Table of Contents
Definition / general | Etiology | Clinical features | WHO classification of lupus nephritis | International Society of Nephrology (ISN) / Renal Pathology Society (RPS) classification of Lupus Nephritis (2004) | Case reports | Treatment | Gross images | Microscopic (histologic) images | Electron microscopy description | Differential diagnosisCite this page: Sangle N. Systemic lupus erythematosus. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneysle.html. Accessed February 3rd, 2023.
Definition / general
- Autoimmune disease of women (90%) with various clinical manifestations
- 40 - 80% have impaired renal function, due to in situ or circulating immune complexes
Etiology
- Most cases idiopathic, but drug induced lupus-like disease is associated with chlorpromazine, hydralazine, isoniazid, methyldopa, procainamide, quinidine
Clinical features
- Adults and children (2/3 present initially at ages 16 - 30 years)
- In children in US, prevance of 10 per 100K Medicaid-enrolled children (Arthritis Rheum 2012;64:2669)
- Most common renal symptoms are proteinuria and microscopic hematuria; also acute nephritis, acute and chronic renal failure, isolated abnormalities in urinary sediment, nephrotic syndrome
- Biopsy is necessary to determine subsequent clinical course and to assist with treatment
- Non-lupus nephritides occasionally present (Hum Pathol 2001;32:1125), including IgA nephropathy (Mod Pathol 1995;8:5)
WHO classification of lupus nephritis
- I: normal or minimal abnormality; no abnormalities identified by H&E, immunofluorescence or EM; asymptomatic; may not actually represent renal disease
- II (10 - 20% of cases): pure mesangial lesions; mesangial expansion but mostly patent capillaries; mesangial immune deposits; mild proteinuria with variable hematuria, but normal renal function
- IIA: minimal light microscopy changes, but immune deposits present in mesangium by immunofluorescence and EM
- IB: glomerular mesangial hypercellularity present by light microscopy, involving center of lobules away from vascular pole; immune deposits only in mesangial region; no significant tubular, interstitial or vascular changes; good prognosis (5 year renal survival > 90%)
- III (30 - 40% of cases): focal proliferative glomerulonephritis; focal and segmental proliferative intra- or extracapillary necrotizing or sclerosing lesions in < 50% of glomeruli; predominantly mesangial and subendothelial immune deposits (Ig, complement); nephritic urinary sediment; variable proteinuria but usually non-nephrotic
- IV (40 - 60%): diffuse proliferative glomerulonephritis; predominantly global proliferative lesions, necrosis, crescents in > 50% of glomeruli, variable sclerosis, prominent inflammatory interstitial infiltrate, often wire loop lesions in thickened capillary walls; predominantly mesangial and subendothelial immune deposits of IgG, often IgM and IgA (all three is called a “full house”); also C3 and C1q, fibrin and fibrinogen; nephritic and nephrotic syndromes, hypertension, variable renal insufficiency; rapidly progresses to renal failure without treatment
- V (10 - 15%): membranous glomerulonephritis; diffuse thickening of capillary walls, subepithelial and mesangial immune deposits (“spike and dome” pattern with silver stain); nephrotic syndrome or severe proteinuria
- VI: advanced sclerosing glomerulonephritis; glomerular obsolescence and segmental glomerulosclerosis, tubular atrophy, interstitial fibrosis; few immune deposits; chronic renal failure that is unlikely to respond to therapy
- Overlap common in classes III and V, IV and V
Table
International Society of Nephrology (ISN) / Renal Pathology Society (RPS) classification of Lupus Nephritis (2004)
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Class I: Minimal Mesangial Lupus Nephritis:
- Glomeruli normal by light microscopy (LM), mesangial deposits by immunofluorescence (IF) / electron microscopy (EM)
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Class II: Mesangial Proliferative Lupus Nephritis:
- Mesangial hypercelullularity and/or mesangial expansion by LM, immune deposits by IF / EM
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Class III: Focal Lupus Nephritis:
- Active or inactive focal, segmental or global endo or extracapillary glomerulonephritis involving < 50% of glomeruli, immune deposits are subendothelial
- Subclassified as A (active lesions), A/C (active and chronic lesions), C (chronic lesions)
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Class IV: Diffuse Lupus Nephritis:
- > 50% glomeruli with active / inactive diffuse, segmental, or global endo and/or extracapillary glomerulonephritis
- Diffuse subendothelial deposits can cause wire-loop appearance
- A (active lesions), A/C (active and chronic lesions), C (chronic lesions)
- Diffuse segmental if > 50% glomeruli show segmental lesions, diffuse global if > 50% show global lesions
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Class V: Membranous Lupus Nephritis:
- Global or segmental involvement, subepithelial immune deposits
- May occur in combination with class III or IV
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Class VI: Advanced Sclerosing Lupus Nephritis:
- > 90% globally sclerosed glomeruli
- References: J Am Soc Nephrol 2004;15:241
Tables
- Tubulointerstitial disease: observed in all classes, severe in classes III and IV; usually composed of lymphocytes, plasma cells and macrophages; severe cases have casts
- Vascular lesions: common, associated with poor prognosis; includes vascular immune deposits, non-inflammatory necrotizing vasculopathy, true vasculitis, thrombotic microangiopathy and non-specific arteriolosclerosis
- Hematoxylin bodies: focal areas of necrosis containing fragmented nuclei; specific for SLE, but only 1 - 2% sensitive
- Alveolar hemorrhage (bland alveolar wall changes) is similar to lupus microangiopathy of kidney; both are caused by immune complex deposition and induction of apoptosis (Arch Pathol Lab Med 2001;125:475)
- Activity index: based on scoring (0 - 3) of (a) glomerular endocapillary proliferation, (b) glomerular neutrophilic infiltration, (c) wire-loop deposits and hyaline thrombi, (d) glomerular fibrinoid necrosis and karyorrhexis, (e) cellular crescents and (f) interstitial inflammation; double the fibrinoid necrosis / karyorrhexis (part d) and cellular crescent (part e) scores; add up (maximum 24)
- Chronicity index: based on scoring (0 - 3) of (a) glomerular sclerosis, (b) fibrous crescents, (c) tubular atrophy and (d) interstitial fibrosis; add up (maximum 12)
Case reports
- 12 year old girl with severe oliguric renal failure (ISN/RPS class IV-G(A)) and spontaneous remission (BMC Nephrol 2012;13:81)
- Two patients with alveolar hemorrhage and class IV lupus nephritis (Arch Pathol Lab Med 2001;125:475)
Treatment
- Steroids, cyclosporine A (Clin Nephrol 2011;76:136), tacrolimus and other immunosuppressants (Tohoku J Exp Med 2012;227:281)
Microscopic (histologic) images
Contributed by Abdullah Al-Fiaar, M.D.
Images hosted on other servers:
Electron microscopy description
- Granular glomerular electron dense deposits; may be organized into curvilinear microtubular or fibrillar structures composed of bands 10 - 15 nm in diameter "fingerprinting"
Differential diagnosis
- Class III lesions resemble Henoch-Schonlein purpura, pauci immune focal segmental necrotizing glomerulonephritis and IgA nephropathy
- Class IV needs to be distinguished from severe forms of IgA nephropathy, membranoproliferative glomerulonephritis and cryoglobulinemic glomerulonephritis
- IgG4 related kidney disease: see Intern Med 2012;51:1731