From the Guidelines
Proteinuria due to fatty liver disease is a significant concern, particularly in patients with advanced stages of non-alcoholic steatohepatitis (NASH), and management should focus on treating the underlying fatty liver disease and proteinuria through lifestyle modifications and medications, as recommended in the most recent guidelines 1.
Key Considerations
- Fatty liver disease can lead to systemic inflammation and insulin resistance, damaging kidney glomeruli and causing protein leakage into urine.
- The metabolic syndrome accompanying fatty liver disease contributes to both conditions through shared pathways of inflammation and oxidative stress.
- Lifestyle modifications, including weight loss of 7-10% of body weight, regular exercise, and a Mediterranean-style diet, are essential for managing fatty liver disease.
- Medications like pioglitazone or vitamin E may be prescribed for non-diabetic NASH patients, while ACE inhibitors or ARBs may be used to reduce protein excretion and protect kidney function.
Management Approach
- A stepwise approach using blood-based scores and imaging techniques is suitable for ruling out advanced fibrosis, which is predictive of liver-related outcomes 1.
- Optimal management of comorbidities, including use of incretin-based therapies for type 2 diabetes or obesity, is advised.
- Bariatric surgery is an option in individuals with fatty liver disease and obesity.
- Resmetirom may be considered for adults with non-cirrhotic MASH and significant liver fibrosis, as it has demonstrated histological effectiveness on steatohepatitis and fibrosis with an acceptable safety and tolerability profile 1.
Monitoring and Follow-up
- Regular monitoring of both liver function tests and urinary protein levels is essential to track disease progression and treatment response.
- Early intervention is crucial, as both conditions can progress to more serious complications if left untreated.
- The most recent guidelines recommend a comprehensive approach to managing fatty liver disease and proteinuria, taking into account the latest evidence and recommendations 1.
From the Research
Proteinuria due to Fatty Liver
- Proteinuria, or the presence of excess proteins in the urine, can be a complication of various liver diseases, including non-alcoholic fatty liver disease (NAFLD) 2.
- NAFLD is a condition characterized by the accumulation of fat in the liver, which can lead to inflammation, scarring, and eventually liver failure 3, 4.
- The relationship between proteinuria and NAFLD is complex, and research suggests that dietary factors, such as protein intake, may play a role in the development and progression of the disease 2.
- Some studies have investigated the effects of certain medications, such as SGLT-2 inhibitors, on proteinuria in patients with diabetes and chronic kidney disease, but the evidence is limited for non-diabetic patients with NAFLD 5, 6.
Dietary Factors and Proteinuria
- A high-protein diet has been associated with an increased risk of NAFLD, while a Mediterranean-style diet, which is rich in fruits, vegetables, and whole grains, may have a protective effect 4.
- The type and amount of protein consumed may also influence the risk of proteinuria, with some studies suggesting that a diet high in branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) may contribute to the development of NAFLD 2.
Medications and Proteinuria
- SGLT-2 inhibitors, such as dapagliflozin, have been shown to reduce proteinuria in patients with diabetes, but their effectiveness in non-diabetic patients with NAFLD is unclear 5, 6.
- A randomized controlled trial found that dapagliflozin did not affect proteinuria in non-diabetic patients with chronic kidney disease, but it did induce a reversible decline in measured glomerular filtration rate (mGFR) and a reduction in body weight 6.