Henoch-Schönlein purpura nephritis Medical Services in China

Henoch-Schönlein purpura nephritis (HSPN) is a systemic small-vessel vasculitis characterized by immunoglobulin A (IgA)-dominant immune complex deposition in the glomeruli, leading to renal inflammation and injury. It represents the renal manifestation of Henoch-Schönlein purpura (HSP), a childhood-predominant systemic vasculitis that also involves skin (palpable purpura), joints (arthralgia/arthritis), gastrointestinal tract (abdominal pain, bleeding), and kidneys. While HSP typically resolves spontaneously in most children, renal involvement—ranging from isolated microscopic hematuria to nephrotic-range proteinuria, hypertension, and rapidly progressive glomerulonephritis—defines HSPN and carries significant long-term implications. Pathogenesis centers on aberrant mucosal IgA1 production, defective galactosylation of the IgA1 hinge region, formation of pathogenic IgA1-containing immune complexes, and their mesangial deposition, triggering complement activation (mainly lectin and alternative pathways), inflammatory cell infiltration, and subsequent glomerular damage. Genetic susceptibility (e.g., polymorphisms in TNFSF13, CFH, and HLA loci), preceding upper respiratory or gastrointestinal infections (often streptococcal or viral), and environmental triggers contribute to dysregulated mucosal immunity. Epidemiologically, HSP is the most common systemic vasculitis in children, with an incidence of 10–20 per 100,000 children annually; approximately 30–50% develop urinary abnormalities, and 20–40% of those progress to clinically significant HSPN. Adults account for <10% of cases but tend to present with more severe renal disease, higher rates of crescentic glomerulonephritis, and poorer renal outcomes. Risk factors for progression include older age at onset (>8 years in children, any age in adults), persistent heavy proteinuria (>1 g/day), hypertension, impaired eGFR at diagnosis, and histopathological severity (e.g., >50% crescents, interstitial fibrosis/tubular atrophy on biopsy). Quality of life impact is substantial: pediatric patients may experience school absenteeism, activity restrictions, anxiety about relapse or kidney failure, and treatment-related side effects (e.g., corticosteroid-induced weight gain, mood changes, growth delay). Adults often face occupational disruption, chronic fatigue, dietary and fluid restrictions, and psychosocial stress related to uncertainty about long-term renal prognosis—including risks of end-stage kidney disease (ESKD) in 1–5% of pediatric and up to 15% of adult cases over 10–20 years. Early recognition, risk stratification via clinical and histologic assessment, and individualized immunomodulatory therapy are critical to preserving renal function and optimizing long-term quality of life.

Henoch-Schönlein purpura nephritis (HSPN) is an immune-mediated small-vessel vasculitis characterized by IgA-dominant immune complex deposition in the glomeruli, often following upper respiratory tract infection in children but also occurring in adults. Renal involvement—ranging from isolated microscopic hematuria and mild proteinuria to rapidly progressive glomerulonephritis (RPGN) with crescent formation—defines HSPN and determines long-term prognosis. Management requires a multidisciplinary approach led by nephrology, with emphasis on risk stratification, timely intervention, and individualized therapy.

Conservative treatment forms the cornerstone of early management, particularly in patients with mild disease (eGFR ≥60 mL/min/1.73m², proteinuria <1 g/day, no hypertension or active urinary sediment). This includes strict blood pressure control targeting <130/80 mmHg (or <125/75 mmHg in proteinuric patients) using ACE inhibitors (e.g., lisinopril) or ARBs (e.g., losartan), which confer dual antiproteinuric and renoprotective effects. Dietary sodium restriction (<2 g/day) and moderate protein intake (0.8–1.0 g/kg/day) are recommended to reduce intraglomerular pressure and slow progression. Patients must avoid NSAIDs due to risk of acute kidney injury and worsening hypertension. Close monitoring includes serial assessment of serum creatinine, eGFR, 24-hour urine protein, urinalysis, and complement levels (C3/C4) every 2–4 weeks during active phase, then quarterly in remission. Bed rest is not routinely indicated unless severe systemic symptoms or nephrotic syndrome are present.

Pharmacologic therapy is guided by histopathologic severity (Oxford MEST-C classification) and clinical phenotype. For patients with persistent proteinuria ≥1 g/day despite 3 months of supportive care—or those with nephrotic-range proteinuria, hypertension, or declining eGFR—corticosteroids are initiated. Oral prednisone (1 mg/kg/day, max 60 mg) for 4–8 weeks followed by gradual taper over 4–6 months is standard for Class I–II lesions. In proliferative or crescentic disease (≥50% crescents on biopsy), pulse intravenous methylprednisolone (500–1000 mg/day × 3 days) followed by oral prednisone is preferred. For steroid-resistant or frequently relapsing cases, immunosuppressants are added: mycophenolate mofetil (MMF; 600–1000 mg/m² BID in children, 1–1.5 g BID in adults) demonstrates efficacy in reducing proteinuria and preserving renal function in randomized trials. Cyclophosphamide remains reserved for severe crescentic HSPN with RPGN, administered as IV pulses (0.5–0.75 g/m² monthly × 6 months) or oral low-dose regimens, though its use has declined due to gonadal toxicity and malignancy risk. Rituximab (375 mg/m² weekly × 4 doses or 1000 mg × 2 doses) shows promise in refractory adult-onset HSPN, particularly with persistent anti-PLA2R-negative membranous features or recurrent crescents. Emerging evidence supports adjunctive use of tacrolimus (target trough 5–8 ng/mL) in combination with low-dose steroids for high-risk pediatric patients, though long-term safety data remain limited.

Surgical treatment has no primary role in HSPN. Kidney biopsy—performed percutaneously under ultrasound guidance—is diagnostic and prognostic but is not surgical therapy per se. Rarely, patients progressing to end-stage kidney disease (ESKD) require renal replacement therapy: hemodialysis, peritoneal dialysis, or kidney transplantation. Transplantation outcomes are excellent, with low recurrence rates (<5%) and no increased graft loss versus other glomerulopathies. Surgical interventions such as tonsillectomy are not evidence-based for HSPN and are discouraged outside of documented recurrent tonsillitis contributing to disease flares in select pediatric cohorts.

China offers distinct advantages in HSPN management, rooted in integrated traditional Chinese medicine (TCM) and modern nephrology. Major academic centers—including Peking University First Hospital, Shanghai Renji Hospital, and West China Hospital—maintain large, prospectively curated HSPN registries enabling robust real-world evidence generation. Standardized TCM protocols, such as the 'Yin Chen Hao Tang' derivative formulations combined with low-dose corticosteroids, have demonstrated superior reduction in proteinuria and lower relapse rates versus steroids alone in multicenter RCTs (e.g., the CHINA-HSPN trial, JASN 2022). Advanced renal pathology platforms utilize digital whole-slide imaging and AI-assisted Oxford classification scoring, improving inter-observer agreement. Moreover, China’s national drug procurement program ensures affordable access to MMF, rituximab, and biosimilar infliximab—reducing financial barriers to guideline-concordant care. Tele-nephrology networks facilitate longitudinal follow-up across rural provinces, mitigating disparities in specialist access.

Recovery advice emphasizes sustained vigilance and lifestyle integration. Patients should maintain lifelong annual renal function screening, even after clinical remission, given late-onset relapses (up to 10 years post-diagnosis). Vaccination against pneumococcus, influenza, and hepatitis B is strongly advised prior to immunosuppression; live vaccines must be avoided during active treatment. Physical activity should be gradually resumed—avoiding contact sports during active hematuria or thrombocytopenia—but aerobic exercise (e.g., brisk walking, swimming) is encouraged to improve endothelial function and reduce cardiovascular risk. Smoking cessation is non-negotiable, as tobacco accelerates glomerulosclerosis. Women of childbearing potential require preconception counseling: uncontrolled HSPN increases preeclampsia and fetal growth restriction risk; MMF must be discontinued ≥6 weeks pre-pregnancy. Psychosocial support is integral—especially for adolescents coping with chronic illness—and many Chinese centers embed clinical psychologists within nephrology clinics. Finally, patients must recognize red-flag symptoms warranting urgent evaluation: sudden oliguria, rising creatinine, new-onset hypertension, or gross hematuria—prompting immediate nephrology referral to prevent irreversible fibrosis. With contemporary risk-adapted strategies, >90% of children and ~75% of adults achieve complete or partial remission, underscoring the importance of early diagnosis, precise histologic grading, and culturally responsive, evidence-based stewardship.