IgA nephropathy Medical Services in China

IgA nephropathy (IgAN), also known as Berger’s disease, is a chronic autoimmune kidney disorder characterized by the deposition of immunoglobulin A (IgA) immune complexes in the glomerular mesangium. This triggers localized inflammation, mesangial cell proliferation, and extracellular matrix expansion—ultimately leading to progressive glomerulosclerosis, tubulointerstitial fibrosis, and declining renal function. Pathogenesis involves a multifactorial interplay: aberrant glycosylation of IgA1 (particularly deficient galactosylation in the hinge region), generation of autoantibodies against these neoepitopes, formation of circulating IgA1-containing immune complexes, impaired hepatic clearance, and subsequent mesangial deposition. Complement activation—especially via the lectin and alternative pathways—amplifies injury, while genetic susceptibility (e.g., variants in CFHR1, DEFA, HLA-DQB1) and environmental triggers (mucosal infections, gut dysbiosis, smoking) modulate disease onset and progression. Epidemiologically, IgAN is the most common primary glomerulonephritis worldwide, with highest prevalence in East Asia (incidence ~2.5–4.5 per 100,000/year), intermediate rates in Europe (~1.0–2.0), and lower incidence in Africa and Latin America. It typically presents in adolescence or early adulthood (peak onset 16–35 years), with a male-to-female ratio of ~2:1. Key risk factors include familial clustering (10–15% of cases), Asian or Caucasian ethnicity, recurrent upper respiratory or gastrointestinal infections, celiac disease, HIV, and liver cirrhosis. Clinical manifestations range from asymptomatic microscopic hematuria and mild proteinuria to episodic macroscopic hematuria (often post-infectious), hypertension, nephrotic-range proteinuria (>3.5 g/day), and progressive chronic kidney disease (CKD). Approximately 20–40% of untreated patients progress to end-stage kidney disease (ESKD) within 20 years. Quality of life is significantly impacted—not only by physical symptoms (fatigue, edema, nocturia) but also by psychological burden (anxiety about progression, treatment adherence challenges), dietary restrictions (low-sodium, low-protein diets), medication side effects (e.g., corticosteroid-induced weight gain, mood changes), and socioeconomic strain from long-term monitoring, dialysis, or transplant preparation. Early diagnosis via renal biopsy remains essential for risk stratification, as clinical presentation alone cannot reliably predict prognosis. Emerging biomarkers—including serum galactose-deficient IgA1, anti-glycan antibodies, and urinary CD89 complexes—are under validation for non-invasive monitoring. With growing understanding of pathogenic mechanisms, targeted therapies (e.g., Nefecon, budesonide targeting gut-associated lymphoid tissue; anti-APRIL agents like atacicept and telitacicept) are reshaping management paradigms beyond conventional supportive care.

IgA nephropathy (IgAN), or Berger’s disease, is the most common primary glomerulonephritis worldwide, characterized by dominant or codominant IgA1-containing immune deposits in the mesangium. Its clinical course is highly variable—ranging from asymptomatic microscopic hematuria and mild proteinuria to progressive chronic kidney disease (CKD) and end-stage kidney disease (ESKD) over decades. Management in nephrology departments emphasizes risk stratification, individualized therapy, and long-term renal protection. Treatment strategies are broadly categorized into conservative (nonpharmacologic) measures, pharmacologic interventions, and—rarely—surgical approaches. Importantly, no single therapy is universally effective; decisions must integrate histopathologic findings (e.g., Oxford MEST-C score), estimated glomerular filtration rate (eGFR), proteinuria level (>0.5–1.0 g/day signals higher risk), hypertension control, and comorbidities.

Conservative treatment forms the cornerstone of IgAN management and should be initiated at diagnosis, regardless of disease activity. This includes strict blood pressure control targeting <120/80 mmHg (per KDIGO 2021 guidelines), achieved preferentially with renin-angiotensin-aldosterone system inhibitors (RAASi)—angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARBs). These agents reduce intraglomerular pressure, attenuate podocyte injury, and exert antiproteinuric effects independent of BP lowering. Dietary sodium restriction (<2 g/day) potentiates RAASi efficacy and mitigates fluid retention. A low-protein diet (0.8 g/kg/day) may slow CKD progression in patients with eGFR <60 mL/min/1.73m², though evidence remains modest and requires nutritional supervision to prevent sarcopenia. Smoking cessation, weight optimization (BMI 18.5–24.9 kg/m²), and avoidance of nephrotoxic agents—including NSAIDs and iodinated contrast—constitute essential lifestyle modifications. Regular monitoring of serum creatinine, urine albumin-to-creatinine ratio (UACR), and eGFR every 3–6 months enables timely intervention escalation.

Pharmacologic therapy is indicated for patients with persistent proteinuria ≥1.0 g/day despite 3–6 months of optimized conservative care and stable eGFR ≥30 mL/min/1.73m². First-line immunosuppression remains controversial; corticosteroids (e.g., 6-month oral prednisone taper) demonstrated benefit in the STOP-IgAN and TESTING trials but carry significant risks—particularly diabetes, osteoporosis, and infection. The TESTING trial confirmed reduced risk of CKD progression with steroid therapy but mandated gastroprotection and stringent infection surveillance. More recently, targeted-release budesonide (Nefecon®), delivered to gut-associated lymphoid tissue to modulate aberrant IgA1 production, received FDA and EMA approval for high-risk IgAN (proteinuria ≥1 g/day, eGFR 35–90 mL/min/1.73m²). In the NefIgArd trial, it significantly reduced proteinuria and slowed eGFR decline over 2 years. Other emerging agents include SGLT2 inhibitors (e.g., dapagliflozin), which—regardless of diabetes status—reduce intraglomerular pressure, tubulointerstitial hypoxia, and inflammation; the DAPA-CKD trial included IgAN subgroups showing consistent renal and cardiovascular benefits. Endothelin receptor antagonists (e.g., atrasentan) and complement inhibitors (e.g., iptacopan, narsoplimab) are under active phase III investigation. Anticoagulation and antiplatelet therapy are not recommended outside specific thrombotic microangiopathy contexts due to lack of proven benefit and bleeding risk.

Surgical treatment has no established role in IgAN pathophysiology. Nephrectomy is contraindicated except in rare cases of unilateral, massive, life-threatening hemorrhage unresponsive to embolization—a scenario virtually nonexistent in routine practice. Kidney transplantation remains the definitive therapy for ESKD secondary to IgAN; however, disease recurrence in the allograft occurs in ~40–60% of recipients, typically within 5 years. Recurrence rarely causes graft loss unless accompanied by aggressive histologic features (e.g., crescents, fibrosis). Pre-transplant evaluation includes assessment of donor-specific antibodies and careful counseling regarding recurrence risk—not surgical intervention per se.

China offers distinct advantages in IgAN management, rooted in integrated traditional Chinese medicine (TCM) and modern nephrology. Over 30 Class I hospitals—including Peking University First Hospital and Shanghai Renji Hospital—operate specialized IgAN clinics with multidisciplinary teams (nephrologists, pathologists, TCM physicians, dietitians). China pioneered large-scale prospective registries (e.g., the China IgAN Registry), enabling real-world evidence generation on treatment patterns and outcomes. TCM adjuncts—such as Tripterygium wilfordii Hook F (TwHF) and Huangkui capsule—have demonstrated antiproteinuric and anti-inflammatory effects in randomized trials, though standardization and quality control remain critical. Moreover, China’s national health insurance covers key therapies—including RAASi, SGLT2 inhibitors, and Nefecon—reducing financial toxicity. Rapid diagnostic infrastructure (e.g., digital pathology platforms for Oxford scoring) and centralized biopsy review networks improve diagnostic accuracy. Clinical trial participation is robust: Chinese sites contributed >25% of global enrollment in the NefIgArd trial, accelerating access to novel therapeutics.

Recovery and long-term prognosis hinge on sustained adherence and proactive self-management. Patients should maintain daily home BP logs, perform monthly UACR spot checks if feasible, and avoid herbal remedies with unknown nephrotoxic potential (e.g., aristolochic acid-containing herbs). Vaccination against influenza, pneumococcus, and hepatitis B is strongly advised, especially before immunosuppression. Annual ophthalmologic screening detects hypertensive or diabetic retinopathy early. Psychological support is integral—chronic kidney disease correlates with elevated depression and anxiety prevalence; structured counseling and peer support groups improve treatment concordance. Women of childbearing age require preconception counseling: ACEi/ARBs and immunosuppressants are teratogenic; pregnancy is generally safe with proteinuria <1 g/day and stable eGFR >70 mL/min/1.73m² but mandates close maternal-fetal surveillance. Finally, transition planning for adolescents with IgAN ensures continuity into adult nephrology care, minimizing gaps during critical developmental windows. With comprehensive, evidence-informed, and patient-centered care, many individuals with IgAN maintain stable kidney function for decades—underscoring that early recognition, rigorous conservative foundation, judicious pharmacotherapy, and holistic support collectively define optimal outcomes.