Hepatorenal syndrome

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Classification according to ICD-10
K76.7 Hepatorenal syndrome
ICD-10 online (WHO version 2019)

The hepatorenal syndrome ( HRS ) or Hepatorenalsyndrom is a functional, progressive and potentially reversible decrease in renal function ( glomerular filtration rate ) with the consequence of oliguric renal failure in patients with liver disease ( cirrhosis or fulminant hepatitis ) in the absence of evidence of other causes of renal failure (diagnosis of exclusion) . Hepatorenal syndrome is a form of functional kidney failure without renal pathology. The release of vasoactive (vasodilating / constricting) substances leads to a deterioration in kidney blood flow.


The combination of portal hypertension and arterial vasodilation in the splanchnic area changes the intestinal capillary pressure with an increase in vascular permeability . This leads to an escape of fluid into the abdominal cavity and the development of ascites . As the disease progresses, this results in a relative intravascular fluid deficiency in the systemic circulation with a decrease in renal excretion of free water and renovascular vasoconstriction in order to maintain the renal perfusion pressure (in adults above 80 mm Hg) (underfill theory). The renin-angiotensin-aldosterone system (RAAS) is also reactively activated, which leads to the retention of sodium and water. This mechanism, which is quite useful in healthy people, leads to a further deterioration of the clinical picture in patients with portal hypertension.

The Merck Manual considers the pathogenesis to be unknown. The symptoms of oliguria and azotemia described there can not be explained solely by "extreme vasodilation" of the arteries in the splanchnic area .


The clinic manifests itself through signs of decompensated cirrhosis of the liver . These include ascites , edema , jaundice, and hepatic encephalopathy .

There are two types of HRS.

When type 1 , a rapidly progressive deterioration of renal function is. Criteria are a doubling of the serum creatinine to over 2.5 mg / dl, or a decrease of the creatinine clearance by half to below 20 ml / min, in each case within two weeks. Triggering factors can often be named for this type, including gastrointestinal bleeding , forced diuretic therapy , nephrotoxic drugs (e.g. non-steroidal anti-inflammatory drugs ), lactulose overdosage or paracentesis without plasma volume expansion.

In type 2 , there is a slowly progressive deterioration in kidney function with a serum creatinine of over 1.5 mg / dl. In contrast to type 1, this form often occurs spontaneously, i.e. without a triggering factor, and is an important cause of therapy-refractory ascites.

Definition and diagnostics

The hepatorenal syndrome is a diagnosis of exclusion . According to the definition of the International Ascites Club , the following main criteria must be met:

  • Creatinine increase to over 1.5 mg / dl or restriction of creatinine clearance to below 40 ml / min.
  • Portal hypertension
  • No circulatory depression
  • pronounced hepatic insufficiency
  • no current bacterial infections
  • no application of nephrotoxic drugs that could explain the kidney failure
  • no improvement in kidney function after expansion of plasma volume
  • No proteinuria above 500 mg / day
  • Urine volume less than 500 ml / day
  • Urine sodium concentration below 10 mmol / l
  • a urine osmolarity that is higher than the serum osmolarity
  • no erythrocyturia of more than 50 cells / visual field
  • Serum sodium concentration below 130 mmol / l

A congestion of the kidney vessels can be detected by a Doppler ultrasound examination of the kidneys. It makes the diagnosis of HRS more likely. Around half of the patients with such a constriction and liver cirrhosis develop an HRS.

The creatinine value can still be in the normal range in the presence of liver cirrhosis despite the kidney failure. Creatinine is released from the muscles. In cirrhosis of the liver, significantly less creatinine is released than in people with healthy liver. In oliguria or anuria , the creatinine level (regardless of the GFR ) will rise because of the increased tubular reabsorption.

In the case of anuria, the GFR cannot be determined; in the case of oliguria, the GFR calculations lead to incorrectly small results. All creatinine-based GFR estimation methods assume that creatinine is not and only minimally reabsorbed tubularly. In the compensation of a liquid lack all uremic substances (including urea , creatinine and cystatin C ) more or less completely with the primary urine exceptionally but reabsorbed tubularly, regardless of the actual GFR. However, high plasma levels of creatinine and cystatin C lead to a small GFR in the usual GFR estimation formulas, because they are in the denominator . - Urine is not available in anuria, so all clearance methods are also not feasible. And all nuclear medicine methods for determining the laterally separated filtrative kidney function (kidney function scintigraphy , kidney scintigraphy , radioisotope nephrography, renography, urography ) only provide the filtration ratio (or even only the elimination ratio ) of both kidneys to each other (with the sum 100%) without specifying the GFR.


The triggering factors must be eliminated therapeutically. The focus is therefore on the treatment of liver disease and heart failure . In addition, the acid-base balance is corrected, anemia is corrected through transfusions , albumin is administered intravenously and nephrotoxic substances are avoided. Under certain circumstances come renal replacement therapy in question, in severe renal tissue damage in rare cases, a kidney transplant . However, liver transplantation is usually the only definitive treatment option. A liver dialysis is rarely displayed .

If the above options are not feasible or insufficient, further options include a TIPS (transjugular intrahepatic portosystemic shunt ) and - for patients in poor general condition or with a contraindication for TIPS - pharmacological treatment with vasopressin analogues ( terlipressin ) or with Alphaadrenergic substances such as noradrenaline and milodril (vasoconstriction in the splanchnic area) in combination with albumin are in question.

Prospect of healing

The prognosis for hepatorenal syndrome is poor. The survival time for type 1 is usually less than a month without therapy, for type 2 the probability of survival is around 20% after two years. Around half of the patients with rapidly progressing Type I can survive for around three months with adequate therapy with a vasopressin analogue and albumin. The cause of death is liver failure in connection with circulatory failure in the context of multiple organ failure (i.e. in shock ) and only rarely is a uremic coma. At the autopsy one finds a severe bilateral nephropathy as a concomitant disease only in exceptional cases .


The Swiss physician Felix Platter ( Platerus , 1536–1614) described the impairment of kidney perfusion "through a blockage of the intestines, especially the liver". A oliguria was "due to a failure of the kidneys' only in the rarest cases. Only twice did he "see in his numerous sections that both kidneys were completely consumed (consumptus)". Felix Platter, the elder, also described the fact that "thick blood" ( viscosity ) reduces the blood flow to the kidneys and thus prevents sufficient primary urine from being " strained ".

The connection between kidney failure and liver cirrhosis was scientifically described for the first time in 1861 by von Frerichs (1819–1885) and in 1863 by Austin Flint II (1836–1915). In 1956 (unlike Felix Platter) the constriction of the renal vessels ( arteria renalis ) was identified as the triggering cause.

Wilhelm Nonnenbruch (1887–1955) described the hepatorenal syndrome in 1937 as kidney failure without kidney disease in liver patients. "Hepatorenal syndrome is a combination of anatomically defined liver disease with sometimes severe functional impairment of kidney function, with the kidneys showing little, if any, histological changes." Even so, until about 1956 the hepatorenal syndrome was not believed to exist. Solomon was the first to recall Nonnenbruch's definition in 1958 ("inexplicable renal insufficiency in cirrhosis of the liver without clinical, laboratory medical or anatomical evidence for other known causes of kidney failure with spontaneous reversibility").

Even Richard Bright (1789-1858) saw a connection between liver disease and kidney failure. The term hepatorenal insufficiency was first used in 1914 by the French doctor Prosper Merklen (born April 25, 1874 in Guebwiller , † April 21, 1939 in Strasbourg ). Even Franz Volhard counted the "Hepatorenal azotemia" to extrarenal nephrosis .


The existence of the hepatorenal syndrome has been questioned repeatedly. These doubts are caused by two different etiological ideas: kidney weakness with or without actual nephropathy. The fact that a patient can have prerenal and intrarenal causes of his kidney failure at the same time makes the diagnosis of the hepatorenal syndrome even more difficult.

If liver diseases reduce cardiac output and thus renal perfusion and glomerular filtration, renal insufficiency always occurs (according to Wilhelm Nonnenbruch), even without an actual kidney disease. The hepatorenal syndrome is one of the extrarenal kidney syndromes , i.e. one of the possibilities of renal insufficiency without parenchymal (and thus histologically or anatomically verifiable) kidney damage.

This hydromechanical pathomechanism contradicts the above requirements (in Chapter 3) that such circulatory depression must not be the cause and that an improvement in kidney function must not occur after an increase in the circulating plasma volume .

The circulatory collapse is one of the dominant causal factors of hepatorenal syndrome. On the other hand, it must by Gerd herald the current "diagnostic criteria" a representation of shock occurrence precisely not exist. Nevertheless, he describes the hepatorenal syndrome as "potentially reversible ".


Individual evidence

  1. Harrison's Internal Medicine. 18th edition. Volume 3, McGraw-Hill, Berlin 2012, ISBN 978-3-940615-20-6 , p. 2815; 19th edition, Volume 3, McGraw-Hill, Berlin 2016, ISBN 978-3-88624-560-4 , p. 2539.
  2. J. Peters: Effects of ventilation on kidney and liver function. In: J. Kilian, H. Benzer, FW Ahnefeld (ed.): Basic principles of ventilation. Springer, Berlin a. a. 1991, ISBN 3-540-53078-9 . (2nd, unchanged edition, ibid. 1994, ISBN 3-540-57904-4 , pp. 364–378; here: p. 365.)
  3. The Merck Manual , 20th Edition, Merck Sharp & Dohme, Kenilworth 2018, pp. 195 f.
  4. a b Gerd Herold u. a .: internal medicine. Self-published , Cologne 2013, p. 552.
  5. a b c H. M. Wadei et al: Hepatorenal Syndrome: Pathophysiology and Management , in: Clinical Journal of the American Society of Nephrology , Volume 1, No. 5, September 2006, pp. 1066-1079. PMID 17699328
  6. a b Gunter Wolf, Tammo von Schrenck: The hepatorenal syndrome: pathophysiology, diagnosis and therapy. In: Deutsches Ärzteblatt , Volume 97, Edition 43/2000, October 27, 2000, pp. A-2858–2862, B-2423, C-2158.
  7. ^ Fritz Scheler , MH Weber, N. Braun: Hepatorenal syndrome. In: Walter Siegenthaler et al. (Hrsg.): Textbook of internal medicine. 3. Edition. Georg Thieme Verlag , Stuttgart / New York 1992, ISBN 3-13-624303-X , pp. 529-531.
  8. Johanna Bleker : The history of kidney diseases , Boehringer Mannheim , Mannheim 1972, p. 25
  9. Felix Platter : Praxeus seu de cognoscendis, praedicendis curandisque affectibus homini incommodantibus , tract tres, Basel 1625, Volume I, p 429th
  10. Johanna Bleker : The history of kidney diseases , Boehringer Mannheim , Mannheim 1972, p. 25.
  11. Werner Creutzfeldt , Gustav Adolf Martini , Georg Strohmeyer: Milestones of gastroenterology and metabolic research , Falk Foundation , 1st edition, Freiburg 1997, ISBN 3-929713-69-1 , S. 210th
  12. ^ Wilhelm Nonnenbruch : "About the inflammatory edema of the kidney and the hepatorenal syndrome", in: Deutsche Medizinische Wochenschrift , 63rd year, number 1/1937, pp. 7-10.
  13. ^ Wilhelm Nonnenbruch : Das hepatorenal syndrome , in: Klinische Wochenschrift , 1939, p. 917 ff.
  14. ^ Wilhelm Nonnenbruch : "The hepatorenal syndrome", in: Wilhelm Nonenbruch: Die double-sided kidney diseases , Ferdinand Enke Verlag , Stuttgart 1949, pp. 174-180, and the bibliography ("The extrarenal kidney syndrome") on p. 198.
  15. Solomon: The role of the kidney in Laënnec 's cirrhosis of the liver , in: Medicine , Volume 37, 1958, p. 299.Source: Werner Creutzfeldt , Gustav Adolf Martini , Georg Strohmeyer: Milestones of Gastroenterology and Metabolic Research , Falk Foundation , Freiburg im Breisgau 1997, ISBN 3-929713-69-1 , p. 211.
  16. Prosper Merklen: hepato-Nephrite - insuffisance hépato-renal , Rev. Méd, born 35, 1916, p.172..
  17. O. Spühler: The interstitial nephritis and the importance of Franz Volhard for their teaching , in: Hans Erhard Bock , Karl-Heinz Hildebrand, Hans Joachim Sarre (ed.): Franz Volhard - Recollections , Schattauer Verlag, Stuttgart 1982, ISBN 3- 7845-0898-X , p. 169S. 168.
  18. ^ I. Bennhold, M. Kessel: Acute kidney failure in connection with diseases of the biliary system. In: Karl Julius Ullrich , Klaus Hierholzer (eds.): Normal and pathological functions of the kidney tubule. Verlag Hans Huber , Bern / Stuttgart 1965, p. 355.
  19. Quote: "Endangering the effective circulatory volume [leads to] a decrease in renal blood flow and glomerular filtration." Source: Hans Joachim Sarre : Kidney Diseases , 4th edition, Georg Thieme Verlag, Stuttgart 1976, ISBN 3-13-392804-X , p. 522.
  20. ^ Wilhelm Nonnenbruch : The hepatorenal syndrome , in: Wilhelm Nonnenbruch: Die double-sided kidney diseases , Ferdinand Enke Verlag , Stuttgart 1949, pp. 174-180.
  21. D. Renner, R. Heintz: The oxygen consumption of kidney and brain tissue as well as of mitochondria in sera from liver and kidney patients , in: Karl Julius Ullrich , Klaus Hierholzer (Ed.): Normal and pathological functions of the kidney tubule , Verlag Hans Huber , Bern / Stuttgart 1965, p. 393. In the bibliography on page 397, two works by Wilhelm Nonnenbruch (including his standard work) are cited.
  22. Gerd Herold : Internal Medicine 2019 , self-published , Cologne 2019, ISBN 978-3-9814660-8-9 , p. 553.