IgA Nephropathy Treatment Guidelines

Introduction to Treatment

The primary treatment for IgA nephropathy should focus on optimized supportive care with RAS blockade (ACEi or ARB) as first-line therapy for patients with proteinuria >0.5 g/day, with addition of SGLT2 inhibitors when eGFR ≥20 ml/min/1.73m², and consideration of glucocorticoid therapy only for high-risk patients with persistent proteinuria >0.75-1 g/day despite maximal supportive care, as recommended by the American Journal of Kidney Diseases and Kidney International 1, 2

Start ACEi (e.g., ramipril) or ARB (e.g., losartan) at maximum tolerated dose for all patients with proteinuria >0.5 g/day, with the goal of reducing proteinuria to <1 g/day, as recommended by the American Journal of Kidney Diseases and Kidney International 1, 2, 3
High-risk patients are defined as those with proteinuria >0.75-1 g/day despite ≥90 days of optimized supportive care, according to the American Journal of Kidney Diseases and Kidney International 1, 2

Add SGLT2 inhibitors (dapagliflozin or empagliflozin) when eGFR ≥20 ml/min/1.73m², or when hypertension or proteinuria persists despite optimal doses of ACEi/ARA-II, as recommended by Diabetes Care and Kidney International 1, 4, 2
DAPA-CKD and EMPA-KIDNEY trials showed significant benefits in non-diabetic kidney disease including IgA nephropathy, with a moderate to high strength of evidence 1

Dietary sodium restriction, smoking cessation, weight control, and regular exercise are recommended lifestyle modifications for patients with IgA nephropathy, as suggested by the American Journal of Kidney Diseases and Kidney International 1, 2

Consider a 6-month course of glucocorticoid therapy for high-risk patients with persistent proteinuria >0.75-1 g/day despite maximal supportive care, with a low to moderate strength of evidence, and include prophylaxis against Pneumocystis pneumonia, gastroprotection, and bone protection, as recommended by the American Journal of Kidney Diseases 1, 2
The TESTING study showed benefit but with increased risk of adverse events, highlighting the need for careful consideration of glucocorticoid therapy 1

Consider targeted-release budesonide (FDA-approved for primary IgA nephropathy with UPCR >1.5 g/g) as an alternative to glucocorticoid therapy, with a moderate strength of evidence, as recommended by the American Journal of Kidney Diseases 1

For Chinese patients, consider mycophenolate mofetil (MMF) as a glucocorticoid-sparing agent, as suggested by Kidney International 2
For Japanese patients, consider tonsillectomy, with a low strength of evidence, as suggested by Kidney International 2
Avoid or use extreme caution with glucocorticoids in patients with eGFR <30 ml/min/1.73m², diabetes, obesity (BMI >30 kg/m²), latent infections, secondary disease, active peptic ulceration, uncontrolled psychiatric disease, or severe osteoporosis, as recommended by Kidney International 2

Monitor renal function and electrolytes 2-4 weeks after initiating or adjusting treatment, and monitor proteinuria every 3 months to evaluate response, with the goal of reducing proteinuria to <1 g/day, as recommended by the American Journal of Kidney Diseases and Kidney International 1, 2, 3, 5
Target blood pressure <130/80 mmHg in patients with proteinuria <1 g/day, and <125/75 mmHg in patients with proteinuria ≥1 g/day, as recommended by Kidney International 6

Thiazide or thiazide-like diuretics should be added when additional blood pressure control is required, with consideration of loop diuretics if eGFR is <30 ml/min/1.73 m², as recommended by Kidney International 3, 5
Calcium channel blockers may be added if hypertension persists, providing additional blood pressure control without significantly affecting proteinuria, according to Kidney International 3, 5
Patients should be instructed to suspend ACEi/ARA-II during episodes of dehydration, and to avoid using ACEi/ARA-II in patients with eGFR <30 ml/min/1.73 m² (except under nephrologic supervision), or in cases of uncontrolled hyperkalemia, as recommended by Kidney International 2, 3

Azathioprine, cyclophosphamide (except in rapidly progressive IgAN), calcineurin inhibitors, and rituximab are not recommended for treatment of IgA nephropathy, with a high strength of evidence, as recommended by Kidney International 2

Delaying initiation of RAS blockade in patients with proteinuria >0.5 g/day, using dual RAS blockade (ACEi + ARB), failing to add SGLT2 inhibitors, initiating glucocorticoids without adequate trial of optimized supportive care, and not providing prophylaxis against Pneumocystis pneumonia when using glucocorticoids, as highlighted by the American Journal of Kidney Diseases 1