Is it Hepato-Renal Syndrome?

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by dr Mohammed Abdel Gawad (drgawad@gmail.com): Nephrology Specialist at Kidney & Urology Center - Alexandria - Egypt.

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Is it Hepato-Renal Syndrome?

  1. 1. Mohammed Abdel Gawad Nephrology Specialist Kidney & Urology Center (KUC) Alexandria - EGY drgawad@gmail.com How to Prevent? How to Treat? How to Diagnose? Is it Hepato-Renal Syndrome? 4th KUC Club – May 2014
  2. 2. Potentially reversible and functional renal failure In patients with advanced liver failure (acute or chronic) and portal hypertension Salerno F, Gerbes A, Gines P, et al. Gut 2007;56:1310–1318. In the absence of any identifiable causes of renal impairment. A DIAGNOSIS OF EXCLUSION Hepato-Renal Syndrome is:
  3. 3. Not all concomitant renal and hepatic impairment is due to the HRS It isn’t even on top of the list A DIAGNOSIS OF EXCLUSION Salerno F, Gerbes A, Gines P, et al. Gut 2007;56:1310–1318.
  4. 4. 4 Levenson D, Korecki KL.. In: Brenner BM, Lazarus JM, eds. Acute Renal Failure. New York: Churchill Livingstone; 1988:535-580. A DIAGNOSIS OF EXCLUSION
  5. 5. HRS is a diagnosis of EXCLUSION
  6. 6. Increased production or activity of vasodilators (with nitric oxide thought to be most important) Ginès P, Schrier RW. N Engl J Med. 2009;361(13):1279. Iwakiri Y. J Clin Gastroenterol. 2007;41 Suppl 3:S288. Splanchnic Steal Syndrome pooling of blood in the splanchnic vascular bed Pathogenesis of HRS
  7. 7. Stadlbauer VP, Wright GA, Banaji M, et al. Gastroenterology 2008;134:111–119. Pathogenesis of HRS
  8. 8. Stimulation of Vasoconstrictor System Stadlbauer VP, Wright GA, Banaji M, et al. Gastroenterology 2008;134:111–119. Pathogenesis of HRS
  9. 9. Pathogenesis of HRS + Loss of renal autoregulation
  10. 10. Pathogenesis of HRS + Loss of renal autoregulation Decrease MAP below the normal range that the autoregulation mechanism can act. Sympathetic mass reflex action
  11. 11. Pathogenesis of HRS + Loss of renal autoregulation
  12. 12. 12 Pere Ginès, M.D., and Robert W. Schrier, M.D. N Engl J Med 2009; 361:1279-1290
  13. 13. 13 Pere Ginès, M.D., and Robert W. Schrier, M.D. N Engl J Med 2009; 361:1279-1290
  14. 14. 14 Septic or cirrhotic cardiomyopathy Ginès P, Schrier RW. N Engl J Med. 2009;361(13):1279.
  15. 15. HRS is a FUNCTIONAL renal impairment Salerno F, Gerbes A, Gines P, et al. Gut 2007;56:1310–1318. + Loss of renal autoregulation
  16. 16. What Is The Prove That The Kidney Is Functionally Normal ? 16 A, Renal angiogram (the arrow marks the edge of the kidney). B, The angiogram carried out in the same kidney at autopsy. Epstein M, Berk DP, Hollenberg NK, et al. Am J Med. 1970; 49:175-185.
  17. 17. Precipitating Factors? Who At Risk? Salerno F, Gerbes A, Gines P, et al. Gut 2007;56:1310–1318.
  18. 18. Precipitating Factors? Who At Risk? 18 Fasolato S, Angeli P, Dallagnese L, et al. Hepatology 2007;45:223–229.
  19. 19. Precipitating Factors? Who At Risk? 19 The best is to PREVENT the occurrence of HRS
  20. 20. How To Prevent? Who At Risk How To Prevent 1- Large volume paracentesis without plasma expansion Give 100 ml 20% human albumin per 1.5L ascities removed 2- Over-Diuresis (weight loss >500g/day for several days in ascitic patient without (or 1kg/day in those with) peripheral edema Judicious use of diuretics, starting with low dose and titrate up slowly. 3- Laxative abuse diarrhea is a dose limiting sign for lactulose 4- GI bleeding Fluid & blood replacement till euvolemia. 5- SBP (any cirrhotic patient + ascities with deteriorating general condition is SBP till proven otherwise) A- antibiotics. B- IV albumin 1.5g/kg at diagnosis and 1g/kg 48hrs later. 6- Alcoholic hepatitis Pentoxifylline (a TNF inhibitor) 400mg tds orally. 7- The use of Nephrotoxic drugs Avoid. 8- Treatment of bleeding and esophageal varices (beta blockers, somatostatin) reduce GFR Monitored carefully
  21. 21. 21 A DIAGNOSIS OF EXCLUSION
  22. 22. 22 Is it HRS? Yes Which Type? HRS Type 1 HRS Type 2 No Pseudo HRS A DIAGNOSIS OF EXCLUSION
  23. 23. Arroyo V, Gines P, Gerbes AL, et al. Hepatology. 1996;23:164-176.
  24. 24. Major Diagnostic Criteria Of HRS (All Must Be Present) 1- Presence of liver disease. 2- Presence of renal impairment. 3- In absence of renal cause. 4- In absence of pre-renal cause. 5- In absence of post-renal cause. 24 A DIAGNOSIS OF EXCLUSION
  25. 25. • 1- Presence of liver disease: - Chronic or acute liver disease with advanced hepatic failure and portal hypertension • 2- Presence of renal impairment: - Low GFR as indicated by a 24-hr creatinine clearance of < 40 mL/min or serum creatinine > 1.5 mg/dL 25Salerno F, Gerbes A, Gines P, et al. Gut 2007;56:1310–1318. Arroyo V, Gines P, Gerbes AL, et al. Hepatology. 1996;23:164-176. Major Diagnostic Criteria Of HRS (All Must Be Present)
  26. 26. 3- In absence of renal cause: 26 Major Diagnostic Criteria Of HRS (All Must Be Present) Salerno F, Gerbes A, Gines P, et al. Gut 2007;56:1310–1318. Arroyo V, Gines P, Gerbes AL, et al. Hepatology. 1996;23:164-176. Imaging: No ultrasonographic findings of parenchymal renal disease. Lab: Proteinuria < 500 mg/dL.History: No exposure to nephrotoxins
  27. 27. 4- In absence of Pre-renal cause: 27 Major Diagnostic Criteria Of HRS (All Must Be Present) Salerno F, Gerbes A, Gines P, et al. Gut 2007;56:1310–1318. Arroyo V, Gines P, Gerbes AL, et al. Hepatology. 1996;23:164-176. Absence of Shock Sepsis Volume depletion
  28. 28. 4- In absence of Pre-renal cause: Major Diagnostic Criteria Of HRS (All Must Be Present) Salerno F, Gerbes A, Gines P, et al. Gut 2007;56:1310–1318. Arroyo V, Gines P, Gerbes AL, et al. Hepatology. 1996;23:164-176. Stop diuretics + Albumin (1 g/kg body weight/day up to 100 g maximum) 1.5 L of normal saline or No sustained improvement in renal function (to creatinine < 1.5 mg/dL or 24-hr CrCl to > 40 mL/min)
  29. 29. 4- In absence of Post-renal cause: Major Diagnostic Criteria Of HRS (All Must Be Present) Salerno F, Gerbes A, Gines P, et al. Gut 2007;56:1310–1318. Arroyo V, Gines P, Gerbes AL, et al. Hepatology. 1996;23:164-176. No ultrasonographic findings of obstructive uropathy
  30. 30. Take Care !!! Use of CREATININE for Renal Function Estimation In HRS 30Silkensen JR, Kasiske BL. Brenner and Rector’s The Kidney, 7th ed. Philadelphia: Saunders, 2004. Less Reliable Sever hyperbilirubinemia interfers with the Jaffe reaction for creatinine quantitification and may cause low results Renal impairment may be present despite a normal serum creatinine (because these patients are malnourished, with reduced lean body mass)
  31. 31. Take Care !!! Use of CREATININE for Renal Function Estimation 31 Serum Cr 2mg/dl Serum Cr 2mg/dl
  32. 32. Take Care !!! Use of UREA for Renal Function Estimation In HRS 32 Less Reliable Presence of gastrointestinal bleeding Low hepatic urea production
  33. 33. 33 Is it HRS? Yes Which Type? HRS Type 1 HRS Type 2 No Pseudo HRS A DIAGNOSIS OF EXCLUSION
  34. 34. Clinical Types of HRS Differentiation
  35. 35. 35 Clinical Types of HRS Prognosis Without treatment Median survival time of type 1 HRS is less than 2 weeks Median survival time of type 2 HRS about 6 months Alessandria C, Ozdogan O, Guevara M, et al. Hepatology 2005;41:1282–1289.
  36. 36. Liver Cirrhosis Liver Transplantation TIPS Vasoconstrictors + Albumin RRT Treatment Principles Regarding Pathophysiology MARS (Removal of toxins, some of which are vasodilators)
  37. 37. Liver Cirrhosis Liver Transplantation TIPS Vasoconstrictors + Albumin RRT Treatment Principles Regarding Pathophysiology MARS (Removal of toxins, some of which are vasodilators)
  38. 38. Treatment Principles Regarding Pathophysiology
  39. 39. Treatment Principles Regarding Pathophysiology
  40. 40. Treatment Principles Regarding Pathophysiology possibility of improvement in liver function
  41. 41. Treatment Principles Regarding Pathophysiology Salerno F, Gerbes A, Gines P, et al. Gut. 2007;56:1310-1318. Kiser TH, Fish DN, Obritsch MD, et al. Nephrol Dial Transplant. 2005;20:1813-1820. Martin-Llahi M, Pepin MN, Guevara M, et al. J Hepatol 2007;46:S36. Wong F. Nat Clin Pract Gastroenterol Hepatol 2007;4:43–51. All patients should receive ALBUMIN 1 g/kg up to 100 g in the first day 20 to 40 g/day afterward
  42. 42. Treatment Principles Miscellaneous Vasodilators: • Low-dose dopamine • Prostaglandin E1 analogues (misoprostol) • Endothelin receptor antagonists. No proven efficacy Angeli P, Volpin R, Gerunda G, et al. Hepatology 1999;29:1690–1697. Gines A, Salmeron JM, Gines P, et al. J Hepatol 1993;17:220–226. Wong F, Moore K, Dingemanse J, Jalan R. Hepatology 2008;47:160–168.
  43. 43. Treatment Principles Miscellaneous N-acetylcysteine (NAC) in combination with systemic vasoconstrictors or endothelin-receptor antagonists Based on a small case study of 12 patients with HRS who showed an improvement in serum creatinine after intravenous infusion of NAC, but it is not standard clinical practice at this time. Holt S, Goodier D, Marley R, et al. Lancet 1999;353:294–295. Izzedine H, Kheder-Elfekih R, Deray G. J Hepatol 2009;50:1055–1056. Sen S, Mookerjee RP, Jalan R. Gastroenterology 2002;123:2160–2161.
  44. 44. Liver Cirrhosis Liver Transplantation TIPS Vasoconstrictors + Albumin RRT Treatment Principles Regarding Pathophysiology MARS (Removal of toxins, some of which are vasodilators)
  45. 45. Liver Cirrhosis Liver Transplantation TIPS Vasoconstrictors + Albumin RRT Treatment Principles Regarding Pathophysiology MARS (Removal of toxins, some of which are vasodilators)
  46. 46. Ginès P, Schrier RW. N Engl J Med. 2009;361(13):1279. Iwakiri Y. J Clin Gastroenterol. 2007;41 Suppl 3:S288. Transjugular Intrahepatic Portosystemic Stent-Shunt (TIPS)
  47. 47. Transjugular Intrahepatic Portosystemic Stent-Shunt (TIPS) The track is dilated (arrow) and stented, creating a shunt as demonstrated on shuntogram. (Courtesy Dr. W. K. Tso, Queen Mary Hospital, Hong Kong.)
  48. 48. Liver Cirrhosis Liver Transplantation TIPS Vasoconstrictors + Albumin RRT Treatment Principles Regarding Pathophysiology MARS (Removal of toxins, some of which are vasodilators)
  49. 49. Liver Cirrhosis Liver Transplantation TIPS Vasoconstrictors + Albumin RRT Treatment Principles Regarding Pathophysiology MARS (Removal of toxins, some of which are vasodilators)
  50. 50. Renal Replacement Therapy
  51. 51. Renal Replacement Therapy
  52. 52. Renal Replacement Therapy Hemodialysis has been used as a short-term bridge to liver transplantation. Witzke O, Baumann M, Patschan D, et al. J Gastroenterol Hepatol 2004;19(12):1369–1373. There is no evidence that it increases long- term survival without transplantation.
  53. 53. Renal Replacement Therapy UF : Take care of systemic hypotension Filter size: Use small sized filters Anticoagulation: Should be avoided. If needed use LMWH. Catheterization: Right jugular and right femoral veins should be preserved for cannulation when going into bypass at the time of liver transplantation. CVVH is preferred
  54. 54. Liver Cirrhosis Liver Transplantation TIPS Vasoconstrictors + Albumin RRT Treatment Principles Regarding Pathophysiology MARS (Removal of toxins, some of which are vasodilators)
  55. 55. Liver Cirrhosis Liver Transplantation TIPS Vasoconstrictors + Albumin RRT Treatment Principles Regarding Pathophysiology MARS (Removal of toxins, some of which are vasodilators)
  56. 56. Liver Transplantation Most patients have high GFR after transplantation, although the majority don’t regain normal renal function, 10% incidence of ESRD at 11 years. 56 The only effective treatment Marik PE, Wood K, Starzl TE. Nephrol Dial Transplant 2006;21:478–482.
  57. 57. Liver Transplantation 57 Pretransplantation reversal of HRS allows achieving better outcome after transplantation Marik PE, Wood K, Starzl TE. Nephrol Dial Transplant 2006;21:478–482. The only effective treatment
  58. 58. Take Home Messages
  59. 59. HRS is a FUNCTIONAL renal impairment
  60. 60. The best is to PREVENT the occurrence of HRS
  61. 61. HRS is a diagnosis of EXCLUSION
  62. 62. Not all concomitant renal and hepatic impairment is due to the HRS It isn’t even on top of the list
  63. 63. Major Diagnostic Criteria Of HRS (All Must Be Present) 1- Presence of liver disease. 2- Presence of renal impairment. 3- In absence of renal cause. 4- In absence of pre-renal cause. 5- In absence of post-renal cause.
  64. 64. All patients should receive ALBUMIN 1 g/kg up to 100 g in the first day 20 to 40 g/day afterward
  65. 65. Hemodialysis has been used as a short- term bridge to liver transplantation. There is no evidence that it increases long- term survival without transplantation.
  66. 66. Catheterization: Right jugular and right femoral veins should be preserved for cannulation when going into bypass at the time of liver transplantation.
  67. 67. Liver Transplantation 70 The only effective treatment
  68. 68. www.kidneyadvances.com
  69. 69. Mohammed Abdel Gawad Thank You

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