Does Hydroxychloroquine (Plaquenil) cause impaired renal function?

From the Guidelines

Hydroxychloroquine (Plaquenil) is generally considered safe for kidney function in most patients, with a low risk of causing impaired renal function, as evidenced by the 2020 update of the joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis 1. The primary concern with Plaquenil is its potential to cause retinal toxicity rather than kidney damage. According to the EULAR/ERA-EDTA recommendations, Hydroxychloroquine (HCQ) is recommended for all patients with lupus nephritis, in the absence of contraindications, as it is linked to reduced risk of kidney flares, end-stage kidney disease (ESKD), and death 1. Key points to consider:

• Plaquenil is primarily metabolized by the liver and only about 20-25% is excreted unchanged through the kidneys, which means it puts minimal stress on kidney function.
• Patients with pre-existing kidney disease can usually take Plaquenil without dose adjustment, but regular monitoring of kidney function through blood tests is recommended during long-term Plaquenil therapy.
• The daily HCQ dose should not exceed 5 mg/kg actual body weight, and dose adjustments (50% reduction) and yearly eye monitoring from onset are recommended for patients with GFR <30 mL/min 1. It is essential to note that while Plaquenil is considered safe for kidney function, other medications used to treat autoimmune conditions may have a higher risk of causing impaired renal function, as discussed in the guidelines for the management of chronic kidney disease in HIV-infected patients 1.

From the FDA Drug Label

1. 11 Renal Toxicity Proteinuria with or without moderate reduction in glomerular filtration rate have been reported with the use of hydroxychloroquine sulfate. Renal biopsy showed phospholipidosis without immune deposits, inflammation, and/or increased cellularity Physicians should consider phospholipidosis as a possible cause of renal injury in patients with underlying connective tissue disorders who are receiving hydroxychloroquine sulfate.

Yes, Hydroxychloroquine (Plaquenil) can cause impaired renal function, as evidenced by proteinuria and moderate reduction in glomerular filtration rate, likely due to phospholipidosis 2.

From the Research

Impaired Renal Function and Hydroxychloroquine

• Hydroxychloroquine has been associated with impaired renal function, particularly in patients with pre-existing kidney disease 3.
• A case report described a patient who developed renal phospholipidosis after 25 years of continuous hydroxychloroquine treatment, highlighting the potential risk of impaired renal function with long-term use 3.
• However, other studies have suggested that hydroxychloroquine may have renoprotective effects in certain conditions, such as IgA nephropathy and membranous nephropathy 4, 5.
• Hydroxychloroquine has been shown to reduce proteinuria and slow disease progression in these conditions, although the exact mechanisms are not fully understood 4, 5.
• Additionally, hydroxychloroquine has been found to inhibit macrophage activation and attenuate renal fibrosis after ischemia-reperfusion injury, suggesting potential anti-fibrotic effects 6.

Key Findings

• Hydroxychloroquine-induced renal phospholipidosis is a potential cause of impaired renal function 3.
• The risk of impaired renal function may be higher in patients with pre-existing kidney disease or those taking hydroxychloroquine for extended periods 3.
• Hydroxychloroquine may have renoprotective effects in certain conditions, such as IgA nephropathy and membranous nephropathy 4, 5.
• Further research is needed to fully understand the effects of hydroxychloroquine on renal function and to determine its potential therapeutic applications 7, 6.