Kidney non-tumor - SLE / systemic lupus erythematosis

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Kidney non-tumor

Associated with systemic conditions

SLE / systemic lupus erythematosis

Reviewers: Nikhil Sangle, M.D. (see Reviewers page)
Revised: 23 December 2012, last major update August 2012
Copyright: (c) 2003-2012, PathologyOutlines.com, Inc.

General
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● Autoimmune disease of women (90%) with various clinical manifestations
● 40-80% have impaired renal function, due to in situ or circulating immune complexes

Etiology
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● Most cases idiopathic, but drug induced lupus-like disease is associated with chlorpromazine, hydralazine, isoniazid, methyldopa, procainamide, quinidine

Clinical features
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● 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
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● 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)

Class II: Mesangial Proloferative 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
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● 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
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● Steroids, cyclosporine A (Clin Nephrol 2011;76:136), tacrolimus and other immunosuppressants (Tohoku J Exp Med 2012;227:281)

Gross images
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Diffuse proliferative lupus nephritis

Micro images
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Membranous lupus nephritis, class II

Membranous lupus nephritis, class III

Membranous lupus nephritis, class IV

Membranous lupus nephritis, classes II to IV

Membranous lupus nephritis, classes V

Membranous lupus nephritis, classes VI

Membranous lupus nephritiss, class IV to VI

WHO class III and IV

Membranous glomerulonephritis-various images

Platelet microthrombi, macrophagic infiltration, activated complement deposition.

Virtual slides
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Membranous glomerulonephritis with wire loops

Electron microscopy description
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● Granular glomerular electron-dense deposits; may be organized into curvilinear microtubular or fibrillar structures composed of bands 10–15 nm in diameter (‘fingerprinting’)

Electron microscopy images
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Class IV lesions

Various features common to lupus nephritis and Hepatis B related nephritis

Differential diagnosis
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● 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

End of Kidney non-tumor > Associated with systemic conditions > SLE / systemic lupus erythematosis

Ref Updated: 8/10/12

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