What is the next step in management of a 45-year-old man with IgA nephropathy on maximally tolerated Farxiga (dapagliflozin), Mounjaro (tirzepatide) and telmisartan presenting with impaired renal function and significant proteinuria?

Next Step in Management

Add finerenone (a non-steroidal mineralocorticoid receptor antagonist) to the current regimen and initiate a 6-month course of corticosteroids using the Pozzi protocol, provided there are no absolute contraindications. 1, 2, 3

Rationale for This Patient

This 45-year-old patient has persistent high-risk proteinuria (2 g/day) despite maximally optimized supportive care with SGLT2 inhibitor (Farxiga), GLP-1 agonist (Mounjaro), and ARB (telmisartan). 1, 3 The creatinine of 2.0 mg/dL suggests an eGFR likely in the 30-50 mL/min/1.73 m² range, placing this patient at the threshold where immunosuppression may still provide benefit. 1, 3

Immediate Actions

1. Verify Optimization of Current Therapy

• Confirm telmisartan is at maximum tolerated dose (80 mg daily) to achieve maximal antiproteinuric effect, not just blood pressure control. 1, 3
• Target blood pressure < 120/70 mmHg (or even < 125/75 mmHg given proteinuria > 1 g/day) using additional antihypertensive agents if needed. 1, 2
• Verify dietary sodium restriction < 2 g/day as this augments the antiproteinuric effect of RAS blockade. 4, 1, 3
• Ensure the patient has been on this optimized regimen for at least 90 days before proceeding to immunosuppression. 1, 3

2. Add Finerenone

• Finerenone is a non-steroidal mineralocorticoid receptor antagonist with greater receptor selectivity and less potassium retention than traditional agents, making it safer in CKD patients. 2
• This represents an additional disease-modifying agent that can be layered onto existing therapy. 2
• Monitor potassium closely after initiation. 3

3. Assess Eligibility for Corticosteroids

Calculate the precise eGFR to determine if the patient meets the threshold for corticosteroid therapy:

• If eGFR ≥ 50 mL/min/1.73 m²: Strong candidate for corticosteroids. 1, 3
• If eGFR 30-50 mL/min/1.73 m²: Consider corticosteroids with extreme caution, weighing individual risk-benefit. 1, 3
• If eGFR < 30 mL/min/1.73 m²: Corticosteroids are contraindicated. 1, 3

Screen for absolute contraindications before initiating steroids: 1, 3

• Diabetes mellitus (patient is on Mounjaro, suggesting diabetes or obesity)
• Obesity (BMI > 30 kg/m²)
• Active or latent infections (screen for tuberculosis, hepatitis B/C, HIV)
• Uncontrolled psychiatric disease
• Severe osteoporosis
• Active peptic ulcer disease

4. If Eligible, Initiate Pozzi Protocol

Recommended corticosteroid regimen: 1, 3

Component	Dose & Schedule
IV methylprednisolone	1 g daily × 3 consecutive days at months 1,3, and 5
Oral prednisone	0.5-0.8 mg/kg every other day for 6 months, then taper by 0.2 mg/kg/day each month over the final 4 months

• This regimen achieved 97% 10-year renal survival versus 53% without immunosuppression in Italian trials. 1, 3
• Provide pneumocystis prophylaxis with trimethoprim-sulfamethoxazole during high-dose steroid therapy. 4
• Administer pneumococcal and influenza vaccines before starting immunosuppression. 4

Critical Decision Point: The Diabetes/Obesity Caveat

If this patient has diabetes or BMI > 30 kg/m² (likely given Mounjaro use), corticosteroids carry significantly higher risk (risk ratio 2.91 for serious adverse events). 2 In this scenario:

• Strongly consider enrollment in a clinical trial for targeted-release budesonide, sparsentan, iptacopan, or complement inhibitors, which may offer superior efficacy and safety. 3, 5
• If clinical trials are unavailable and proteinuria remains > 2 g/day, the decision to use corticosteroids must weigh the 97% vs 53% renal survival benefit against steroid-related mortality risk. 1, 2, 3
• In the presence of diabetes/obesity, finerenone addition becomes even more critical as a safer alternative to escalate therapy. 2

Monitoring Strategy

During the first 3 months after any medication adjustment: 1

• Serum creatinine, potassium, and spot urine protein-to-creatinine ratio monthly
• Blood pressure at each visit
• Adjust medications to maintain BP < 120/70 mmHg

If corticosteroids are initiated: 1

• Monitor monthly for hyperglycemia, weight gain, mood changes, bone density loss
• Continue monthly proteinuria and renal function assessments
• Discontinue steroids if eGFR falls > 30% from baseline and persists beyond 8 weeks 2

Long-term follow-up: 1

• Assess proteinuria and eGFR every 3-6 months indefinitely
• Goal: sustained proteinuria < 1 g/day (ideally < 0.5 g/day)

Therapies to Avoid in This Patient

• Mycophenolate mofetil: Not recommended in non-Chinese patients. 3
• Cyclophosphamide or azathioprine: Reserved only for crescentic IgAN with > 50% crescents and rapidly progressive renal decline. 3
• Rituximab: No demonstrated efficacy. 3
• Dual ACE inhibitor + ARB: Increases adverse events without additional benefit. 3

Common Pitfalls to Avoid

• Do not initiate corticosteroids if the patient has not completed at least 90 days of maximally optimized supportive care (max-dose ARB, SGLT2 inhibitor, BP control, sodium restriction). 1, 3
• Do not discontinue telmisartan if creatinine rises ≤ 30% from baseline; this modest rise predicts better long-term renal protection. 3
• Do not use corticosteroids if eGFR < 30 mL/min/1.73 m² as harms outweigh benefits. 1, 3
• Do not overlook the need for infection screening and prophylaxis before starting immunosuppression. 4
• Do not forget to hold ARB and diuretics during intercurrent illnesses that cause volume depletion. 3