Lupus Nephritis in Children
Introduction to Lupus Nephritis in Children
Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE) that affects approximately 50-60% of children with SLE. It is characterized by inflammation and damage to the kidneys, which can lead to significant morbidity and mortality if not properly managed.
Key points:
- LN is more common and often more severe in pediatric SLE compared to adult-onset SLE
- Early diagnosis and aggressive treatment are crucial for preserving renal function
- Management requires a multidisciplinary approach involving pediatric rheumatologists, nephrologists, and other specialists
Pathophysiology of Lupus Nephritis in Children
The pathophysiology of LN involves complex interactions between autoantibodies, complement, and inflammatory mediators:
- Autoantibody production: Anti-double-stranded DNA (anti-dsDNA) and anti-nucleosome antibodies are particularly important in LN
- Immune complex formation: These autoantibodies form immune complexes that deposit in the glomeruli
- Complement activation: Deposited immune complexes activate the complement system, leading to inflammation
- Inflammatory cascade: Cytokines, chemokines, and adhesion molecules recruit inflammatory cells to the kidney
- Tissue damage: Prolonged inflammation results in glomerular and tubulointerstitial damage
Genetic factors, environmental triggers, and hormonal influences contribute to the development and progression of LN in children.
Clinical Presentation of Lupus Nephritis in Children
The clinical presentation of LN in children can be variable and may include:
- Asymptomatic proteinuria or hematuria: Often detected on routine urinalysis
- Nephrotic syndrome: Edema, proteinuria, hypoalbuminemia, and hyperlipidemia
- Nephritic syndrome: Hematuria, proteinuria, hypertension, and decreased renal function
- Hypertension: May be the initial presenting sign
- Acute kidney injury: In severe cases or during disease flares
- Extra-renal manifestations: Fatigue, fever, rash, arthritis, and other SLE symptoms
Regular monitoring of renal function and urine analysis is essential in all children with SLE, even in the absence of overt renal symptoms.
Diagnosis of Lupus Nephritis in Children
Diagnosis of LN involves a combination of clinical, laboratory, and histological findings:
- Urinalysis: Proteinuria, hematuria, cellular casts
- Blood tests:
- Serum creatinine and estimated GFR
- Complement levels (C3, C4)
- Anti-dsDNA antibodies
- Antinuclear antibodies (ANA)
- 24-hour urine collection: Quantify proteinuria
- Renal biopsy: Gold standard for diagnosis and classification
- Light microscopy
- Immunofluorescence
- Electron microscopy
- Imaging studies: Renal ultrasound to assess kidney size and echogenicity
Early referral to a pediatric nephrologist is recommended for children with suspected LN.
Classification of Lupus Nephritis in Children
The International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification is used for LN in both children and adults:
| Class | Description |
|---|---|
| I | Minimal mesangial LN |
| II | Mesangial proliferative LN |
| III | Focal LN (<50% of glomeruli) |
| IV | Diffuse LN (≥50% of glomeruli) |
| V | Membranous LN |
| VI | Advanced sclerosing LN |
Classes III and IV are further subdivided based on active (A) or chronic (C) lesions. Class V can occur in combination with class III or IV.
Treatment of Lupus Nephritis in Children
Treatment of LN in children aims to induce remission, prevent flares, and preserve renal function. The approach is based on the ISN/RPS class and disease severity:
Induction Therapy:
- Class I and II: Usually managed with hydroxychloroquine and low-dose corticosteroids
- Class III and IV:
- High-dose corticosteroids (oral or IV pulse)
- Cyclophosphamide OR Mycophenolate mofetil
- Class V:
- Corticosteroids
- Mycophenolate mofetil OR Calcineurin inhibitors
Maintenance Therapy:
- Lower-dose corticosteroids
- Mycophenolate mofetil OR Azathioprine
- Hydroxychloroquine
Adjunctive Therapies:
- ACE inhibitors or ARBs for proteinuria and hypertension
- Statins for hyperlipidemia
- Calcium and vitamin D supplementation
- Immunizations (avoid live vaccines during immunosuppression)
Rituximab and belimumab may be considered for refractory cases. Careful monitoring of drug toxicities and growth parameters is essential in pediatric patients.
Prognosis of Lupus Nephritis in Children
The prognosis of LN in children has improved significantly with earlier diagnosis and more aggressive treatment strategies. However, it remains a serious condition with potential long-term complications:
- Renal survival: 5-year renal survival rates are approximately 85-90%
- Prognostic factors:
- ISN/RPS class (worse prognosis for proliferative classes III and IV)
- Degree of chronic damage on biopsy
- Response to initial therapy
- Frequency and severity of flares
- Long-term complications:
- Chronic kidney disease
- End-stage renal disease requiring dialysis or transplantation
- Cardiovascular disease
- Growth impairment
- Infertility
Regular follow-up and adherence to therapy are crucial for optimizing outcomes. Transition to adult care should be carefully planned for adolescents with LN.
Lupus Nephritis in Children
- Q: What is lupus nephritis?
A: Kidney inflammation caused by systemic lupus erythematosus (SLE) - Q: What percentage of children with SLE develop lupus nephritis?
A: Approximately 50-75% - Q: Which gender is more commonly affected by pediatric lupus nephritis?
A: Females - Q: What is the most common age of onset for pediatric lupus nephritis?
A: Adolescence (12-16 years) - Q: How is lupus nephritis classified?
A: Using the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, from class I to VI - Q: Which class of lupus nephritis is associated with the worst prognosis?
A: Class IV (diffuse proliferative lupus nephritis) - Q: What is the gold standard for diagnosing and classifying lupus nephritis?
A: Renal biopsy - Q: Which immunoglobulin is typically found in the glomerular deposits of lupus nephritis?
A: IgG - Q: What is the characteristic immunofluorescence pattern seen in lupus nephritis?
A: "Full house" pattern (IgG, IgA, IgM, C3, and C1q) - Q: Which serological marker is highly specific for SLE and lupus nephritis?
A: Anti-double stranded DNA (anti-dsDNA) antibodies - Q: What is the initial treatment for severe lupus nephritis in children?
A: Induction therapy with high-dose corticosteroids and either cyclophosphamide or mycophenolate mofetil - Q: What is the typical duration of induction therapy for lupus nephritis?
A: 3-6 months - Q: Which medication is commonly used for maintenance therapy in pediatric lupus nephritis?
A: Mycophenolate mofetil - Q: What is the role of hydroxychloroquine in the treatment of lupus nephritis?
A: It is used as an adjunctive therapy to reduce disease activity and flares - Q: What is the target urine protein-to-creatinine ratio for remission in lupus nephritis?
A: Less than 0.5-0.7 mg/mg - Q: How often should children with lupus nephritis be monitored during active disease?
A: Every 1-2 weeks - Q: What is the most common long-term complication of poorly controlled lupus nephritis in children?
A: Progression to end-stage renal disease - Q: What percentage of children with lupus nephritis progress to end-stage renal disease within 5 years of diagnosis?
A: Approximately 10-20% - Q: What is the role of rituximab in the treatment of pediatric lupus nephritis?
A: It is used as a rescue therapy for refractory cases - Q: How does pregnancy affect the management of adolescents with lupus nephritis?
A: It requires careful planning and monitoring due to increased risk of disease flares and potential teratogenic effects of some medications
