What is the recommended treatment for nephritis?

Treatment of Nephritis

The treatment of nephritis depends critically on the underlying cause, but for lupus nephritis—the most common and well-studied form—mycophenolic acid (MMF 3 g/day for 6 months) or low-dose intravenous cyclophosphamide combined with glucocorticoids represents first-line therapy for proliferative disease (Class III/IV), with the goal of preserving renal function and preventing progression to kidney failure. 1

Diagnostic Approach First

Before initiating treatment, obtain a renal biopsy to establish the specific type and severity of nephritis, as clinical and laboratory findings alone cannot accurately predict histological patterns 1. The biopsy should be classified using the ISN/RPS 2003 system to guide treatment decisions 1.

Treatment by Nephritis Type

Lupus Nephritis (Most Common)

Class III/IV Proliferative Disease (Initial Treatment)

For Class IIIA or IVA nephritis, choose one of two equally effective regimens 1:

• Mycophenolic acid: MMF 3 g/day for 6 months (or equivalent MPA sodium dose)
• Low-dose cyclophosphamide: Total 3 g IV over 3 months

Both must be combined with glucocorticoids 1:

• Start with 3 consecutive pulses of IV methylprednisolone 500-750 mg
• Follow with oral prednisone 0.5 mg/kg/day for 4 weeks
• Taper to ≤10 mg/day by 4-6 months

Important caveat: In patients with adverse prognostic factors (acute renal function deterioration, substantial cellular crescents, or fibrinoid necrosis), higher-dose cyclophosphamide may be warranted (0.75-1 g/m² monthly for 6 months or oral 2-2.5 mg/kg/day) 1.

Class V Membranous Disease

For pure Class V with nephrotic-range proteinuria (>1 g/24h despite ACE inhibitor/ARB therapy) 1:

• First-line: MMF 3 g/day for 6 months plus oral prednisone 0.5 mg/kg/day (better efficacy/toxicity ratio)
• Alternatives: Cyclophosphamide, calcineurin inhibitors (tacrolimus, cyclosporine), or rituximab for non-responders 1

The 2024 KDIGO guideline supports voclosporin as an option, with median time to proteinuria reduction to <0.5 mg/mg being 3.6 months 2.

Maintenance Therapy (After Initial Response)

Continue immunosuppression for at least 3 years 1:

• If started on MPA: Continue MPA at lower dose (MMF 2 g/day) plus prednisone 5-7.5 mg/day
• If pregnancy planned: Switch to azathioprine 2 mg/kg/day at least 3 months before conception 1
• Alternative: Azathioprine 2 mg/kg/day (though higher flare risk) 1

Gradual drug withdrawal can be attempted after 3 years, withdrawing glucocorticoids first 1.

Refractory Disease

If treatment fails (defined as failure to achieve ≥50% reduction in proteinuria by 6 months or complete response by 12 months) 1:

• Switch from MPA to cyclophosphamide, or vice versa
• Consider rituximab 1

Acute Interstitial Nephritis

For drug-induced or infection-related AIN 3:

1. Immediately discontinue the offending agent
2. Treat underlying infection or systemic disease
3. Corticosteroids (prednisolone) improve renal outcomes based on meta-analysis, though optimal dosing and duration remain unclear
4. Mycophenolate mofetil can be considered for steroid-refractory cases

Infection-Related Glomerulonephritis

For post-streptococcal or staphylococcal GN 4:

• Supportive care is primary: fluid/salt restriction, diuretics for volume overload, calcium channel blockers for stage 2 hypertension
• Antibiotics for active staphylococcal infection, endocarditis, or shunt nephritis
• Immunosuppression only for crescentic IRGN or rapidly progressive disease

Essential Adjunctive Therapies (All Nephritis Types)

These improve outcomes and must not be overlooked 1:

• ACE inhibitors or ARBs: For proteinuria >50 mg/mmol or hypertension 1
• Hydroxychloroquine: Reduces renal flares and cardiovascular damage in lupus nephritis 1
• Statins: Target LDL <100 mg/dL for persistent dyslipidemia 1
• Anticoagulation: Consider if nephrotic syndrome with albumin <20 g/L, especially with antiphospholipid antibodies 1
• Aspirin: In patients with antiphospholipid antibodies 1

Treatment Goals and Monitoring

Target complete renal response 1:

• Proteinuria <50 mg/mmol (UPCR)
• Normal or near-normal GFR (within 10% of normal if previously abnormal)

Acceptable partial response by 6 months (no later than 12 months) 1:

• ≥50% reduction in proteinuria to subnephrotic levels
• Normal or near-normal renal function

Monitor every 2-4 weeks initially, then every 3-6 months lifelong 1:

• Serum creatinine, eGFR, proteinuria, urinary sediment
• Serum albumin, C3/C4, anti-dsDNA antibodies
• Blood pressure, complete blood count

Common Pitfalls to Avoid

1. Delaying biopsy: Clinical findings cannot predict histology accurately—biopsy is indispensable 1
2. Inadequate glucocorticoid tapering: Failure to reduce to ≤10 mg/day by 4-6 months increases toxicity without added benefit 1
3. Switching maintenance agents unnecessarily: Patients responding to MPA should stay on MPA unless pregnancy is planned 1
4. Ignoring adjunctive therapies: ACE inhibitors/ARBs and hydroxychloroquine are not optional—they improve long-term outcomes 1
5. Azathioprine as first-line: Only use when MPA or cyclophosphamide are contraindicated, not tolerated, or unavailable—it carries higher flare risk 1

The evidence strongly supports that early, aggressive combination therapy with appropriate maintenance prevents progression to end-stage renal disease and improves quality of life, which are the outcomes that matter most for patient morbidity and mortality 1.