Hepatorenal Syndrome (Clinical)

Etiology

Hepatorenal syndrome Hepatorenal Syndrome Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of HRS is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Hepatorenal Syndrome ( HRS HRS Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of hrs is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Hepatorenal Syndrome) is associated with portal hypertension Portal hypertension Portal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Portal Hypertension due to:^[1]

• Cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
• Severe alcoholic Alcoholic Persons who have a history of physical or psychological dependence on ethanol. Mallory-Weiss Syndrome (Mallory-Weiss Tear) hepatitis
• Metastatic tumors
• Any cause of fulminant liver failure Liver failure Severe inability of the liver to perform its normal metabolic functions, as evidenced by severe jaundice and abnormal serum levels of ammonia; bilirubin; alkaline phosphatase; aspartate aminotransferase; lactate dehydrogenases; and albumin/globulin ratio. Autoimmune Hepatitis

Pathophysiology

1. Portal hypertension Portal hypertension Portal hypertension is increased pressure in the portal venous system. This increased pressure can lead to splanchnic vasodilation, collateral blood flow through portosystemic anastomoses, and increased hydrostatic pressure. There are a number of etiologies, including cirrhosis, right-sided congestive heart failure, schistosomiasis, portal vein thrombosis, hepatitis, and Budd-Chiari syndrome. Portal Hypertension triggers arterial vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs in the splanchnic circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment. ^[1–3,7]
2. This causes: ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites → arterial hypovolemia Hypovolemia Sepsis in Children → activation of renin-angiotensin-aldosterone system Renin-angiotensin-aldosterone system A blood pressure regulating system of interacting components that include renin; angiotensinogen; angiotensin converting enzyme; angiotensin i; angiotensin ii; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to angiotensin II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal vascular smooth muscle, leading to retention of salt and water in the kidney and increased arterial blood pressure. In addition, angiotensin II stimulates the release of aldosterone from the adrenal cortex, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down bradykinin, a powerful vasodilator and component of the kallikrein-kinin system. Adrenal Hormones ( RAAS RAAS A blood pressure regulating system of interacting components that include renin; angiotensinogen; angiotensin converting enzyme; angiotensin i; angiotensin ii; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to angiotensin II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal vascular smooth muscle, leading to retention of salt and water in the kidney and increased arterial blood pressure. In addition, angiotensin II stimulates the release of aldosterone from the adrenal cortex, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down bradykinin, a powerful vasodilator and component of the kallikrein-kinin system. Adrenal Hormones)
3. Activation of RAAS RAAS A blood pressure regulating system of interacting components that include renin; angiotensinogen; angiotensin converting enzyme; angiotensin i; angiotensin ii; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to angiotensin II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal vascular smooth muscle, leading to retention of salt and water in the kidney and increased arterial blood pressure. In addition, angiotensin II stimulates the release of aldosterone from the adrenal cortex, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down bradykinin, a powerful vasodilator and component of the kallikrein-kinin system. Adrenal Hormones causes: renal vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure → hypoperfusion of the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy → oliguria Oliguria Decreased urine output that is below the normal range. Oliguria can be defined as urine output of less than or equal to 0. 5 or 1 ml/kg/hr depending on the age. Renal Potassium Regulation → anuria Anuria Absence of urine formation. It is usually associated with complete bilateral ureteral (ureter) obstruction, complete lower urinary tract obstruction, or unilateral ureteral obstruction when a solitary kidney is present. Acute Kidney Injury → progressive kidney failure 

Trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation factors are any interventions or conditions that cause arterial hypovolemia Hypovolemia Sepsis in Children:

• Drainage of ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites
• Bacterial infection 
• Gastrointestinal bleeding Gastrointestinal bleeding Gastrointestinal bleeding (GIB) is a symptom of multiple diseases within the gastrointestinal (GI) tract. Gastrointestinal bleeding is designated as upper or lower based on the etiology’s location to the ligament of Treitz. Depending on the location of the bleeding, the patient may present with hematemesis (vomiting blood), melena (black, tarry stool), or hematochezia (fresh blood in stools). Gastrointestinal Bleeding
• Excessive use of diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication

Clinical Presentation and Diagnosis

Diagnostic criteria may vary depending on practice location. The following information is based on US, UK, and European recommendations.

Clinical presentation^[3,7]

• New-onset signs of renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome with no other identifiable cause:
  • Oliguria Oliguria Decreased urine output that is below the normal range. Oliguria can be defined as urine output of less than or equal to 0. 5 or 1 ml/kg/hr depending on the age. Renal Potassium Regulation (< 500 mL urine per day) → anuria Anuria Absence of urine formation. It is usually associated with complete bilateral ureteral (ureter) obstruction, complete lower urinary tract obstruction, or unilateral ureteral obstruction when a solitary kidney is present. Acute Kidney Injury → acute kidney injury Acute Kidney Injury Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury ( AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury)
  • In the early phase of HRS HRS Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of hrs is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Hepatorenal Syndrome, urine output is often normal.
• Signs of water retention:
  • Edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • Ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites
  • Pleural effusion Pleural Effusion Pleural effusion refers to the accumulation of fluid between the layers of the parietal and visceral pleura. Common causes of this condition include infection, malignancy, autoimmune disorders, or volume overload. Clinical manifestations include chest pain, cough, and dyspnea. Pleural Effusion
• Signs and symptoms of cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis:
  • Jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice
  • Gynecomastia Gynecomastia Gynecomastia is a benign proliferation of male breast glandular ductal tissue, usually bilateral, caused by increased estrogen activity, decreased testosterone activity, or medications. The condition is common and physiological in neonates, adolescent boys, and elderly men. Gynecomastia
  • Asterixis Asterixis Hepatic Encephalopathy

Classification and diagnostic criteria

HRS HRS Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of hrs is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Hepatorenal Syndrome is a diagnosis of exclusion. There has been a recent shift in the classification of HRS HRS Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of hrs is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Hepatorenal Syndrome. Because AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury is common in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis for a multitude of reasons, the International Club of Ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites proposed the following staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis and classification:

AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury definition and staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis:^[1,3,7,13]

• General definition:
  • ↑ Serum creatinine ≥ 0.3 mg/dL within 48 hours, OR
  • Increase of ≥ 50% from baseline creatinine within prior 7 days
• Stage 1 Stage 1 Trypanosoma brucei/African trypanosomiasis:
  • ↑ Serum creatinine ≥ 0.3 mg/dL OR
  • ↑ Serum creatinine up to 2-fold from baseline
• Stage 2: ↑ Serum creatinine 2‒3-fold from baseline
• Stage 3:
  • ↑ Serum creatinine > 3-fold from baseline OR
  • ↑ Serum creatinine ≥ 4 mg/dL with:
    • Acute rise of ≥ 0.3 mg/dL OR
    • Initiation of renal replacement therapy

HRS HRS Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of hrs is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Hepatorenal Syndrome classification with diagnostic criteria:

• HRS-AKI (also referred to as type 1 Type 1 Spinal Muscular Atrophy HRS HRS Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of hrs is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Hepatorenal Syndrome):^{[1,3,7,11‒13,15]}
  • Cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis and ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites present
  • AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury present (some texts specify AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury stage 2 or 3)
  • No response to the following after ≥ 2 consecutive days:
    • Diuretic withdrawal 
    • Volume expansion with 1g/kg albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests administration (maximum: 100 g/day)
  • Absence of shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock
  • No current or recent history of nephrotoxic medications (e.g., NSAIDs NSAIDS Primary vs Secondary Headaches)
  • No signs of structural kidney injury, including a lack of:
    • Proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children (> 500 mg/day)
    • Microhematuria (> 50 RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology/high-power field (HPF))
    • Findings on renal ultrasonography
• HRS-NAKI (also referred to as type 2 HRS Type 2 HRS Hepatorenal Syndrome, or “diuretic-resistant ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites”; the kidney function impairment is less severe than that observed with HRS-AKI/ type 1 Type 1 Spinal Muscular Atrophy disease) is subdivided into:^[1,5,12,15]
  • HRS-acute kidney disease (AKD):
    • Does not quite meet the criteria of AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury (e.g., creatinine rise < 50% of baseline)
    • Time period: < 3 months
    • Absence of other/structural causes
  • HRS-chronic kidney disease ( CKD CKD Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease):
    • Time period: ≥ 3 months
    • Absence of other/structural causes

Differential diagnoses to consider^[3,8]

The history and workup should focus on ruling out other potential causes of renal dysfunction, such as:

• Hypovolemia Hypovolemia Sepsis in Children (e.g., diuretic use)
• Acute tubular necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage (ATN; e.g., from sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock, shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock, nephrotoxic agents Nephrotoxic Agents Surgical Complications)
• Bile Bile An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts; cholesterol; and electrolytes. It aids digestion of fats in the duodenum. Gallbladder and Biliary Tract: Anatomy cast nephropathy (associated with hyperbilirubinemia Hyperbilirubinemia A condition characterized by an abnormal increase of bilirubin in the blood, which may result in jaundice. Bilirubin, a breakdown product of heme, is normally excreted in the bile or further catabolized before excretion in the urine. Jaundice)
• Glomerulonephritis (e.g., membranoproliferative glomerulonephritis Membranoproliferative Glomerulonephritis Membranoproliferative glomerulonephritis (MPGN) is also known as mesangiocapillary glomerulonephritis. Membranoproliferative glomerulonephritis is a pattern of glomerular injury characterized by mesangial hypercellularity, endocapillary proliferation, and thickening of the glomerular basement membrane (double contour formation). Membranoproliferative Glomerulonephritis associated with hepatitis B Hepatitis B Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Most individuals with acute HBV infection are asymptomatic or have mild, self-limiting symptoms. Chronic infection can be asymptomatic or create hepatic inflammation, leading to liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B Virus or C)
• Postrenal obstruction

Laboratory evaluation^{[1,7,10‒12]}

Laboratory studies may demonstrate the following findings in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with HRS HRS Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of hrs is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Hepatorenal Syndrome:

• Serum:
  • ↑ Creatinine (Note: Levels may be affected by malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries, muscle wasting Muscle Wasting Duchenne Muscular Dystrophy, and hyperbilirubinemia Hyperbilirubinemia A condition characterized by an abnormal increase of bilirubin in the blood, which may result in jaundice. Bilirubin, a breakdown product of heme, is normally excreted in the bile or further catabolized before excretion in the urine. Jaundice.)
  • ↑ BUN (blood urea Urea A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. Urea Cycle nitrogen Nitrogen An element with the atomic symbol n, atomic number 7, and atomic weight [14. 00643; 14. 00728]. Nitrogen exists as a diatomic gas and makes up about 78% of the earth’s atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. Urea Cycle):creatinine (Cr) ratio (> 20:1)
• Urine studies:
  • Protein: no or minimal proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children (< 500 mg/day)
  • Sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia:
    • Usually very ↓ (< 10–15 mEq/dL) 
    • May be affected by diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication
  • RBC: < 50 cells/HPF (unless catheter in place)
  • Fractional excretion of sodium Fractional excretion of sodium Acute Kidney Injury (FENa):
    • Can be < 1% (often unhelpful in differentiating from prerenal AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury or ATN in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis)
    • May be affected by diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication
  • Benign Benign Fibroadenoma urinary sediment may distinguish HRS HRS Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of hrs is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Hepatorenal Syndrome from ATN.

Imaging^[1,10,14]

Imaging, such as ultrasonography, may be used to exclude obstruction or parenchymal kidney disease.

Management

Management may vary depending on practice location and availability of therapeutics. The following information is based on US, UK, and European recommendations for HRS-AKI. Information on optimal therapy for HRS-NAKI is currently lacking. See your local guidelines for additional recommendations.

General considerations^[1,3,7]

• Discontinue potentially causative medications:
  • Diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication
  • Beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers)
  • Other antihypertensive agents
  • Potentially nephrotoxic agents Nephrotoxic Agents Surgical Complications (e.g., aminoglycosides Aminoglycosides Aminoglycosides are a class of antibiotics including gentamicin, tobramycin, amikacin, neomycin, plazomicin, and streptomycin. The class binds the 30S ribosomal subunit to inhibit bacterial protein synthesis. Unlike other medications with a similar mechanism of action, aminoglycosides are bactericidal. Aminoglycosides)
• Treat infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease with antibiotics, if present.
• Treat any acute causes of liver failure Liver failure Severe inability of the liver to perform its normal metabolic functions, as evidenced by severe jaundice and abnormal serum levels of ammonia; bilirubin; alkaline phosphatase; aspartate aminotransferase; lactate dehydrogenases; and albumin/globulin ratio. Autoimmune Hepatitis (e.g., alcoholic Alcoholic Persons who have a history of physical or psychological dependence on ethanol. Mallory-Weiss Syndrome (Mallory-Weiss Tear) hepatitis, decompensated hepatitis B Hepatitis B Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Most individuals with acute HBV infection are asymptomatic or have mild, self-limiting symptoms. Chronic infection can be asymptomatic or create hepatic inflammation, leading to liver cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B Virus infection).
• Specialty referrals may include:
  • Nephrology
  • Hepatology
  • Transplant team
• Monitor urine output closely.

Management of hypovolemia Hypovolemia Sepsis in Children^[1,7]

The following measures can be implemented to correct potential AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury from hypovolemia Hypovolemia Sepsis in Children:

• Give IV albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests 1 g/kg daily for 2 days (maximum: 100 g/day). 
• If still no improvement, the diagnosis is likely HRS HRS Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of hrs is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Hepatorenal Syndrome.

Pharmacotherapy for HRS HRS Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of hrs is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Hepatorenal Syndrome

Once the diagnosis of HRS-AKI is established, vasoconstrictors and albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests are the mainstay of therapy. Vasoconstrictors are generally continued until the patient’s creatinine returns to baseline (or up to 14 days). 

If terlipressin is available:^[3,4,7,9]

• Terlipressin ( vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure in splanchnic region → reduces portal pressure): 
  • IV bolus: 1 mg every 4–6 hours for 48 hours, then adjust dose based on serum creatinine:^[3,7]
    • If not ↓ > 25% from baseline: increase dose by 2 mg every 4–6 hours (maximum: 12 mg/day)
    • Otherwise, maintain current dose
    • If creatinine ≥ baseline: discontinue
  • May also consider continuous infusion:^[3,10]
    • 2 mg/day
    • Increased every 24–48 hours until creatinine decreases (maximum: 12 mg/day) 
    • May reduce ischemic side effects
  • Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation:
    • Asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma
    • Ischemic cardiovascular disease
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with a serum creatinine > 5 mg/dL are unlikely to benefit.
  • Monitor for evidence of ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage.
• Albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests:
  • IV bolus 1 g/kg/day (maximum: 100 g) for 2 days (if not already given)
  • Followed by 20–50 g/day until terlipressin is discontinued^[3,7,8]
  • Monitor for evidence of volume overload, such as pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema.

Alternative 1:^[3,7,9]

• Norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS:
  • Give IV norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS by continuous infusion (0.5‒3 mg/hr) 
  • Goal:
    • Raise the mean arterial pressure Mean Arterial Pressure Mean arterial pressure (MAP) is the average systemic arterial pressure and is directly related to cardiac output (CO) and systemic vascular resistance (SVR). The SVR and MAP are affected by the vascular anatomy as well as a number of local and neurohumoral factors. Vascular Resistance, Flow, and Mean Arterial Pressure (MAP) by ≥ 10 mm Hg OR
    • Increase urine output > 200 mL/4 hr
  • Idea is to counteract splanchnic arterial vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs
  • Appears to be equally effective as terlipressin
  • Requires an ICU ICU Hospital units providing continuous surveillance and care to acutely ill patients. West Nile Virus setting and central venous access
• Albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests:
  • IV bolus 1 g/kg/day (maximum: 100 g) for 2 days (if not already given)
  • Then, given to maintain central venous pressure Central venous pressure The blood pressure in the central large veins of the body. It is distinguished from peripheral venous pressure which occurs in an extremity. Central Venous Catheter ( CVP CVP The blood pressure in the central large veins of the body. It is distinguished from peripheral venous pressure which occurs in an extremity. Central Venous Catheter) at 4‒10 mm Hg

Alternative 2 (all 3 should be given; lower efficacy than the above options):^[3,7]

• Midodrine Midodrine An ethanolamine derivative that is an adrenergic alpha-1 agonist. It is used as a vasoconstrictor agent in the treatment of hypotension. Sympathomimetic Drugs (an alpha-1 agonist which increases arteriolar and venous tone → elevation of systolic and diastolic blood pressures)
  • Oral
  • Start with 7.5 mg 
  • Increase to 12.5–15 mg every 8 hours, as needed 
  • Maximum: 45 mg/day
• Octreotide Octreotide A potent, long-acting synthetic somatostatin octapeptide analog that inhibits secretion of growth hormone and is used to treat hormone-secreting tumors; diabetes mellitus; hypotension, orthostatic; hyperinsulinism; hypergastrinemia; and small bowel fistula. Antidiarrheal Drugs (a synthetic analog of somatostatin Somatostatin A 14-amino acid peptide named for its ability to inhibit pituitary growth hormone release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of thyroid-stimulating hormone; prolactin; insulin; and glucagon besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, srif-28 with a 14-amino acid extension at the n-terminal. Gastrointestinal Secretions, which binds to somatostatin Somatostatin A 14-amino acid peptide named for its ability to inhibit pituitary growth hormone release, also called somatotropin release-inhibiting factor. It is expressed in the central and peripheral nervous systems, the gut, and other organs. SRIF can also inhibit the release of thyroid-stimulating hormone; prolactin; insulin; and glucagon besides acting as a neurotransmitter and neuromodulator. In a number of species including humans, there is an additional form of somatostatin, srif-28 with a 14-amino acid extension at the n-terminal. Gastrointestinal Secretions receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors, including those in the splanchnic vasculature → inhibits the release of endogenous vasodilators Vasodilators Drugs used to cause dilation of the blood vessels. Thromboangiitis Obliterans (Buerger’s Disease) → splanchnic vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure):
  • IV infusion: 50 µg/hour OR 
  • Subcutaneously: 100–200 µg 3 times a day
• Albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests:
  • IV bolus 1 g/kg per day (maximum: 100 g) for 2 days (if not already given)
  • Followed by 20–50 g/day until midodrine Midodrine An ethanolamine derivative that is an adrenergic alpha-1 agonist. It is used as a vasoconstrictor agent in the treatment of hypotension. Sympathomimetic Drugs and octreotide Octreotide A potent, long-acting synthetic somatostatin octapeptide analog that inhibits secretion of growth hormone and is used to treat hormone-secreting tumors; diabetes mellitus; hypotension, orthostatic; hyperinsulinism; hypergastrinemia; and small bowel fistula. Antidiarrheal Drugs are discontinued.

Additional therapies^[3,7,10]

The following options should be considered based on specialty recommendations and clinical scenario:

• Liver transplantation Liver transplantation The transference of a part of or an entire liver from one human or animal to another. Hepatocellular Carcinoma (HCC) and Liver Metastases:
  • Only curative treatment, but kidney recovery is not predictable
  • In those unlikely to recover kidney function, simultaneous kidney transplantation Kidney Transplantation The transference of a kidney from one human or animal to another. Organ Transplantation may be considered.
• Transjugular intrahepatic portosystemic shunt Transjugular intrahepatic portosystemic shunt A type of surgical portosystemic shunt to reduce portal hypertension with associated complications of esophageal varices and ascites. It is performed percutaneously through the jugular vein and involves the creation of an intrahepatic shunt between the hepatic vein and portal vein. The channel is maintained by a metallic stent. The procedure can be performed in patients who have failed sclerotherapy and is an additional option to the surgical techniques of portocaval, mesocaval, and splenorenal shunts. It takes one to three hours to perform. Ascites (TIPS):
  • May be used as bridging therapy in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who do not respond to medical therapy and are awaiting transplantation
  • Contraindicated in advanced liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy dysfunction
  • Generally not recommended in HRS-AKI because of a paucity of information and association with multiple complications
  • Considered as a last resort in selected patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
• Dialysis Dialysis Renal replacement therapy refers to dialysis and/or kidney transplantation. Dialysis is a procedure by which toxins and excess water are removed from the circulation. Hemodialysis and peritoneal dialysis (PD) are the two types of dialysis, and their primary difference is the location of the filtration process (external to the body in hemodialysis versus inside the body for PD). Peritoneal Dialysis and Hemodialysis:
  • Controversial
  • May be used as a bridge to liver transplantation Liver transplantation The transference of a part of or an entire liver from one human or animal to another. Hepatocellular Carcinoma (HCC) and Liver Metastases or liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy recovery in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with a reversible form of liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy injury

Prevention^[3,6,7,9,10]

Avoiding precipitating factors is important in preventing HRS-AKI, including:

• Albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests administration with large-volume paracentesis Paracentesis A procedure in which fluid is withdrawn from a body cavity or organ via a trocar and cannula, needle, or other hollow instrument. Portal Hypertension (6–8 g albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests per liter of ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites removed)
• Prompt treatment of infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
• In spontaneous bacterial peritonitis Spontaneous Bacterial Peritonitis Ascites ( SBP SBP Ascites):
  • Administer IV albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests (1.5 g/kg) on day 1.
  • Give a 2nd dose (1 g/kg) on day 3 of antibiotics.
• Consider SBP SBP Ascites prophylaxis Prophylaxis Cephalosporins with oral norfloxacin Norfloxacin A synthetic fluoroquinolone (fluoroquinolones) with broad-spectrum antibacterial activity against most gram-negative and gram-positive bacteria. Norfloxacin inhibits bacterial DNA gyrase. Fluoroquinolones 400 mg/day in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis if they have:
  • Ascitic fluid Ascitic fluid The serous fluid of ascites, the accumulation of fluids in the peritoneal cavity. Ascites total protein Total protein Liver Function Tests < 1.5 g/dL and either of these 2 criteria:
    • Child-Pugh score Child-Pugh Score Cirrhosis > 9 points and serum bilirubin Bilirubin A bile pigment that is a degradation product of heme. Heme Metabolism > 3 mg/dL
    • Serum creatinine > 1.2 mg/dL, BUN > 20 mg/dL, or serum sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia < 130 mEq/L
  • Decreases 1-year probability Probability Probability is a mathematical tool used to study randomness and provide predictions about the likelihood of something happening. There are several basic rules of probability that can be used to help determine the probability of multiple events happening together, separately, or sequentially. Basics of Probability of SBP SBP Ascites and HRS HRS Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of hrs is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Hepatorenal Syndrome

Prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas^[1,3,15]

• An earlier diagnosis of HRS-AKI is associated with a higher response to treatment.
• Around 40% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with HRS HRS Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of hrs is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Hepatorenal Syndrome and acute kidney injury Acute Kidney Injury Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury do not respond to treatment and will die within weeks.^[5]
• Factors that may affect outcomes:
  • Model for End-Stage Liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy Disease (MELD) score
  • Pretreatment creatinine
  • Oliguria Oliguria Decreased urine output that is below the normal range. Oliguria can be defined as urine output of less than or equal to 0. 5 or 1 ml/kg/hr depending on the age. Renal Potassium Regulation
  • Sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock and systemic inflammation Systemic Inflammation Surgical Site Infections
  • Extrahepatic organ failure

Differential Diagnosis

Prerenal disease: presents with similar laboratory findings (↑ serum creatinine and ↑ BUN:creatinine ratio BUN:creatinine Ratio Kidney Function Tests) and similar urine findings (low sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia excretion in urine). Hepatorenal syndrome Hepatorenal Syndrome Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of HRS is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Hepatorenal Syndrome can be differentiated from prerenal failure through an IV fluid volume expansion challenge with intravenous albumin Albumin Serum albumin from humans. It is an essential carrier of both endogenous substances, such as fatty acids and bilirubin, and of xenobiotics in the blood. Liver Function Tests. Giving fluids improves prerenal disease, but not HRS HRS Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of hrs is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Hepatorenal Syndrome. In patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis, prerenal disease can be caused by GI fluid losses ( diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea), bleeding, diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication, or NSAIDs NSAIDS Primary vs Secondary Headaches.

Acute tubular necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage (ATN): parenchymal kidney disease, such as membranoproliferative glomerulonephritis Membranoproliferative Glomerulonephritis Membranoproliferative glomerulonephritis (MPGN) is also known as mesangiocapillary glomerulonephritis. Membranoproliferative glomerulonephritis is a pattern of glomerular injury characterized by mesangial hypercellularity, endocapillary proliferation, and thickening of the glomerular basement membrane (double contour formation). Membranoproliferative Glomerulonephritis, IgA IgA Represents 15-20% of the human serum immunoglobulins, mostly as the 4-chain polymer in humans or dimer in other mammals. Secretory iga is the main immunoglobulin in secretions. Immunoglobulins: Types and Functions nephropathy, or diabetic nephropathy Diabetic nephropathy Kidney injuries associated with diabetes mellitus and affecting kidney glomerulus; arterioles; kidney tubules; and the interstitium. Clinical signs include persistent proteinuria, from microalbuminuria progressing to albuminuria of greater than 300 mg/24 h, leading to reduced glomerular filtration rate and end-stage renal disease. Chronic Diabetic Complications, can be associated with AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury but may also coexist with HRS HRS Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of hrs is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Hepatorenal Syndrome. Nephrotoxic agents Nephrotoxic Agents Surgical Complications such as aminoglycosides Aminoglycosides Aminoglycosides are a class of antibiotics including gentamicin, tobramycin, amikacin, neomycin, plazomicin, and streptomycin. The class binds the 30S ribosomal subunit to inhibit bacterial protein synthesis. Unlike other medications with a similar mechanism of action, aminoglycosides are bactericidal. Aminoglycosides or radiocontrast agents can precipitate ATN that is reversible after withdrawing the offending agent. Addressing the underlying cause of AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury is essential because of the marked difference in prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas than with HRS HRS Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of hrs is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Hepatorenal Syndrome alone. Most causes of prerenal disease and ATN are reversible. 

Infection ( sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock or spontaneous bacterial peritonitis Spontaneous Bacterial Peritonitis Ascites ( SBP SBP Ascites): infection can be associated with AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with chronic liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease/ cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis. However, the presence of SBP SBP Ascites does not exclude the diagnosis of HRS HRS Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of hrs is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Hepatorenal Syndrome. An episode of sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock with hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension can cause a rapid rise in creatinine, contrasted with the more gradual rise with HRS HRS Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of hrs is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Hepatorenal Syndrome. Treatment of the infection usually results in restoration of renal perfusion and an improvement in kidney function. However, with HRS HRS Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of hrs is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Hepatorenal Syndrome not due to infection, the prognosis Prognosis A prediction of the probable outcome of a disease based on a individual’s condition and the usual course of the disease as seen in similar situations. Non-Hodgkin Lymphomas is poor.

Beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers): often used in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis and ascites Ascites Ascites is the pathologic accumulation of fluid within the peritoneal cavity that occurs due to an osmotic and/or hydrostatic pressure imbalance secondary to portal hypertension (cirrhosis, heart failure) or non-portal hypertension (hypoalbuminemia, malignancy, infection). Ascites but may cause hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension and AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury. Discontinuing beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers) may lead to resolution of the renal function decline and clarify that the diagnosis is not HRS HRS Hepatorenal syndrome (HRS) is a potentially reversible cause of acute kidney injury that develops secondary to liver disease. The main cause of hrs is hypovolemia, often as a result of forced diuresis or drainage of ascites. This leads to renal vasoconstriction resulting in hypoperfusion of the kidneys. Hepatorenal Syndrome.