What is the first line treatment for a patient with IgA (Immunoglobulin A) nephropathy, impaired renal function, and non-nephrotic proteinuria?

First-Line Treatment for IgA Nephropathy with Creatinine 1.5 mg/dL and Non-Nephrotic Proteinuria

Start immediately with an ACE inhibitor or ARB titrated to the maximum tolerated dose, targeting blood pressure <120 mmHg systolic, and continue this optimized supportive care for at least 90 days before considering any immunosuppressive therapy. 1, 2

Initial Management: Optimized Supportive Care

The cornerstone of treatment is renin-angiotensin system (RAS) blockade, which should be instituted regardless of blood pressure if proteinuria exceeds 0.5 g/day 1. With a creatinine of 1.5 mg/dL (estimated GFR likely 40-60 mL/min/1.73m²), this patient has sufficient renal function to safely initiate and benefit from ACE inhibitor or ARB therapy 2, 3.

Blood Pressure and RAS Blockade Strategy

• Target systolic blood pressure <120 mmHg using standardized office measurement, though practically 120-130 mmHg is achievable in most glomerular disease patients 1
• Uptitrate ACE inhibitor or ARB to maximum tolerated dose as first-line therapy for proteinuria reduction 1, 2
• Accept modest increases in serum creatinine up to 30% during uptitration, as this reflects appropriate hemodynamic changes rather than true kidney injury 1, 4
• Monitor labs frequently (potassium, creatinine) after initiation and dose changes 1

Essential Lifestyle Modifications

• Restrict dietary sodium to <2.0 g/day (<90 mmol/day) to maximize the antiproteinuric effect of RAS blockade 1, 4
• Normalize body weight and exercise regularly as synergistic measures for blood pressure and proteinuria control 1
• Stop smoking if applicable 1

When to Consider Immunosuppression

If proteinuria remains ≥0.75-1 g/day after at least 90 days of optimized supportive care, the patient has high risk of progressive kidney function loss and may be considered for a 6-month course of glucocorticoid therapy 1, 2. However, this decision requires careful assessment given the creatinine of 1.5 mg/dL.

Glucocorticoid Therapy Considerations

The 2021 KDIGO guidelines recommend glucocorticoids with extreme caution or complete avoidance in patients with 1:

• eGFR <30 mL/min/1.73m² (this patient likely has eGFR 40-60, so not an absolute contraindication)
• Diabetes, obesity (BMI >30), latent infections, or severe osteoporosis

If glucocorticoids are appropriate after 90 days of failed supportive care, two regimens are recommended 2:

• IV methylprednisolone 1g for 3 consecutive days at months 1,3, and 5, plus oral prednisone 0.5 mg/kg every other day for 6 months, OR
• Oral prednisone starting at 0.8-1 mg/kg/day for 2 months, then reduced by 0.2 mg/kg/day per month for the next 4 months

Critical Monitoring During Steroid Therapy

The risk of adverse events from corticosteroids increases with declining renal function—from 2.3% at GFR 90 mL/min to 15.4% at GFR 34 mL/min 3. Therefore:

• Monitor closely for glucose intolerance, hypertension, and infection risk 2
• Reassess proteinuria at 3-6 months after starting ACE inhibitor/ARB to determine actual need for steroids 2

Therapies to Avoid

• Do NOT use mycophenolate mofetil (MMF) as evidence shows no benefit in IgA nephropathy 1, 2
• Do NOT use corticosteroids combined with cyclophosphamide or azathioprine unless crescentic disease (>50% crescents with rapidly progressive deterioration) develops 1, 2, 5
• Do NOT use antiplatelet agents or pursue tonsillectomy as routine therapy 1

Adjunctive Considerations

Fish oil may be considered if proteinuria persists ≥1 g/day despite optimized supportive care, as evidence is conflicting but risk is minimal 1, 2.

Treatment Goal

The primary goal is achieving time-average proteinuria <1 g/day, which is associated with favorable long-term outcomes regardless of how achieved 2, 3. This should be the target before escalating to immunosuppression.

Common Pitfalls to Avoid

• Do not start immunosuppression before completing 90 days of optimized supportive care 1
• Do not stop ACE inhibitor/ARB for modest creatinine increases up to 30% 1
• Do not use immunosuppression if eGFR falls below 30 mL/min/1.73m² unless crescentic disease is present 1
• Counsel patients to hold ACE inhibitor/ARB during volume depletion (sick days) 1