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Acute Renal Failure and Cirhosis

Acute Renal Failure and Cirhosis. By Syed Rizwan, MD. Differential Diagnosis- not always straightforward. Mainly invlove, ATN Volume Depletion Hepatoprenal Syndrome. CIRHOSIS. Involves complex Pathophysiologic changes in body. Ascites-most common complication

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Acute Renal Failure and Cirhosis

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  1. Acute Renal Failure and Cirhosis By Syed Rizwan, MD

  2. Differential Diagnosis- not always straightforward. • Mainly invlove, • ATN • Volume Depletion • Hepatoprenal Syndrome

  3. CIRHOSIS • Involves complex Pathophysiologic changes in body. • Ascites-most common complication • Hydraulic and Oncotic pressures determine net capillary pressure and Ascites formation • Portal Pressure > 12 mmHg required for Ascites formation

  4. CIRHOSIS • Ascites results from • Anatomic • Pathophysiologic • Biochemical Changes • Theory involving the Areterial Vasodilatation Hypothesis best explains Development of Ascites

  5. CIRHOSIS • Redution in Systemic Vascular Resistance • Lower mean arterial pressure • Increased cardiac output • Hyperdynamic Circulation • Reduced SVR is more prominent in the Splanchnic circulation- Ascites formation

  6. Mechanisms of Vasodilation inCIRHOSIS • Increased circulation of vasodilators • Vasoactive intestinal peptide • Substance P • Platelet Activating factor • Glucagon • Praotagladins • Nitric Oxide – most important

  7. NITRIC OXIDE(NO) • NO synthase activity higher in cirhotic rat with ascites. • Nitrite and Nitrate higher in Patients with cirhosis. • Inhibition of NO increase SVR, BP in cirhotic rats.

  8. NITRIC OXIDE(NO) • Increased NO synthesis is possibly because of, • Increased endotoxin absorption from GI tract. • Decreased clearance by liver because of Portasystemic shunts. • Decreased Reticuloenthelial Cell Function

  9. NITRIC OXIDE(NO) • NO concetration higher in Portal vein than peripheral veins • Correlation between serum nitrite and nitrate and endotaxin levels • Oral antiboiotic colistin reduce endotoxin level and nitrite and nitrate. • Bacterial DNA in cirhotic Patients blood.

  10. Activation of Vasoconstrictors • Low MAP/SVR – reduced pressure in carotid and Renal baroreceptors, to activate • Sympathetic nervous System • Renin-angiotensin system • Antidiueretic Harmone

  11. Consequences of Vasodilation • Increased endogenous Vasoconstrictors. • Sodium retention • Water retention • Renal vasoconstrition

  12. Sodium Retention • Vasodilation leads to third spacing and reduce central blood volume • “Effective Volume Depletion” leads to impaired Sodium excretion. • Low Sodium excretion could predict poor prognosis

  13. Water Retention • Increased ADH because of Low Effective Volume. • More rention with Ascites and Progression of liver disease. • Water renetion leads to Hyponatremia. • Poor prognostic indicator

  14. Renal Vasoconstriction • Vasodilation leads to activation of Vasoconstrictor System, • Reduce renal blood flow • Renal vasoconstrction • Renal Nitric oxide and Prostracylin production try to maintain renal blood flow initially

  15. Renal Vasoconstriction • Protective mechanism (Nitric oxide and Prostracycline ) production are overcome with Progresive liver diseae. • Gradual Decline in GFR could lead to Hepatorenal syndrome.

  16. Estimation of Renal Functionin Cirhosis • Serum Creatinine not reliable, • Low muscle mass • Low protein intake • Blood Urea could be low or high • Low Protein intake • Lower Urea production • GI Bleed

  17. Estimation of Renal Functionin Cirhosis GFR estimation may be better with creatinine clearance than serum creatinine.

  18. Differential Diagnosis- not always straightforward. • Mainly invlove, • ATN • Volume Depletion • Hepatoprenal Syndrome

  19. ARF and Cirhosis Hepatorenal Syndromeis a diagnosisof exclusion

  20. ARF and Cirhosis Diagnosis is difficult because, • Low urine in all settings • Low urine sodium even with ATN • Hyperbilirubinemia can induce Granular and Epithelial cast in urine even in Volume depleted Patient. • Diuretics may interfere Urine Sodium

  21. ARF and Cirhosis Differential diagnosis is important because of variable prognosis and management

  22. Hepatorenal Syndrome • Classically charaterised by • Oligouria • Benign Urine sediments • Low Urine Sodium • Rise in creatinie

  23. Hepatorenal Syndrome“Dianostic Criteria” • Advance Hepatic failure • Plasma creatinine > 1.5 • Exclude other causes of ARF • Low Urine Sodium(<10 meg/L) • Low Urine Protein(<500mg/Day) • Lack of imparovement with Voluma Exapnsion

  24. Hepatorenal Syndrome • Incidence increased with duration of Liver disease. • Higher risk with, • Hyponatremia • High renin activity • Precipated by acute insult, • Spontaneous Bacterial peritonitis, • GL bleed, • Infections • Diuretics are blamed but may not cause

  25. Hepatorenal SyndromeTYPES • Type 1 Hepatorenal Syndrome • More serious • Rapid onset- with 2weeks • Type 2 Hepatorenal syndrome • Less severe • Resistant to diuretics • Better prognosis

  26. ARF and CirhosisTreatment • Hold Diuretics • Volume Expansion • Rx any cause for ARF • Rx of Liver disease/Liver Transplant • Midodrine and Octreotid • Hemodialysis /CVVHD • TIPS/ Portasystemic shunts • Peritoneovenous Shunt • Prevention

  27. ARF and CirhosisTreatment • If volume contracted, • Hold Diuretic • Volume Expansion- Normal Saline at least 1-2 liters

  28. ARF and CirhosisTreatment • Prevent/Rx ARF, • Stop ACEI • Stop NSAID • Maintain BP • Rx of infection • Avoid IV contrast • Albumin after large volume Paracentesis

  29. ARF and CirhosisTreatment • Rx of Liver Disease, - Hepatitis B • Liver Transplantation

  30. ARF and CirhosisTreatment Midodrine and Octreotide • Midodrine – selctive Alpha-1 adrenergic agonist causes systemic vasoconstriction. • Octreotoide- a somatostatin analog inhibits endogenous vasodilators release. • Combined therapy effective

  31. ARF and CirhosisTreatment Midodrine and Octreotide Reversal of Type 1 Hepatorenal Syndrome with Midodrine and Octreotide (Angeli, P, Volpin, R, Gerunda, G et al. Hepatology 1999 29: 1690)

  32. ARF and CirhosisTreatment Midodrine and Octreotide • 13 Patients • Group A- 8 • Group B-5(Midodrine and Octreotide) • Both received IV Albumin • Dopamine to maintain BP • Similar characteristics Reversal of Type 1 Hepatorenal Syndrome with Midodrine and Octreotide (Angeli, P, Volpin, R, Gerunda, G et al. Hepatology 1999 29: 1690)

  33. ARF and CirhosisTreatment Midodrine and Octreotide Group B: 2 liver Tx, 1 lived > 472 days 1 died of Pneumonia(ARF resolved) 1 stoped Rx – died 15 days after dicharge Group A: 7 died with in 12 days 1 transplanted Reversal of Type 1 Hepatorenal Syndrome with Midodrine and Octreotide (Angeli, P, Volpin, R, Gerunda, G et al. Hepatology 1999 29: 1690)

  34. ARF and CirhosisTreatment Midodrine and Octreotide Group B vs Group A • Lower creatinine 1.8 vs 5.0 mg/dl • Better GFR 46vs 10 ml/min. • Urine volume 1540 vs 680 cc Reversal of Type 1 Hepatorenal Syndrome with Midodrine and Octreotide (Angeli, P, Volpin, R, Gerunda, G et al. Hepatology 1999 29: 1690)

  35. ARF and CirhosisTreatment Midodrine and Octreotide Midodrine /Octreotide therapy improves survival in Type-1 Hepatorenal Syndrome(abstract) (analysis of 53 treated and 21 controls Gastroenterlogy 2003; 124:A718. Esrailian,E, et al)

  36. ARF and CirhosisTreatment Midodrine and Octretide • Retrospective study • 53 Rx with Midodrine and Octretide • 21 control(non-randomized) • All had IV Albumin • Mortality Reduction(49 vs 67%) and lower creatinine (30 vs 14 %) in treated group vs controls Midodrine /Octreotide therapy improves survival in Type-1 Hepatorenal Syndrome (analysis of 53 treated and 21 controls Gastroenterlogy 2003; 124:A718. Esrailian,E, et al)

  37. ARF and CirhosisTreatment Drugs with variable Benefits • Ornipressin(Vasopressin analog) • Reduce splanchnic vasidilation • Induce ischemia • Misoprostol(Prostaglandin Analog) • Used with IV Albumin • Conflicting data • Norepinephrine with Albumin • Risk of Myocardial ischemia • N-acetylcysteine- • Reduce splanchnic vasodialtion • Need to be furhter studied

  38. ARF and CirhosisTreatment Hemodialysis/CVVHD • Usually difficult b/o low BP but can be done. • Consider in Pt waiting for liver Tranlplant or has chance for any recovery from liver injury. • Consider CVVHD(Continous Venovenous Heomdialysis) in Patients with lower BP.

  39. ARF and CirhosisTreatment Peritoneovenous Shunts • Improves hemodynamics • Reduce serum creatinie • Survival not improved • Unstable Patients with higher complications

  40. ARF and CirhosisTreatment TIPS (Transjugular intrahepatic portosystemic Shunt) • In refractory Ascites can improve renal function. • In Hepatorenal Syndrome- much less information.

  41. ARF and CirhosisTreatment TIPS (Transjugular intrahepatic portosystemic Shunt) TIPS in Hepatorenal syndrome. Lancet 1997; 349:697 Brensing, KA, Textor, J, Strunk, H, et al

  42. ARF and CirhosisTreatment TIPS (Transjugular intrahepatic portosystemic Shunt) • 16 Patients • 6 with severe Hepatorenal Syndrome(S.Cr>2.5) • 13 out of 16 had • Deceased S.Creatinine • Improved creatinine clearance • Increased urine out put • Renal functions improved with in 2 weeks. • Further improvement in ensuing 6-8 weeks. TIPS in Hepatorenal syndrome. Lancet 1997; 349:697 Brensing, KA, Textor, J, Strunk, H, et al

  43. ARF and CirhosisTreatment TIPS (Transjugular intrahepatic portosystemic Shunt) TIPS in Hepatorenal Syndrome Hepatology 1998; 28:416 Guevera, M Gines, P, Bandi, JC et al

  44. ARF and CirhosisTreatment TIPS (Transjugular intrahepatic portosystemic Shunt) • 7 Patients with Hepatorenal Syndrome. • Increased creatinine even with Volume expansion. • With TIPS GFR increased 9 to 27 TIPS in Hepatorenal Syndrome.Hepatology 1998; 28:416 Guevera, M Gines, P, Bandi, JC et al

  45. ARF and CirhosisTreatment TIPS (Transjugular intrahepatic portosystemic Shunt) • Pts. Too ill to undergo TIPS • Scoring System suggested by Malinchoc (A model to predict poor survival in Patients undergoing TIPS. Hepatology 2000 ; 31:864) • MELD risk score > 18 not candidate for TIPS • High risk of encephalopathy • Consider as a last resort or for Pt. Waiting for Liver Transplant.

  46. ARF and CirhosisTreatment Prevention • IV Albumin shown to prevent Hepatorenal syndrome in SBP(Spontenous Bacterial Peritonitis) • NEJM 1999; 341:403(Sort, P, Navasa, M, Arroyo, V et al • Albumin 1.5g/kg at the time of diagnosis and another dose 1.0g/kg on third day of Antibiotic Rx • Reduce incidence of ARF • Did not reduce mortality or Hospitalization.

  47. ARF and Cirhosis Summary • Hold Diuretics • IV Fluid Challenge/ IV Albumin/FFP • Pressors to Support BP(Dopamine) • Midiodrine/Octreotide. • Hemodialysis/CVVHD in Selected Pts. • TIPS in selected Pts. • Liver Transplant • Prevent by Rx of infections / iv Albumin

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