How should I treat a patient who started Skyrizi (risankizumab) one month ago and now presents with bilateral lower‑extremity pitting edema, impaired renal function (GFR 41 mL/min, creatinine 1.35 mg/dL), and thrombocytopenia (platelet count 71 × 10⁹/L) while taking hydrochlorothiazide 12.5 mg daily?

Management of Bilateral Lower Extremity Edema in a Patient on Skyrizi with Renal Impairment and Thrombocytopenia

Immediately discontinue Skyrizi (risankizumab) and switch from hydrochlorothiazide to furosemide while urgently investigating for drug-induced thrombocytopenia and acute kidney injury, as the combination of new-onset edema, worsening renal function (GFR 41), and thrombocytopenia (platelet 71) one month after starting a biologic raises serious concern for drug toxicity.

Immediate Actions and Diagnostic Workup

Discontinue Skyrizi and Reassess Causality

• Stop risankizumab immediately given the temporal relationship between drug initiation (1 month ago) and development of edema, thrombocytopenia, and worsening renal function. Post-marketing surveillance has identified unexpected adverse events with risankizumab including thrombosis, cardiac disorders, and renal complications that were not in the original drug label 1.
• Obtain a complete blood count with peripheral smear to evaluate for drug-induced thrombocytopenia, hemolysis, or other hematologic abnormalities 2.
• Check urinalysis with microscopy to assess for proteinuria, hematuria, or cellular casts that might indicate immune-mediated nephritis 2.
• Monitor serum creatinine, electrolytes (sodium, potassium), and calculate creatinine clearance using the Cockroft-Gault formula for accurate medication dosing 2.

Evaluate for Serious Complications

• Rule out heparin-induced thrombocytopenia (HIT) if the patient has had any heparin exposure (including heparin flushes), as thrombocytopenia with a platelet count of 71 warrants immediate evaluation. Calculate the 4T score (thrombocytopenia, timing, thrombosis, other causes) to assess pre-test probability 3.
• Assess for signs of thrombosis given the combination of edema and thrombocytopenia—obtain duplex Doppler ultrasound of lower extremities to exclude deep vein thrombosis 4.
• Evaluate for cardiac causes of edema by checking BNP or NT-proBNP to confirm or exclude heart failure 4.
• Consider nephrology consultation for persistent grade 3 renal impairment (GFR 41) or if creatinine continues to rise, as immune checkpoint inhibitor-related nephritis can occur with biologics 2.

Diuretic Management

Switch from Thiazide to Loop Diuretic

• Discontinue hydrochlorothiazide 12.5 mg immediately as thiazides are ineffective when GFR is below 30-40 mL/min and may worsen renal function in this setting 2.
• Initiate furosemide 20-40 mg daily as loop diuretics remain effective even with reduced GFR and are the mainstay for managing edema in patients with renal impairment 5, 4.
• If response to furosemide is inadequate after 2-3 days, consider switching to torsemide which has superior absorption and longer duration of action 5.

Monitoring During Diuresis

• Limit weight loss to 1 kg/day in patients with peripheral edema to prevent diuretic-induced renal failure 5.
• Monitor serum electrolytes, creatinine, and blood pressure closely during the first weeks of treatment, checking every 2-3 days initially 5, 4.
• Discontinue diuretics if severe hyponatremia (sodium <120 mmol/L), acute kidney injury, or worsening clinical status develops 5, 4.
• Watch for severe hypokalemia which requires stopping furosemide 5.

Management of Thrombocytopenia

Determine Etiology and Severity

• With a platelet count of 71 × 10⁹/L, the patient has moderate thrombocytopenia that requires investigation but typically does not require platelet transfusion unless there is active bleeding 3.
• Send anti-PF4 antibody testing if HIT is suspected, but do not delay treatment decisions while awaiting results 3.
• Consider drug-induced thrombocytopenia from risankizumab as a diagnosis of exclusion after ruling out HIT, immune thrombocytopenia, and other causes 1.

Bleeding Risk Assessment

• Perform a thorough vascular examination including assessment of skin integrity and signs of petechiae or purpura 4, 3.
• Avoid invasive procedures unless absolutely necessary until platelet count improves.
• If severe bleeding occurs or platelet count drops below 20-30 × 10⁹/L, consider platelet transfusion 6.

Renal Function Optimization

Conservative Management for CKD Stage 3b

• With GFR 41 mL/min and creatinine 1.35 mg/dL, this patient has moderate-to-severe chronic kidney disease requiring aggressive blood pressure control 2.
• Target blood pressure ≤125/80 mmHg using ACE inhibitors or angiotensin receptor blockers as first-line agents for renoprotection 2.
• Ensure all medications are renally dosed using Cockroft-Gault formula to prevent drug accumulation and toxicity 2.
• Monitor for worsening renal function—if creatinine rises >0.3 mg/dL or GFR drops further, consider renal biopsy to evaluate for drug-induced interstitial nephritis 2.

Address Potential Secondary Causes

• Correct any volume depletion that may be contributing to acute-on-chronic kidney injury.
• Review all medications for nephrotoxic agents (NSAIDs, aminoglycosides, contrast agents) and discontinue if possible 2.
• Consider ultrasound of kidneys and bladder to exclude obstruction or structural abnormalities 2.

Special Considerations and Pitfalls

Avoid Excessive Diuresis

• Do not aggressively diurese as this can lead to intravascular volume depletion, hypotension, and worsening renal dysfunction in a patient with baseline GFR 41 5.
• Following mobilization of edema, reduce diuretic dosage to maintain minimal or no edema while avoiding complications 5.

Monitor for Complications

• Watch for muscle cramps during diuresis—if they occur, consider albumin infusion or baclofen administration 5.
• Monitor for signs of hepatic encephalopathy, severe hyponatremia, or acute kidney injury which require immediate diuretic discontinuation 4.
• If hyperkalemia develops (common with ACE inhibitors in CKD), adjust medications accordingly 4.

Long-term Management After Skyrizi Discontinuation

• Once edema resolves and platelet count normalizes, consider alternative biologic therapy for the underlying condition (likely psoriasis or inflammatory bowel disease) that does not have the same adverse event profile 7, 8.
• Continue monitoring renal function and platelet count for several weeks after stopping risankizumab as some adverse events may persist 1.
• Maintain compression therapy with 20-30 mmHg graduated compression stockings if chronic venous insufficiency contributes to edema 4.