Introduction

Chief cause of childhood morbidity and mortality in systemic lupus erythematosus (SLE).
Occurs in 50-80% of pediatric patients.
Higher incidence and more severe course in childhood compared to adult-onset SLE.

Pathophysiology

Driven by nuclear antigen-based immune complex-mediated type 3 hypersensitivity reaction.
Autoantibody formation leads to immune complex deposition in vessel walls and glomeruli.
Complement system activation recruits leukocytes (neutrophils, monocytes).
Release of lysosomal enzymes and toxic free radicals causes tissue injury and fibrinoid necrosis.
Podocytopathy observed without complex antibody deposits; linked to type 2 helper cell (Th2) overexpression and interleukin-13 (IL-13) overproduction.

Urinalysis: Persistent proteinuria >0.5 g/day, cellular casts (red blood cell, granular, tubular, mixed).
Serology: Elevated anti-dsDNA levels correlate with active disease.
Complement: Decreased C3, C4, and C1q levels; C4 and C1q reduced to a greater extent than C3.
Renal Biopsy: Essential for diagnosis, staging, and therapeutic decision-making.
Histopathology: Fibrinoid necrosis.
Immunofluorescence: Granular lumpy deposits of immunoglobulin and complement ("full house deposits").

Class	Description	Histological Findings
Class I	Minimal mesangial	Normal light microscopy (LM); mesangial immune deposits on immunofluorescence (IF).
Class II	Mesangial proliferative	Mesangial hypercellularity or matrix expansion on LM; mesangial immune deposits.
Class III	Focal proliferative	Active/inactive focal endocapillary/extracapillary glomerulonephritis (GN) involving <50% glomeruli.
Class IV	Diffuse proliferative	Active/inactive diffuse endocapillary/extracapillary GN involving ≥50% glomeruli; severe form.
Class V	Membranous	Global/segmental subepithelial immune deposits; manifests as nephrotic syndrome.
Class VI	Advanced sclerosing	≥90% global glomerulosclerosis without residual activity; irreversible chronic damage.

Therapeutic goals include achieving prompt renal remission, avoiding flares, and minimizing iatrogenic toxicity.

Class	Treatment Protocol
Class I & II	No induction needed unless extrarenal involvement dictates. For heavy proteinuria: Prednisolone (2 mg/kg/day) tapering + Azathioprine.
Class III & IV	Aggressive induction and maintenance required.
Class V	Corticosteroids + oral Mycophenolate Mofetil (MMF), calcineurin inhibitors, or Azathioprine.
Class VI	Angiotensin-converting enzyme (ACE) inhibitors; treat extrarenal manifestations.

Guided by Childhood Arthritis Rheumatology Research Alliance (CARRA) consensus.
Duration: 6 months.
Regimen: High-dose glucocorticoids combined with either intravenous (IV) Cyclophosphamide or oral MMF.
Pulse IV methylprednisolone (15-20 mg/kg/dose) indicated for renal insufficiency.
MMF dose: 600 mg/m2 twice daily (up to 1500 mg twice daily).
Cyclophosphamide dose: 500-1000 mg/m2 IV monthly. Euro-Lupus protocol (500 mg fixed dose every 2 weeks for 3 months) considered for adult-weight adolescents.

Duration: Minimum 30 months following induction.
Regimen: Tapering low-dose prednisolone (0.2-0.3 mg/kg/day) combined with MMF or Azathioprine (1-2 mg/kg/day).
MMF generally preferred.
Refractory cases warrant Calcineurin inhibitors (Tacrolimus, Cyclosporine) or Rituximab.
Belimumab improves renal outcomes when added to standard therapy.

Hydroxychloroquine recommended for all patients to prevent flares and improve survival.
Calcium and Vitamin D supplementation.
ACE inhibitors for hypertension and proteinuria.
Aspirin if antiphospholipid antibodies present.