What is the treatment plan for a young adult male with IgA (Immunoglobulin A) nephropathy, presenting with recurrent episodes of hematuria, especially following respiratory or gastrointestinal infections, and impaired renal function?

Treatment of IgA Nephropathy in a Young Adult Male

Begin with optimized supportive care for at least 90 days, including maximally tolerated RAS blockade and blood pressure control, then add a 6-month course of glucocorticoids only if proteinuria remains >0.75-1 g/day and eGFR is ≥30 mL/min/1.73 m² 1, 2.

Initial Management: Optimized Supportive Care (First 3-6 Months)

RAS Blockade

• Start ACE inhibitor or ARB immediately for all patients with proteinuria >0.5 g/day, regardless of blood pressure status 1, 2.
• Uptitrate to the maximally tolerated dose to achieve proteinuria <1 g/day 1.
• This is Grade 1B evidence and forms the cornerstone of therapy 1, 2.

Blood Pressure Targets

• Target BP <125/75 mmHg given the impaired renal function and recurrent hematuria 1, 2.
• This aggressive target is specifically indicated when proteinuria is >1 g/day 1.

Additional Supportive Measures

• Dietary sodium restriction to <2.0 g/day (<90 mmol/day) 1.
• Weight control and cardiovascular risk factor modification 1, 2.
• Smoking cessation if applicable 3.
• Consider dietary protein restriction based on degree of proteinuria and kidney function 1.

Risk Stratification and Monitoring

Clinical Assessment

• Measure proteinuria, blood pressure, and eGFR at diagnosis and regularly during follow-up 1, 2.
• Proteinuria >1 g/day is the key threshold indicating high risk for progression 1, 4.
• Use the International IgAN Prediction Tool (available at Calculate by QxMD) to assess prognosis 1, 2.

Histologic Assessment

• Document MEST-C score (mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, crescents) 1, 2.
• Note: Neither MEST-C score nor crescent presence alone determines treatment choice, but helps with prognostication 1.

Immunosuppressive Therapy Decision Point (After 90 Days)

When to Add Glucocorticoids

If proteinuria remains >0.75-1 g/day despite at least 90 days of optimized supportive care AND eGFR ≥30 mL/min/1.73 m², consider a 6-month course of glucocorticoids 1, 2.

Glucocorticoid Contraindications and Cautions

Do NOT use or use with extreme caution if the patient has 1:

• eGFR <30 mL/min/1.73 m²
• Diabetes mellitus
• Obesity (BMI >30 kg/m²)
• Metabolic syndrome
• Latent infections (tuberculosis, hepatitis B/C, HIV)
• Active peptic ulceration
• Uncontrolled psychiatric disease
• Severe osteoporosis

Important Caveat About Glucocorticoids

The TESTING trial showed efficacy in reducing proteinuria (average 2.4 g/day) but at the expense of significant treatment-associated morbidity and mortality 1. The risk-benefit profile must be individually discussed with each patient 1.

Special Clinical Scenarios

Rapidly Progressive IgAN (RPGN Pattern)

If the patient develops rapidly declining GFR with extensive crescent formation (>50% of glomeruli), treat immediately with cyclophosphamide and glucocorticoids using the same regimen as for ANCA-associated vasculitis 1, 5, 2.

Critical distinction: Crescents on biopsy WITHOUT rapid GFR decline does not constitute RPGN and does not warrant cyclophosphamide 1, 5. These patients need close monitoring only.

Acute Kidney Injury from Gross Hematuria

• Provide supportive care for AKI 1.
• Consider repeat kidney biopsy if kidney function does not improve within 2 weeks after hematuria cessation 1.

IgAN with Minimal Change Disease Features

• Treat according to minimal change disease protocols if biopsy shows mesangial IgA deposits with otherwise minimal change histology 1.

Therapies NOT Recommended

Avoid the following in routine IgAN management 1, 2:

• Azathioprine
• Cyclophosphamide (except in rapidly progressive IgAN)
• Calcineurin inhibitors
• Rituximab
• Mycophenolate mofetil (exception: may consider in Chinese patients as glucocorticoid-sparing agent) 1, 2
• Tonsillectomy (exception: may consider in Japanese patients) 1, 2

Treatment Goals and Follow-up

Primary Target

Reduce proteinuria to <1 g/day, which serves as a surrogate marker for improved kidney outcomes 1, 2.

Monitoring Schedule

• Assess proteinuria, blood pressure, and eGFR regularly 1, 2.
• Note that proteinuria may recur after stopping glucocorticoids, requiring ongoing surveillance 1.
• A 40% or greater decline in eGFR over 2-3 years indicates treatment failure 1.

Emerging Therapies

Consider Clinical Trial Enrollment

Strongly consider enrolling this young patient in clinical trials evaluating 1, 2:

• SGLT2 inhibitors
• Enteric-coated budesonide (recently received FDA accelerated approval for primary IgAN with UPCR >1.5 g/g) 2
• Sparsentan, atrasentan
• Complement inhibitors
• B-cell targeting therapies

These novel agents may provide benefit with potentially fewer adverse effects than traditional glucocorticoids 1.

Common Pitfalls to Avoid

• Do not start immunosuppression before completing at least 90 days of optimized supportive care 1, 2.
• Do not assume all crescents require cyclophosphamide—only true RPGN with rapid GFR decline warrants this aggressive therapy 1, 5.
• Do not continue glucocorticoids beyond 6 months in the initial treatment course 1.
• Do not ignore cardiovascular risk factors—sub-nephrotic proteinuria is a cardiovascular risk factor independent of renal function 1.