IgA nephropathy is staged using a combination of CKD stages 1 through 5 (based on eGFR), proteinuria measurements, and the Oxford MEST-C biopsy classification. Early stages are often asymptomatic and detected on routine urinalysis. Mid-stages (3 and 4) are when active treatment becomes critical to slow progression. Advanced stages (4 to 5) require planning for kidney replacement therapy. Newer treatments are slowing progression rates substantially.
Standard CKD Staging Applied to IgA Nephropathy
| Stage | eGFR (mL/min/1.73 m²) | Description |
|---|---|---|
| Stage 1 | 90 or above | Normal kidney function with kidney damage signs (proteinuria or hematuria) |
| Stage 2 | 60 to 89 | Mild kidney function decline with damage |
| Stage 3a | 45 to 59 | Mild to moderate decline |
| Stage 3b | 30 to 44 | Moderate to severe decline |
| Stage 4 | 15 to 29 | Severe decline; preparing for replacement therapy |
| Stage 5 | Under 15 | Kidney failure; dialysis or transplant typically required |
Proteinuria Categories
| Category | Urine Protein-to-Creatinine Ratio (UPCR) | Risk Implication |
|---|---|---|
| A1 (normal to mild) | Under 30 mg/g | Lower progression risk |
| A2 (moderate) | 30 to 300 mg/g | Moderate risk; treatment indicated |
| A3 (heavy) | Over 300 mg/g (or 1 g daily) | High risk; aggressive treatment |
The Oxford MEST-C Score
The Oxford classification grades five histologic features of kidney biopsy samples to predict outcomes:
- M (Mesangial hypercellularity): M0 = normal, M1 = increased mesangial cells
- E (Endocapillary hypercellularity): E0 = absent, E1 = present
- S (Segmental glomerulosclerosis): S0 = absent, S1 = present
- T (Tubular atrophy/interstitial fibrosis): T0 = under 25 percent, T1 = 26 to 50 percent, T2 = over 50 percent
- C (Crescents): C0 = none, C1 = up to 25 percent of glomeruli, C2 = over 25 percent
Higher T and C scores predict more rapid progression and may justify more intensive treatment.
Symptoms by Stage
Stage 1 to 2 (Early)
- Often no symptoms
- Blood or protein in urine on routine testing
- Episodes of visible blood in urine following respiratory or GI infections (synpharyngitic hematuria)
- Detected during evaluation for high blood pressure
Stage 3 (Moderate)
- Fatigue or low energy
- Mild swelling of feet, ankles, around eyes
- Higher blood pressure
- Decreased appetite
- Increased proteinuria, sometimes foamy urine
- Mild anemia
Stage 4 (Severe)
- Persistent swelling
- Nausea and metallic taste
- Difficulty concentrating
- Sleep disturbance
- Itching
- Reduced urine output in some
- Significant anemia
- Bone and mineral changes
Stage 5 (Kidney Failure)
- Severe fatigue and weakness
- Persistent nausea and vomiting
- Confusion
- Pruritus and skin changes
- Cardiovascular complications
- Edema, fluid overload
- Need for dialysis or kidney transplant
Treatment by Stage
Stage 1 to 2
- Blood pressure control with ACE inhibitor or ARB
- Address modifiable risk factors (smoking, weight, dyslipidemia)
- Annual urine and blood monitoring
- Tonsillectomy in selected cases (more common in some Asian protocols)
Stage 3 to Early 4
- Aggressive RAS blockade with ACE/ARB
- Sparsentan (dual endothelin and angiotensin receptor blocker, FDA-approved for IgA nephropathy with proteinuria)
- Targeted-release budesonide (Tarpeyo) for some patients with persistent proteinuria
- SGLT-2 inhibitors (dapagliflozin, empagliflozin) increasingly used to slow progression
- Corticosteroids in selected high-risk cases
- Lifestyle: low salt, moderate protein, weight management
- Statins if indicated
Late Stage 4 to Stage 5
- Preparation for dialysis or transplant
- Vascular access planning (AV fistula or AV graft)
- Transplant evaluation
- Symptom management
- Phosphorus, potassium, and fluid restriction
- Anemia treatment with iron and ESAs
- Bone and mineral disease management
Newer Treatments Changing Outcomes
- Sparsentan (FDA-approved 2023): reduces proteinuria substantially in trials
- Targeted-release budesonide (Tarpeyo): reduces proteinuria with less systemic steroid exposure
- SGLT-2 inhibitors: initially developed for diabetes, now widely used in IgA nephropathy
- Selective endothelin receptor antagonists: emerging
- B-cell targeting therapies: in trials for refractory cases
What Determines Progression Rate
- Proteinuria (single most important predictor)
- Blood pressure control
- eGFR at diagnosis
- MEST-C biopsy score
- Adherence to treatment
- Smoking, weight, lifestyle factors
- Coexisting diseases (diabetes, hypertension)
- Time from symptom onset to diagnosis
Related Reading
For more on kidney disease and complications, see our guides on treatment options and prediabetes basics.
The Bottom Line
IgA nephropathy is staged using CKD stages 1 to 5 (based on eGFR), proteinuria categories (A1 to A3), and the Oxford MEST-C biopsy score. Early stages are often asymptomatic; moderate stages bring fatigue, swelling, and blood pressure changes; advanced stages may require dialysis or transplant. Treatment intensifies as stage advances — from blood pressure control alone in stage 1 to multi-agent regimens including sparsentan, targeted-release budesonide, SGLT-2 inhibitors, and corticosteroids in stages 3 to 4. Newer treatments are slowing progression rates substantially compared to historical outcomes. Staging combines functional, urine, and biopsy data to guide individualized care.
