What is the management approach for a patient with chronic kidney disease (CKD) and worsening hematuria due to IgA nephropathy?

Management of CKD with Worsening Hematuria in IgA Nephropathy

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

Immediate Assessment of Worsening Hematuria

Determine the Underlying Pathology

• 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

• 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

• Define crescentic IgAN as >50% of glomeruli showing crescents with rapidly progressive renal deterioration 1

Risk Stratification

• Use the International IgAN Prediction Tool to assess disease prognosis and guide treatment intensity 1

• Recognize that persistent hematuria independently predicts progression to ESRD, with 30.4% of patients with persistent hematuria reaching ESRD versus 10.6% with minimal/negative hematuria 2

• Time-averaged hematuria is an independent predictor of ESRD alongside proteinuria, baseline renal function, and tubulointerstitial fibrosis 2

Optimized Supportive Care (First-Line for All Patients)

RAS Blockade

• Initiate ACE inhibitor or ARB regardless of blood pressure if proteinuria >0.5 g/day 1

• Titrate upward to maximum tolerated dose to achieve proteinuria <1 g/day 1

• Continue therapy unless serum creatinine increases >30% within 4 weeks of initiation 3

Blood Pressure Targets

• Target <125/75 mmHg if proteinuria >1 g/day 1

• Target <130/80 mmHg if proteinuria <1 g/day 1

Lifestyle and Dietary Modifications

• Restrict dietary sodium to <2 g/day (<90 mmol/day) 1, 3

• Encourage 150 minutes weekly of moderate-intensity physical activity 1

• Achieve smoking cessation and maintain BMI 20-25 kg/m² 1, 3

• Consider dietary protein restriction based on degree of proteinuria and kidney function 1

Immunosuppressive Therapy Decision Algorithm

When to Consider Corticosteroids

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 1

• eGFR >50 ml/min per 1.73 m² (some guidelines suggest >30 ml/min per 1.73 m²) 1

• Absence of contraindications: diabetes, obesity (BMI >30 kg/m²), latent infections, liver cirrhosis, active peptic ulceration, uncontrolled psychiatric disease, or severe osteoporosis 1

Critical caveat: The clinical benefit of glucocorticoids in IgAN is not established, and a retrospective study showed no benefit from immunosuppressive therapy in stage 3-4 CKD compared with supportive care alone 1, 4

Crescentic IgAN (Rapidly Progressive Disease)

• Use steroids plus cyclophosphamide analogous to ANCA vasculitis treatment if crescents in >50% of glomeruli with rapidly progressive renal deterioration 1

• This is the only scenario where aggressive immunosuppression is recommended in advanced CKD 1

What NOT to Use

• Do not use MMF in IgAN 1

• Do not combine corticosteroids with cyclophosphamide or azathioprine unless crescentic IgAN 1

• Do not use immunosuppressive therapy if eGFR <30 ml/min per 1.73 m² unless crescentic IgAN 1

• Do not perform tonsillectomy 1

• Do not use antiplatelet agents 1

Additional Therapies to Consider

Fish Oil

• Consider fish oil supplementation for persistent proteinuria ≥1 g/day despite 3-6 months of optimized supportive care 1

SGLT2 Inhibitors

• 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 5, 6

Cardiovascular Risk Reduction

• Prescribe statin therapy for all adults ≥50 years with CKD 5, 7

• Target hemoglobin A1c approximately 7% in diabetic patients 5

Monitoring Strategy

Frequency

• Monitor eGFR and proteinuria at least annually, more frequently (3-4 times per year) for higher-risk patients 1, 7

• Check serum creatinine, potassium, and bicarbonate 2-4 weeks after medication changes 3

Defining Progression

• A change in eGFR >20% on subsequent testing exceeds expected variability and warrants evaluation 1

• Among patients initiating hemodynamically active therapies, GFR reductions >30% exceed expected variability 1

• Doubling of ACR on subsequent testing exceeds laboratory variability 1

Nephrology Referral

• Refer when 5-year kidney failure risk is 3-5% or when eGFR <30 ml/min per 1.73 m² 1, 5

• Use disease-specific validated prediction equations for IgAN 1

Critical Pitfalls to Avoid

• Do not assume all worsening hematuria requires immunosuppression—most episodes represent reversible acute tubular necrosis 1

• Do not delay repeat biopsy beyond 5 days if kidney function continues to worsen with macroscopic hematuria, as this may represent undiagnosed crescentic disease 1

• Do not use immunosuppression in advanced CKD (eGFR <30 ml/min per 1.73 m²) unless biopsy confirms crescentic IgAN 1

• Recognize that hematuria remission significantly improves outcomes—the rate of renal function decline changes from -6.45 to -0.18 ml/min per 1.73 m² per year after hematuria disappearance 2

• Do not overlook that even "low-risk" patients with proteinuria <0.88 g/g have 20% risk of kidney failure within 10 years, emphasizing the need for aggressive supportive care in all patients 8