Can Skyrizi (Risankizumab) cause proteinuria?

Skyrizi (Risankizumab) and Proteinuria

Skyrizi (risankizumab) is not known to cause proteinuria as a common or significant side effect based on the available evidence.

Mechanism and Safety Profile of Risankizumab

Risankizumab is a humanized IgG1 monoclonal antibody that specifically targets the p19 subunit of interleukin-23 (IL-23), inhibiting IL-23-dependent cell signaling 1, 2. It is primarily approved for the treatment of moderate to severe plaque psoriasis.

Unlike some other biologics and targeted therapies that have documented renal effects, the clinical trials and long-term safety data for risankizumab do not highlight proteinuria as a significant adverse event:

• In phase II and III clinical trials, risankizumab was generally well-tolerated with no specific renal adverse effects reported 1
• The LIMMitless open-label extension study, which followed patients for up to 5 years, showed low rates of treatment-emergent adverse events (TEAEs) without mentioning proteinuria as a safety concern 3

Monitoring Kidney Function with Biologics

While risankizumab itself is not associated with proteinuria, it's important to understand the relationship between inflammatory conditions and kidney function:

1. Baseline Assessment:

   • Patients with inflammatory conditions may have underlying kidney issues
   • Assess baseline kidney function before initiating any biologic therapy

2. Regular Monitoring:

   • Monitor kidney function periodically during treatment
   • Check for proteinuria as part of routine laboratory evaluations

Proteinuria Management if Detected

If proteinuria is detected during risankizumab treatment, it's more likely related to other factors rather than the medication itself. Management should follow established guidelines for proteinuria:

• For mild proteinuria (0.5-1 g/day), ACEi or ARB therapy is suggested with a target BP <130/80 mmHg 4
• For moderate proteinuria (1-3.5 g/day), ACEi or ARB therapy should be titrated to maximum tolerated dose with a target BP <125/75 mmHg 4
• Regular monitoring of serum creatinine, potassium, and proteinuria is necessary after initiation or dose increase of ACEi or ARB 4

Differential Diagnosis of Proteinuria in Patients on Risankizumab

If proteinuria develops during risankizumab treatment, consider:

1. Pre-existing kidney disease
2. Underlying inflammatory condition (psoriasis can be associated with kidney manifestations)
3. Concomitant medications (some drugs are known to cause proteinuria)
4. Hypertension (a risk factor for proteinuria) 5
5. Reduced kidney function (eGFR <90 mL/min/1.73 m² increases risk of proteinuria) 5

Conclusion

Based on the available evidence, risankizumab (Skyrizi) does not appear to cause proteinuria as a direct side effect. The long-term safety data from clinical trials extending up to 5 years does not identify proteinuria as a significant concern 3. If proteinuria is detected in a patient receiving risankizumab, other etiologies should be investigated, and management should follow standard guidelines for proteinuria treatment.