Pediatric Hepatorenal Syndrome

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Hepatorenal syndrome (HRS) is a functional, reversible form of acute kidney injury in patients with acute or chronic severe liver disease in the absence of any other identifiable causes of renal pathology. The condition is characterized by peripheral vasodilation with subsequent profound intrarenal vasoconstriction, resulting in decreased glomerular filtration. Renal vasoconstriction starts early in patients with liver disease, even before renal dysfunction is clinically evident. [1] In addition to arterial vasodilatation, progressive deterioration in cardiac function is also partly responsible for the development of HRS. [2]

Two types of HRS are described. Type 1 HRS is mainly associated with acute liver failure or alcoholic cirrhosis [3] but can also develop as a result of other forms of liver failure. It is characterized by rapid deterioration of renal function that usually occurs within 2 weeks, with an increase in serum creatinine and BUN levels and a substantial decrease in the glomerular filtration rate (GFR). Hyponatremia and other electrolyte abnormalities are common findings.

Type 2 HRS has a more insidious onset and is characterized by a steady and progressive decline in the renal function over weeks and sometimes months, as well as recurrent, diuretic-resistant ascites. It generally occurs more often in patients with hepatic dysfunction less severe than that observed in type 1. Both type 1 and type 2 HRS are associated with a poor prognosis.

Although the exact pathophysiologic mechanisms leading to HRS are not known, decreased renal blood flow caused by severe renal arterial and arteriolar vasoconstriction plays a major role. It is comprises the most advanced stage of hemodynamic dysfunction that begins early in the course of severe liver disease. [2] A paradoxical interplay between local and systemic factors, which lead to both vasoconstriction and vasodilatation, appear to perpetuate severe systemic arterial hypoperfusion. Although not directly responsible for the development of hepatorenal syndrome, lowered mean arterial pressure is frequently observed in patients with severe liver disease; this decrease is most likely secondary to release of local hepatic vasodilatory substances. Thus, a culmination of several factors leads to the development of HRS. These include inter alia: (1) portal hypertension, (2) altered peripheral blood circulation, (3) activation of the sympathetic nervous system, and (4) the release ofchemicalmediators.

This release is also accompanied by enhanced dilation of the splanchnic vascular beds due to portal hypertension, resulting in the opening of portosystemic shunts and minor arteriovenous (AV) fistulae. Renal venous pressure may also be increased because of compression of the inferior vena cava by ascites.

Dilation of the splanchnic vascular bed from locally produced nitric oxide, carbon monoxide, prostacyclin, and other vasodilatory substances decreases renal perfusion pressure (mean arterial pressure – renal vein pressure) and thus decreases renal blood flow. Renal perfusion is initially maintained because of the local production of vasodilatory factors, such as prostaglandin E, prostacyclin, and nitric oxide. However, as liver disease continues to advance, splanchnic blood flow increases, and systemic perfusion reduces further.

To maintain renal homeostasis and perfusion, several vasoconstrictor systems and substances are simultaneously activated. These include the renin-angiotensin-aldosterone system (RAAS), the sympathetic nervous system (SNS), and vasopressin, which lead to intense renal arterial and arteriolar vasoconstriction. As activation substantially increases, arterial and renal underfilling ensues and progresses, and hepatorenal syndrome develops. The final result is a severely decreased GFR and renal failure in the setting of no structural or intrinsic parenchymal renal disease.

Another theory attributes renal hypoperfusion directly to the diseased liver without any pathogenetic relationship to the hemodynamic changes. Two mechanisms support this theory: (1) decreased synthesis or release of a liver-borne factor that produces renal vasodilation and (2) the presence of a hepatorenal reflex that regulates the renal function, as demonstrated in experimental animals.

The hemodynamic changes that develop in cirrhosis in the splanchnic circulation are phenomenon that happen over time as a direct consequence of longstanding portal hypertension and are characterized by the following:

Splanchnic vasodilatation

IReduced effective arterial blood volume

Hyperdynamic circulation with increased cardiac output

Reduced systemic vascular resistance

Vasoconstriction of various extrasplanchnic vascular beds, including the renal and cerebral circulations

Increased activity of the renal angiotensin-aldosterone and sympathetic nervous systems and nonosmotic release of vasopressin (antidiuretic hormone)

These hemodynamic changes include tachycardia, increased cardia output, and abnormally low peripheral vascular resistance with decreased arterial blood pressure.

Cardiac dysfunction in cirrhosis is an important event. If circulatory dysfunction in cirrhosis was solely due to the progression of splanchnic arterial vasodilation and the hyperdynamic circulation, a compensatory mechanism of this disorder, cardiac output should increase as part of the homeostatic mechanism of effective arterial filling. Cardiac output is similar in patients with compensated cirrhosis, nonazotemic patients with cirrhosis and ascites, and patients with type 2 HRS despite the progressive increase in plasma levels of renin and norepinephrine during the course of cirrhosis, leading to increasing arterial vasodilation.

However, the heart rate may not increase despite the progressive stimulation of the sympathetic nervous system. This suggests that circulatory dysfunction in cirrhosis is related not only to progressive arterial vasodilation but also to an inability of the heart to increase cardiac output in response to a decrease in cardiac preload. The demonstration that type 1 hepatorenal syndrome occurs in the setting of a significant decrease in cardiac output in nonazotemic patients with cirrhosis and spontaneous bacterial peritonitis further supports the view that cardiac dysfunction is an important event in the pathogenesis of the impairment in circulatory and renal function in decompensated cirrhosis.

International

The prevalence of HRS has dramatically decreased in recent years, probably as a result of the improved management of cirrhotic patients and the wide use of prophylactic antibiotics for prevention of severe bacterial peritonitis. [4]

The annual incidence of HRS among adults with ascites and cirrhosis is approximately 8%. In addition, among adults with cirrhosis and portal hypertension, 20% develop hepatorenal syndrome in the first year after diagnosis, and as many as 40% of patients develop hepatorenal syndrome within 5 years after diagnosis. Recent data indicate a cumulative probability of developing HRS of 11.4% at 5 years. [5] These data included only patients with an initial episode of ascites with less advanced disease with the prevalence of HRS increasing with progression of liver disease. The incidence is much higher in patients with advanced liver disease awaiting liver transplantation, with a prevalence reaching as high as 48%. [6] Incidence data in children are scarce in the literature; therefore, the incidence of HRS in children is essentially unknown at this time.

The median survival of adults with type 1 HRS is estimated to be 2 weeks, and the hospital survival of the same patients is about 10% after 3 months. In contrast, the median survival of individuals with type 2 HRS is about 6 months. Recent data show improved survival in type 1 of (20%) and type 2 of (40%). [7] However, HRS carries the worst survival among all causes of acute kidney injury in cirrhotic patients with acute kidney injury. [8] Currently, mortality and morbidity rates in pediatric patients with HRS are unknown.

Survival and the recovery of renal function depend on the recovery of hepatic function, which is usually accomplished with liver transplantation in a minority of patients.

About 1-7% of patients with HRS develop end-stage renal disease and require dialysis despite liver transplantation and recovery of hepatic function.

Complications

Complications include the following:

Irreversible liver failure

Chronic, disabling hepatic encephalopathy

Death

End-stage renal disease

Recurrent, diuretic-resistant ascites

No data suggest that any particular race group is at risk. Thus, people of all races with chronic liver disease are likely to be at risk for hepatorenal syndrome.

To date, no data support any predilection for either sex.

In most reports in adults, patients are in their fourth to eighth decades of life.

Kastelan S, Ljubicic N, Kastelan Z, Ostojic R, Uravic M. The role of duplex-doppler ultrasonography in the diagnosis of renal dysfunction and hepatorenal syndrome in patients with liver cirrhosis. Hepatogastroenterology. 2004 Sep-Oct. 51(59):1408-12. [Medline].

Wadei HM. Hepatorenal syndrome: a critical update. Semin Respir Crit Care Med. 2012 Feb. 33(1):55-69. [Medline].

Wong F. Treatment to improve acute kidney injury in cirrhosis. Curr Treat Options Gastroenterol. 2015 Mar 15. [Medline].

Gines A, Escorsell A, Gines P, et al. Incidence, predictive factors, and prognosis of the hepatorenal syndrome in cirrhosis with ascites. Gastroenterology. 1993 Jul. 105(1):229-36. [Medline].

Planas R, Montoliu S, Balleste B, et al. Natural history of patients hospitalized for management of cirrhotic ascites. Clin Gastroenterol Hepatol. 2006 Nov. 4(11):1385-94. [Medline].

Wong LP, Blackley MP, Andreoni KA, Chin H, Falk RJ, Klemmer PJ. Survival of liver transplant candidates with acute renal failure receiving renal replacement therapy. Kidney Int. 2005 Jul. 68(1):362-70. [Medline].

Salerno F, Cazzaniga M, Merli M, et al. Diagnosis, treatment and survival of patients with hepatorenal syndrome: a survey on daily medical practice. J Hepatol. 2011 Dec. 55(6):1241-8. [Medline].

Stadlbauer V, Mookerjee RP, Hodges S, Wright GA, Davies NA, Jalan R. Effect of probiotic treatment on deranged neutrophil function and cytokine responses in patients with compensated alcoholic cirrhosis. J Hepatol. 2008 Jun. 48(6):945-51. [Medline].

Arroyo V, Gines P, Gerbes AL, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. International Ascites Club. Hepatology. 1996 Jan. 23(1):164-76. [Medline].

Salerno F, Gerbes A, Gines P, Wong F, Arroyo V. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007 Sep. 56(9):1310-8. [Medline]. [Full Text].

Remer EM, Papanicolaou N, Casalino DD, et al, for the Expert Panel on Urologic Imaging. ACR appropriateness criteria renal failure [online publication]. Reston, Va: American College of Radiology (ACR); 2013. Available at http://guideline.gov/content.aspx?id=47681. Accessed: March 19, 2015.

Nassar Junior AP, Farias AQ, D’ Albuquerque LA, Carrilho FJ, Malbouisson LM. Terlipressin versus Norepinephrine in the Treatment of Hepatorenal Syndrome: A Systematic Review and Meta-Analysis. PLoS One. 2014. 9(9):e107466. [Medline]. [Full Text].

Parson CE, Nelson R, Book L, Jensen MK. The use of renal replacement therapy in infants and children with hepatorenal syndrome awaiting liver transplantation: A case control study. Liver Transpl. 2014 Sep 1. [Medline].

Guevara M, Gines P, Bandi JC, et al. Transjugular intrahepatic portosystemic shunt in hepatorenal syndrome: effects on renal function and vasoactive systems. Hepatology. 1998 Aug. 28(2):416-22. [Medline].

Brensing KA, Textor J, Perz J, Schiedermaier P, Raab P, Strunk H. Long term outcome after transjugular intrahepatic portosystemic stent-shunt in non-transplant cirrhotics with hepatorenal syndrome: a phase II study. Gut. 2000 Aug. 47(2):288-95. [Medline].

Guerrini GP, Pleguezuelo M, Maimone S, et al. Impact of tips preliver transplantation for the outcome posttransplantation. Am J Transplant. 2009 Jan. 9(1):192-200. [Medline].

Davenport A. Renal replacement therapy in the patient with acute brain injury. Am J Kidney Dis. 2001 Mar. 37(3):457-66. [Medline].

Alessandria C, Debernardi-Venon W, Carello M, Ceretto S, Rizzetto M, Marzano A. Midodrine in the prevention of hepatorenal syndrome type 2 recurrence: a case-control study. Dig Liver Dis. 2009 Apr. 41(4):298-302. [Medline].

Alessandria C, Ottobrelli A, Debernardi-Venon W, Todros L, Cerenzia MT, Martini S. Noradrenalin vs terlipressin in patients with hepatorenal syndrome: a prospective, randomized, unblinded, pilot study. J Hepatol. 2007 Oct. 47(4):499-505. [Medline].

Barnardo DE, Baldus WP, Maher FT. Effects of dopamine on renal function in patients with cirrhosis. Gastroenterology. 1970 Apr. 58(4):524-31. [Medline].

Bataller R, Sort P, Gines P, Arroyo V. Hepatorenal syndrome: definition, pathophysiology, clinical features and management. Kidney Int Suppl. 1998 May. 66:S47-53. [Medline].

[Guideline] Bush WH Jr, Choyke PL, Bluth RI, et al. Renal failure. ACR Appropriateness Criteria renal failure. 2005. [Full Text].

Cardenas A. Hepatorenal syndrome: a dreaded complication of end-stage liver disease. Am J Gastroenterol. 2005 Feb. 100(2):460-7. [Medline].

Carl DE, Sanyal A. The management of hepatorenal syndrome. Minerva Gastroenterol Dietol. 2009 Jun. 55(2):207-26. [Medline].

Charlton MR, Wall WJ, Ojo AO, Gines P, Textor S, Shihab FS. Report of the first international liver transplantation society expert panel consensus conference on renal insufficiency in liver transplantation. Liver Transpl. 2009 Nov. 15(11):S1-34. [Medline].

Eason JD, Gonwa TA, Davis CL, Sung RS, Gerber D, Bloom RD. Proceedings of Consensus Conference on Simultaneous Liver Kidney Transplantation (SLK). Am J Transplant. 2008 Nov. 8(11):2243-51. [Medline].

Epstein M. The hepatorenal syndrome–newer perspectives. N Engl J Med. 1992 Dec 17. 327(25):1810-1. [Medline].

Fabrizi F, Dixit V, Messa P, Martin P. Terlipressin for hepatorenal syndrome: A meta-analysis of randomized trials. Int J Artif Organs. 2009 Mar. 32(3):133-40. [Medline].

Follo A, Llovet JM, Navasa M, et al. Renal impairment after spontaneous bacterial peritonitis in cirrhosis: incidence, clinical course, predictive factors and prognosis. Hepatology. 1994 Dec. 20(6):1495-501. [Medline].

Fullen WD. Hepatorenal syndrome: reversal by peritoneovenous shunt. Surgery. 1977 Sep. 82(3):337-41. [Medline].

Gines P, Arroyo V, Quintero E, Planas R, Bory F, Cabrera J. Comparison of paracentesis and diuretics in the treatment of cirrhotics with tense ascites. Results of a randomized study. Gastroenterology. 1987 Aug. 93(2):234-41. [Medline].

Gines P, Guevara M, Arroyo V, Rodes J. Hepatorenal syndrome. Lancet. 2003 Nov 29. 362(9398):1819-27. [Medline].

Gonwa TA, Morris CA, Goldstein RM, et al. Long-term survival and renal function following liver transplantation in patients with and without hepatorenal syndrome–experience in 300 patients. Transplantation. 1991 Feb. 51(2):428-30. [Medline].

Guevara M, Gines P, Fernandez-Esparrach G, et al. Reversibility of hepatorenal syndrome by prolonged administration of ornipressin and plasma volume expansion. Hepatology. 1998 Jan. 27(1):35-41. [Medline].

Guevara M, Rodes J. Hepatorenal syndrome. Int J Biochem Cell Biol. 2005 Jan. 37(1):22-6.

Gulberg V, Bilzer M, Gerbes AL. Long-term therapy and retreatment of hepatorenal syndrome type 1 with ornipressin and dopamine. Hepatology. 1999 Oct. 30(4):870-5. [Medline].

Henriksen JH. Cirrhosis: ascites and hepatorenal syndrome. Recent advances in pathogenesis. J Hepatol. 1995. 23 Suppl 1:25-30. [Medline].

Kiser TH, Fish DN, Obritsch MD, et al. Vasopressin, not octreotide, may be beneficial in the treatment of hepatorenal syndrome: a retrospective study. Nephrol Dial Transplant. 2005 Sep. 20(9):1813-20. [Medline].

Levy M. Hepatorenal syndrome. Kidney Int. 1993 Mar. 43(3):737-53. [Medline].

Magan AA, Khalil AA, Ahmed MH. Terlipressin and hepatorenal syndrome: what is important for nephrologists and hepatologists. World J Gastroenterol. 2010 Nov 7. 16(41):5139-47. [Medline].

Maroto A, Gines A, Salo J, et al. Diagnosis of functional kidney failure of cirrhosis with Doppler sonography: prognostic value of resistive index. Hepatology. 1994 Oct. 20(4 Pt 1):839-44. [Medline].

Moller S, Henriksen JH, Bendtsen F. Pathogenetic background for treatment of ascites and hepatorenal syndrome. Hepatol Int. 2008 Dec. 2(4):416-28. [Medline].

[Guideline] Murray KF, Carithers RL Jr. AASLD practice guidelines: Evaluation of the patient for liver transplantation. Hepatology. 2005 Jun. 41(6):1407-32. [Medline].

Neuschwander-Tetri BA. Organ interactions in the hepatorenal syndrome. New Horiz. 1994 Nov. 2(4):527-44. [Medline].

O’Beirne JP, Heneghan MA. Current management of the hepatorenal syndrome. Hepatol Res. 2005 Aug. 32(4):243-9. [Medline].

Ortega R, Gines P, Uriz J, et al. Terlipressin therapy with and without albumin for patients with hepatorenal syndrome: results of a prospective, nonrandomized study. Hepatology. 2002 Oct. 36(4 Pt 1):941-8. [Medline].

Peron JM, Bureau C, Gonzalez L, et al. Treatment of hepatorenal syndrome as defined by the international ascites club by albumin and furosemide infusion according to the central venous pressure: a prospective pilot study. Am J Gastroenterol. 2005 Dec. 100(12):2702-7. [Medline].

Roberts LR, Kamath PS. Ascites and hepatorenal syndrome: pathophysiology and management. Mayo Clin Proc. 1996 Sep. 71(9):874-81. [Medline].

Ruiz-del-Arbol L, Monescillo A, Jimenez W, Garcia-Plaza A, Arroyo V, Rodes J. Paracentesis-induced circulatory dysfunction: mechanism and effect on hepatic hemodynamics in cirrhosis. Gastroenterology. 1997 Aug. 113(2):579-86. [Medline].

Ruiz-del-Arbol L, Urman J, Fernandez J, et al. Systemic, renal, and hepatic hemodynamic derangement in cirrhotic patients with spontaneous bacterial peritonitis. Hepatology. 2003 Nov. 38(5):1210-8. [Medline].

Sacerdoti D, Bolognesi M, Merkel C, et al. Renal vasoconstriction in cirrhosis evaluated by duplex Doppler ultrasonography. Hepatology. 1993 Feb. 17(2):219-24. [Medline].

Salo J, Gines A, Quer JC, et al. Renal and neurohormonal changes following simultaneous administration of systemic vasoconstrictors and dopamine or prostacyclin in cirrhotic patients with hepatorenal syndrome. J Hepatol. 1996 Dec. 25(6):916-23. [Medline].

Skagen C, Einstein M, Lucey MR, Said A. Combination treatment with octreotide, midodrine, and albumin improves survival in patients with type 1 and type 2 hepatorenal syndrome. J Clin Gastroenterol. 2009 Aug. 43(7):680-5. [Medline].

Soper CP, Latif AB, Bending MR. Amelioration of hepatorenal syndrome with selective endothelin-A antagonist. Lancet. 1996 Jun 29. 347(9018):1842-3. [Medline].

Strang J, Ramlow W, Mitzner S, et al. Dialysis against a recycled albumin solution enables the removal of albumin-bound toxins. Artificial Organs. 1993. 17:809-13.

Testino G, Ferro C, Sumberaz A, Messa P, Morelli N, Guadagni B. Type-2 hepatorenal syndrome and refractory ascites: role of transjugular intrahepatic portosystemic stent-shunt in eighteen patients with advanced cirrhosis awaiting orthotopic liver transplantation. Hepatogastroenterology. 2003 Nov-Dec. 50(54):1753-5. [Medline].

Umgelter A, Schmid RM. [Terlipressin for hepatorenal syndrome – what is the role of plasma expansion and hemodynamic monitoring?]. Z Gastroenterol. 2009 Mar. 47(3):307-8. [Medline].

Van Roey G, Moore K. The hepatorenal syndrome. Pediatr Nephrol. 1996 Feb. 10(1):100-7. [Medline].

Wadei HM, Mai ML, Ahsan N, Gonwa TA. Hepatorenal syndrome: pathophysiology and management. Clin J Am Soc Nephrol. 2006 Sep. 1(5):1066-79. [Medline].

Witzke O, Baumann M, Patschan D, et al. Which patients benefit from hemodialysis therapy in hepatorenal syndrome?. J Gastroenterol Hepatol. 2004 Dec. 19(12):1369-73. [Medline].

Wong F, Pantea L, Sniderman K. Midodrine, octreotide, albumin, and TIPS in selected patients with cirrhosis and type 1 hepatorenal syndrome. Hepatology. 2004 Jul. 40(1):55-64. [Medline].

Xu X, Ling Q, Zhang M, et al. Outcome of patients with hepatorenal syndrome type 1 after liver transplantation: Hangzhou experience. Transplantation. 2009 May 27. 87(10):1514-9. [Medline].

Rajendra Bhimma, MBChB, MD, PhD, DCH (SA), FCP(Paeds)(SA), MMed(Natal) Associate Professor of Pediatrics, Principal Specialist, Department of Pediatrics and Child Health, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, South Africa

Rajendra Bhimma, MBChB, MD, PhD, DCH (SA), FCP(Paeds)(SA), MMed(Natal) is a member of the following medical societies: African Association of Nephrology, American Association for the Advancement of Science, International Pediatric Nephrology Association, International Society of Nephrology, National Kidney Foundation, South African Medical Association, South African Paediatric Association, South African Renal Society

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Barry J Evans, MD Assistant Professor of Pediatrics, Temple University Medical School; Director of Pediatric Critical Care and Pulmonology, Associate Chair for Pediatric Education, Temple University Children’s Medical Center

Barry J Evans, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society, Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Timothy E Corden, MD Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children’s Hospital of Wisconsin

Timothy E Corden, MD is a member of the following medical societies: American Academy of Pediatrics, Phi Beta Kappa, Society of Critical Care Medicine, Wisconsin Medical Society

Disclosure: Nothing to disclose.

G Patricia Cantwell, MD, FCCM Professor of Clinical Pediatrics, Chief, Division of Pediatric Critical Care Medicine, University of Miami Leonard M Miller School of Medicine/ Holtz Children’s Hospital, Jackson Memorial Medical Center; Medical Director, Palliative Care Team, Holtz Children’s Hospital; Medical Manager, FEMA, South Florida Urban Search and Rescue, Task Force 2

G Patricia Cantwell, MD, FCCM is a member of the following medical societies: American Academy of Hospice and Palliative Medicine, American Academy of Pediatrics, American Heart Association, American Trauma Society, National Association of EMS Physicians, Society of Critical Care Medicine, Wilderness Medical Society

Disclosure: Nothing to disclose.

The author would like to thank Mr. Duran Ramsuran and the staff of Medscape Drugs & Diseases for the help in reviewing this article.

Pediatric Hepatorenal Syndrome

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