Can doxycycline (antibiotic) cause proteinuria (excess protein in urine)?

From the Guidelines

Doxycycline can cause renal dysfunction, which may manifest as proteinuria, although the risk is lower compared to other tetracyclines. According to the British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD) published in 2017 1, doxycycline is associated with various adverse effects, including renal dysfunction. While the guidelines do not specifically mention proteinuria as a side effect, renal dysfunction can lead to proteinuria. The exact mechanism of doxycycline-induced renal dysfunction is not fully understood, but it may be related to direct tubular toxicity or an immune-mediated hypersensitivity reaction.

Key points to consider:

• The risk of renal dysfunction with doxycycline is lower compared to other tetracyclines 1
• Patients on higher doses of doxycycline, prolonged therapy, or those with pre-existing kidney disease may be at increased risk of developing renal dysfunction and subsequent proteinuria
• Regular monitoring of kidney function may be recommended for patients on long-term doxycycline therapy, particularly those with risk factors for kidney disease
• If proteinuria occurs, it may resolve after discontinuation of the medication

It is essential to note that the guidelines highlight various other potential side effects of doxycycline, including cardiac, dermatological, gastrointestinal, haematological, hepatotoxic, immunological, infections, neurological, and respiratory adverse effects 1. However, in the context of proteinuria, the primary concern is renal dysfunction. Patients experiencing unusual urinary changes, swelling in the extremities, or decreased urination while on doxycycline should contact their healthcare provider immediately.

From the Research

Doxycycline and Proteinuria

• Doxycycline has been studied for its potential to reduce proteinuria in various conditions, including diabetic nephropathy 2, 3.
• In patients with diabetic nephropathy, doxycycline has been shown to decrease proteinuria after 2-3 months of treatment 2, 3.
• The mechanism of doxycycline's effect on proteinuria is thought to be related to its inhibition of matrix metalloproteinases (MMPs), which contribute to the deposition of extracellular matrix proteins and the pathogenesis of diabetic nephropathy 2.
• However, there is also evidence to suggest that doxycycline can exacerbate renal failure in some patients, particularly those with pre-existing renal impairment 4.
• In animal studies, doxycycline has been shown to protect against renal ischemia-reperfusion injury and reduce proteinuria 5.
• Additionally, doxycycline has been reported to decrease proteinuria in a patient with crescentic glomerulonephritis, suggesting a potential benefit of metalloproteinase inhibitors in the treatment of proliferative glomerulonephritis 6.

Key Findings

• Doxycycline can reduce proteinuria in patients with diabetic nephropathy 2, 3.
• Doxycycline's effect on proteinuria is thought to be related to its inhibition of MMPs 2.
• Doxycycline can exacerbate renal failure in some patients, particularly those with pre-existing renal impairment 4.
• Doxycycline may have a protective effect against renal ischemia-reperfusion injury and reduce proteinuria in animal models 5.
• Doxycycline may be beneficial in reducing proteinuria in patients with crescentic glomerulonephritis 6.