26th June 2023

Hepatic and lung disease and the kidney

Hepatorenal syndrome

The hepatorenal syndrome (HRS) is a serious complication in patients with severe liver disease. These patients are predisposed to developing acute kidney injury in response to relatively minor insults such as bleeding or infection, and in the absence of any other identifiable renal pathology. Individuals with cirrhosis and alcoholic hepatitis are the most likely to be affected by HRS. Deterioration in liver function leads to portal hypertension and dilatation of the splanchnic circulation. This causes reduced mean arterial pressure and sympathetic nervous system and renin-angiotensin-aldosterone system (RAAS) activation. Renal vasoconstriction and hypoperfusion, and subsequent reduced function, occurs through activation of the RAAS, stimulation of the sympathetic nervous system, and increased synthesis of vasoactive mediators. The increased salt and fluid retained through activation of the RAAS then lead to worsening of ascites. Patients with hepatorenal syndrome are often difficult to treat by dialysis and have poor prognosis.

HRS can be separated into two types:

• Type 1 is often a severe, hemodynamically mediated type of renal failure secondary to severe hepatic dysfunction and has a very poor prognosis.
• Type 2 occurs in those patients with diuretic resistant ascites.

Identifying patients most at risk and starting adequate antibiotics against spontaneous bacterial peritonitis is an important step in the prevention of HRS. Medical therapy with albumin can be effective at increasing the circulating volume, and other treatments, such as terlipressin or noradrenaline, may be used. Procedures such as transjugular intrahepatic portosystemic shunts (TIPPS) can be performed to reduce portal hypertension but HRS is usually fatal unless a liver transplant is conducted.

It is also worth noting that IgA nephropathy is more common in patients with liver disease.

Pulmonary-renal syndrome

Pulmonary-renal syndrome (PRS) is a dramatic presentation with renal and respiratory failure and has a high mortality rate. It occurs as a consequence of ANCA-positive vasculitis or of Goodpasture syndrome (also known as anti-glomerular basement membrane (anti-GBM) disease). PRS should be considered in anyone presenting with symptoms consistent with pulmonary haemorrhage and small vessel vasculitis. The way to differentiate GPA (granulomatosis with polyangiitis) from anti-GBM disease is the involvement of the upper respiratory tract, which will occur in GPA but never in anti-GBM disease.

The exact cause of anti-GBM disease is unknown but there is a predisposition in those individuals who exhibit HLA-DR15. Anti-GBM antibodies target a domain of the alpha-3 chain of type 4 collagen, which is predominantly found in the basement membranes of glomerular and alveolar capillaries, explaining the pulmonary and renal involvement of this disease. The most accurate way of achieving a diagnosis is with a renal biopsy.

PRS can also occur in pesticide poisoning with compounds such as paraquat or infection with legionella and leptospirosis. Cardiogenic shock can mimic a pulmonary renal syndrome and lead to haemoptysis due to pulmonary oedema and renal failure secondary to inadequate kidney blood flow. Treatment of PRS is predominantly with immunosuppressive medications such as steroids, cyclophosphamide, and rituximab to prevent the formation of new antibodies. In severe cases, plasmapheresis may be required to filter out the antibodies in the plasma.