Treatment for Patients with Lupus Nephritis and Impaired Renal Function
For patients with lupus nephritis and impaired renal function, mycophenolic acid (MPA) is the recommended treatment due to its favorable efficacy and safety profile in this specific population. 1
Initial Treatment Recommendations
Class III-IV Lupus Nephritis with Impaired Renal Function
- MPA (mycophenolate mofetil [MMF] target dose: 3 g/day for 6 months, or MPA sodium at equivalent dose) is recommended as initial treatment for most cases of class III-IV lupus nephritis in patients with impaired renal function 1
- Post hoc analysis in patients with baseline GFR <30 ml/min/1.73 m² supports the use of MPA in patients with impaired renal function 1
- For MMF dosing in severe renal impairment (GFR <25 mL/min/1.73 m²), doses greater than 1 g twice a day should be avoided to minimize toxicity 2
- Initial treatment should be combined with glucocorticoids: three consecutive pulses of intravenous methylprednisolone 500-750 mg, followed by oral prednisone 0.5 mg/kg/day for 4 weeks, reducing to ≤10 mg/day by 4-6 months 1
- Lower initial glucocorticoid doses (≤0.5 mg/kg/day) following IV pulse therapy provide similar efficacy with fewer serious adverse events compared to higher doses 3
Class V Lupus Nephritis with Impaired Renal Function
- For pure class V nephritis with nephrotic-range proteinuria, MPA (MMF target dose 3 g/day for 6 months) in combination with oral prednisone (0.5 mg/kg/day) is recommended as initial treatment 1
- Calcineurin inhibitors can be considered in selected cases with preserved renal function 1
Monitoring and Dose Adjustments
- In patients with GFR <30 ml/min/1.73 m², monitoring MPA blood levels should be considered to minimize harm and increase efficacy 1
- For patients with severe chronic renal impairment (GFR <25 mL/min/1.73 m²), MMF doses should not exceed 1 g twice daily 2
- Regular monitoring of renal function, proteinuria, and drug levels is essential 1
- Patients should be carefully observed for signs of drug toxicity, particularly in the setting of impaired renal function 2
Subsequent Treatment
- For patients improving after initial treatment, subsequent immunosuppression with MPA at lower doses (initial target MMF dose 2 g/day) is recommended for at least 3 years 1
- If MPA was successful as initial treatment, continuation of MPA is recommended for maintenance therapy 1
- Gradual drug dosage titration may be attempted to ensure the best possible efficacy/toxicity ratio 1
Treatment for Refractory Disease
- For patients not responding to MPA within 3-4 months, consider switching to cyclophosphamide 1
- Alternative options for non-responders include rituximab, calcineurin inhibitors, or intravenous immunoglobulin 1
Adjunctive Treatment
- Hydroxychloroquine (6.5 mg/kg/day or 400 mg/day, whichever is lower) is recommended for all patients with lupus nephritis; dose adjustments may be necessary in patients with GFR <30 ml/min 1
- Renin-angiotensin-aldosterone system (RAAS) blockers are recommended for all patients who are not pregnant with significant proteinuria or hypertension 1
- Blood pressure target should be <130/80 mm Hg 1
Important Considerations
- Cyclophosphamide can be considered in patients with adverse prognostic factors (acute deterioration in renal function, substantial cellular crescents and/or fibrinoid necrosis) 1
- Azathioprine may be considered as an alternative to MPA in selected patients without adverse prognostic factors, or when MPA is contraindicated, not tolerated, or unavailable 1
- Women of reproductive potential must use acceptable contraception during MPA therapy and for 6 weeks after stopping treatment 2
- MPA is contraindicated during pregnancy due to increased risk of first trimester pregnancy loss and congenital malformations 2
By following these recommendations, patients with lupus nephritis and impaired renal function can achieve optimal outcomes with minimized treatment-related toxicity.