Hepatorenal syndrome

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Hepatorenal syndrome
Classification and external resources
Cirrhosis high mag.jpg
Liver histology is altered in HRS while kidney histology is normal. The upper image is a trichrome stain (chicken wire appearance) cirrhosis of the liver, the most common cause of HRS. The lower image is a PAS stain of normal kidney histology.
Glomerulus pas.JPG
ICD-10 K76.7
ICD-9 572.4
DiseasesDB 5810
MedlinePlus
eMedicine med/1001 article/907429
MeSH D006530

Hepatorenal syndrome (HRS) is a life-threatening medical condition that consists of rapid deterioration in kidney function in individuals with cirrhosis or fulminant liver failure. HRS is usually fatal unless a liver transplant is performed, although various treatments, such as dialysis, can prevent advancement of the condition.

Contents

HRS can affect individuals with cirrhosis, severe alcoholic hepatitis, or liver failure, and usually occurs when liver function deteriorates rapidly because of a sudden insult such as an infection, bleeding in the gastrointestinal tract, or overuse of diuretic medications. HRS is a relatively common complication of cirrhosis, occurring in 18% of people within one year of their diagnosis, and in 39% within five years of their diagnosis. Deteriorating liver function is believed to cause changes in the circulation that supplies the intestines, altering blood flow and blood vessel tone in the kidneys. The kidney failure of HRS is a consequence of these changes in blood flow, rather than direct damage to the kidney. The diagnosis of hepatorenal syndrome is based on laboratory tests of individuals susceptible to the condition. Two forms of hepatorenal syndrome have been defined: Type 1 HRS entails a rapidly progressive decline in kidney function, while type 2 HRS is associated with ascites (fluid accumulation in the abdomen) that does not improve with standard diuretic medications.

The risk of death in hepatorenal syndrome is very high; the mortality of individuals with type 1 HRS is over 50% over the short term, as determined by historical case series. The only long-term treatment option for the condition is liver transplantation. While awaiting transplantation, people with HRS often receive other treatments that improve the abnormalities in blood vessel tone, including supportive care with medications, or the insertion of a transjugular intrahepatic portosystemic shunt (TIPS), which is a small shunt placed to reduce blood pressure in the portal vein. Some patients may require hemodialysis to support kidney function, or a newer technique called liver dialysis which uses a dialysis circuit with albumin-bound membranes to bind and remove toxins normally cleared by the liver, providing a means of extracorporeal liver support until transplantation can be performed.

Classification

The development of ascites (as shown on this abdominal ultrasound) in cirrhotics that is refractory to the use of diuretic medications is associated with type 2 HRS. Ascites ultrasound 2.JPG
The development of ascites (as shown on this abdominal ultrasound) in cirrhotics that is refractory to the use of diuretic medications is associated with type 2 HRS.

Hepatorenal syndrome is a particular and common type of kidney failure that affects individuals with liver cirrhosis or, less commonly, with fulminant liver failure. [1] The syndrome involves constriction of the blood vessels of the kidneys and dilation of blood vessels in the splanchnic circulation, which supplies the intestines. [2] The classification of hepatorenal syndrome identifies two categories of kidney failure, termed type 1 and type 2 HRS, which both occur in individuals with either cirrhosis or fulminant liver failure. In both categories, the deterioration in kidney function is quantified either by an elevation in creatinine level in the blood, or by decreased clearance of creatinine in the urine. [3]

Type 1 hepatorenal syndrome

Type 1 HRS is characterized by rapidly progressive kidney failure, with a doubling of serum creatinine to a level greater than 221 μmol/L (2.5 mg/dL) or a halving of the creatinine clearance to less than 20 mL/min over a period of less than two weeks. The prognosis of individuals with type 1 HRS is particularly grim, with a mortality rate exceeding 50% after one month. [4] Patients with type 1 HRS are usually ill, may have low blood pressure, and may require therapy with drugs to improve the strength of heart muscle contraction (inotropes) or other drugs to maintain blood pressure (vasopressors). [5] Unlike type II, in type I hepatorenal syndrome the kidney failure improves with treatment and stabilizes. Vasoconstrictors and volume expanders are the mainstay of treatment. [6]

In 2015, the International Club of Ascites updated their definition of HRS Type 1 in light of recent studies. Termed HRS-AKI, no minimum creatinine value is needed , that is, HRS-AKI can be diagnosed even when the serum creatinine is below 2.5mg/dl (221umol/L).

Requirement for HRS-AKI are:

  1. Increase in serum creatinine >0.3mg/L 26umol/L within 48 hrs OR increase by >1.5 times from baseline (reading from the last 3 months)
  2. No response to withdrawal of diuretics or administration of 1g/kg of albumin 20% over the last 2 days
  3. Cirrhosis with ascites
  4. Absence of
    1. Shock state
    2. Current or recent use of nephrotoxins (eg. NSAIDS, contrast dyes
    3. Signs of structural kidney disease
      1. proteinuria
      2. haematuria
      3. Abnormal findings on renal US

Type 2 hepatorenal syndrome

In contrast, type 2 HRS is slower in onset and progression, and is not associated with an inciting event. It is defined by an increase in serum creatinine level to >133 μmol/L (1.5 mg/dL) or a creatinine clearance of less than 40 mL/min, and a urine sodium < 10 μmol/L. [7] It also carries a poor outlook, with a median survival of approximately six months unless the affected individual undergoes liver transplantation. Type 2 HRS is thought to be part of a spectrum of illness associated with increased pressures in the portal vein circulation, which begins with the development of fluid in the abdomen (ascites). The spectrum continues with diuretic-resistant ascites, where the kidneys are unable to excrete sufficient sodium to clear the fluid even with the use of diuretic medications. Most individuals with type 2 HRS have diuretic-resistant ascites before they develop deterioration in kidney function. [8]

Similarly to the updated HRS-AKI, functional kidney injury in patients with cirrhosis that does not meet the criteria for HRS-AKI is termed HRS-NAKI. It can be divided into two groups, HRS-AKD, defined by eGFR <60ml/min/1.72 for less than 3 months, and HRS-CKD, defined by eGFR <60ml/min/1.72 for more than 3 months.

Signs and symptoms

Both types of hepatorenal syndrome share three major components: altered liver function, abnormalities in circulation, and death. As these phenomena may not necessarily produce symptoms until late in their course, individuals with hepatorenal syndrome are typically diagnosed with the condition on the basis of altered laboratory tests. Most people who develop HRS have cirrhosis, and may have signs and symptoms of the same, which can include jaundice, altered mental status, evidence of decreased nutrition, and the presence of ascites. [2] Specifically, the production of ascites that is resistant to the use of diuretic medications is characteristic of type 2 HRS. Oliguria, which is a decrease in urine volume, may occur as a consequence of kidney failure; however, some individuals with HRS continue to produce a normal amount of urine. [3] As these signs and symptoms may not necessarily occur in HRS, they are not included in the major and minor criteria for making a diagnosis of this condition; instead HRS is diagnosed in an individual at risk for the condition on the basis of the results of laboratory tests, and the exclusion of other causes. [3]

Causes

Hepatorenal syndrome usually affects individuals with cirrhosis and elevated pressures in the portal vein system (termed portal hypertension). While HRS may develop in any type of cirrhosis, it is most common in individuals with alcoholic cirrhosis, particularly if there is concomitant alcoholic hepatitis identifiable on liver biopsies. [9] HRS can also occur in individuals without cirrhosis, but with acute onset of liver failure, termed fulminant liver failure. [3] [9]

Certain precipitants of HRS have been identified in vulnerable individuals with cirrhosis or fulminant liver failure. These include bacterial infection, acute alcoholic hepatitis, or bleeding in the upper gastrointestinal tract. Spontaneous bacterial peritonitis, which is the infection of ascites fluid, is the most common precipitant of HRS in cirrhotic individuals. HRS can sometimes be triggered by treatments for complications of liver disease: iatrogenic precipitants of HRS include the aggressive use of diuretic medications or the removal of large volumes of ascitic fluid by paracentesis from the abdominal cavity without compensating for fluid losses by intravenous replacement. [9]

Diagnosis

There can be many causes of kidney failure in individuals with cirrhosis or fulminant liver failure. Consequently, it is a challenge to distinguish hepatorenal syndrome from other entities that cause kidney failure in the setting of advanced liver disease. As a result, additional major and minor criteria have been developed to assist in the diagnosis of hepatorenal syndrome. [3]

The major criteria include liver disease with portal hypertension; kidney failure; the absence of shock, infection, recent treatment with medications that affect the function of the kidney (nephrotoxins), and fluid losses; the absence of sustained improvement in kidney function despite treatment with 1.5 litres of intravenous normal saline; the absence of proteinuria (protein in the urine); and, the absence of kidney disease or obstruction of kidney outflow as seen on ultrasound. [3]

The minor criteria are the following: a low urine volume (less than 500 mL (18 imp fl oz; 17 US fl oz) per day), low sodium concentration in the urine, a urine osmolality that is greater than that in the blood, the absence of red blood cells in the urine, and a serum sodium concentration of less than 130 mmol/L. [3]

Many other diseases of the kidney are associated with liver disease and must be excluded before making a diagnosis of hepatorenal syndrome. Individuals with pre-renal kidney failure do not have damage to the kidneys, but as in individuals with HRS, have kidney dysfunction due to decreased blood flow to the kidneys. Also, similarly to HRS, pre-renal kidney failure causes the formation of urine that has a very low sodium concentration. In contrast to HRS, however, pre-renal kidney failure usually responds to treatment with intravenous fluids, resulting in reduction in serum creatinine and increased excretion of sodium. [3] Acute tubular necrosis (ATN) involves damage to the tubules of the kidney, and can be a complication in individuals with cirrhosis, because of exposure to toxic medications or the development of decreased blood pressure. Because of the damage to the tubules, ATN affected kidneys usually are unable to maximally resorb sodium from the urine. As a result, ATN can be distinguished from HRS on the basis of laboratory testing, as individuals with ATN will have urine sodium measurements that are much higher than in HRS; however, this may not always be the case in cirrhotics. [5] Individuals with ATN also may have evidence of hyaline casts or muddy-brown casts in the urine on microscopy, whereas the urine of individuals with HRS is typically devoid of cellular material, as the kidneys have not been directly injured. [3] Some viral infections of the liver, including hepatitis B and hepatitis C can also lead to inflammation of the glomerulus of the kidney. [10] [11] Other causes of kidney failure in individuals with liver disease include drug toxicity (notably, the antibiotic gentamicin) or contrast nephropathy, caused by intravenous administration of contrast agents used for medical imaging tests. [3]

Pathophysiology

Schematic demonstrating the underfill theory to explain the pathophysiology of both ascites and hepatorenal syndrome. HRS and ascites pathophysiology.svg
Schematic demonstrating the underfill theory to explain the pathophysiology of both ascites and hepatorenal syndrome.
Diagram showing hypothesized correlation between clinical features and pathophysiology of ascites and hepatorenal syndrome. HRS spectrum.svg
Diagram showing hypothesized correlation between clinical features and pathophysiology of ascites and hepatorenal syndrome.

The kidney failure in hepatorenal syndrome is believed to arise from abnormalities in blood vessel tone in the kidneys. [2] The predominant theory (termed the underfill theory) is that blood vessels in the kidney circulation are constricted because of the dilation of blood vessels in the splanchnic circulation (which supplies the intestines), which is mediated by factors released by liver disease. [4] [12] Nitric oxide, [13] prostaglandins, [2] [14] and other vasoactive substances [2] have been hypothesized as powerful mediators of splanchnic vasodilation in cirrhosis. [2] The consequence of this phenomenon is a decrease in the "effective" volume of blood sensed by the juxtaglomerular apparatus, leading to the secretion of renin and the activation of the renin–angiotensin system, which results in the vasoconstriction of vessels systemically and in the kidney specifically. [2] However, the effect of this is insufficient to counteract the mediators of vasodilation in the splanchnic circulation, leading to persistent "underfilling" of the kidney circulation and worsening kidney vasoconstriction, leading to kidney failure. [12]

Studies to quantify this theory have shown that there is an overall decreased systemic vascular resistance in hepatorenal syndrome, but that the measured femoral and kidney fractions of cardiac output are respectively increased and reduced, suggesting that splanchnic vasodilation is implicated in the kidney failure. [15] Many vasoactive chemicals have been hypothesized as being involved in mediating the systemic hemodynamic changes, including atrial natriuretic factor, [16] prostacyclin, thromboxane A2, [17] and endotoxin. [4] In addition to this, it has been observed that the administration of medications to counteract splanchnic vasodilation (such as ornipressin, [16] terlipressin, [18] and octreotide) [19] leads to improvement in glomerular filtration rate (which is a quantitative measure of kidney function) in patients with hepatorenal syndrome, providing further evidence that splanchnic vasodilation is a key feature of its pathogenesis.

The underfill theory involves activation of the renin–angiotensin–aldosterone system, which leads to an increase in absorption of sodium from the kidney tubule (termed renal sodium avidity) mediated by aldosterone, which acts on mineralocorticoid receptors in the distal convoluted tubule. [8] [12] This is believed to be a key step in the pathogenesis of ascites in cirrhotics as well. It has been hypothesized that the progression from ascites to hepatorenal syndrome is a spectrum where splanchnic vasodilation defines both resistance to diuretic medications in ascites (which is commonly seen in type 2 HRS) and the onset of kidney vasoconstriction (as described above) leading to hepatorenal syndrome. [8]

Prevention

Picture of the esophagus at the time of endoscopy showing prominent esophageal varices. Bleeding from esophageal varices can be a precipitant for hepatorenal syndrome in individuals with cirrhosis, and can be prevented by early diagnosis and treatment. Esophageal varices - wale.jpg
Picture of the esophagus at the time of endoscopy showing prominent esophageal varices. Bleeding from esophageal varices can be a precipitant for hepatorenal syndrome in individuals with cirrhosis, and can be prevented by early diagnosis and treatment.

The risk of death in hepatorenal syndrome is very high; consequently, there is a significant emphasis on the identification of patients who are at risk for HRS, and prevention of triggers for onset of HRS. As infection (specifically spontaneous bacterial peritonitis) and gastrointestinal hemorrhage are both complications in individuals with cirrhosis, and are common triggers for HRS, specific care is made in early identification and treatment of cirrhotics with these complications to prevent HRS. [5] Some of the triggers for HRS are induced by treatment of ascites and can be preventable. The aggressive use of diuretic medications should be avoided. In addition, many medications that are either used to treat cirrhotic complications (such as some antibiotics) or other conditions may cause sufficient impairment in kidney function in the cirrhotic to lead to HRS. [4] [5] Also, large volume paracentesis—which is the removal of ascites fluid from the abdomen using a needle or catheter in order to relieve discomfort—may cause enough alteration in hemodynamics to precipitate HRS, and should be avoided in individuals at risk. The concomitant infusion of albumin can avert the circulatory dysfunction that occurs after large-volume paracentesis and may prevent HRS. [20] Conversely, in individuals with very tense ascites, it has been hypothesized that removal of ascitic fluid may improve kidney function if it decreases the pressure on the renal veins. [21]

Individuals with ascites that have become infected spontaneously (termed spontaneous bacterial peritonitis or SBP) are at an especially high risk for the development of HRS. [2] In individuals with SBP, one randomized controlled trial found that the administration of intravenous albumin on the day of admission and on the third day in hospital reduced both the rate of kidney insufficiency and the mortality rate. [22]

Treatment

Transplantation

The definitive treatment for hepatorenal syndrome is liver transplantation, and all other therapies can best be described as bridges to transplantation. [1] [23] While liver transplantation is by far the best available management option for HRS, the mortality of individuals with HRS has been shown to be as high as 25% within the first month after transplantation. [24] Individuals with HRS and evidence of greater hepatic dysfunction (quantified as MELD scores above 36) have been found to be at greatest risk of early mortality after liver transplantation. [24] A further deterioration of kidney function even after liver transplantation in individuals with HRS has been demonstrated in several studies; however, this is transient and thought to be due to the use of medications with toxicity to the kidneys, and specifically the introduction of immunosuppressants such as tacrolimus and cyclosporine that are known to worsen kidney function. [2] Over the long-term, however, individuals with HRS who are the recipients of liver transplants almost universally recover kidney function, and studies show that their survival rates at three years are similar to those who have received liver transplants for reasons other than HRS. [1] [2]

In anticipation of liver transplantation (which may be associated with considerable in-hospital delay), several other strategies have been found to be beneficial in preserving kidney function. These include the use of intravenous albumin infusion, medications (for which the best evidence is for analogues of vasopressin, which causes splanchnic vasoconstriction), radiological shunts to decrease pressure in the portal vein, dialysis, and a specialized albumin-bound membrane dialysis system termed molecular adsorbents recirculation system (MARS) or liver dialysis. [2]

Medical therapy

Many major studies showing improvement in kidney function in patients with hepatorenal syndrome have involved expansion of the volume of the plasma with albumin given intravenously. [2] [25] [26] The quantity of albumin administered intravenously varies: one cited regimen is 1 gram of albumin per kilogram of body weight intravenously on the first day, followed by 20 to 40 grams daily. [27] Notably, studies have shown that treatment with albumin alone is inferior to treatment with other medications in conjunction with albumin; most studies evaluating pre-transplant therapies for HRS involve the use of albumin in conjunction with other medical or procedural treatment. [2] [28]

Midodrine is an alpha-agonist and octreotide is an analogue of somatostatin, a hormone involved in regulation of blood vessel tone in the gastrointestinal tract. The medications are respectively systemic vasoconstrictors and inhibitors of splanchnic vasodilation, and were not found to be useful when used individually in treatment of hepatorenal syndrome. [1] [2] [29] However, one study of 13 patients with hepatorenal syndrome showed significant improvement in kidney function when the two were used together (with midodrine given orally, octreotide given subcutaneously and both dosed according to blood pressure), with three patients surviving to discharge. [30] Another nonrandomized, observational study of individuals with HRS treated with subcutaneous octreotide and oral midodrine showed that there was increased survival at 30 days. [1] [31]

The vasopressin analogue ornipressin was found in a number of studies to be useful in improvement of kidney function in patients with hepatorenal syndrome, [1] [25] [32] but has been limited in its use, as it can cause severe ischemia to major organs. [1] [25] Terlipressin is a vasopressin analogue that has been found in one large study to be useful for improving kidney function in patients with hepatorenal syndrome with a lesser incidence of ischemia. [1] [26] A randomized control trial led by Florence Wong demonstrated improved renal function in individuals with Type 1 HRS treated with terlipressin and albumin over placebo. [33] A key criticism of all of these medical therapies has been heterogeneity in the populations investigated and the use of kidney function, instead of mortality, as an outcome measure. [34]

Other agents that have been investigated for use in treatment of HRS include pentoxifylline, [35] acetylcysteine, [36] and misoprostol. [1] [37] The evidence for all of these therapies is based on either case series, or in the case of pentoxifylline, extrapolated from a subset of patients treated for alcoholic hepatitis. [1]

Procedural treatments

TIPS, shown in progress here, has been shown to improve kidney function in individuals with HRS if portal pressures decrease after the procedure. Fluoroscopic image of transjugular intrahepatic portosystemic shunt (TIPS) in progress.jpg
TIPS, shown in progress here, has been shown to improve kidney function in individuals with HRS if portal pressures decrease after the procedure.

A transjugular intrahepatic portosystemic shunt (TIPS) involves the decompression of the high pressures in the portal circulation by placing a small stent between a portal and hepatic vein. This is done through radiologically guided catheters which are passed into the hepatic vein either through the internal jugular vein or the femoral vein. Theoretically, a decrease in portal pressures is thought to reverse the hemodynamic phenomena that ultimately lead to the development of hepatorenal syndrome. TIPS has been shown to improve kidney function in patients with hepatorenal syndrome. [8] [38] [39] Complications of TIPS for treatment of HRS include the worsening of hepatic encephalopathy (as the procedure involves the forced creation of a porto-systemic shunt, effectively bypassing the ability of the liver to clear toxins), inability to achieve adequate reduction in portal pressure, and bleeding. [8] [38]

Liver dialysis involves extracorporeal dialysis to remove toxins from the circulation, usually through the addition of a second dialysis circuit that contains an albumin-bound membrane. The molecular adsorbents recirculation system (MARS) has shown some utility as a bridge to transplantation in patients with hepatorenal syndrome, yet the technique is still nascent. [8] [40]

Renal replacement therapy may be required to bridge individuals with hepatorenal syndrome to liver transplantation, although the condition of the patient may dictate the modality used. [41] The use of dialysis, however, does not lead to recuperation or preservation of kidney function in patients with HRS, and is essentially only used to avoid complications of kidney failure until transplantation can take place. In patients who undergo hemodialysis, there may even be an increased risk of mortality due to low blood pressure in patients with HRS, although appropriate studies have yet to be performed. As a result, the role of renal replacement therapy in patients with HRS remains unclear. [2]

Epidemiology

As the majority of individuals with hepatorenal syndrome have cirrhosis, much of the epidemiological data on HRS comes from the cirrhotic population. The condition is quite common: approximately 10% of individuals admitted to hospital with ascites have HRS. [9] A retrospective case series of cirrhotic patients treated with terlipressin suggested that 20.0% of acute kidney failure in cirrhotics was due to type 1 HRS, and 6.6% was due to type 2 HRS. [18] It is estimated that 18% of individuals with cirrhosis and ascites will develop HRS within one year of their diagnosis with cirrhosis, and 39% of these individuals will develop HRS within five years of diagnosis. [9] Three independent risk factors for the development of HRS in cirrhotics have been identified: liver size, plasma renin activity, and serum sodium concentration. [9]

The prognosis of these patients is grim with untreated patients having an extremely short survival. [4] [9] [23] The severity of liver disease (as evidenced by the MELD score) has been shown to be a determinant of outcome. [24] [42] Some patients without cirrhosis develop HRS, with an incidence of about 20% seen in one study of ill patients with alcoholic hepatitis. [35]

History

The first reports of kidney failure occurring in individuals with chronic liver diseases were from the late 19th century by Frerichs and Flint. [9] However, the hepatorenal syndrome was first defined as acute kidney failure that occurred in the setting of biliary surgery. [1] [43] The syndrome was soon re-associated with advanced liver disease, [23] and, in the 1950s, was clinically defined by Sherlock, Hecker, Papper, and Vessin as being associated with systemic hemodynamic abnormalities and high mortality. [9] [44] Hecker and Sherlock specifically identified that individuals with HRS had low urinary output, very low sodium in the urine, and no protein in the urine. [1] Murray Epstein was the first to characterize splanchnic vasodilation and kidney vasoconstriction as the key alterations in hemodynamics in patients with the syndrome. [45] The functional nature of the kidney impairment in HRS was crystallized by studies demonstrating that kidneys transplanted from patients with hepatorenal syndrome returned to function in the new host, [46] leading to the hypothesis that hepatorenal syndrome was a systemic condition and not a kidney disease. The first systematic attempt to define hepatorenal syndrome was made in 1994 by the International Ascites Club, a group of liver specialists. The more recent history of HRS has involved elucidation of the various vasoactive mediators that cause the splanchnic and kidney blood flow abnormalities of the condition. [9]

Related Research Articles

Nephrology is a specialty for both adult internal medicine and pediatric medicine that concerns the study of the kidneys, specifically normal kidney function and kidney disease, the preservation of kidney health, and the treatment of kidney disease, from diet and medication to renal replacement therapy. The word "renal" is an adjective meaning "relating to the kidneys", and its roots are French or late Latin. Whereas according to some opinions, "renal" and "nephro" should be replaced with "kidney" in scientific writings such as "kidney medicine" or "kidney replacement therapy", other experts have advocated preserving the use of renal and nephro as appropriate including in "nephrology" and "renal replacement therapy", respectively.

<span class="mw-page-title-main">Proteinuria</span> Presence of an excess of serum proteins in the urine

Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein, less than 150 mg/day; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy. Severe proteinuria can cause nephrotic syndrome in which there is worsening swelling of the body.

<span class="mw-page-title-main">Ascites</span> Abnormal build-up of fluid in the abdomen

Ascites is the abnormal build-up of fluid in the abdomen. Technically, it is more than 25 ml of fluid in the peritoneal cavity, although volumes greater than one liter may occur. Symptoms may include increased abdominal size, increased weight, abdominal discomfort, and shortness of breath. Complications can include spontaneous bacterial peritonitis.

<span class="mw-page-title-main">Nephrotic syndrome</span> Symptoms resulting from kidney damage

Nephrotic syndrome is a collection of symptoms due to kidney damage. This includes protein in the urine, low blood albumin levels, high blood lipids, and significant swelling. Other symptoms may include weight gain, feeling tired, and foamy urine. Complications may include blood clots, infections, and high blood pressure.

<span class="mw-page-title-main">Kidney failure</span> Disease where the kidneys fail to adequately filter waste products from the blood

Kidney failure, also known as end-stage renal disease (ESRD), is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as either acute kidney failure, which develops rapidly and may resolve; and chronic kidney failure, which develops slowly and can often be irreversible. Symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, and confusion. Complications of acute and chronic failure include uremia, hyperkalemia, and volume overload. Complications of chronic failure also include heart disease, high blood pressure, and anaemia.

<span class="mw-page-title-main">Furosemide</span> Loop diuretic medication

Furosemide, sold under the brand name Lasix among others, is a loop diuretic medication used to treat edema due to heart failure, liver scarring, or kidney disease. Furosemide may also be used for the treatment of high blood pressure. It can be taken intravenously or orally. When given intravenously, furosemide typically takes effect within five minutes; when taken orally, it typically metabolizes within an hour.

<span class="mw-page-title-main">Portal hypertension</span> Abnormally increased portal venous pressure

Portal hypertension is defined as increased portal venous pressure, with a hepatic venous pressure gradient greater than 5 mmHg. Normal portal pressure is 1–4 mmHg; clinically insignificant portal hypertension is present at portal pressures 5–9 mmHg; clinically significant portal hypertension is present at portal pressures greater than 10 mmHg. The portal vein and its branches supply most of the blood and nutrients from the intestine to the liver.

<span class="mw-page-title-main">Acute kidney injury</span> Sudden decrease in kidney function that develops within 7 days

Acute kidney injury (AKI), previously called acute renal failure (ARF), is a sudden decrease in kidney function that develops within 7 days, as shown by an increase in serum creatinine or a decrease in urine output, or both.

Spontaneous bacterial peritonitis (SBP) is the development of a bacterial infection in the peritoneum, despite the absence of an obvious source for the infection. It is specifically an infection of the ascitic fluid – an increased volume of peritoneal fluid. Ascites is most commonly a complication of cirrhosis of the liver. It can also occur in patients with nephrotic syndrome. SBP has a high mortality rate.

Chronic liver disease in the clinical context is a disease process of the liver that involves a process of progressive destruction and regeneration of the liver parenchyma leading to fibrosis and cirrhosis. "Chronic liver disease" refers to disease of the liver which lasts over a period of six months. It consists of a wide range of liver pathologies which include inflammation, liver cirrhosis, and hepatocellular carcinoma. The entire spectrum need not be experienced.

<span class="mw-page-title-main">Renal vein thrombosis</span> Medical condition

Renal vein thrombosis (RVT) is the formation of a clot in the vein that drains blood from the kidneys, ultimately leading to a reduction in the drainage of one or both kidneys and the possible migration of the clot to other parts of the body. First described by German pathologist Friedrich Daniel von Recklinghausen in 1861, RVT most commonly affects two subpopulations: newly born infants with blood clotting abnormalities or dehydration and adults with nephrotic syndrome.

<span class="mw-page-title-main">Hypoalbuminemia</span> Abnormally low levels of albumin in the blood

Hypoalbuminemia is a medical sign in which the level of albumin in the blood is low. This can be due to decreased production in the liver, increased loss in the gastrointestinal tract or kidneys, increased use in the body, or abnormal distribution between body compartments. Patients often present with hypoalbuminemia as a result of another disease process such as malnutrition as a result of severe anorexia nervosa, sepsis, cirrhosis in the liver, nephrotic syndrome in the kidneys, or protein-losing enteropathy in the gastrointestinal tract. One of the roles of albumin is being the major driver of oncotic pressure in the bloodstream and the body. Thus, hypoalbuminemia leads to abnormal distributions of fluids within the body and its compartments. As a result, associated symptoms include edema in the lower legs, ascites in the abdomen, and effusions around internal organs. Laboratory tests aimed at assessing liver function diagnose hypoalbuminemia. Once identified, it is a poor prognostic indicator for patients with a variety of different diseases. Yet, it is only treated in very specific indications in patients with cirrhosis and nephrotic syndrome. Treatment instead focuses on the underlying cause of the hypoalbuminemia. Albumin is an acute negative phase respondent and not a reliable indicator of nutrition status.

Congenital nephrotic syndrome is a rare kidney disease which manifests in infants during the first 3 months of life, and is characterized by high levels of protein in the urine (proteinuria), low levels of protein in the blood, and swelling. This disease is primarily caused by genetic mutations which result in damage to components of the glomerular filtration barrier and allow for leakage of plasma proteins into the urinary space.

<span class="mw-page-title-main">Nodular regenerative hyperplasia</span> Medical condition

Nodular regenerative hyperplasia (NRH) is a rare liver disease, characterised by the growth of nodules within the liver, resulting in liver hyperplasia. While in many cases it is asymptomatic and thus goes undetected – or is only discovered incidentally while investigating some other medical condition – in some people it results in non-cirrhotic portal hypertension (NCPH). NCPH is generally less severe than the much more common portal hypertension due to cirrhosis. Complications of NCPH can include jaundice, ascites, splenomegaly, and bleeding esophageal varices. Most people with NRH retain normal liver function – even among the subset who go on to develop NCPH – and liver failure in NRH is uncommon. Only a small proportion of NRH patients will ever require liver transplantation.

Glomerulonephrosis is a non-inflammatory disease of the kidney (nephrosis) presenting primarily in the glomerulus as nephrotic syndrome. The nephron is the functional unit of the kidney and it contains the glomerulus, which acts as a filter for blood to retain proteins and blood lipids. Damage to these filtration units results in important blood contents being released as waste in urine. This disease can be characterized by symptoms such as fatigue, swelling, and foamy urine, and can lead to chronic kidney disease and ultimately end-stage renal disease, as well as cardiovascular diseases. Glomerulonephrosis can present as either primary glomerulonephrosis or secondary glomerulonephrosis.

<span class="mw-page-title-main">Cirrhosis</span> Chronic disease of the liver, characterized by fibrosis

Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is a condition of the liver in which the normal functioning tissue, or parenchyma, is replaced with scar tissue (fibrosis) and regenerative nodules as a result of chronic liver disease. Damage to the liver leads to repair of liver tissue and subsequent formation of scar tissue. Over time, scar tissue and nodules of regenerating hepatocytes can replace the parenchyma, causing increased resistance to blood flow in the liver's capillaries—the hepatic sinusoids—and consequently portal hypertension, as well as impairment in other aspects of liver function. The disease typically develops slowly over months or years.

A liver support system or diachysis is a type of therapeutic device to assist in performing the functions of the liver. Such systems focus either on removing the accumulating toxins, or providing additional replacement of the metabolic functions of the liver through the inclusion of hepatocytes to the device. A diachysis machine is used for acute care i.e. emergency care, as opposed to a dialysis machine which are typically used over the longer term. These systems are being trialed to help people with acute liver failure (ALF) or acute-on-chronic liver failure.

<span class="mw-page-title-main">Tyrosinemia type I</span> Medical condition

Tyrosinemia type I is a genetic disorder that disrupts the metabolism of the amino acid tyrosine, resulting in damage primarily to the liver along with the kidneys and peripheral nerves. The inability of cells to process tyrosine can lead to chronic liver damage ending in liver failure, as well as renal disease and rickets. Symptoms such as poor growth and enlarged liver are associated with the clinical presentation of the disease. If not detected via newborn screening and management not begun before symptoms appear, clinical manifestation of disease occurs typically within the first two years of life. The severity of the disease is correlated with the timing of onset of symptoms, earlier being more severe. If diagnosed through newborn screening prior to clinical manifestation, and well managed with diet and medication, normal growth and development is possible.

<span class="mw-page-title-main">Hepatic hydrothorax</span> Medical condition

Hepatic hydrothorax is a rare form of pleural effusion that occurs in people with liver cirrhosis. It is defined as an effusion of over 500 mL in people with liver cirrhosis that is not caused by heart, lung, or pleural disease. It is found in 5–10% of people with liver cirrhosis and 2–3% of people with pleural effusions. In cases of decompensated liver cirrhosis, prevalence rises significantly up to 90%. Over 85% of cases occurring on the right, 13% on the left, and 2% on both. Although it is most common in people with severe ascites, it can also occur in people with mild or no ascites. Symptoms are not specific and mostly involve the respiratory system.

<span class="mw-page-title-main">Florence Wong</span> Canadian scientist and physician

Florence Wong is a Canadian hepatologist and scientist best known for her research into the development and management of complications of cirrhosis. She is a professor of gastroenterology at the University of Toronto and a physician in the Division of Gastroenterology and Hepatology at the University Health Network.

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47. Smith and Aitkenhead's Textbook of Anaesthesia 7th edition

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