Hepatorenal Disease – Beyond the syndrome

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In general, when we are asked to evaluate a patient with liver disease for the development of acute renal failure, the three top differentials are usually: true hepatorenal syndrome, a prerenal picture (often 2/2 overdiuresis) and ATN. Cholemic nephrosis can also be considered but it usually requires very high bilirubin levels. These causes were previously discussed on prior blogs. However, I wanted to focus on some more atypical etiologies that we should keep in our list in case things don’t look as straight forward.

The first key point is to always carefully look at the urine on microscopy and quantify the proteinuria. The latter is important since some conditions that have proteinuria do not show on dipstick (not related to albuminuria), like AL amyloidosis, which can also be a cause of liver disease.

The presence of active urine sediment opens a whole new list of differentials, which can be narrowed down by using the primary cause of liver disease as a starting point:

1) Alcoholic cirrhosis: Mesangial IgA deposition associated with chronic liver disease, is the most common form of secondary IgA nephropathy. An imparied removal IgA-containing complexes by the Kupffer cells in the liver is thought to predispose to IgA deposition in the kidney. Despite the frequency of glomerular IgA deposits in advanced liver disease, most adults have no clinical signs of glomerular disease. It is unclear why some patients are predisposed to renal manifestations while others are not.

2) Viral hepatitis (HBV or HCV): might lead to variable glomerular lesions. It is important to add complements and cryo to your workup.

  • MPGN: (low C3 and C4) Renal manifestations range from hematuria to nephrotic syndrome. In some cases, its associated with mixed cryoglobulenemia (positive Cryo and low C4). Cryos picture tends to be associated with purpura, arthralgia and lymphadenopathy.
  • Membranous nephropathy (normal complements): thought to be related to HBeAg and anti-HBe deposition on subepithelial space.
  • Secondary polyarteritis nodosa (vasculitis): typically occurs within 4 months after the onset of HBV infection (also cases with HCV) and has similar clinical features as the idiopathic form – systemic symptoms (fever, weight loss, fatigue) + Skin signs (purpura/livedo reticularis) + neuropathy + GI symptoms (pain/bleeding) + HTN.
Don’t forget about potential drugs used for treatment of hepatitis that can be nephrotoxic to the tubules (e.g. adefovir)

3) If an auto-immune disease is the cause of liver failure, like primary sclerosing cholangitis (PSC), you have to think about a possible concomitant auto-antibody process. Interestingly, more than 75% of patients with PSC have either ANA or pANCA. A small proportion also have either anti-GBM or anticardiopilin antibody (antiphospholipid syndrome). Finally, more than 90% of patients with PSC also have ulcerative colitis. The latter may predispose to secondary amyloidosis (amyloid A deposition 2/2 chronic inflammation) or its treatment with sulfazalazine (type of NSAID) might lead to AIN or nephrotic syndrome.

Overall, just be thorough in your evaluations and don’t let the routine of patient care limit your differentials.

Picture: Chihuly amazing work on glass that is being exposed in Boston now! Truly outside the box.

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