01Approach to the Critical Patient/attcp64

Immediate priorities

›Life threats to exclude before accepting HRS-AKI

›Hemorrhagic or septic shock

›Shock physiology excludes HRS-AKI by definition

›Treat shock aggressively before diagnostic labeling

›Variceal hemorrhage

›Hematemesis or melena with hemodynamic instability

›Massive transfusion pathway if bleeding is ongoing

›Spontaneous bacterial peritonitis with sepsis

›Fever, abdominal pain, or worsening encephalopathy with known ascites

›Diagnostic paracentesis before antibiotics if feasible

›Refractory hyperkalemia from progressive AKI

›K+ > 6.0 mmol/l with ECG changes

›Peaked T waves, QRS widening, or bradycardia

›Precipitant identification and reversal

›Nephrotoxin exposure

›Hold NSAIDs, aminoglycosides, and iodinated contrast

›Hold ACE inhibitors and ARBs

›Diuretic and paracentesis review

›Recent dose escalation or large volume paracentesis without albumin

›Withdraw diuretics pending diagnostic clarification

›Window for reversibility

›Early albumin challenge before committing to an HRS-AKI diagnosis

›Delayed recognition worsens renal recovery and transplant outcomes

Monitoring and targets

›Perfusion and renal targets

›Mean arterial pressure

›Target MAP >= 65 mmHg

02History/hx55

Presentation pattern

›Renal presentation

›Progressive oliguria

›Days to weeks in the more indolent pattern

›Rapid decline over days in the more aggressive pattern

›Absence of urinary symptoms

›No dysuria or flank pain

›No gross hematuria reported

›Systemic decompensation clues

›Worsening ascites

›Increasing abdominal girth

›New diuretic resistance

›Worsening encephalopathy

›Confusion or day-night reversal

›Family-reported personality change

›Weight change

›Recent weight loss from aggressive diuresis

›Recent weight gain from fluid retention

Precipitant screen

›Infection symptoms

›Fever or chills

›Spontaneous bacterial peritonitis concern

›Abdominal pain with known ascites

›Worsening pain or new tenderness

›Cough, dysuria, or skin infection

›Alternative infectious source

›Gastrointestinal bleeding

›Hematemesis or melena

03Physical Exam/exam37

Volume and hemodynamic assessment

›Hemodynamic snapshot

›Blood pressure

›Chronic relative hypotension is typical in decompensated cirrhosis

›A drop from the patient's own baseline matters more than an absolute number

›Heart rate

›Relative tachycardia from a hyperdynamic circulation

›Perfusion signs

›Warm extremities despite low blood pressure

›Distinguishes vasodilatory physiology from cold, hypoperfused shock

›Effective volume assessment

›Ascites and edema can coexist with a contracted effective circulating volume

›Total body volume overloaded, intravascular volume relatively underfilled

›Jugular venous pressure

›Often not elevated despite total body fluid excess

Cirrhosis stigmata and complications

›Chronic liver disease findings

›Jaundice

›Scleral icterus

›Spider angiomata and palmar erythema

›Upper trunk and hands

›Ascites

›Shifting dullness and fluid wave

›Peripheral edema

›Dependent pitting edema

›Complication screen

›Asterixis

›Encephalopathy overlap

04Differential Diagnosis/ddx52

Exclusion criteria for HRS-AKI

›Diagnostic requirements, all must be met

›Cirrhosis with ascites

›The clinical substrate for splanchnic vasodilation and effective hypovolemia

›AKI by International Club of Ascites criteria

›Increase in serum creatinine >= 26.5 micromol/l within 48 hours

›Or increase in serum creatinine >= 50% from a baseline known or presumed to have occurred within the prior 7 days

›Absence of shock

›No hemorrhagic, septic, or cardiogenic shock at the time of diagnosis

›No current or recent nephrotoxic drug exposure

›NSAIDs, aminoglycosides, or iodinated contrast

›No macroscopic structural kidney injury

›Proteinuria <= 500 mg/day

›Microscopic hematuria <= 50 red blood cells per high power field

›Normal renal ultrasonography

›No improvement after volume expansion

›Diuretic withdrawal plus albumin 1 g/kg/day IV, maximum 100 g/day, for 2 consecutive days

›Failure of serum creatinine to fall to within 26.5 micromol/l of baseline defines a positive challenge

›Diagnosis of exclusion

›Every criterion above must be satisfied before the label is applied

›A single unmet criterion redirects the workup to an alternative or coexisting cause

Other causes of AKI in cirrhosis

›Prerenal azotemia from true volume depletion

›Gastrointestinal losses, over-diuresis, or hemorrhage

›Responds to the same albumin or crystalloid challenge that HRS-AKI fails

›Most common cause of AKI in cirrhosis

›Must be excluded first by the volume expansion trial

›Acute tubular necrosis

05Laboratory Tests/lt55

Core diagnostic labs

›Renal function

›Serum creatinine

›Compare to pre-illness baseline, not the admission value

›Sarcopenia in cirrhosis lowers muscle mass and can underestimate the true reduction in GFR, a lab-interpretation trap

›Urea

›Elevated urea disproportionate to creatinine with gastrointestinal bleeding

›Electrolytes

›Potassium for hyperkalemia

›Sodium, hyponatremia is common and worsens prognosis

›Liver function and severity

›Bilirubin

›Severity marker and MELD-Na component

›Marked hyperbilirubinemia can falsely lower creatinine on some assay methods, a second lab-interpretation trap

›INR

›Synthetic dysfunction and MELD-Na component

›Albumin

›Chronic severity marker, distinct from therapeutic albumin dosing below

›Hematology

›Complete blood count

›Leukocytosis for infection

›Thrombocytopenia from portal hypertension

›Hemoglobin trend for occult bleeding

Urinalysis and structural exclusion

›Urinalysis with microscopy

›Proteinuria

›<= 500 mg/day supports HRS-AKI

›Higher values suggest glomerular disease

06Diagnostic Tests/dt58

Scoring Systems

›International Club of Ascites AKI staging

›Stage 1

›Serum creatinine rise >= 26.5 micromol/l within 48 hours or 1.5 to 1.9x baseline

›Stage 2

›Serum creatinine 2.0 to 2.9x baseline

›Stage 3

›Serum creatinine >= 3.0x baseline or >= 353.6 micromol/l or renal replacement therapy initiation

›MELD-Na score

›Components

›Bilirubin, INR, creatinine, and sodium

›Clinical use

›Transplant allocation priority

›Higher scores correlate with worse HRS-AKI prognosis

›Child-Pugh classification

›Components

›Bilirubin, albumin, INR, ascites, and encephalopathy grade

›Clinical use

›Class C disease affects TIPS candidacy and vasoconstrictor risk tolerance

Albumin volume expansion challenge

›The challenge is the diagnostic test

›Regimen

›Discontinue diuretics

›Albumin 1 g/kg/day IV, maximum 100 g/day, for 2 consecutive days

›Endpoint

›Serum creatinine measured at completion of the 2-day course

›Fall to within 26.5 micromol/l of baseline indicates a volume-responsive process, not HRS-AKI

›Persistent elevation confirms the diagnosis and supports starting vasoconstrictor therapy

07Disposition/dispo39

Level of care selection

›Admission indications

›Any confirmed or suspected HRS-AKI

›Requires inpatient albumin challenge and monitoring

›Active precipitant

›Suspected infection or gastrointestinal bleeding

›Dangerous electrolyte or acid-base state

›K+ > 6.0 mmol/l

›ICU criteria

›Vasoconstrictor infusion requirement

›Terlipressin or norepinephrine with hemodynamic monitoring

›Shock or respiratory failure

›Concurrent sepsis or variceal hemorrhage

›Renal replacement therapy initiation

›Refractory hyperkalemia, acidosis, or volume overload

Transplant and specialty coordination

›Early transplant center discussion

›Every HRS-AKI diagnosis

›Liver transplantation is the only definitive therapy

›Delay worsens waitlist and post-transplant renal outcomes

›Simultaneous liver-kidney transplant evaluation

›Consider with sustained dialysis dependence, roughly 6 weeks or more

›Coordinated by the transplant center, not decided in the emergency department

›Transfer criteria

›No terlipressin availability or no ICU-level vasoconstrictor capability

›Transfer to a center offering vasoconstrictor therapy and renal replacement therapy

›No transplant center affiliation

›Early transfer to a transplant-capable facility once stabilized

08Treatment/t149

Precipitant-directed therapy

›Spontaneous bacterial peritonitis

›Antibiotic therapy

›Ceftriaxone 2 g IV daily

›Narrow per culture and local resistance

›Albumin regimen that prevents HRS

›Albumin 1.5 g/kg IV within 6 hours of diagnosis

›Then 1 g/kg IV on day 3

›Reduces the incidence of HRS-AKI and mortality in spontaneous bacterial peritonitis

›Class I recommendation for albumin in this setting per cirrhosis guidelines

›Gastrointestinal bleeding

›Variceal hemorrhage bundle

›Octreotide 50 microgram IV bolus

›Then 50 microgram per hour infusion

›Ceftriaxone 1 g IV daily prophylaxis

›Continue through the bleeding episode

›Urgent endoscopy

›Definitive hemostasis and rebleed risk reduction

›Diuretic and paracentesis-related precipitants

›Over-diuresis

›Discontinue diuretics

›Do not resume until HRS-AKI is excluded or resolved

›Large volume paracentesis without albumin cover

›Albumin 6 g to 8 g IV per liter of ascitic fluid removed beyond 5 liters

›Given at the time of or immediately after paracentesis, not delayed

›Drug and toxin review

›Discontinue nephrotoxins

›NSAIDs

›Inhibit renal prostaglandin-mediated vasodilation, the specific mechanism by which this routine analgesic worsens HRS-AKI

›ACE inhibitors and ARBs

›Remove the efferent arteriolar compensation the kidney depends on in this state

›Aminoglycosides and iodinated contrast

›Avoid unless no alternative exists

Albumin volume expansion

›Diagnostic and initial therapeutic dosing

›Albumin 1 g/kg/day IV, maximum 100 g/day, for 2 consecutive days

›Confirms the diagnosis if creatinine fails to improve

›Continue albumin into vasoconstrictor therapy rather than stopping at day 2

›Maintenance during vasoconstrictor therapy

›Albumin 20 g to 40 g IV daily

›Titrate to central venous pressure or clinical volume status

›Reduce or hold for pulmonary edema

›Monitoring during albumin administration

›Daily weight and volume exam

›Lung crackles or a rising oxygen requirement

›Suggests over-expansion, hold the next dose

Vasoconstrictor therapy

›Terlipressin, strongest evidence where available

›Dosing

›1 mg IV every 4 to 6 hours

›Increase to 2 mg IV every 4 to 6 hours if serum creatinine fall < 25% at 48 hours

›Continuous infusion alternative

›2 mg per day initial rate, increase by 2 mg per day every 2 days if response is inadequate

›Maximum 12 mg per day

›Continue up to 14 days, or until complete response, or until 2 days at maximum dose without response

›Adverse effects

›Pulmonary edema and volume overload

›Compounded by concurrent albumin, monitor oxygenation closely

›Splanchnic, digital, and myocardial ischemia

›Discontinue immediately for chest pain, limb pallor, or new ischemic ECG changes

›Bradycardia and abdominal cramping

›Usually does not require discontinuation alone

›Contraindications

›Coronary artery disease or peripheral vascular disease

›The ischemic mechanism directly threatens these territories

›Uncontrolled hypertension or a recent cardiovascular event

›Severe asthma or COPD

›Relative caution from pulmonary edema risk, not an absolute contraindication

›Pregnancy

›Vasoconstrictor effect on the uteroplacental circulation

›Norepinephrine, ICU alternative where terlipressin is unavailable

›Dosing

›0.5 to 3 microgram/kg/min IV infusion

›Titrate every 4 to 6 hours to an increase in mean arterial pressure of at least 10 mmHg

›No fixed maximum, escalate per response

›Given with albumin 20 g to 40 g IV daily, as above

›Requirements

›ICU setting with an arterial line

›Continuous hemodynamic monitoring

›Adverse effects

›Peripheral and digital ischemia at higher doses

›Same class effect as terlipressin, monitor extremities

Lower-efficacy combination therapy

›Midodrine plus octreotide plus albumin

›Used where terlipressin and ICU-level norepinephrine are unavailable

›Evidence and response rates are lower than for terlipressin

›Midodrine

›7.5 mg to 12.5 mg PO three times daily, titrated to a maximum of 15 mg three times daily, 45 mg/day maximum

›Target increase in mean arterial pressure of at least 15 mmHg

›Octreotide

›100 microgram to 200 microgram subcutaneous three times daily, or continuous IV infusion 25 to 50 microgram/hour

›Distinct dosing from the variceal hemorrhage regimen above, do not confuse the two indications

›Albumin

›20 g to 40 g IV daily during combination therapy

›Same regimen as maintenance dosing above, titrated to volume status

Renal replacement and TIPS as bridges

›Renal replacement therapy

›Indications

›Standard AKI indications unresponsive to medical therapy

›Refractory hyperkalemia, severe acidosis, or volume overload

›Role

›Bridge to liver transplantation

›Not shown to improve renal recovery independent of transplant

›Therapy-not-working troubleshooting

›No improvement in volume status or electrolytes despite an adequate dialysis prescription

›Reassess transplant timeline and candidacy urgently

›Transjugular intrahepatic portosystemic shunt

›Indications

›Bridge for HRS-NAKI with preserved liver synthetic function

›Contraindications

›Advanced hepatic dysfunction

›Child-Pugh class C or overt hepatic encephalopathy

›High MELD-Na score

Liver transplantation and iatrogenic harm review

›Liver transplantation

›The only definitive therapy

›Renal function typically recovers after a successful transplant

›Simultaneous liver-kidney transplant

›Consider with sustained dialysis dependence, roughly 6 weeks or more

›Decision made by the transplant center

›Iatrogenic harm review, routine ED interventions this patient may receive

›Intubation

›Induction hypotension in an already vasodilated circulation

›Etomidate favored over propofol for hemodynamic stability

›Avoid succinylcholine if hyperkalemic

›Sedation

›Reduced hepatic clearance of benzodiazepines and opioids

›Precipitates or masks hepatic encephalopathy

›Use the lowest effective dose of short-acting agents

›Fluid loading

›Crystalloid boluses do not correct splanchnic vasodilation

›Risk worsening ascites, dilutional hyponatremia, and pulmonary edema

›Albumin, not crystalloid, is the correct volume expander here

›Oxygen

›Routine high-flow oxygen is not indicated without hypoxia

›New hypoxia may signal hepatopulmonary syndrome or vasoconstrictor-related pulmonary edema

›Vasopressors

›Norepinephrine for concurrent shock differs from HRS-directed vasoconstrictor dosing

›Reconcile the two indications rather than layering doses uncritically

›Mechanical circulatory support, including intra-aortic balloon pump

›No role in HRS-AKI

›Not a cardiogenic process, and balloon pump ischemic risk compounds vasoconstrictor ischemic risk

›Anticoagulation

›Cirrhotic coagulopathy is not protective against thrombosis

›Individualize VTE prophylaxis against variceal bleeding risk

›Fibrinolysis

›Relatively contraindicated

›Baseline coagulopathy and bleeding risk from varices

›Analgesia

›NSAIDs contraindicated

›Same prostaglandin mechanism that precipitates HRS-AKI

›Acetaminophen preferred first line

›Maximum 2 g per day in cirrhosis

›Opioids at reduced dose and frequency

›Avoid meperidine, its active metabolite accumulates and is neurotoxic

09Special Populations/sp40

Pregnancy

›Pregnancy considerations

›Rare presentation

›Cirrhosis with pregnancy is uncommon, but acute liver disease of pregnancy can mimic the picture

›Vasoconstrictor caution

›Terlipressin and midodrine are avoided

›Uteroplacental vasoconstriction risk

›Albumin

›Generally considered safe for volume expansion

›Same diagnostic challenge dosing applies

›Multidisciplinary care

›Maternal-fetal medicine and hepatology co-management

›Early transplant center discussion if the diagnosis is confirmed

Geriatric

›Older adult considerations

›Higher baseline cardiovascular disease prevalence

›Raises the risk of terlipressin- and midodrine-related ischemia

›Screen for coronary and peripheral vascular disease before starting

›Polypharmacy

›NSAID and diuretic use are more common

›Reconciliation is part of the exclusion pathway

›Reduced physiologic reserve

›Lower tolerance for volume shifts during albumin therapy

›More frequent reassessment for pulmonary edema

›Transplant candidacy

›Age alone is not an absolute exclusion

›Functional status and comorbidity burden drive the decision

10Background/b36

Epidemiology

›Incidence and burden

›HRS-AKI accounts for a minority of AKI episodes in hospitalized cirrhosis

›Well behind prerenal azotemia and acute tubular necrosis as causes

›Cumulative risk in cirrhosis with ascites

›Roughly 18% develop hepatorenal syndrome within 1 year

›Roughly 39% by 5 years

›Prognosis without treatment

›Untreated HRS-AKI carries a median survival of roughly 2 weeks

›Mortality remains high even with vasoconstrictor therapy in the absence of transplantation

Pathophysiology

›Mechanism of injury

›Splanchnic arterial vasodilation

›Portal hypertension drives nitric oxide-mediated splanchnic vasodilation

›Reduces effective arterial blood volume despite total body fluid excess

›Compensatory neurohormonal activation

›Renin-angiotensin-aldosterone system and sympathetic activation

›Renal vasoconstriction as a compensatory response

›Renal consequence

›Progressive reduction in renal blood flow and glomerular filtration

›Kidneys remain structurally normal, the defect is functional

›Precipitant physiology

›Spontaneous bacterial peritonitis

›Bacterial translocation amplifies systemic inflammation and vasodilation

›Gastrointestinal bleeding and over-diuresis

›Further reduce effective circulating volume on top of baseline vasodilation

Therapeutic Considerations

›Core principles

11Patient Discharge Instructions/pdi21

copy discharge instructions

›Cirrhosis and kidney warning signs home care

›Weigh yourself daily and record the number

›Measure abdominal girth if instructed by your clinician

›Take only medications approved by your liver clinician

›Avoid ibuprofen, naproxen, and other anti-inflammatory medicines

›Limit acetaminophen to no more than 2 g per day unless told otherwise

›Sick-day rules

›Hold diuretics during vomiting, diarrhea, or poor oral intake

›Do not restart diuretics until your clinician reviews your kidney tests

›Seek care before any planned large volume paracentesis if you feel unwell

›Warning signs to return to ER

›Little or no urine output

›Rapid weight gain or worsening abdominal swelling

›Confusion or excessive drowsiness

›Vomiting blood or black tarry stools

›Fever or shaking chills

›Swelling of the legs or new shortness of breath

›Follow up

›Blood test to recheck kidney and liver function within 2 to 3 days

›Hepatology or transplant center visit as scheduled

›Bring an updated list of all medications to every visit

12References/r11

Guidelines and key sources

›Guideline sources

›AASLD Practice Guidance on management of ascites, spontaneous bacterial peritonitis, and hepatorenal syndrome in cirrhosis

›EASL Clinical Practice Guidelines for the management of decompensated cirrhosis

›International Club of Ascites consensus revision of AKI and hepatorenal syndrome definitions

›Landmark trials

›Sort et al, New England Journal of Medicine, albumin in spontaneous bacterial peritonitis

›CONFIRM trial, New England Journal of Medicine, terlipressin plus albumin for HRS-AKI

›Randomized trials comparing terlipressin with midodrine, octreotide, and albumin for HRS reversal

›Coding standards

›ICD-10 K76.7 hepatorenal syndrome

›SNOMED CT hepatorenal syndrome disorder concept

Evidence & Review

Evidence & Review