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Role of Congestion and Hypoperfusion in the Cardiorenal Syndrome

Role of Congestion and Hypoperfusion in the Cardiorenal Syndrome. Ihab Wahba, MD, FACP, FASN Associate Professor of Clinical Medicine University of Pennsylvania Perelman School of Medicine. Case. A 65-y-old man with morbid obesity (BMI>65), severe pulmonary hypertension, edema

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Role of Congestion and Hypoperfusion in the Cardiorenal Syndrome

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  1. Role of Congestion and Hypoperfusion in the Cardiorenal Syndrome Ihab Wahba, MD, FACP, FASNAssociate Professor of Clinical Medicine University of Pennsylvania Perelman School of Medicine

  2. Case • A 65-y-old man with morbid obesity (BMI>65), severe pulmonary hypertension, edema • Admitted with wt gain, oliguria, High JVP, severe edema, abd distension, BP 105/60 • Meds: Carvedilol 6.25 mg bid, lisinopril 20 mg qd, lasix 40 mg bid, opioids, gabapentin • Creat rises from 1.5 to 3 mg/dL over 3 days, FeNa<0.1%, bland urine sediment, no response to IV furosemide • Echo: Normal LV function, dilated RV

  3. Renal dysfunction is common in patients with HF Meta-analysis of > 80,000 pts Smith GL et al. J Am Coll Cardiol 47:1987, 2006

  4. Renal dysfunction confers ↑ risk of mortality in patients with HF Smith GL et al. J Am Coll Cardiol 47:1987, 2006

  5. Renal dysfunction and hypotension best predictors of mortality in HF • > 65,000 pts from ADHERE cohort • Best predictors of mortality (out of 39 variables) • BUN ≥ 43 mg/dL (best) • Systolic BP < 115 mm Hg • Creat ≥ 2.75 mg/dL Fonarow GC et al. JAMA 293:572, 2005

  6. Widely accepted pathophysiology of cardiorenal syndrome Schrier & Abraham. N Engl J Med 8:577, 1999

  7. Renal hemodynamics in HF ↑CVP Ljungman S et al. Drugs 39:10, 1990

  8. Case • 64-y-old woman admitted for resection of meningioma • Developed hypotension, desaturation and tachypnea on POD # 9 • CT angiogram: massive PE • Massive IVFs + pressors • Oliguria, normal creat, massive edema, normal urine sediment Dadfarmay S & Wahba I. NDT Plus 4:295-298, 2011

  9. Oliver TB. Thorax 1998

  10. Perfusion pressure = MAP - CVP BP = PVR x CO CO = SV x HR

  11. Effect of ↑ Venous Pressure on Renal Function

  12. Effect of ↑RVP or ↓Art pressure in isolated dog heart-lung kidney prep Winton FR. J Physiol 72:49, 1931

  13. Raised venous pressure lowers GFR and causes Na retention in animals Graded venous hypertension to 25 mmHg in isolated perfused kidneys ‘In some clinical situations (e.g. cor pulmonale), an increased pressure in the systemic venous circulation may play an important part in causing renal sodium retention’ Firth et al. Lancet 1988

  14. Renal venous hypertension documented in man 230 108 Maxwell MH et al. J Clin Invest 29:342,1950

  15. Venous congestion correlates with low GFR in patients with PAH • Aim: Study relationship of venous congestion (CVP) to RBF & GFR • Patients: Pulmonary hypertension • Procedures • Right heart cath for hemodynamics • Iothalamate and Hippuran Cl for RBF & GFR • Stats: Cor coef, multiv regression Damman K et al. Eur J Heart Fail 9:872, 2007

  16. Venous congestion correlates with low GFR in patients with PAH Damman K et al. Eur J Heart Fail 9:872, 2007

  17. High CVP and not CI predicts AKI in patients with HF • Mullens W et al. J Am Coll Cardiol 53:588, 2009 • Damman K et al. J Am Coll Cardiol 53:582, 2009 • Guglin M et al. Clin Cardiol 34:113, 2010

  18. Diuresis improves Renal Function in patients with RV Failure Testani JM et al. Am J Cardiol 105:511, 2010

  19. Case • 65 y-old woman with DM, increasing lower extremity edema and WRF • Exam: JVP, TR, edema, hepatomegaly • Labs: Creat 2.3, minimal proteinuria • Echo, Rt H cath: EF 65%, PAH (75/35) • Rx: Diuretics with massive diuresis • Labs after 3 days: Cr 1.3 mg/dL

  20. CKD is prevalent in patients with PAH and normal LV function • Aim • Prevalence of CKD in patients with PAH • Is PAH an independent predictor of CKD? • Methods • Retrospective cohort, 75 pts with a mean PAP ≥ 25 mm Hg & normal PCWP, 6 ys • MDRD GFR initially & at f-up • Outcome: Development of stage 3 CKD Cedergreen, Markin & Wahba. Am J Respir Crit Care Med 179: A4864, 2009

  21. CKD is prevalent in patients with PAH and normal LV function Prevalence % Cedergreen, Markin & Wahba. Am J Respir Crit Care Med 179: A4864, 2009

  22. CKD is prevalent in patients with PAH and normal LV function Probability of progression to CKD 3 Patients with initial CKD II more likely to progress to CKD III (HR 23±3, P=0.02, vs CKD I) Cedergreen, Markin & Wahba. Am J Respir Crit Care Med 179: A4864, 2009

  23. PAH is prevalent in CKD and associates with high CVP and mortality 1088 pts with PAH 32% had CKD3 and 4% CKD4 ↑CVP but not ↓EF associated with CKD A 5 ml/min lower GFR associated with 5% increased hazard for death Naveenathan S et al. Clin J Am Soc Nephrol 9:855, 2014

  24. Case • 36-y-old woman with DCM from adriamycin (EF 10-20%), admitted for worsening CHF • Started on dobutamine, dopamine, IV lasix 20/hr, metolazone 5 mg bid, but net fluid balance +3L • On HD #8 oliguria to 10 ml/hr. BP 88/44, HR 80, RR 20, JVP elevated, clear lungs, S3, tense ascites, 2+ edema. CVP 24, WP 32, CI 2.3, SVR 1020 • Labs: Na 126, K 5.0, Cl 88, CO2 26, BUN 57, Cr 1.5  3 mg/dL, bland sediment • 4.5 L paracentesis  immediate diuresis (UO 125 ml/hr) and a fall in cr to 1.8

  25. Causes of Increased IAP • Primary • Space occupying lesions, ascites • Secondary • Massive IVFs

  26. High IAP in man reduces GFR Bradley & Bradley. J Clin Invest 26:1010, 1947

  27. High IAP reduces GFR via increased renal vein pressure • Increased renal vein pressure may be solely responsible for the reduced GFR • Ureteral compression ruled out • Low Urine Na Bradley & Bradley. J Clin Invest 26:1010, 1947

  28. ↑ IAP reduces GFR via ↑RVP and not renal parenchymal compression Doty et al. J Trauma 47:1000, 1999 Doty et al. J Trauma 48:874, 2000

  29. Shibagaki, Tai, Nayak & Wahba. Nephrol Dial Transplant 12:3567, 2006

  30. Increased IAP is associated with renal failure in patients with HF Hemodynamic assessment included Abdominal Perfusion Pressure (MAP-IAP) Mullens W et al. J Am Coll Cardiol 51:300, 2008

  31. Paracentesis or UF reduces IAP and improves renal function 9 pts with acute HF, class 3 or 4, with ascites or refractory to med Rx Paracentesis or SCUF for 12 hrs Measurement of IAP, hemodynamics and Cr Mullens W et al. J Cardiac Fail 14:508, 2008

  32. Effect of Perfusion Pressure

  33. CVP & Perfusion Pressure but not EF correlate with GFR Lower GFR with lower perfusion pressure Guglin M et al. Clin Cardiol 34:113, 2010

  34. Reduction of systolic BP in ADHF associates with WRF Cross sectional study of ESCAPE (386 pts) BP reduction associated with greater use of Vasodilators mm Hg P<0.001, larger reduction associated with greater odds for WRF Testani JM et al. Eur J Heart Fail 13:877-844, 2011

  35. Lower perfusion pressure associates with dialysis need after SCUF 63 pts at CCF 2004-09, all with CRS requiring SCUF Primary EP: RF requiring dialysis Secondary EP: Mortality at 3 and 12 months Wehbe E et al. J Cardiac Fail 21:108-115, 2015

  36. Lower perfusion pressure associates with dialysis need after SCUF Mortality 81% at 3 months, 95% at 12 months for those needing dialysis Wehbe E et al. J Cardiac Fail 21:108-115, 2015

  37. Case • A 52 y-old male with severe dilated cardiomyopathy is admitted for low Na 115 mEq/L (excess ETOH), and AKI (cr 2 mg/dL), BP 150-160/90, high JVP • Given IV lasix, Na corrects, creat 1.5 • Anuric after 2 days, BP 110/60, Creat 3.5 • Had received dilaudid 2-4 mg every 2 hrs x 6 • Dilaudid d/ced BP & GFR improved, urine output restored

  38. Oliguric AKI in obese patients (BMI>40) with relative hypotension and ↓ perfusion pressure

  39. “Has the medication had any side effects?”

  40. Pathophysiology of the Cardiorenal Syndrome RV dysfunction/PAH LV dysfunction BP-lowering drugs Ascites, Visceral edema ↓ Cardiac output ↑ IAP ↑ Renal vein pressure/ venous congestion ↓ BP ↓ Perfusion Pressure AKI/ Diuretic Resistance

  41. Case • A 65-y-old man with morbid obesity (BMI>65), severe pulmonary hypertension, edema • Admitted with wt gain, oliguria, High JVP, severe edema, abd distension, BP 105/60 • Meds: Carvedilol 6.25 mg bid, lisinopril 20 mqd, lasix 40 mg bid, opioids, gabapentin • Creat rises from 1.5 to 3 mg/dL over 3 days, FeNa<0.1%, bland urine sediment, no response to IV furosemide • Echo: Normal LV function, dilated RV

  42. Summary • Perfusion pressure (MAP-CVP) affects renal function • AKI is common in patients with high CVP and may be precipitated by low MAP • MAP is affected by drugs • Improving BP and venous congestion may improve renal function

  43. Research Recommendations • Effect of therapies that reduce congestion and improve perfusion pressure in AKI • Targeted therapy for PAH • Raising MAP and reducing CVP in ADHF and diuretic resistance (withholding ACEIs, BB, vasodilators, opioids, etc..)

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