Lupus nephritis and systemic disease: SAQ

This girl has proliferative lupus nephritis. The combination of an active urinary sediment (haematuria with dysmorphic red cells and red cell casts), proteinuria, mild renal impairment, low complement (both C3 and C4), and strongly positive anti-dsDNA antibodies in an adolescent girl with systemic lupus features is diagnostic of lupus nephritis. The biopsy confirms Class IV diffuse proliferative disease, the most common and most severe paediatric pattern, defined by proliferative lesions affecting 50 percent or more of glomeruli with subendothelial deposits, wire-loop changes, and cellular crescents. The full-house immunofluorescence pattern is the histological hallmark. ^[1]

Question 1 (10 marks)

Outline your initial management of this child, including the choice of induction therapy, the role of glucocorticoids, and the specific counselling required before starting treatment. ^[2]

The overriding principle is prompt induction of the active proliferative inflammation to prevent irreversible glomerular scarring, because the cellular crescents and fibrinoid necrosis on her biopsy mark severe active disease that is reversible only if treated early. I would first stabilise her hypertension with amlodipine and manage her fluid status with salt restriction, because uncontrolled hypertension worsens the renal injury. I would involve a paediatric nephrologist and rheumatologist on the day of the biopsy result. ^[2]

For induction, my first-line choice is mycophenolate mofetil, because the pivotal trials established that it is non-inferior to cyclophosphamide for induction while avoiding gonadal toxicity, which is the critical consideration in a 13-year-old girl approaching reproductive age. I would target a dose of 2 to 3 g per day in two divided doses, starting lower and up-titrating to manage gastrointestinal side effects. This would be combined with intravenous methylprednisolone pulses (500 mg to 1 g daily for 3 days) followed by oral prednisolone (0.5 to 1 mg per kg per day, maximum 60 mg per day) tapered to the lowest effective dose. Low-dose Euro-Lupus cyclophosphamide (500 mg every 2 weeks for 6 doses) would be the alternative if she failed mycophenolate or had very severe disease with a high crescent burden. ^[2]

The specific counselling before starting treatment centres on the teratogenicity of mycophenolate, which demands reliable contraception and pregnancy avoidance in an adolescent girl. I would also counsel about the side effects of glucocorticoids (growth suppression, weight gain, glucose intolerance, osteoporosis, mood changes) and the need for bone protection with calcium and vitamin D. I would screen for latent tuberculosis, hepatitis, and HIV before immunosuppression, ensure her vaccinations (pneumococcal, influenza, hepatitis B, human papillomavirus) are up to date while avoiding live vaccines, and start hydroxychloroquine at 5 mg per kg per day for its proven benefit in reducing flares and improving renal outcomes. ^[2]

I would set a treat-to-target goal of a complete renal response: a urine protein-to-creatinine ratio below 0.5 with her creatinine at baseline, monitored at every clinic visit alongside the complement and anti-dsDNA titre. ^[2]