Treatment of IgA Nephropathy in Patients with Uncontrolled Diabetes

Introduction to Treatment

The KDIGO guidelines recommend avoiding glucocorticoids in patients with diabetes due to increased risk of serious adverse events, including infections and metabolic complications 1, 2
In patients with IgA nephropathy and uncontrolled diabetes where steroids are contraindicated, focus exclusively on maximally optimized supportive care with RAS blockade, blood pressure control to target <125/75 mmHg, and consider mycophenolate mofetil (MMF) if the patient is of Chinese ancestry 1, 2

Institute ACE inhibitors or ARBs regardless of blood pressure status if proteinuria >0.5 g/day (Grade 1B) 1, 2, 3
Titrate to maximally tolerated doses before considering any other interventions 1, 3
Target blood pressure <125/75 mmHg if proteinuria >1 g/day 4
Target <130/80 mmHg if proteinuria <1 g/day 3
Dietary sodium restriction to <2.0 g/day (<90 mmol/day) 1
Dietary protein restriction may be considered based on degree of proteinuria and kidney function 1
Cardiovascular risk factor modification including smoking cessation, weight control, and regular physical activity 1, 2
Optimize diabetes control 1

If the patient is of Chinese ancestry, mycophenolate mofetil may be used as a glucocorticoid-sparing agent 1, 2, 4
KDIGO 2021 specifically states MMF may be used as a glucocorticoid-sparing agent in Chinese patients with IgAN 1, 2
MMF is not recommended in non-Chinese patients with IgAN 1, 2

Assess disease severity and prognosis using MEST-C histologic scoring and the International IgAN Prediction Tool 1, 2
Initiate maximally optimized supportive care for at least 90 days, including ACE inhibitor or ARB, blood pressure control, dietary sodium restriction, and cardiovascular risk factor modification 1, 2, 3, 4
Reassess proteinuria after 90 days, and consider MMF if proteinuria remains >0.75-1 g/day and the patient is of Chinese ancestry 1, 2, 4

Do not use azathioprine, cyclophosphamide, calcineurin inhibitors, rituximab, or fish oil in routine IgAN management 1, 2, 3, 5

Consider enrollment in clinical trials evaluating SGLT2 inhibitors, enteric-coated budesonide, sparsentan, atrasentan, or complement inhibitors 1, 2, 5

Target proteinuria reduction to <1 g/day as a surrogate marker of improved kidney outcomes 1, 2, 4
Monitor proteinuria every 3 months, blood pressure at each visit, and eGFR every 3-6 months 1, 3, 4

Do not initiate immunosuppression without first optimizing supportive care for at least 90 days 1, 2, 3
Do not use steroids in patients with uncontrolled diabetes due to increased risk of infection and metabolic complications 1, 2
Do not use MMF in non-Chinese patients as routine therapy, as evidence does not support efficacy 1, 2, 5