IgA Nephropathy

Primary GNmedium

A 31-year-old man is evaluated for persistent hematuria and proteinuria found on a routine physical, with a history of two episodes of gross hematuria during upper respiratory infections. Serum creatinine is 1.1 mg/dL (eGFR 82 mL/min/1.73m2) and urine protein:creatinine ratio is 0.85 g/g. Biopsy confirms IgA nephropathy (Oxford MEST-C: M1 E0 S1 T0 C0). After 3 months of maximally tolerated RAS blockade with blood pressure well controlled, his proteinuria remains 0.7 g/g. Which of the following is the most appropriate next step per the KDIGO 2025 IgA nephropathy guideline?

  1. A.Add systemic corticosteroids at 0.5-1 mg/kg/day of prednisone
  2. B.Continue current supportive care unchanged and reassess proteinuria in 6 months
  3. C.Add an SGLT2 inhibitor to the existing supportive careCorrect
  4. D.Begin cyclophosphamide combined with high-dose corticosteroids

Explanation

The KDIGO 2025 IgA nephropathy guideline broadened supportive care: patients at risk of progressive kidney function loss should receive an SGLT2 inhibitor (2B), regardless of diabetes status, when eGFR is >20 mL/min/1.73m2. This patient has persistent proteinuria (>0.5-0.75 g/g) despite maximally tolerated RAS blockade and adverse histologic features (M1, S1), placing him at risk of progression, so adding an SGLT2 inhibitor is the appropriate next step rather than simply waiting. Systemic corticosteroids are not routinely recommended given the excess serious adverse events seen with full-dose regimens (e.g., the TESTING trial) and uncertain net benefit; they are considered only in selected high-risk patients after supportive care is optimized. Sparsentan and targeted-release budesonide (Nefecon) are additional options, but among the choices here, adding an SGLT2 inhibitor is the guideline-endorsed next step. Cyclophosphamide has no role in this non-crescentic, slowly progressive presentation.

Why each option

A.
Routine systemic corticosteroids are not recommended in KDIGO 2025 because serious adverse effects outweigh benefit in most patients with preserved function.
B.
Leaving therapy unchanged delays kidney-protective treatment in a patient already at risk despite optimized RAS blockade.
C.
Correct. KDIGO 2025 recommends an SGLT2 inhibitor for progression-risk IgAN with eGFR >20 as part of supportive care.
D.
Cyclophosphamide is not indicated for slowly progressive, non-crescentic IgAN.

Reference: KDIGO 2025 Clinical Practice Guideline for the Management of IgA Nephropathy and IgA Vasculitis. Kidney Int. 2025 (executive summary).

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