What is the optimal treatment strategy for recurrent IgA nephropathy in an adult kidney transplant recipient without contraindications?

Treatment of Recurrent IgA Nephropathy in Kidney Transplant Recipients

For recurrent IgA nephropathy in kidney transplant recipients, initiate ACE inhibitor or ARB therapy as first-line treatment when proteinuria is present, and reserve corticosteroids with or without cyclophosphamide only for patients with crescentic disease or rapidly progressive graft dysfunction after optimizing supportive care. 1, 2

Screening and Early Detection

Establish systematic monitoring to detect recurrence early:

• Measure microhematuria once in the first month post-transplant to establish baseline 1, 2
• Screen every 3 months during the first year, then annually thereafter 1, 2
• Monitor proteinuria using the same schedule: baseline in first month, every 3 months for year one, then annually 2
• Obtain allograft biopsy when screening suggests treatable recurrent disease, particularly with new proteinuria >3.0 g/day or unexplained graft dysfunction 1

Critical pitfall: Recurrent IgAN rarely manifests clinically before 3 years post-transplantation, so maintain long-term surveillance even when early screening is negative. 3

First-Line Treatment: Optimized Supportive Care

Begin with renin-angiotensin system blockade as the cornerstone of therapy:

• Initiate ACE inhibitor or ARB for any patient with recurrent glomerulonephritis and proteinuria 1
• Target proteinuria <1 g/day by uptitrating to maximum tolerated dose 2
• Achieve blood pressure <130/80 mmHg if proteinuria <1 g/day, or <125/75 mmHg if proteinuria >1 g/day 2
• Continue this supportive care for at least 90 days before considering immunosuppressive escalation 2

The KDIGO guidelines provide Grade 2C evidence for ACE-I/ARB use in recurrent glomerulonephritis, making this the most strongly supported intervention despite the moderate quality of evidence. 1

Second-Line Treatment: Corticosteroid Therapy

Consider corticosteroids only after adequate trial of supportive care fails:

• Eligibility criteria: Proteinuria remains >0.75-1 g/day after at least 90 days of optimized ACE-I/ARB therapy AND eGFR >50 ml/min/1.73 m² 2
• Regimen: 6-month course of corticosteroid therapy 2
• Age adjustment essential: In elderly patients, reduce doses given increased risk of infection, metabolic complications, and bone loss 2

Important caveat: The KDIGO guidelines explicitly recommend against corticosteroids in IgAN with eGFR <30 ml/min/1.73 m² unless there is crescentic disease with rapidly deteriorating function. 1

Aggressive Disease: Crescentic or Rapidly Progressive IgAN

For crescentic IgAN (>50% of glomeruli with crescents) or rapid graft deterioration:

• Treat with high-dose corticosteroids PLUS cyclophosphamide, analogous to ANCA-associated vasculitis treatment 1, 2
• Cyclophosphamide dosing: 2-3 mg/kg for 2-3 months, with dose adjustment for reduced GFR or older age 2
• This is the only scenario where cyclophosphamide is recommended for recurrent IgAN in transplant 1, 2

The evidence supporting this approach comes from extrapolation of treatment for ANCA vasculitis and anti-GBM disease, where the combination has Grade 2D support. 1

Therapies NOT Recommended

Avoid these interventions based on guideline evidence:

• Mycophenolate mofetil (MMF): KDIGO explicitly recommends against using MMF in IgAN (Grade 2C) 1, though there may be limited benefit in Asian patients if corticosteroids fail 1
• Routine tonsillectomy: Should not be performed for IgAN (Grade 2C) 1
• Antiplatelet agents: Not recommended for IgAN treatment (Grade 2C) 1

Emerging Therapies with Limited Evidence

Rituximab has been reported in three transplant cases with recurrent IgAN showing endocapillary proliferation, using 375 mg/1.73m² monthly for 4 months, resulting in decreased proteinuria and slow disease progression at 20-month follow-up. 4 However, this lacks guideline support and should be considered only when standard therapies fail.

Steroid pulse therapy plus tonsillectomy has one case report showing success 10 years post-transplant, but this combination is not guideline-recommended. 5

Monitoring Treatment Response

• Repeat biopsy if serum creatinine has not returned to baseline after treatment of acute rejection 1
• Continue surveillance for proteinuria and hematuria even after treatment initiation 1, 2
• Adjust immunosuppression cautiously, as the clinical expression of post-transplant IgAN is modified by immunosuppression 6

Key Clinical Pitfalls to Avoid

• Do not delay biopsy when there is unexplained proteinuria >3.0 g/day or persistent graft dysfunction—biopsy is mandatory for diagnosis 1, 7
• Do not use corticosteroids in patients with eGFR <30 ml/min/1.73 m² unless crescentic disease is present 1, 2
• Do not assume recurrence is benign—recurrent IgAN is a significant cause of graft loss and affects long-term graft survival 6, 7, 3
• Do not stop ACE-I/ARB therapy prematurely—this remains the foundation even when adding immunosuppression 1, 2