What is considered a high dose of immunosuppressants, such as prednisone, in a patient with glomerulonephritis and impaired renal function?

High-Dose Prednisone in Glomerulonephritis

High-dose prednisone is defined as doses warranting prophylactic antimicrobial coverage, which KDIGO guidelines specifically identify in the context of immunosuppression requiring TMP-SMX prophylaxis. 1

Specific Dose Thresholds

Standard High-Dose Definitions in Glomerulonephritis

For FSGS and nephrotic syndrome, high-dose corticosteroids are explicitly defined as:

• 1 mg/kg/day (maximum 80 mg daily), OR 1, 2
• 2 mg/kg alternate-day (maximum 120 mg alternate-day) 1, 2

These doses are maintained for a minimum of 4 weeks and up to 16 weeks depending on response 1

Lupus Nephritis Context

In lupus nephritis, high-dose glucocorticoid regimens include:

• Starting doses ≥40 mg/day, which one retrospective study of 206 LN patients demonstrated superior 1-year complete response rates compared to ≤30 mg/day, without increased glucocorticoid-related damage 1

Safety Threshold for Chronic Toxicity

The critical safety threshold for long-term adverse effects is much lower than induction doses:

• Mean doses of 5-7.5 mg/day prednisone are associated with multiple glucocorticoid-related side effects in multivariable analyses 1
• This lower threshold is relevant for maintenance therapy and tapering decisions, not initial high-dose induction 1

Prophylaxis Requirements

KDIGO guidelines explicitly state that prophylactic TMP-SMX should be considered in patients receiving:

• High-dose prednisone (without specifying exact mg threshold) 1
• Other immunosuppressive agents (rituximab, cyclophosphamide) 1

This practice point implies that "high-dose" in the glomerulonephritis context refers to the induction-level doses (≥40-80 mg/day range) rather than maintenance doses 1

Impaired Renal Function Considerations

In patients with glomerulonephritis and impaired renal function:

• Prednisone and methylprednisolone do not require dose adjustments based on GFR levels, making them preferable immunosuppressants in CKD 3
• However, immunosuppressive therapy should generally be avoided in patients with GFR <30 mL/min/1.73 m² unless there is crescentic glomerulonephritis with rapidly deteriorating kidney function 3
• The intensity of induction therapy must be predicated on severity of presenting symptoms, type of glomerulonephritis, and the level of GFR for determining safe dosage 1

Clinical Context

The definition of "high-dose" is functionally tied to the clinical indication and duration. Induction therapy at 1 mg/kg/day (40-80 mg) for weeks to months represents high-dose treatment requiring infection prophylaxis and close monitoring 1. In contrast, maintenance doses below 10 mg/day, while still carrying cumulative toxicity risks, are not typically classified as "high-dose" in clinical practice 1