Lupus nephritis

Definition

Lupus nephritis is glomerulonephritis caused by systemic lupus erythematosus (SLE). It results from deposition of immune complexes composed of nuclear antigens (especially DNA) and complement-fixing autoantibodies in the glomeruli.

Classification

ISN/RPS classification

The histologic ISN/RPS classification (2003, revised 2018) distinguishes six classes:

• Class I – minimal mesangial: normal on light microscopy, immune complexes only on immunofluorescence or electron microscopy
• Class II – mesangial proliferative: immune complexes in the mesangium only, mesangial hypercellularity; possibly microscopic hematuria or proteinuria
• Class III – focal: endocapillary and extracapillary proliferation in < 50% of glomeruli, usually segmental
• Class IV – diffuse: proliferation in ≥ 50% of glomeruli; most common form, often with hypertension, nephrotic syndrome and elevated creatinine
• Class V – membranous: thickened basement membrane with subepithelial and intramembranous immune complexes; usually nephrotic syndrome with normal or slightly elevated creatinine
• Class VI – advanced sclerosing: ≥ 90% of glomeruli globally sclerosed without residual activity; bland sediment and kidney failure

Overlap and transitions between classes are common.

Occurrence & epidemiology

Lupus nephritis occurs in 20–60% of people with SLE. In the United States, African American patients are disproportionately affected.

Clinical features

The other manifestations of SLE are usually in the foreground. Renal findings include hematuria, proteinuria (often nephrotic-range, ≥ 3 g/day), edema, hypertension and, in advanced stages, kidney failure. Antiphospholipid syndrome nephropathy with microthrombi and ischemic cortical atrophy may additionally be present in up to one third of patients with SLE.

Histology

Depending on the class, immune complexes lie subendothelially, intramembranously, subepithelially or in the mesangium. Immunofluorescence shows complement and IgG, IgA and IgM in varying proportions; epithelial cell proliferation may form crescents.

Diagnosis

• In everyone with SLE: urinalysis with sediment (hematuria, red blood cell casts), protein-to-creatinine ratio and serum creatinine
• Anti-dsDNA antibodies and complement C3 and C4: high anti-dsDNA titers and low complement suggest active lupus nephritis.
• Kidney biopsy if findings are abnormal, especially with declining GFR or confirmed proteinuria: confirmation of the diagnosis and determination of the ISN/RPS class
• Lupus nephritis is also considered in unexplained hypertension, elevated creatinine or abnormal urinalysis with clinical features of lupus.

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Further reading (open access)

1. MSD Manual Professional: Lupus Nephritis
2. Gasparotto M et al.: Lupus nephritis: clinical presentations and outcomes in the 21st century (Rheumatology 2020)

Cross-references