification • Type I –Acute CV  AKI • Type II – Chronic CV  CKD • Type III – AKI  Acute CV • Type IV – CKD  Chronic CV • Type V – Systemic process (sepsis)  AKI & Acute CV

6. Cardiorenal Physiology Cardiovascular Renal • Systemic Perfusion • Maintained by CO and SR • In HF, perfusion can become compromised • End organ damage • Volume homeostasis • Electrolyte balance • pH • Systemic Resistance via RAAS

7. Cardiorenal Physiology • Intravascular Volume increases • Diuresis • With CKD this can contribute to volume overload • Kidneys are hypoperfused •  Intravascular volume •  CO • Vascular disease •  Systemic Resistance • Increase RAAS

8. Cardiorenal Physiology • RAAS •  BP • Inflammatory pathways •  Renal Perfusion • Sodium Retention • Potassium Loss • Evolutionarily Protective • Harmful in the setting of chronic disease

9. Chronic Kidney Disease • GFR <60 mL/min (KDOQI) • Stage I – normal >90 • Stage II – mild 89-60 • Stage IIIa – 59-45 • Stage IIIb – 44-30 • Stage IV – 29-15 • Stage V - <15 (ESRD) • Treatment • Control volume status • Salt reduction • Protect remaining renal function • Try to avoid Loop diuretics • Start ACE-I/ARB • Avoid NSAIDS • Control Hypertension • Controlled Diabetes • At Stage IV, d/c ACE-I/ARB • Stage V, restart ACE, hemodialysis

10. Heart Failure • “a complex clinical syndrome that can result from any structural or functional cardiac disorder that impairs the ability of the ventricle to fill with or eject blood” Hunt et al. Circulation 2009 • American Heart Association • Stages A and B have risk factors with no current dysfunction • Stage C – current or past symptoms of Heart Failure • Stage D – symptoms refractory to standard therapy • Treatment • Preventative measures • Eg. HTN control, smoking cessation, Lipid goals… • Reduce workload • ACE/ARB (neurohormonal) • Beta blocker • Possibly diuretics • Aldosterone Antagonist • Inotropes • Manage decompensation • Fluid overload, dysrhythmias

11. Treatment Problem Volume Overload Effects • Common complication of HF • Impacted by Renal Function • Decrease in GFR due to renal injury (AKI) • Activation of RAAS • Increase in Systemic Resistance and thus Workload • RAAS Activation activates proinflammatory and hypercoaguable state • Modest decrease in GFR (<70) • Sig. increase in mortality for pts with HF • Perspective • In 2003, 4.7% GFR (<60) • 6.3% had persistent albuminuria • With increase in chronic diseases, they may be an underestimation

12. Treatment Problem Preventing decompensation Furosemide • Maintain Euvolemic state • Salt restriction • Most frequent drug class • Loop Diuretics! • Antagonizes Na/K/Cl symporter in ascending Loop of Henle • Loss of Na and K salts and water • Excreted Renally • Can be nephrotoxic in CKD • Increased RAAS activation • In animal models show progression of renal fibrosis

13. Potential solutions? • Low dose Loop Diuretic • Sigmoidal response curve thus ineffective until high enough dose reached • RAAS antagonism • Could mitigate negative effects of diuretic use • Despite the negative effects of diuretics on renal function, they are still associated with a lower mortality rate than inotropes in acute decompensated heart failure!

14. Discussion Treatment of Volume Overload How to monitor • Loop Diuretics • RAAS activation • Worsening renal function • Negatively effects volume status and cardiovascular status • Increased risk of adverse outcome • Traditionally • BNP and EF • Clinical assessment • Smith et al. 2006 • Renal impairment holds equal risk as decreased EF • Combining BNP and GFR more predictive for adverse outcome than either alone • Degree of Renal dysfunction directly associated with HF outcomes

15. Discussion • Decompensation and hospitalization inevitable • Renal function frequently impacted • Even transient renal damage independently predicts increased risk for death or readmission • Even after excluding pts with cardiogenic shock, renal damage from other causes still very common • Mechanism? • Renal and Hepatic dysfunction • Mullens et al. 2009 identifies venous congestion as significant contributor to renal dysfunction

16. Recommended Management Types 1 & 3 CRS Types 2 & 4 CRS • Type 1 – Acute HF • Treat underlying cause • PCI, Inotropes, Inpatient • Type 3 – AKI • Euvolemia, electrolytes • Dialysis? • Though different etiologies, uniform treatment • Maintaining Cardiac function is Primary Goal! • Renal Function is secondary but not insignificant • Naturally functioning renal system is best management tool for hemodynamics

17. Conclusions • Patients with Cardiorenal Syndrome can have many etiologies • Provide an interesting and challenging problem for PCPs • Approach to treatment begins with understanding the pathophysiology

18. Questions? Benjamin Grant, MS, PA-S benjamin-grant@ouhsc.edu Contact for a copy of presentation or paper

19. Resources • 1) Ronco C, Haapio M, House AA, et al. Cardiorenal syndrome. J Am Coll Cardiol 2008; 52:1527. • 2) Ito S. Cardiorenal syndrome: an evolutionary point of view. Hypertension 2012. 60(3):589-95. • 3) National Kidney Foundation. KDOQI Clinical Practice Guidelines and Clinical Practice Recommendations for 2006 Updates: Hemodialysis Adequacy, Peritoneal Dialysis Adequacy and Vascular Access. Am J Kidney Dis 48:S1-S322, 2006 (suppl 1). • 4) Hunt SA, Abraham WT, Chin MH, et al. 2009 focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation 2009; 119:e391. • 5) Dries DL, Exner DV, Domanski MJ, et al. The prognostic implications of renal insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction. J Am Coll Cardiol 2000; 35:681. • 6) Coresh J, Astor BC, Greene T, et al. Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. Am J Kidney Dis 2003; 41:1. • 7) Basraon J, Deedwani PC. Diuretics in heart failure: practical considerations. Med Clin North Am 2012. 96(5):933-42.

20. Resources • 8) Brilla CG, Pick R, Tan LB, et al. Remodeling of the rat right and left ventricles in experimental hypertension. Circulation 1990; 67(6):1355-64. • 9) Costanzo MR, Johannes RS, Pine M, et al. The safety of intravenous diuretics alone versus Diuretics plus parenteral vasoactive therapies in hospitalized patients with acutely decompensated heart failure: a propensity score and instrumental variable analysis using the Acutely Decompensated Heart Failure National Registry (ADHERE) database. Am Heart J 2007; 154:267. • 10) Smith GL, Lichtman JH, Bracken MB, et al. Renal impairment and outcomes in heart failure: systematic review and meta-analysis. J Am Coll Cardiol 2006; 47:1987. • 11) van Kimmenade RR, Januzzi JL Jr, Baggish AL, et al. Amino-terminal pro-brain natiretic Peptide, renal function, and outcomes in acute heart failure: redefining the cardiorenal interaction?. J Am Coll Cardiol 2006; 48(8):1621-7. • 12) Logeart D, Tabet JY, Hittinger L, et al. Transient worsening of renal function during hospitalization for acute heart failure alters outcome. Int J Cardiol 2008; 127:228. • 13) Poelzl G, Ess M, Von der Heidt A, et al. Concomitant renal and hepatic dysfunctions in chronic heart failure: Clinical implications and prognostic significance. Eur J Intern Med. 2012; epub ahead of print. • 14) Mullens W, Abrahams Z, Francis GS, et al. Importance of venous congestion for worsening of renal function in advanced decompensated heart failure. J Am Coll Cardiol 2009; 53(7):589-96.

21. Resources • 15) Smith GL, Vaccarino V, Kosiborod M, et al. Worsening renal function: what is a clinically meaningful change in creatinine during hospitalization with heart failure? J Card Fail 2003; 9:13. • 16) Testani JM, McCauley BD, Chen J, et al. Clinical characteristics and outcomes of patients with improvement in renal function during the treatment of decompensated heart failure. J Card Fail 2011;17:993.  • 17) Ben-Shoshan J, Entin-Meer M, Guzner-Gur H, et al. The cardiorenal syndrome: a mutual approach to concomitant cardiac and renal failure. Isr Med Assoc J 2012. 14(9):570-6. • 18) Bart BA, Goldsmith SR, Lee KL, et al. Ultrafiltration in decompensated heart failure with cardiorenal syndrome. N Engl J Med. 2012; 367(24):2296-304. • 19) Bock JS, Gottlieb SS. Cardiorenal syndrome: new perspectives. Circulation 2010. 121:2592. • 20) Testani JM, Chen J, McCauley BD, et al. Potential effects of aggressive decongestion during the treatment of decompensated heart failure on renal function and survival. Circulation 2010; 122:265.