Hepatorenal Syndrome

Use an AKI threshold of serum creatinine increase of at least 0.3 mg/dL within 48 hours or at least 50% from baseline within 7 days. AKI occurs in approximately 27% to 53% of hospitalized patients with cirrhosis and ascites; prerenal azotemia and acute tubular necrosis are the most common etiologies. ccjm+1ccjmPrint Article | Cleveland Clinic Journal of medicineccjmDiagnosis and management of ascites, spontaneous ...

At presentation, identify and reverse hemodynamic or nephrotoxic triggers: shock, infection, gastrointestinal hemorrhage or fluid loss, excess diuresis, nephrotoxic exposure, and recent large-volume paracentesis without appropriate albumin replacement. HRS-AKI should not be assigned until hypovolemia or shock, nephrotoxins, intrinsic kidney disease, and obstructive disease have been actively excluded. ScienceDirect+2ScienceDirectHepatorenal Syndrome–Acute Kidney Injury in Liver TransplantationccjmPrint Article | Cleveland Clinic Journal of medicineccjmDiagnosis and management of ascites, spontaneous ...

Obtain urinalysis with urine microscopy, urine protein assessment, and renal ultrasonography while evaluating volume status and infection. Hematuria, pyuria, substantial proteinuria, casts suggestive of tubular injury, or urinary obstruction should redirect management toward intrinsic or postrenal AKI rather than a purely functional HRS phenotype. Wolters Kluwer+2Wolters KluwerHepatorenal Syndrome Type 1: From Diagnosis Ascertainment... : Kidney360ScienceDirectHepatorenal Syndrome–Acute Kidney Injury in Liver TransplantationScienceDirectRenal damage in Hepatorenal Syndrome: A still unsolved issue - ScienceDirect

Use point-of-care ultrasound as an adjunct when physical examination and routine laboratory indices do not resolve volume status. In one reported cohort, 62% of patients clinically labeled HRS had high cardiac filling pressures on right-heart catheterization and improved creatinine after volume expansion was stopped and diuretics were started; congestive physiology should therefore prevent reflexive albumin escalation. Oxford AcademicOxford AcademicAcute kidney injury and point-of-care ultrasound in liver cirrhosis: redefining hepatorenal syndrome | Clinical Kidney Journal | Oxford Academic

Current AKI-era terminology replaces HRS type 1 with HRS-AKI and recognizes HRS-NAKI for the former type 2 phenotype. HRS-AKI occurs in advanced cirrhosis with portal-hypertensive vasodilation and inflammatory activation, but the clinical diagnosis remains dependent on excluding prerenal, intrinsic, and obstructive causes. ScienceDirect+2ScienceDirectRenal damage in Hepatorenal Syndrome: A still unsolved issue - ScienceDirectNatureReappraising the spectrum of AKI and hepatorenal syndrome in patients with cirrhosis | Nature Reviews NephrologyScienceDirectHepatorenal Syndrome Type 1: Diagnosis and Treatment

Do not wait for an arbitrary creatinine concentration before acting. AKI-based HRS criteria were designed to identify clinically meaningful renal deterioration earlier than historical creatinine-threshold definitions, and earlier terlipressin initiation at lower creatinine has been associated with greater treatment effectiveness. Wiley+1WileyHepatorenal syndrome in the era of acute kidney injury - SoléWolters KluwerUse of Terlipressin in AKI Associated with Hepatorenal... : Kidney360

A conventional approach is to withhold obvious precipitants and give intravenous albumin-based volume expansion for up to 48 hours before designating HRS-AKI. This remains a useful diagnostic maneuver when hypovolemia is plausible, but it must be balanced against pulmonary edema and venous congestion, especially when ultrasound suggests high filling pressures. Wolters Kluwer+1Wolters KluwerHepatorenal Syndrome Type 1: From Diagnosis Ascertainment... : Kidney360Oxford AcademicAcute kidney injury and point-of-care ultrasound in liver cirrhosis: redefining hepatorenal syndrome | Clinical Kidney Journal | Oxford Academic

Interpret urine indices cautiously. Fractional excretion of sodium and urine sodium are included among tools used to phenotype AKI in cirrhosis, but structural biomarkers may add greater discrimination when acute tubular injury remains a serious alternative. Urinary NGAL, IL-18, KIM-1, and L-FABP were significantly higher in adjudicated acute tubular necrosis than in other AKI etiologies in cirrhosis. Wiley+2WileyKidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury - Belcher - 2014 - Hepatology - Wiley Online LibraryWolters KluwerHepatorenal Syndrome Type 1: From Diagnosis Ascertainment... : Kidney360WileyKidney biomarkers and differential diagnosis of patients ...

For patients meeting a persistent HRS-AKI phenotype after correction of reversible causes, combine vasoconstrictor therapy with albumin-based management. Vasoconstrictors including terlipressin, norepinephrine, and midodrine plus octreotide act on the splanchnic circulation to improve renal function; terlipressin has the strongest evidence base and is more effective than albumin alone for HRS kidney-injury reversal. Wolters Kluwer+1Wolters KluwerUse of Terlipressin in AKI Associated with Hepatorenal... : Kidney360Wolters KluwerSafety and efficacy of continuous terlipressin... : Liver Transplantation

In the United States, terlipressin is FDA-approved to improve kidney function in adults with HRS accompanied by rapid reduction in kidney function. The FDA label states that patients with serum creatinine above 5 mg/dL are unlikely to benefit, making delayed initiation a poor-value strategy when the diagnosis is established. accessdata fdaaccessdata fda022231Orig1s000 - accessdata.fda.gov

Terlipressin requires respiratory-risk stratification before the first dose. Obtain baseline SpO2, monitor continuously by pulse oximetry during therapy, and discontinue terlipressin if SpO2 falls below 90% or if hypoxia or respiratory symptoms develop. Fluid overload increases respiratory-failure risk; reduce or discontinue albumin and other fluids and use diuretics judiciously until volume status improves. accessdata fdaaccessdata fda022231Orig1s000 - accessdata.fda.gov

Avoid terlipressin in ACLF grade 3 because of substantial respiratory-failure risk. Also assess for ischemic risk and transplant implications: terlipressin-related respiratory failure or ischemia can render a listed patient ineligible for transplantation, so a patient with worsening oxygenation or volume overload should have treatment interrupted rather than continued solely to pursue creatinine improvement. accessdata fda+1accessdata fda022231Orig1s000 - accessdata.fda.govWolters KluwerUse of Terlipressin in AKI Associated with Hepatorenal... : Kidney360

Norepinephrine plus albumin is an alternative vasoconstrictor strategy, particularly where close hemodynamic monitoring is available. Midodrine plus octreotide is used off label in the United States but is less effective than terlipressin in comparative evidence and should not be considered equivalent therapy when terlipressin is appropriate and available. Wolters Kluwer+1Wolters KluwerUse of Terlipressin in AKI Associated with Hepatorenal... : Kidney360Wolters KluwerSafety and efficacy of continuous terlipressin... : Liver Transplantation

After paracentesis exceeding 5 L, infuse 20% or 25% albumin at 8 g per liter of ascites removed. For paracentesis below 5 L, the same dose can be considered in ACLF or in patients at high risk for post-paracentesis AKI. BMJ+1BMJGuidelines on the management of ascites in cirrhosis - GutBMJGuidelines on the management of ascites in cirrhosis

In spontaneous bacterial peritonitis with increased or rising serum creatinine, administer albumin 1.5 g/kg within 6 hours of diagnosis and 1 g/kg on day 3. This is a renal-protective adjunct to infection management and should occur before persistent renal dysfunction is attributed solely to HRS-AKI. BMJBMJGuidelines on the management of ascites in cirrhosis - Gut

For refractory ascites, consider transjugular intrahepatic portosystemic shunt in appropriately selected patients. In contrast, automated low-flow ascites pumps should be restricted to special circumstances with robust clinical governance, audit, or research arrangements because survival benefit has not been demonstrated. BMJ+1BMJGuidelines on the management of ascites in cirrhosis - GutBMJGuidelines on the management of ascites in cirrhosis

Initiate or expedite liver-transplant evaluation when HRS-AKI is identified. Liver transplantation is the definitive treatment for HRS-AKI and other advanced cirrhosis complications; terlipressin-based treatment is commonly used as a bridge while transplant candidacy, renal trajectory, and need for renal replacement therapy are reassessed. Wolters Kluwer+1Wolters KluwerUse of Terlipressin in AKI Associated with Hepatorenal... : Kidney360Wolters KluwerSafety and efficacy of continuous terlipressin... : Liver Transplantation

Follow serum creatinine trajectory, oxygenation, respiratory examination, and volume status during vasoconstrictor therapy. A fall in creatinine supports response, whereas progressive AKI should prompt renewed evaluation for acute tubular injury, occult infection, persistent hypovolemia, venous congestion, or another unrecognized structural process rather than automatic continuation of an ineffective HRS-directed course. Wiley+2WileyKidney biomarkers and differential diagnosis of patients with cirrhosis and acute kidney injury - Belcher - 2014 - Hepatology - Wiley Online LibraryWolters KluwerHepatorenal Syndrome Type 1: From Diagnosis Ascertainment... : Kidney360Oxford AcademicAcute kidney injury and point-of-care ultrasound in liver cirrhosis: redefining hepatorenal syndrome | Clinical Kidney Journal | Oxford Academic

Respond to terlipressin toxicity immediately. Discontinue the drug for SpO2 below 90%; interrupt, reduce, or discontinue treatment during volume overload until improvement; and reassess for ischemic complications. These events matter both for short-term safety and because respiratory failure or ischemia may affect transplant eligibility. accessdata fdaaccessdata fda022231Orig1s000 - accessdata.fda.gov

Renal replacement therapy may be needed for selected patients with severe renal dysfunction as a bridge in the transplant pathway. Terlipressin treatment has been associated with less renal replacement therapy use and better post-transplant kidney function in reported analyses, but it does not replace definitive transplant planning. Wolters Kluwer+1Wolters KluwerUse of Terlipressin in AKI Associated with Hepatorenal... : Kidney360Wolters KluwerSafety and efficacy of continuous terlipressin... : Liver Transplantation