Management of CKD with Worsening Hematuria in IgA Nephropathy

Diagnosis and Assessment

The primary approach is to assess whether the worsening hematuria represents acute tubular necrosis from intratubular erythrocyte obstruction versus crescentic disease, then optimize supportive care with RAS blockade while avoiding immunosuppression unless crescentic IgAN is confirmed 1, 2
If macroscopic hematuria with acute kidney injury (AKI): Provide general supportive care initially, as this typically represents acute tubular necrosis from intratubular erythrocyte casts and hemoglobin-mediated oxidative stress 1, 3
Perform repeat kidney biopsy if kidney function does not improve after 5 days from onset of worsening to differentiate acute tubular necrosis from crescentic IgAN 1, 4
Define crescentic IgAN as >50% of glomeruli showing crescents with rapidly progressive renal deterioration 1, 3, 4

Use the International IgAN Prediction Tool to assess disease prognosis and guide treatment intensity 2

Initiate ACE inhibitor or ARB regardless of blood pressure if proteinuria >0.5 g/day 2
Titrate upward to maximum tolerated dose to achieve proteinuria <1 g/day 1, 4
Continue therapy unless serum creatinine increases >30% within 4 weeks of initiation 5
Target <125/75 mmHg if proteinuria >1 g/day 1, 4
Target <130/80 mmHg if proteinuria <1 g/day 1, 4
Restrict dietary sodium to <2 g/day (<90 mmol/day) 2, 5
Encourage 150 minutes weekly of moderate-intensity physical activity 6
Achieve smoking cessation and maintain BMI 20-25 kg/m² 2, 5
Consider dietary protein restriction based on degree of proteinuria and kidney function 2

Only consider corticosteroids if ALL of the following criteria are met: persistent proteinuria ≥0.75-1 g/day despite at least 90 days of optimized supportive care, eGFR >50 ml/min per 1.73 m², and absence of contraindications 1, 2, 4
Use steroids plus cyclophosphamide analogous to ANCA vasculitis treatment if crescents in >50% of glomeruli with rapidly progressive renal deterioration 1, 3, 4
Do not use MMF in IgAN 1, 4
Do not combine corticosteroids with cyclophosphamide or azathioprine unless crescentic IgAN 1, 4
Do not use immunosuppressive therapy if eGFR <30 ml/min per 1.73 m² unless crescentic IgAN 1, 4

Consider fish oil supplementation for persistent proteinuria ≥1 g/day despite 3-6 months of optimized supportive care 1, 4
Initiate SGLT2 inhibitors if eGFR ≥20 ml/min per 1.73 m² with type 2 diabetes, ACR ≥200 mg/g, or heart failure to reduce kidney failure risk 7
Prescribe statin therapy for all adults ≥50 years with CKD 7, 8
Target hemoglobin A1c approximately 7% in diabetic patients 7

Monitor eGFR and proteinuria at least annually, more frequently (3-4 times per year) for higher-risk patients 6, 8, 9
Check serum creatinine, potassium, and bicarbonate 2-4 weeks after medication changes 5
A change in eGFR >20% on subsequent testing exceeds expected variability and warrants evaluation 9
Among patients initiating hemodynamically active therapies, GFR reductions >30% exceed expected variability 9
Doubling of ACR on subsequent testing exceeds laboratory variability 9
Refer when 5-year kidney failure risk is 3-5% or when eGFR <30 ml/min per 1.73 m² 6, 7, 9