Effective Management Strategies for IgA Nephropathy: A Comprehensive, Evidence-Based Approach

Understanding IgA Nephropathy: More Than Just "Chronic Nephritis"

While many patients and even some clinicians refer to IgA nephropathy as "chronic glomerulonephritis," this label oversimplifies a complex, immune-mediated kidney disease with distinct triggers, progression patterns, and treatment pathways. First identified in the 1960s, IgA nephropathy is the most common primary glomerular disease worldwide—and particularly prevalent across East Asia. It's characterized by abnormal IgA1 antibody deposits in the glomeruli (the kidney's filtering units), leading to inflammation, scarring, and progressive loss of kidney function over time.

Recognizing the Classic Clinical Pattern

One hallmark feature that sets IgA nephropathy apart is its "synpharyngitic hematuria"—a term describing visible or microscopic blood in the urine that appears within hours to days following an upper respiratory infection (like a cold or sore throat) or, less commonly, gastrointestinal illness. This isn't coincidental: research shows mucosal immune dysregulation—especially in the tonsils and gut—drives the production of galactose-deficient IgA1, which forms immune complexes that get trapped in the kidneys. Patients may also experience transient proteinuria (excess protein in urine), swelling (edema), or elevated blood pressure—though many remain asymptomatic until routine lab tests reveal abnormalities.

Diagnosis: Beyond Symptoms—The Critical Role of Kidney Biopsy

Definitive diagnosis requires a renal biopsy, where tissue samples are examined under light microscopy, immunofluorescence, and electron microscopy. The gold-standard finding? Granular IgA-dominant immune deposits in the mesangial areas—often accompanied by complement C3 and sometimes IgG. Importantly, biopsy isn't just diagnostic—it's prognostic. Pathologists assess features like cellular crescents, interstitial fibrosis, and tubular atrophy to estimate long-term risk and guide therapy intensity.

Treatment Tailored to Proteinuria Levels: A Risk-Stratified Framework

Current international guidelines—including those from KDIGO (Kidney Disease: Improving Global Outcomes) and the American Society of Nephrology—emphasize proteinuria quantification as the strongest modifiable predictor of disease progression. Treatment decisions hinge on 24-hour urine protein or urine protein-to-creatinine ratio (UPCR) results:

Mild Proteinuria (UPCR < 1 g/g or 24-h protein < 1 g)

For low-risk patients, first-line therapy focuses on renoprotective support:

ACE inhibitors (e.g., lisinopril) or ARBs (e.g., losartan)—used at maximally tolerated doses to reduce intraglomerular pressure and protein leakage;
Lifestyle optimization: strict blood pressure control (<125/75 mmHg target in proteinuric CKD), sodium restriction (<2 g/day), smoking cessation, and weight management;
Emerging evidence supports adjunctive use of SGLT2 inhibitors (e.g., dapagliflozin) even in non-diabetic IgA patients—shown in the DAPA-CKD trial to significantly slow eGFR decline and reduce cardiovascular events.

Moderate-to-Severe Proteinuria (UPCR ≥ 1 g/g or 24-h protein ≥ 1 g)

Persistent heavy proteinuria signals higher risk of progression. Per the 2021 KDIGO update, a 3–6 month therapeutic trial of supportive care is recommended before escalating. If proteinuria fails to drop by ≥50% or remains >0.5 g/day, immunosuppression becomes indicated:

First-line immunosuppression: 6 months of oral corticosteroids (e.g., prednisone tapering from 0.8 mg/kg/day) combined with supportive care;
Second-line options for steroid intolerance or relapse: mycophenolate mofetil (MMF), rituximab, or newer targeted agents like budesonide (Nefecon®)—an enteric-coated formulation delivering drug directly to gut-associated lymphoid tissue (GALT), the suspected origin of pathogenic IgA1.

Preventing Flares: Targeting the Mucosal Triggers

Since IgA nephropathy originates from mucosal immune dysfunction, prevention centers on upper airway and gastrointestinal health:

Tonsillectomy may be considered in recurrent tonsillitis cases—particularly in Asian populations where studies show reduced hematuria and proteinuria post-surgery;
Vaccination adherence (flu, pneumococcal, COVID-19) lowers infection-related flares;
Gut health matters: Avoid NSAIDs (which impair renal perfusion and worsen injury); treat acute gastroenteritis promptly; consider probiotics under medical guidance to support intestinal barrier integrity;
Complementary approaches—such as traditional herbal formulas (e.g., Tripterygium wilfordii extract) or acupuncture—may offer adjunctive anti-inflammatory benefits but should only be used alongside conventional care and under nephrologist supervision due to potential herb–drug interactions.

Long-Term Monitoring & Hope for the Future

Living with IgA nephropathy means partnering closely with a nephrology team. Regular tracking includes serum creatinine/eGFR, UPCR, blood pressure, and urinalysis every 3–6 months. Excitingly, several phase III trials are evaluating novel therapies—including anti-BLyS agents (e.g., belimumab), complement inhibitors (e.g., iptacopan), and APRIL-targeting drugs—that aim to disrupt the core pathogenic cascade. With early detection, precision treatment, and proactive lifestyle integration, many individuals maintain stable kidney function for decades—proving that effective, personalized management truly makes all the difference.