What is the initial management for a patient diagnosed with IgA (Immunoglobulin A) nephropathy after biopsy?

Initial Management of IgA Nephropathy After Biopsy

All patients with IgA nephropathy should immediately begin optimized supportive care consisting of RAS blockade with ACE inhibitors or ARBs (regardless of blood pressure), strict blood pressure control, and lifestyle modifications—this forms the foundation of treatment for at least 3-6 months before considering any immunosuppressive therapy. 1, 2

Immediate Post-Biopsy Assessment

Risk Stratification

• Evaluate proteinuria level, blood pressure, and eGFR at diagnosis to determine disease trajectory and treatment intensity 1, 2
• Apply the Oxford MEST-C pathological scoring system (Mesangial hypercellularity, Endocapillary hypercellularity, Segmental glomerulosclerosis, Tubular atrophy/interstitial fibrosis, Crescents) from the biopsy report, as this provides independent prognostic information beyond clinical parameters 1, 3
• Use the International IgAN Prediction Tool to assess long-term prognosis, though recognize it cannot predict response to specific treatments 2

Exclude Secondary Causes

• Screen for systemic lupus erythematosus, liver disease, inflammatory bowel disease, and other conditions that can cause secondary IgA deposition 4
• In adults, perform age- and sex-appropriate malignancy screening 1

First-Line Supportive Care (All Patients)

RAS Blockade

• Initiate ACE inhibitors or ARBs for all patients with proteinuria >0.5 g/day, even if normotensive (Grade 1B recommendation) 2, 5
• Titrate to maximally tolerated doses during the initial 3-6 month optimization period 1, 2

Blood Pressure Targets

• Target <130/80 mm Hg for proteinuria <1 g/day 1
• Target <125/75 mm Hg for proteinuria >1 g/day 1, 5
• These aggressive targets reflect meta-analysis trends showing improved outcomes with tighter control in proteinuric patients, though based on expert opinion rather than RCT data 1

Lifestyle and Cardiovascular Risk Management

• Restrict dietary sodium to <2.0 g/day (<90 mmol/day) 2
• Administer pneumococcal and influenza vaccines 2
• Consider statin therapy for any proteinuria >0.5 g/day, as sub-nephrotic proteinuria independently increases cardiovascular risk 3
• Counsel on smoking cessation, weight management, and regular exercise 6
• Ensure high fluid intake and avoid nephrotoxins 6

Early Chronic Kidney Disease Management

• Initiate low protein/low phosphate diet with phosphate binders early if eGFR is declining 6

Reassessment After 3-6 Months of Optimized Supportive Care

This waiting period is critical—the 2021 KDIGO guidelines emphasize that at least 90 days (3 months) of maximal supportive care must be completed before considering immunosuppression 1, 2. The goal is to achieve proteinuria reduction to <1 g/day, which is associated with favorable prognosis regardless of initial proteinuria level 3, 7.

For Patients with Persistent Proteinuria >0.75-1 g/day Despite Optimization

Consider a 6-month course of glucocorticoid therapy (Grade 2B) for patients meeting ALL of the following criteria: 1, 2

• Proteinuria remains ≥1 g/day after 3-6 months of optimized supportive care
• eGFR >30 ml/min per 1.73 m² (some sources suggest >50 ml/min per 1.73 m²) 1
• No contraindications to glucocorticoids

Critical caveat: The TESTING trial showed efficacy in reducing proteinuria (average 2.4 g/day at baseline) but at the expense of significant treatment-associated morbidity and mortality 1. Therefore:

• Conduct detailed risk-benefit discussion addressing patient-specific factors 1, 2
• Assess toxicity risk stratification: advanced age, metabolic syndrome, obesity, latent infections (TB, HIV, HBV, HCV) 1
• Strongly consider enrollment in clinical trials of newer agents (SGLT2 inhibitors, sparsentan, enteric-coated budesonide, complement inhibitors) as an alternative to traditional glucocorticoids 1, 2

For Patients Achieving Proteinuria <1 g/day

• Continue optimized supportive care indefinitely 2, 7
• Monitor proteinuria and eGFR regularly as surrogate markers of disease activity 2

Special Clinical Scenarios Requiring Different Management

IgA Nephropathy with Minimal Change Disease Features

• Treat according to minimal change disease protocols (Chapter 5 of KDIGO guidelines) if biopsy shows mesangial IgA deposition with otherwise MCD histology 1

Rapidly Progressive IgAN (Crescentic >50% of Glomeruli with Declining GFR)

• Treat with cyclophosphamide and glucocorticoids following ANCA-associated vasculitis protocols 1, 2
• Note: Crescents without GFR decline do NOT constitute rapidly progressive IgAN—these patients need close monitoring only 1

IgAN with Acute Kidney Injury from Gross Hematuria

• Provide supportive care for AKI 1
• Consider repeat biopsy if kidney function fails to improve within 2 weeks after hematuria cessation 1

Therapies NOT Recommended for Standard IgAN

The following should be avoided in typical IgAN cases: 2

• Mycophenolate mofetil (except in Chinese patients as glucocorticoid-sparing agent) 1, 2
• Azathioprine 2
• Cyclophosphamide (except rapidly progressive IgAN) 1, 2
• Calcineurin inhibitors 2
• Rituximab 2
• Fish oil (previously suggested in 2012 guidelines but not emphasized in 2021 update) 1

Population-Specific Considerations

• Japanese patients: Consider tonsillectomy (not recommended for non-Japanese) 1, 2
• Chinese patients: Mycophenolate mofetil may be used as glucocorticoid-sparing agent (not recommended for non-Chinese) 1, 2
• Children: Insufficient data to recommend adult protocols; glucocorticoids used more liberally in pediatric practice, though trial evidence is lacking 1

Monitoring Strategy

• Target proteinuria reduction to <1 g/day as primary treatment goal 2, 7
• Monitor eGFR slope: reduction in decline rate indicates favorable response 2
• A 40% or greater decline in eGFR over 2-3 years suggests poor outcome requiring treatment intensification 2
• Recognize that even patients with "low-risk" proteinuria (0.44-0.88 g/g) have approximately 20-30% risk of kidney failure within 10 years, emphasizing the importance of aggressive supportive care 8