The kidneys stop working. There is nothing wrong with the kidneys.
That paradox is hepatorenal syndrome. Advanced liver disease causes profound dilation of the splanchnic circulation — the blood vessels supplying the gut. Blood pools there. The body senses that the arterial circulation is underfilled and responds by clamping down the renal arteries.
The kidney, starved of blood flow, shuts down. Its tissue remains structurally normal. A kidney from a patient with hepatorenal syndrome, transplanted into someone with a healthy liver, works.
Why this is a diagnosis of exclusion
Everything else that causes kidney failure in cirrhosis must be ruled out first, because those things are treatable and this is not, easily.
Volume depletion, often from the diuretics used to treat ascites. Withdraw the diuretic, give albumin, and see whether creatinine falls. This step is mandatory and it is the one most often skipped.
Spontaneous bacterial peritonitis. Infection of ascitic fluid. It precipitates hepatorenal syndrome and it is treatable. Every patient with cirrhosis and rising creatinine needs a diagnostic paracentesis.
Nephrotoxic drugs — NSAIDs, aminoglycosides, contrast.
Acute tubular necrosis, from hypotension or sepsis.
Intrinsic kidney disease — IgA nephropathy is common in cirrhosis, hepatitis B and C both cause glomerular disease.
Only when all of these are excluded, and creatinine does not respond to two days of albumin with diuretics held, is the diagnosis made.
Two forms
The old labels were Type 1 and Type 2. Current nomenclature, set by the International Club of Ascites and carried into the 2024 ADQI consensus, is different — and the change matters, because it altered the diagnostic threshold.
HRS-AKI (formerly Type 1) is rapid. It is diagnosed on a rise in creatinine of 0.3 mg/dL within 48 hours, or a 1.5-fold rise from baseline within the preceding week. That is a far lower bar than the old criterion of a creatinine above 2.5, and it exists so treatment can begin earlier. Median survival without treatment is measured in weeks.
HRS-NAKI (formerly Type 2) is slower, presents with refractory ascites, and is subdivided by duration: HRS-AKD when eGFR is below 60 for under three months, HRS-chronic kidney disease (CKD) when it persists beyond that.
If you are told you have Type 1 hepatorenal syndrome, that vocabulary is a decade out of date, and it may mean the older, higher creatinine threshold is being used to decide when to treat you.
Treatment
Terlipressin with albumin is first-line, and is now approved in the United States. It constricts the splanchnic circulation, restores effective arterial volume, and reverses the renal vasoconstriction. It carries a real risk of ischemic complications and respiratory failure, and patients require monitoring.
Midodrine, octreotide, and albumin where terlipressin is unavailable. Less effective.
Norepinephrine with albumin in the intensive care unit.
TIPS — a shunt that decompresses the portal circulation — in selected patients.
Dialysis as a bridge, not a destination. It does not treat the syndrome. It buys time for a liver.
The only definitive treatment
Liver transplantation.
Everything above is a bridge to it. A patient with hepatorenal syndrome who receives a liver usually recovers kidney function, sometimes completely.
The longer the kidneys have been failing beforehand, the less likely full recovery becomes — which is why the diagnosis needs to be made quickly, treatment started quickly, and transplant evaluation begun immediately rather than after medical therapy has failed.
What we do
We run the exclusion protocol properly, because a treatable cause found is a patient saved. We manage the vasoconstrictor therapy and the albumin. We provide dialysis when it bridges to transplant, and we say plainly when it does not.
And we work alongside hepatology throughout, because the kidney's future here depends entirely on the liver.