Can Rinvoq (upadacitinib) cause proteinuria?

Upadacitinib (Rinvoq) and Proteinuria

Upadacitinib (Rinvoq) can potentially cause proteinuria, although it is not listed among its common adverse effects in current guidelines and monitoring recommendations focus primarily on other parameters.

Mechanism and Risk Assessment

Upadacitinib is a selective Janus kinase 1 (JAK1) inhibitor used in treating various autoimmune conditions. Based on the available evidence:

• The 2024 American College of Rheumatology (ACR) guidelines mention monitoring requirements for JAK inhibitors including upadacitinib, but do not specifically list proteinuria as a common adverse effect requiring routine monitoring 1

• Unlike some other medications such as CNIs (cyclosporine, tacrolimus) which have well-documented nephrotoxicity profiles including proteinuria, JAK inhibitors like upadacitinib are not primarily associated with renal adverse effects

• Research evidence suggests upadacitinib may actually have renoprotective properties in certain contexts, as demonstrated in a 2022 study showing it protected against cisplatin-induced renal dysfunction 2

Monitoring Recommendations

For patients taking upadacitinib, the following monitoring is recommended:

• Baseline screening: Hepatitis B virus, hepatitis C virus, and latent TB screening before initiation
• Regular monitoring: CBC with differential and CMP at baseline, 4-8 weeks after starting, and every 3 months thereafter
• Lipid monitoring: At baseline, 4-8 weeks after starting, then annually 1

Notably, urinalysis or specific monitoring for proteinuria is not included in the standard monitoring recommendations for upadacitinib, unlike medications with known renal effects such as cyclophosphamide, which requires regular urinalysis 1.

Renal Considerations

A pharmacokinetic study specifically examining upadacitinib in renal impairment found:

• Renal impairment has only a limited effect on upadacitinib pharmacokinetics
• Urinary excretion plays a limited role in upadacitinib elimination
• No dose adjustment is necessary for patients with impaired renal function 3

Comparison with Other Medications Known to Cause Proteinuria

Several medications are well-documented to cause or worsen proteinuria:

• Calcineurin inhibitors (CNIs) like cyclosporine and tacrolimus can cause nephrotoxicity and proteinuria through effects on glomerular permeability 1
• Anti-angiogenic agents like axitinib have been shown to accelerate proteinuria in animal models 4
• Tenofovir is known to potentially cause proximal tubular dysfunction and proteinuria 1

Clinical Implications

If a patient on upadacitinib develops proteinuria:

1. Consider other more common causes of proteinuria (underlying disease, concomitant medications, comorbidities)
2. Assess for other signs of renal dysfunction (elevated creatinine, decreased GFR)
3. Consider measuring the albumin-to-protein ratio in urine to distinguish between glomerular and tubular proteinuria
4. Monitor renal function parameters if proteinuria is detected

Conclusion

While proteinuria is not specifically highlighted as a common adverse effect of upadacitinib in current guidelines, monitoring renal function in patients on any immunomodulatory therapy is prudent clinical practice. If proteinuria develops in a patient taking upadacitinib, careful evaluation should be undertaken to determine the cause, as it may be related to the underlying disease rather than the medication itself.