Paper II
Question
Define nephrotic syndrome. Describe the gross and microscopic changes in kidney in Systemic Lupus Erythematosus
Answer
Definition of nephrotic syndrome
- A clinical syndrome characterized by heavy (nephrotic-range) proteinuria (≥3.5 g/24 hours), hypoalbuminaemia, generalized oedema, and hyperlipidaemia/lipiduria, resulting from increased glomerular capillary wall permeability to plasma proteins
Renal changes in Systemic Lupus Erythematosus (Lupus Nephritis)
Gross
- Kidney size and appearance vary with the class/severity of lupus nephritis — may appear grossly normal in mild disease, or show a pale, granular, shrunken surface in advanced/chronic disease with significant scarring
Microscopic (based on ISN/RPS classification, class-dependent)
- Class I (minimal mesangial): Normal light microscopy, mesangial immune deposits only on immunofluorescence/EM
- Class II (mesangial proliferative): Mesangial hypercellularity and matrix expansion
- Class III (focal): Focal (affecting <50% of glomeruli) proliferative changes, with segmental or global involvement
- Class IV (diffuse): Most common and most severe form — diffuse (affecting ≥50% of glomeruli) proliferative glomerulonephritis, with “wire-loop” lesions (thickened capillary walls from massive subendothelial immune complex deposition), fibrinoid necrosis, crescents may be present
- Class V (membranous): Diffuse thickening of the glomerular capillary walls due to subepithelial immune complex deposits, resembling primary membranous nephropathy
- Class VI (advanced sclerosing): Global sclerosis of ≥90% of glomeruli, representing the end-stage of chronic lupus nephritis
Immunofluorescence
- “Full house” pattern — deposition of IgG, IgA, IgM, C3, and C1q, reflecting the multiple autoantibody specificities characteristic of SLE
Electron microscopy
- Subendothelial, subepithelial, and/or mesangial electron-dense immune complex deposits, with the location/pattern determining the ISN/RPS class