RRT in Advanced Heart Failure and Liver Failure When to start and when to stop?

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1 Critical Care Medicine Apollo Hospitals RRT in Advanced Heart Failure and Liver Failure When to start and when to stop? Ramesh Venkataraman, AB (Int. Med), AB (CCM) Senior Consultant, Critical Care Medicine Apollo Hospitals Chennai

2 My Talk Advanced heart failure Mechanistic Insights Rationale for UF Diuresis vs. UF? Clinical data Conclusion Advanced liver failure Acute liver failure Cirrhosis MARS Conclusion

3 RRT in Advanced Heart Failure

4 Cardiorenal or Renocardiac? Pathophysiologic disorder of the heart and kidneys, whereby acute or chronic dysfunction in one organ induces acute or chronic dysfunction in the other

5 Cardiorenal Syndrome - Types ADVANCED Type I Acute Cardiorenal Syndrome Type II Chronic Cardiorenal Syndrome Type III Acute Renocardiac Syndrome Type IV Chronic Renocardiac Syndrome Type V Secondary Cardiorenal Syndrome

6 Nomenclature

7 Why does the kidney fail? It has got to be the low cardiac output silly!!!!! Decreased renal blood flow or perfusion pressure Inotropes improve renal function in the short-term No correlation between baseline or delta hemodynamics and worsening renal function (WRF) WRF not associated with increased mortality Baseline or discharge renal insufficiency linked Nohria A et al. J Am Coll Cardiol. 2008;51(13):

8 Role of Increased CVP and IAP Bock S et al. Circulation. 2010; 121;

9 Salt and water overload Salt and fluid removal Improves symptoms Improves RV dilatation Improves IAP Improves Renal Venous Pressure Attenuates neurohumoral response

10 Does fluid removal impact outcome? N = 336 Mean NYHA Class % Dyspnea at rest 84% Orthopnea

11 Diuresis - Challenges Diuretics intolerance ACE-I and Beta blockers Hypotension GFR changes unpredictable Preload changes Decreased RV dilatation Decreased IAP and renal venous pressure Diuretic resistance Intravascular volume depletion Increase in sodium retaining hormones Hypoalbuminemia

12 Peritoneal Dialysis Improved NYHA and decreased hospitalization days Improved LVEF and decreased hospitalization days

13 Ultrafiltration Removal of isotonic fluid from the venous compartment via filtration of plasma across a semipermeable membrane Isotonic fluid removal Adjustable fluid removal rates Electrolyte homeostasis Tubuloglomerular Feedback not triggered Decreased neurohumoral activity Improve diuretic responsiveness

14 Ultrafiltration in Heart Failure Ross EA et al. Blood Purif. 2012;34:

15 UF or Diuretics in ADHF? Higher fluid removal and wt. loss at 24 hrs Decreased 90 day rehospitalization in UF group

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17 CARESS-HF Study EF 30-35% S. Creatinine 2.0mg/dl

18 When should I consider UF?

19 59% CRRT conversion 14% RRT dependent 30% Mortality 6% Hospice

20 N =37 Median survival 15.5 days 62% In hospital mortality

21 Predictors of mortality: Vasopressor use HR 9.9 for death Age > % Mortality Biventricular dysfunction

22 When to start RRT? Traditional indications for RRT No data to guide candidate selection High mortality once on RRT UF when diuretics fail or not possible/tolerated Hemodynamic instability Arrhythmias Impaired renal function Severe hypoalbuminemia Severe hypernatremia Diuretic resistance

23 When to stop RRT? Avoid if Age > 70 Vasopressor dependent Biventricular dysfunction No data to guide decision on termination Individualize decision to terminate Pre-admission age and functional status Type and severity of organs involved Co-existing medical conditions Suitability for transplant Cost Patient/family goals

24 RRT in Advanced Liver Failure

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26 RRT in Advanced Liver Failure Acute Liver Failure Chronic Liver Failure Patients listed for transplantation Patients evaluated for transplantation Patients unsuitable for transplantation Use of MARS

27 RRT in Acute Liver Failure Increased Intracranial Pressure - leading cause of death in ALF Autoregulation absent Changes in ICP occur during RRT Intradialytic hypotension alters CPP More prone to hypotension Rapid fall in serum osmolality Rapid clearance of plasma urea Thermal losses and cooling with CRRT Improved hemodynamics Davenport A. Seminars in Dialysis 22(2): 2009:

28 Data on CRRT in ALF INR, Bilirubin, MELD and SOFA score improved by day 5 (N =10) N = 33 Improved encephalopathy and hemodynamics (N =22)

29 Renal Failure and Cirrhosis Significantly alters prognosis MELD Score Incorporates serum creatinine AKI and cirrhosis without transplantation - Mortality 90% 47% for cirrhosis without AKI RIFLE criteria predicts mortality High risk of death while awaiting transplant Increased complications Reduced survival after transplantation Provision of RRT is difficult Hypotension and coagulopathy

30 Increase in S. Creatinine > 0.3mg/dl within 48 hours (Or) Percentage increase S. Creatinine > 50% from baseline known or presumed to have occurred within prior 7 days

31 Hemodynamics in HRS Cardiac output Splanchnic vasodilation SVR Renal Vasoconstriction RAAS/SNS and ADH Ascites Compensated Hyponatremia Cirrhosis HRS

32 RRT in Cirrhosis What is the cause of renal failure? Is this HRS? Is there a reversible component? What is the impact of renal failure on outcomes? What is the prognosis of patients needing RRT? Is this patient awaiting transplant? Is this patient being evaluated for a transplant? Renal failure in patient deemed not a transplant candidate!!!! How long should we continue the RRT trial?

33 Cirrhosis with ascites AKI according to new criteria S. creatinine > 1.5 mg/dl Not VALID anymore No improvement in S. creatinine after 2 consecutive days off diuretics and volume expansion with albumin 1g/kg (upto 100g/day) Absence of shock No current/recent use of nephrotoxic drugs No macroscopic evidence of structural kidney injury

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35 ONLY 24/44 had HRS/ATN 7 patients on RRT

36 Marta Martin Llahi et al N = 562 Infection 46% Hypovolemia -32% HRS - 13% Parenchymal - 9%

37 N = % survival to discharge or transplantation 94% mortality if no transplant done 1 yr mortality - 30% vs. 9.7% (higher if RRT)

38 >25000 patients 5 yr survival > 60%

39 What about cirrhotic patients not candidates for LTX?

40 RRT in Cirrhosis Traditional indications Severe Lactic Acidosis Advantages Cardiovascular stability Predictable and steady solute removal Gradual correction of hyponatremia Peritransplant Removal of ammonia Davenport A. Seminars in Dialysis 22(2): 2009:

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42 MARS for liver failure

43 Hepatic Survival Encephalopathy

44 Renal Failure in Cirrhosis Renal failure in cirrhosis wide spectrum Non HRS causes quite common - multifactorial Difficult to separate HRS from other causes Etiology of renal failure impacts outcome HRS Trial of terlipressin and albumin offers benefits

45 RRT in Advanced Liver Failure Consider CRRT in patients with ALF and renal failure In Cirrhosis HRS Type I Reasonable to offer if being evaluated or awaiting transplantation Good 5 year survival once transplanted AVOID in patients not candidates for transplantation Offering a short RRT trial in non HRS causes of renal failure reasonable To assess reversibility and prognosticate? Hasten clearing ammonia MARS Expensive and experimental

46 When to stop RRT? ALF Continue CRRT till patient ICP normalizes Continue CRRT through transplant Transition to IHD post transplant Cirrhosis Till patient clinical status improves or transplanted 2-3 day trial and stop if no improvement or deterioration Individualize Preadmission functional status, co-morbidities, type/number and degree of organ dysfunction

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48 Erythropoietin Anemia independent adverse prognostic factor in heart failure patients 1 Erythropoietin decreased in renal failure and elevated in heart failure Elevated erythropoietin associated with poor survival independent of hemoglobin level 2? Decreased sensitivity to erythropoietin Erythropoietin Decreases cardiac myocyte apoptosis 1- Young JB et al. Am J Cardiol. 2008;101: Geroge J et al. Arch Intern Med. 2005;165:

49 Cardiorenal Syndrome Improving cardiac function Cardiac resynchronization therapy, LVADs Salt and water removal Sodium restriction Fluid restriction Hyponatremia as a guide Diuretics Aldosterone antagonism Renin-AT aldosterone antagonism Vasodilators Ultrafiltration

50 Biomarkers Elevated Troponin strongly predicts Poor prognosis irrespective of creatinine clearance 1 Higher risk of death in ESRD patients without symptoms of ACS 2 Nonischemic cardiomyopathy Microvascular disease with LVH Cystatin C levels correlated with morality in HF 3 Risk factor for cardiovascular disease in general population Along with pro- BNP adds to prognostic value 1- Aviles RJ et al. NEJM 2002;346: Khan NA et al. Circulation 2005; 112: Lassus J et al. Eur Heart J 2007; 28:

51 Chronic Sympathetic Stimulation Reduction in receptor density Receptor uncoupling from intracellular signalling Contribute to LVH Increased cardiomyocyte apoptosis Increased Neuropeptide Y Increased atherosclerosis Decreased clearance of catecholamines in renal failure Bristow MR et al. NEJM. 1982;307(4): Jackson G et al. BMJ. 2000; 328:

52 Biomarkers - BNP Increased production Vs. Decreased clearance Production cardiac stretch vs. other factors

53 Shaw BN et al. Int J of Nephrol. 2011; Article ID AT II activates NADPH Oxidase

54 Epidemiology Renal failure in heart failure 30-40% prevalence of moderate/severe impairment 1 WRF in patients on treatment for acute/chronic HF 2 Baseline renal function important prognostic factor Cardiovascular mortality in patients with renal impairment 44% deaths in ESRD patients cardiovascular times higher risk of cardiac death than general population Renal transplantation improved EF 3 1- Adams KF et al. Am Heart J 2005;149: Damman K et al. J Card Fail. 2007;13(8): Wali RK et al. J Am Coll Cardiol. 2005;

55 Renal Sympathetic Stimulation Krum H et al. Lancet. 2009;373:

56 Therapeutic implications CRS? mortality iatrogenically worsened Increased creatinine perceived as overdiuresis Reluctance in initiation of ACE-inhibitors/ARB Inadequate fluid resuscitation in septic patients Early initiation of RRT Prolonged use of RRT Interventions to remove fluid overload may decrease renal perfusion Nesiritide saga Inotropes do not improve renal or overall outcomes Fenoldopam no outcome benefits Bock S et al. Circulation. 2010; 121;

57 Summary

58 Conclusions Complex cross-talk exists between the heart and the kidney Dysfunction of one organ has been shown to be associated with dysfunction of other Linked pathophysiologically and epidemiologically Biomarkers of one disease helps in the prognostication of the other Heart-kidney interaction has several important therapeutic implications Although definite relationship exists, causation vs. association unclear

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61 Gut translocation of bacteria Release of vasodilators Decreased SVR Compensatory increase in CO Increased Plasma Volume Worsening of liver disease Failure of compensation Marked reduction in SVR RAAS/SNS activation Nonosmotic hypersecretion of vasopressin Marked reduction in RBF Intra-renal vasoconstriction

62 Summary ACE-I/ARB Betablockers Vasodilators Inotropes LVAD Diuretics UF

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