What is the recommended treatment for a patient with a history of IgA (Immunoglobulin A) nephropathy in a transplanted kidney?

Management of Recurrent IgA Nephropathy in Transplanted Kidney

For a kidney transplant recipient with recurrent IgA nephropathy in the allograft, initiate ACE inhibitor or ARB therapy if proteinuria exceeds 0.5 g/day, and consider a 6-month course of corticosteroids if proteinuria persists above 0.75-1 g/day despite at least 90 days of optimized supportive care. 1

Initial Assessment and Monitoring

Establish baseline disease activity and monitor progression:

• Screen for microhematuria at least once in the first month post-transplant to establish baseline 1
• Monitor microhematuria every 3 months during the first year, then annually thereafter 1
• Measure urine protein excretion once in the first month, every 3 months during the first year, and annually thereafter 1
• Obtain kidney allograft biopsy when there is new onset proteinuria, unexplained proteinuria >3.0 g/day, or persistent unexplained increase in serum creatinine 1

Optimized Supportive Care (First-Line Treatment)

All patients with recurrent IgA nephropathy require comprehensive supportive management before considering immunosuppression:

• Initiate ACE inhibitor or ARB therapy for proteinuria >0.5 g/day, regardless of blood pressure status 1
• Target blood pressure <130/80 mmHg if proteinuria <1 g/day, or <125/75 mmHg if proteinuria >1 g/day 1
• Uptitrate ACE inhibitor or ARB to maximum tolerated dose, aiming for proteinuria <1 g/day 1
• Implement cardiovascular risk reduction including smoking cessation, weight control, and exercise 1
• Provide dietary counseling focusing on low protein/low phosphate intake if renal impairment develops 2

Immunosuppressive Therapy Considerations

For patients with persistent high-risk proteinuria despite optimized supportive care:

• Consider a 6-month course of corticosteroid therapy if proteinuria remains >0.75-1 g/day after at least 90 days of optimized supportive care and eGFR >50 ml/min/1.73 m² 1
• One treatment protocol that showed benefit used intravenous methylprednisolone 500 mg daily for 3 consecutive days at months 1,3, and 5, plus oral prednisone 0.5 mg/kg every other day for 6 months 3
• Corticosteroids probably prevent progression to ESKD and may induce complete remission in patients with proteinuria >1 g/day 4

Critical contraindications and cautions for corticosteroid therapy:

• Avoid or use extreme caution if eGFR <30 ml/min/1.73 m² 1
• Avoid in patients with diabetes, obesity (BMI >30 kg/m²), latent infections (viral hepatitis, tuberculosis), liver cirrhosis, active peptic ulceration, uncontrolled psychiatric disease, or severe osteoporosis 1

Immunosuppressive Agents NOT Recommended

The following agents should not be used for recurrent IgA nephropathy in the transplant setting:

• Azathioprine or cyclophosphamide (except in crescentic IgAN with rapidly progressive kidney function decline) 1, 4
• Mycophenolate mofetil in non-Chinese patients 1, 4
• Calcineurin inhibitors as specific treatment for IgAN (though maintained as part of baseline transplant immunosuppression) 4
• Rituximab 5

Management of Rapidly Progressive Crescentic IgAN

For the rare presentation of crescentic IgAN (>50% crescents on biopsy) with rapidly deteriorating kidney function:

• Treat with high-dose corticosteroids and cyclophosphamide, analogous to ANCA vasculitis treatment 1
• This represents an exception to the general avoidance of cyclophosphamide in IgAN 1

Baseline Transplant Immunosuppression Management

Maintain standard transplant immunosuppression while managing recurrent IgAN:

• Continue calcineurin inhibitor (CNI) at therapeutic levels to prevent rejection and minimize development of donor-specific antibodies 1
• Monitor CNI blood levels every other day during immediate post-operative period, with changes in medication, or with decline in kidney function 1
• Do not reduce baseline transplant immunosuppression unless there are specific complications (infection, malignancy) requiring adjustment 1

Common Pitfalls to Avoid

• Do not delay biopsy when there is unexplained proteinuria >3.0 g/day or persistent increase in creatinine, as early recurrence can occur as soon as 19 days post-transplant 1, 5
• Do not use immunosuppressive therapy in patients with eGFR <30 ml/min/1.73 m² unless there is crescentic IgAN with rapidly deteriorating function 1
• Do not initiate corticosteroids without first ensuring at least 90 days of optimized supportive care including maximally tolerated ACE inhibitor/ARB therapy 1
• Do not confuse the management of recurrent IgAN with the management of failing allograft from other causes—recurrent IgAN requires disease-specific treatment while maintaining transplant immunosuppression 1