What is the correlation between Rheumatoid Arthritis (RA) and Proteinuria?

From the Guidelines

Rheumatoid arthritis is associated with proteinuria, and patients should be regularly screened for proteinuria, especially when on nephrotoxic medications, with management involving addressing the underlying cause and implementing renoprotective strategies such as blood pressure control and ACE inhibitors or ARBs if appropriate. The correlation between rheumatoid arthritis and proteinuria is complex, involving both the disease itself and its treatments. The inflammatory process in rheumatoid arthritis can directly damage the kidneys, particularly through the development of secondary amyloidosis where inflammatory proteins deposit in kidney tissue. Additionally, medications commonly used to treat rheumatoid arthritis, such as non-steroidal anti-inflammatory drugs (NSAIDs), disease-modifying antirheumatic drugs (DMARDs), and certain biologics, can cause nephrotoxicity resulting in proteinuria 1.

Key Considerations

• Patients with rheumatoid arthritis should have regular urinalysis to monitor for proteinuria, with typical screening recommended every 3-6 months, especially when on nephrotoxic medications.
• If proteinuria is detected, quantification through a 24-hour urine collection or protein-to-creatinine ratio should be performed, followed by appropriate nephrology referral if significant proteinuria (>500 mg/24 hours) is found.
• Management typically involves addressing the underlying cause, which may require adjusting rheumatoid arthritis medications, controlling disease activity, and implementing renoprotective strategies such as blood pressure control and ACE inhibitors or ARBs if appropriate, as suggested by recent guidelines 1.
• The use of ACE inhibitors or ARBs is recommended for patients with proteinuria ≥ 0.5 g per 24 hours, as they reduce proteinuria and delay the progression of renal disease 1.

Recent Guidelines and Recommendations

• The 2023 KDOQI US commentary on the 2021 KDIGO clinical practice guideline for the management of glomerular diseases suggests testing kidney markers at the time of initial SLE presentation or flares and recommends consideration of biopsy if proteinuria is >500 mg/d or if eGFR is worsening 1.
• The 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus emphasizes the importance of monitoring renal response and preventing disease flares, which contribute significantly to organ damage accrual and worse outcomes 1.

Clinical Implications

• The most recent and highest quality study 1 supports the use of renoprotective strategies, such as ACE inhibitors or ARBs, in patients with rheumatoid arthritis and proteinuria, to reduce the risk of renal disease progression and improve outcomes.
• Clinicians should prioritize the management of proteinuria in patients with rheumatoid arthritis, using a combination of medication adjustment, disease activity control, and renoprotective strategies to minimize the risk of kidney damage and improve quality of life.

From the Research

Rheumatoid Arthritis and Proteinuria Correlation

• Rheumatoid arthritis (RA) is associated with various renal manifestations, including proteinuria, which can be a sign of underlying kidney disease 2, 3, 4.
• Studies have shown that patients with RA are at increased risk of developing kidney disease, including amyloidosis, membranous glomerulonephritis, and mesangial glomerulonephritis 2, 4.
• Proteinuria is a common finding in patients with RA, and its presence is associated with a higher risk of kidney disease progression and cardiovascular disease 3, 5.
• The measurement of proteinuria, including 24-h urine protein excretion, urine albumin-to-creatinine ratio, and protein-to-creatinine ratio, can be useful in assessing kidney disease severity and predicting long-term renal outcomes in patients with RA 5.
• The treatment of RA, including the use of immunosuppressants, biological drugs, and anti-hypertensive drugs, can help to reduce proteinuria and slow kidney disease progression 2, 3.
• Strict inflammatory control and optimal control of hypertension are important in managing RA-associated kidney disease and reducing the risk of proteinuria and kidney disease progression 2, 3.

Key Findings

• A study published in 2012 found that complete remission of proteinuria was observed in 4 out of 9 patients with severe nephrotic renal AA amyloidosis secondary to RA, and that strict inflammatory control and optimal control of hypertension were associated with improved renal outcomes 2.
• A study published in 2018 found that chronic kidney disease in RA is more likely to be caused by cardiovascular risk factors than uncontrolled RA disease severity, and that the use of methotrexate and biologic medications can help to reduce the risk of kidney disease 3.
• A study published in 1995 found that the most common histopathologic finding in patients with RA and kidney disease was mesangial glomerulonephritis, followed by amyloidosis, membranous glomerulonephritis, and focal proliferative glomerulonephritis 4.
• A study published in 2020 found that acute phase proteins, including fibrin and fibrinogen, play a key role in the pathogenesis of RA and are involved in disease autoimmunity, inflammatory responses, and the heightened risk of cardiovascular disease 6.