Systemic lupus erythematosus

Kidney nontumor

Glomerular disease

SLE and related autoantibody mediated glomerulonephritis

Author: Nikhil Sangle, M.D.

Topic Completed: 3 March 2014

Minor changes: 9 December 2020

Copyright: 2002-2021, PathologyOutlines.com, Inc.

PubMed Search: Systemic lupus erythematosis [title]

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Table of Contents

Cite this page: Sangle N. Systemic lupus erythematosus. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneysle.html. Accessed January 22nd, 2021.

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)

Class I: Minimal Mesangial Lupus Nephritis:

Glomeruli normal by light microscopy (LM), mesangial deposits by immunofluorescence (IF) / electron microscopy (EM)

Class II: Mesangial Proliferative Lupus Nephritis:

Mesangial hypercelullularity and/or mesangial expansion by LM, immune deposits by IF / EM

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

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

Platelet microthrombi,
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