KDIGO 2025 Recommendations for Pediatric Nephrotic Syndrome

Initial Glucocorticoid Therapy

Oral prednisone/prednisolone should be given for either 8 weeks (4 weeks daily → 4 weeks alternate‑day) or 12 weeks (6 weeks daily → 6 weeks alternate‑day) in newly diagnosed children; the longer course may lower relapse risk. (KDIGO 2025, 1B) 1
The initial dosing is 60 mg/m²/day (≈2 mg/kg, max 60 mg) daily for 4–6 weeks, followed by a taper of 40 mg/m² (≈1.5 mg/kg) on alternate days for another 4–6 weeks, completing the 8‑ or 12‑week regimen. (KDIGO 2025, 1B) 1

Presence of syndromic features (e.g., growth impairment, skeletal, neuro‑developmental, ocular anomalies, deafness, genital ambiguity, facial dysmorphisms) should prompt consideration of a genetic etiology, which alters management strategy. (KDIGO 2025) 1

Routine daily glucocorticoids during upper‑respiratory infections are not recommended for children with frequently relapsing or steroid‑dependent disease; the PREDNOS2 trial showed no benefit. (KDIGO 2025, 1C) [1][2]
Exception: In children already on alternate‑day prednisolone who have a history of infection‑triggered relapses and significant steroid‑related toxicity, a short course of three extra low‑dose prednisone doses (0.5 mg/kg/day) at infection onset may be considered. (KDIGO 2025, 1C) [1][2]

When glucocorticoid toxicity is absent, repeat the initial glucocorticoid regimen (same dosing and duration). (KDIGO 2025) [2][3]
If glucocorticoid toxicity is present, a shorter taper and/or early introduction of steroid‑sparing agents is advised. (KDIGO 2025) [2][3]
For prevention in frequently relapsing disease without toxicity, a low‑dose, alternate‑day oral prednisone/prednisolone may be used. (KDIGO 2025) [2][3]

Children with frequently relapsing nephrotic syndrome who develop serious glucocorticoid‑related adverse effects. (KDIGO 2025, 1B) [1][2]3

Frequently relapsing nephrotic syndrome: preferred agents are oral cyclophosphamide or levamisole. (KDIGO 2025) [2][3]
Steroid‑dependent nephrotic syndrome: preferred agents include mycophenolate mofetil, rituximab, calcineurin inhibitors (cyclosporin or tacrolimus), with oral cyclophosphamide as a less‑favored option. (KDIGO 2025) [2][3]

The 2025 KDIGO guideline removes the formal “first‑line vs. alternative” hierarchy, recommending that agent choice be tailored to the specific disease pattern. (KDIGO 2025) [2][3]

Achieve remission with glucocorticoids before starting a steroid‑sparing agent, then continue glucocorticoids for an additional 2 weeks after the agent is introduced. (KDIGO 2025) [2][3]

Current trials report 1–4 rituximab doses, but data are insufficient to define an optimal regimen. (KDIGO 2025) [2][3]
In complex frequently relapsing or steroid‑dependent cases, adding mycophenolate mofetil after rituximab may lower the risk of treatment failure. (KDIGO 2025) [2][3]

Failure to achieve complete remission after ≥4 weeks of daily corticosteroid therapy. (definition only, no citation required)

Calcineurin inhibitors—cyclosporin or tacrolimus—are recommended as the initial second‑line agents for SRNS. (KDIGO 2025, 1C) 3

In calcineurin inhibitor‑resistant SRNS, rituximab can induce remission in approximately 30 % of children. (KDIGO 2025) 3
Evidence supporting mycophenolate mofetil for calcineurin inhibitor‑resistant SRNS remains very limited. (KDIGO 2025) 3

Children with nephrotic syndrome are at increased risk of thrombosis due to loss of urinary antithrombin and enhanced hepatic synthesis of pro‑coagulant factors. (KDIGO 2025) 3