Hepatorenal syndrome: some help from the renal service

Hepatorenal syndrome (HRS) is a frequent consult encountered on the nephrology service. The criteria have recently been revised. Conall reviewed the revised criteria on a prior post last year. To review the pathophysiology of HRS click here.

In a cirrhotic patient with AKI, HRS commonly appears in the top 3 of a differential diagnosis. However, when a large database was reviewed (single center), the major causes of AKI in a cirrhotic patients in descending order of frequency were:

*32% infection-induced renal failure
*24% parenchymal renal disease
*22% prerenal
*11% ATN
*8% HRS
*3% nephrotoxic renal failure

Potential therapies- Albumin, octreotide and midodrine have shown some benefit and a retrospective study of 53 pts showed some survival benefit with octreotide and midodrine combination in these patients. Prostaglandin analogues, ACEi, NAC and endothelin receptor antagonist have all been looked at, but these data are inconclusive. A randomized study of 46 patients in Spain and a randomized double blinded study of 112 pts in the US compared the use of terlipressin (a vasopressin analogue) and albumin together versus albumin (+ placebo) alone. The results showed improvement in renal function but the overall survival was not different in the two groups. There was, however, some increase in the risk of cardiovascular side effects. At this time terlipressin is not approved by the FDA in the US.

Dialysis typically only offered when liver recovery is expected or possible (acute liver injury) or when liver transplant is a valid option. Conventional dialysis in often proves challenging as hypotension is common in patients with liver failure. However, some simple changes can minimize hypotension. These include: use of less negatively charged dialyzer membrane, circuit priming with isotonic NaHCO3 (instead of normal saline), cooling, increasing Na in dialysate, low UF, citrate anticoagulation and midodrine/terlipressin before HD.

Extracorporeal albumin dialysis (ECAD) using molecular adsorbents recirculating system (MARS) is something new on the horizon. Basically, this is hemodialysis with an albumin-containing dialysate. Charcoal and anion exchange columns are connected to a hemodialysis or hemoperfusion apparatus. This system effectively removes albumin-bound substances, including bilirubin, bile acids, aromatic amino acids, medium chain fatty, NO and cytokines. So, it functions more like a liver substitute (in removing albumin bound substances) in addition to providing dialysis.

In small and mostly uncontrolled studies ECAD has been shown to decrease mortality and improved renal function. In a prospective randomized controlled study it was shown to improve hepatic encephalopathy. The major downsides are hypotension, increased bleeding, cost hypoglycemia and non cardiogenic pulmonary edema. Results of ongoing clinical trials will shed more light on this form of therapy.

A liver or a simultaneous liver and a kidney (SLK) transplant is the best options for these patients. About 50% of the times, HRS resolves following the liver transplant but some patients remain dialysis dependant. This raises the question of SLK transplant. Although no strict guidelines apply, according to the Consensus Conference held in 2008 (ASTS, AST, UNOS, ASN), AKI or hepatorenal syndrome with SCr ≥ 2.0 mg/dL and dialysis ≥ 8 weeks, qualify for a SLK. Even with these advances HRS continues to be a diagnosis associated with considerable morbidity and mortality associated with it.

Tarun Kaur, MD