How should I manage a 26-year-old man with biopsy-proven IgA nephropathy, proteinuria approximately 900 mg/day, and serum creatinine 1.4 mg/dL?

Treatment of IgA Nephropathy with 900 mg/day Proteinuria and Creatinine 1.4 mg/dL

Start this 26-year-old man immediately on an ACE inhibitor or ARB, uptitrate to the maximum tolerated dose over 3-6 months while targeting blood pressure <130/80 mmHg, and if proteinuria remains ≥0.75-1 g/day after this optimized supportive care period, consider adding a 6-month course of corticosteroids given his preserved kidney function (eGFR approximately 60-70 mL/min/1.73 m²). 1

Initial Management: Optimized Supportive Care (Months 0-3)

RAS Blockade as Foundation

• Begin ACE inhibitor or ARB therapy immediately, regardless of blood pressure status, since proteinuria exceeds 0.5 g/day 1
• Uptitrate the medication to the maximum tolerated dose, aiming to reduce proteinuria below 1 g/day 1
• Monitor serum creatinine and potassium closely during uptitration; accept up to a 30% increase in creatinine as this represents hemodynamic changes rather than drug toxicity 1
• Do not discontinue therapy unless creatinine continues rising beyond 30% or refractory hyperkalemia develops 1

Blood Pressure Targets

• Target blood pressure <130/80 mmHg given proteinuria is close to 1 g/day 1
• Some guidelines recommend even stricter control (<125/75 mmHg) when proteinuria exceeds 1 g/day, though this patient is just below that threshold 1

Lifestyle and Dietary Modifications

• Restrict dietary sodium to <2.0 g/day (<90 mmol/day) to enhance antiproteinuric effects of RAS blockade 1
• Counsel on weight normalization, smoking cessation, and regular physical activity 1
• Consider moderate protein restriction given the proteinuria level, though this should be balanced against nutritional needs in a young patient 1

Reassessment at 3-6 Months: Decision Point for Immunosuppression

Critical Threshold Analysis

At 900 mg/day, this patient sits at a crucial decision point. The evidence shows:

• Proteinuria >1 g/day (especially time-averaged values) predicts progressive kidney disease with approximately 3 mL/year GFR loss 1
• The threshold where risk begins to increase may be as low as 0.5 g/day, though most treatment trials use 1 g/day as the intervention threshold 1
• Reduction of proteinuria to <1 g/day associates with favorable long-term prognosis regardless of initial proteinuria level 1

When to Add Corticosteroids

If proteinuria remains ≥0.75-1 g/day after 3-6 months of optimized supportive care, add corticosteroids using one of these regimens 1:

Preferred Regimen (Pozzi Protocol):

• Methylprednisolone 1 g IV for 3 consecutive days at months 1,3, and 5 1
• PLUS oral prednisone 0.5 mg/kg every other day for 6 months, tapering by 0.2 mg/kg/day per month over the final 4 months 1
• This regimen showed 10-year renal survival of 97% versus 53% without immunosuppression 1

Key Eligibility Criteria for Corticosteroids:

• eGFR >50 mL/min/1.73 m² (this patient qualifies with creatinine 1.4 mg/dL) 1
• Absence of contraindications: diabetes, obesity (BMI >30), active infections, uncontrolled psychiatric disease, severe osteoporosis 1
• At age 26 without mentioned comorbidities, this patient is an ideal candidate for corticosteroid therapy if proteinuria persists 1

Alternative if Proteinuria Drops Below 0.75 g/day

• Continue ACE inhibitor/ARB at maximum tolerated dose indefinitely 1
• Monitor proteinuria and kidney function every 3-6 months 1
• Maintain strict blood pressure control and lifestyle modifications 1

What NOT to Do

Avoid These Therapies

• Do not use cyclophosphamide or azathioprine unless crescentic IgAN with rapidly deteriorating function develops 1
• Do not use mycophenolate mofetil in non-Chinese patients (no proven benefit) 1
• Do not use calcineurin inhibitors as first-line therapy; reserve for specific nephrotic-range proteinuria scenarios 1
• Do not use rituximab (not recommended in IgAN) 1

Critical Pitfalls to Avoid

• Do not delay ACE inhibitor/ARB initiation waiting for blood pressure elevation—start immediately for proteinuria >0.5 g/day 1
• Do not prematurely stop ACE inhibitor/ARB if creatinine rises <30% from baseline; this is expected hemodynamic effect 1
• Do not start corticosteroids before completing 3-6 months of optimized supportive care, as many patients respond to RAS blockade alone 1
• Do not use corticosteroids if eGFR drops below 30 mL/min/1.73 m² (though this patient is far from that threshold) 1

Prognostic Context

Risk Stratification

This patient's proteinuria at 900 mg/day places him in an intermediate-risk category:

• Proteinuria <500 mg/day: low risk of progression 2
• Proteinuria 0.5-1 g/day: intermediate risk, warrants close monitoring 1
• Proteinuria >1 g/day: high risk, 25-fold faster decline in renal function compared to <500 mg/day 2
• Proteinuria >3 g/day: very high risk of progression 2

Importance of Early Intervention

• Early reduction of proteinuria serves as both a treatment target and a marker of better long-term outcomes 3
• The "proteinuria index" (duration in years × proteinuria in g/day) correlates with progression, emphasizing the importance of early aggressive management in this young patient 2
• Achieving complete remission (proteinuria <1 g/day) significantly improves renal survival rates 3, 4

Monitoring Strategy

During Initial 3-6 Month Period

• Check serum creatinine, potassium, and spot urine protein-to-creatinine ratio monthly during ACE inhibitor/ARB uptitration 1
• Measure blood pressure at each visit, adjusting medications to meet targets 1

If Corticosteroids Are Started

• Monitor for steroid-related adverse effects: hyperglycemia, weight gain, mood changes, bone density 1
• Continue monthly proteinuria and kidney function monitoring 1
• Screen for latent infections (tuberculosis, hepatitis) before initiating therapy 1

Long-Term Follow-Up

• Assess proteinuria and eGFR every 3-6 months indefinitely 1
• The goal is sustained proteinuria <1 g/day, ideally <0.5 g/day 1, 2