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hepatorenal syndrome; acute kidney injury in cirrhosis

Etiology: 1) liver failure a) terminal hepatic cirrhosis b) alcoholic hepatitis [11,12] c) acute Wilson's disease 2) pre-renal hypoperfusion a) diuretics b) gastrointestinal bleeding c) paracentesis 3) toxic agents that damage both the liver & kidney a) carbon tetrachloride b) leptospirosis c) amyloidosis d) methoxyflurane 4) vasculitis Epidemiology: 1) occurs in 40-50% of patients with terminal cirrhosis 2) generally develops in a hospital setting 3) some degree of functional renal impairment occurs in 1/2 of patients with cirrhosis & ascites [7] Pathology: 1) liver failure resulting in renal hypoperfusion 2) endothelin levels are 10 X normal 3) leukotriene abnormalities suggested 4) activated sympathetic nervous system 5) activated renin-angiotensin axis 6) splanchnic vasodilation & a decrease in systemic vascular resistance results in effective circulating volume depletion, renal vasoconstriction & hypoperfusion [17] 7) shunting of renal plasma flow from cortical to medullary segments 8) transition to acute tubular necrosis is possible 9) recovery occurs in about 10% of patients 10) histology does NOT suggest primary renal disease Clinical manifestations: 1) ascites 2) portal hypertension 3) jaundice 4) progressive azotemia & oliguria 5) hypotension/low blood pressure 6) esophageal varices may be present Diagnostic criteria: 1) major criteria* a) acute or chronic liver disease with advanced hepatic failure & portal hypertension - cirrhosis with ascites b) low glomerular filtration rate - serum creatinine > 1.5 mg/dL - creatinine clearance < 40 mL/min - diagnosis of acute kidney injury - increase in serum creatinine of >0.3 mg/dL within 48 hours - increase in serum creatinine of >50% within 7 days c) absence of - treatment with nephrotoxic agents - shock - infection - significant recent fluid lo d) no sustained improvement of renal function after discontinuation of diuretics & - administration of 1.5 L of normal saline - administration of albumin (1 g/kg body weight daily) e) proteinuria < 500 mg/dL, urine RBC < 50 cells/HPF, & no ultrasonographic evidence of obstruction or renal parenchymal disease 2) minor criteria** - urine volume < 500 mL/day - urine Na+ < 10 meq/L - urine osmolality > plasma osmolality - urine RBC < 50/hpf - serum [Na+] < 130 meq/L * must be present for diagnosis ** based on criteria of low GFR & avid Na+ retention Laboratory: (in addition to above) 1) low serum sodium: hyponatremia 2) high serum potassium: hyperkalemia 3) low serum albumin: hypoalbuminemia 4) high urine sodium in the absence of diuretics suggests another diagnosis 5) increased serum creatinine (>1.5 mg/dL) - diminished GFR (<50 mL/min) 6) increased serum urea (>30 mg/dL) 7) urine creatinine, fractional excretion of Na+ (FENA) < 1% 8) high plasma renin activity 9) low plasma osmolality, high urine osmolality Special laboratory: - diagnostic paracentesis if ascites Complications: - mortality is high (59%) [15] Differential diagnosis: - prerenal azotemia [17] Management: 1) supportive measures a) discontinue diuretics & other potentially offending agents b) optimized central & renal hemodynamics c) volume expansion with IV albumin - assess component of prerenal azotemia (first line) [3] - IV albumin useful for anti-inflammatory effects [16] d) sodium restriction, restrict free water if hyponatremia e) vasocontriction - terlipressin + epinephrine first line [20,21] - terlipressin may be given through a peripheral line [21] - norepinephrine may delay mortality (1st line agent in U.S.) [5,18] - terlipressin facilitates reversal of hepatorenal syndrome & may improve mortality, but increases risk of serious events [19] - combination of octreotide + midodrine + vasopressin [14,15] - conflicting evidence regarding efficacy [15,18] - dobutamine (NEJM) [20] - if no benefit of maximum dose of vasopressor in 4 days, further benefit unlikely [18] f) low dose (renal) dopamine g) high doses of spironolactone (Aldactone) 2) hemodialysis - if patient does not respond to octreotide + midodrine or norepinephrine - hyperkalemia - metabolic acidosis - pulmonary edema refractory to medical therapy - symptoms of uremia - drug intoxication 3) surgery a) LeVeen shunt b) liver transplantation is treatment of choice 4) prognosis: 3-6 month survival is ~ 20-40% 5) prevention: - IV albumin in patients with cirrhosis & spontaneous bacterial peritonitis reduces incidence of hepatorenal syndrome [3] - predisolone + pentoxifylline may reduce incidence of hepatorenal syndrome in patients with alcoholic hepatitis [12]

Related

peritoneal venous shunt; LeVeen shunt

General

liver disease acute renal failure (ARF) syndrome

References

  1. Stedman's Medical Dictionary 26th ed, Williams & Wilkins, Baltimore, 1995
  2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 596
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 18. American College of Physicians, Philadelphia 1998, 2009, 2012, 2018. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. Medical Guidelines for Determining Prognosis in non-Cancer Diseases, 2nd edition, Stuart et al (eds), National Hospice Organization, Arlington, VA, 1996
  5. Journal Watch 22(18):145, 2002 Duvoux C et al, Hepatology 36:374, 2002 Gines P & Guevara M, Hepatology 36:504, 2002
  6. eMedicine: Hepatorenal Syndrome http://www.emedicine.com/med/topic1001.htm
  7. Montoliu S et al. Incidence and prognosis of different types of functional renal failure in cirrhotic patients with ascites. Clin Gastroenterol Hepatol 2010 Jul; 8:616. PMID: 20399905
  8. Garcia-Tsao G, Parikh CR, Viola A Acute kidney injury in cirrhosis. Hepatology. 2008 Dec;48(6):2064-77 PMID: 19003880
  9. Gines P, Schrier RW. Renal failure in cirrhosis. N Engl J Med. 2009 Sep 24;361(13):1279-90 PMID: 19776409
  10. Nadim MK, Kellum JA, Davenport A et al Hepatorenal syndrome: the 8th International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2012 Feb 9;16(1):R23. Review. PMID: 22322077 Free PMC Article
  11. Rana R, Wang SL, Li J, Xia L, Song MY, Yang CQ. A prognostic evaluation and management of alcoholic hepatitis. Minerva Med. 2017 Jun 9. PMID: 28602070
  12. Lee YS, Kim HJ, Kim JH et al Treatment of Severe Alcoholic Hepatitis With Corticosteroid, Pentoxifylline, or Dual Therapy: A Systematic Review and Meta- Analysis. J Clin Gastroenterol. 2017 Apr;51(4):364-377. PMID: 27636406
  13. Glass L, Sharma P. Evidence-Based Therapeutic Options for Hepatorenal Syndrome. Gastroenterology. 2016 Apr;150(4):1031-3. PMID: 26922867
  14. Colle I, Laterre PF. Hepatorenal syndrome: the clinical impact of vasoactive therapy. Expert Rev Gastroenterol Hepatol. 2018 Feb;12(2):173-188. Review. PMID: 29258378
  15. Best LM, Freeman SC, Sutton AJ et al. Treatment for hepatorenal syndrome in people with decompensated liver cirrhosis: A network meta-analysis. Cochrane Database Syst Rev 2019 Sep 12; 9:CD013103 PMID: 31513287 https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013103.pub2/full
  16. China L, Freemantle N, Forrest E et al. A randomized trial of albumin infusions in hospitalized patients with cirrhosis. N Engl J Med 2021 Mar 4; 384:808 PMID: 33657293 https://www.nejm.org/doi/10.1056/NEJMoa2022166
  17. NEJM Knowledge+ Question of the Week. June 8, 2021 https://knowledgeplus.nejm.org/question-of-week/1918/
  18. Biggins SW et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome: 2021 practice guidance by the American Association for the Study of Liver Diseases. Hepatology 2021 Aug; 74:1014 PMID: 33942342 https://aasldpubs.onlinelibrary.wiley.com/doi/10.1002/hep.31884
  19. Pitre T et al. The comparative effectiveness of vasoactive treatments for hepatorenal syndrome: A systematic review and network meta-analysis. Crit Care Med 2022 Oct 1; 50:1419. PMID: 35777925 https://journals.lww.com/ccmjournal/Fulltext/2022/10000/The_Comparative_Effectiveness_of_Vasoactive.1.aspx
  20. NEJM Knowledge+ Complex Medical Care
  21. Garcia-Tsao G et al. AGA clinical practice update on the use of vasoactive drugs and intravenous albumin in cirrhosis: Expert review. Gastroenterology 2024 Jan; 166:202. PMID: 37978969 https://www.gastrojournal.org/article/S0016-5085(23)05143-0/fulltext