Kidney nontumor
Glomerular disease
SLE and related autoantibody mediated glomerulonephritis
Systemic lupus erythematosus
Author: Nikhil Sangle, M.D.
Last author update: 3 March 2014
Last staff update: 7 June 2022
Copyright: 2002-2022, PathologyOutlines.com, Inc.
PubMed Search: Systemic lupus erythematosis [title]
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 August 17th, 2022.
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)
-
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
-
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)
Gross images
Images hosted on other servers:
Diffuse proliferative lupus nephritis
Microscopic (histologic) images
Contributed by Abdullah Al-Fiaar, M.D.
Membranous glomerulonephritis
Images hosted on other servers:
Membranous lupus nephritis, class II
Membranous lupus nephritis, class IV
Membranous lupus nephritis, classes II to IV
Membranous lupus nephritiss, class IV to VI
macrophagic infiltration,
activated complement
deposition
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
