Lupus Nephritis
On this page
Direct answer
Class before treatment: the ISN/RPS biopsy classification decides everything in lupus nephritis. Classes III and IV — focal and diffuse proliferative disease — demand induction with mycophenolate mofetil or the Euro-Lupus low-dose intravenous cyclophosphamide regimen of 500 mg fortnightly for six doses, followed by long maintenance on mycophenolate or azathioprine. Class V behaves like membranous nephropathy and class VI is burnt-out disease no immunosuppression can revive. Hydroxychloroquine belongs to every lupus patient whose retina permits it, complement and anti-dsDNA titres are read serially rather than singly, and the modern additions voclosporin and belimumab sit on top of, not instead of, this scaffold.
What you must remember
- Classes: III focal proliferative (under half of glomeruli), IV diffuse (half or more, subdivided segmental and global), V membranous, VI advanced sclerotic; crescents complicate any proliferative class, and mixed III+V or IV+V disease carries the worst prognosis and lowest remission rates.
- Euro-Lupus regimen: 500 mg intravenous cyclophosphamide every two weeks for six doses — equal efficacy to high-dose NIH schedules with far less infection and gonadal toxicity.
- Mycophenolate equivalence: 2–3 g daily matches cyclophosphamide for induction in most proliferative disease and wins in Black and Hispanic populations in the pivotal trials.
- Maintenance: mycophenolate or azathioprine 2 mg/kg for years, with the lowest steroid dose that holds remission.
- Remission target: complete remission — proteinuria below 0.5 g/day with stable function — ideally within 6–12 months; a 50 per cent proteinuria fall by month six predicts long-term kidney survival.
- Serology: falling C3 and C4 with rising anti-dsDNA signal flare; anti-C1q antibodies correlate most closely with nephritis activity — a viva favourite.
- Newer agents: belimumab on standard therapy (BLISS-LN) and voclosporin with mycophenolate (AURORA) both improved renal outcomes in their trials.
- Hydroxychloroquine: reduces flares, thrombosis and renal involvement; screen retinal function from year five.
Choosing induction for one biopsy
A 24-year-old woman presents with oedema, arthritis, oral ulcers, proteinuria 3.8 g/day, creatinine 1.3 mg/dL, C3 and C4 both low, anti-dsDNA strongly positive. Biopsy: class IV-G with cellular crescents in a fifth of glomeruli — diffuse global proliferative disease, the classic induction candidate. Step one: the regimen choice. She is twenty-four, newly married and fertility-sensitive, which tilts her to mycophenolate 2.5 g daily (or the Euro-Lupus schedule if her centre favours it) plus glucocorticoids — pulses for three days, then oral prednisolone tapering toward 5 mg by month six. Step two: hydroxychloroquine starts now and never stops. Step three: surveillance at months three and six — complement recovery, dsDNA fall and, above all, proteinuria trajectory; a 50 per cent drop by month six predicts good long-term outcome, while static proteinuria earns a repeat biopsy to exclude smouldering activity before escalation to belimumab or a cyclophosphamide switch. Step four: pregnancy planning — if she conceives, mycophenolate becomes teratogenic and must be swapped for azathioprine before conception attempts, a counselling point that is itself examinable. In the Indian setting, add step zero: screen for latent tuberculosis before intensive immunosuppression, because reactivation under cyclophosphamide or rituximab in a high-prevalence country is a complication no guideline for this region lets you ignore.
How the exam frames it
Stems test three reflexes. A lupus patient with arthritis and low C3 but no urinary symptoms still gets a spot protein-creatinine ratio — nephritis is sought, not awaited. A class V patient with nephrotic-range proteinuria is not managed like idiopathic membranous nephropathy: mycophenolate or cyclophosphamide with steroids comes first, calcineurin inhibitors for refractory disease. And a transplant question hides in plain sight: dialysis or transplantation is best delayed until lupus has been quiescent for six to twelve months on reduced immunosuppression — extraserosal activity, not serology alone, decides. The serology trap deserves the last word: a persistently positive anti-dsDNA with normal complement and quiet urine is a risk marker, not a treatment indication.
Frequently asked questions
What is the Euro-Lupus cyclophosphamide regimen?
500 mg intravenously every two weeks for six total doses — low-dose induction that matches high-dose protocols with less toxicity.
Which maintenance drugs follow induction?
Mycophenolate mofetil or azathioprine, continued for years with minimal steroids; belimumab may be layered on for persistent risk.
Why does every lupus patient receive hydroxychloroquine?
It reduces flares, renal involvement and thrombosis while aiding long-term survival — with annual retinal screening after five years.
Which serology best tracks nephritis activity?
Anti-C1q antibodies correlate most closely with active nephritis; C3, C4 and anti-dsDNA are read as trends, never single values.
How is class V lupus nephritis with nephrotic syndrome treated?
Immunosuppression first — mycophenolate or cyclophosphamide with steroids — rather than the idiopathic membranous pathway.
When is transplantation considered in lupus?
After six to twelve months of clinically quiescent disease, with outcomes matching other causes of kidney failure.