What is the ISN/RPS classification of lupus nephritis?

Updated: Mar 04, 2019
  • Author: Lawrence H Brent, MD; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Answer

The classification of lupus nephritis was revised by the International Society of Neurology and the Renal Pathology Society (ISN/RPS) in 2003 and is based on light microscopy, immunofluorescence, and electron microscopy findings from renal biopsy specimens. The ISN/RPS classification itself is based on earlier classifications by the World Health Organization (WHO) in 1974 and 1982 (see Table 2 below). [41]

Table 2. International Society of Nephrology/Renal Pathology Society 2003 Classification of Lupus Nephritis (Open Table in a new window)

Class I

Minimal mesangial lupus nephritis

Light microscopy findings

Normal

Immunofluorescence electron microscopy findings

Mesangial immune deposits

Clinical manifestations

Mild proteinuria

Class II

Mesangial proliferative lupus nephritis

Light microscopy findings

Purely mesangial hypercellularity or mesangial matrix expansion with mesangial immune deposits

Immunofluorescence electron microscopy findings

Mesangial immune deposits; few immune deposits in subepithelial or subendothelial deposits possible

Clinical manifestations

Mild renal disease such as asymptomatic hematuria or proteinuria that usually does not warrant specific therapy

Class III

Focal lupus nephritis

Class III (A)

Active lesions - Focal proliferative lupus nephritis

Class III (A/C)

Active and chronic lesions - Focal proliferative and sclerosing lupus nephritis

Class III (C)

Chronic inactive lesions - Focal sclerosing lupus nephritis

Light microscopy findings

Active or inactive focal, segmental, or global glomerulonephritis involving < 50% of all glomeruli

Immunofluorescence electron microscopy findings

Subendothelial and mesangial immune deposits

Clinical manifestations

Active generalized SLE and mild-to-moderate renal disease with hematuria and moderate proteinuria in many patients; worsening renal function in significant minority, potentially progressing to class IV lupus nephritis

Class IV

Diffuse lupus nephritis

Class IV-S (A)

Active lesions - Diffuse segmental proliferative lupus nephritis

Class IV-G (A)

Active lesions - Diffuse global proliferative lupus nephritis

Class IV-S (A/C)

Active and chronic lesions - Diffuse segmental proliferative and sclerosing lupus nephritis

Class IV-G (A/C)

Active and chronic lesions - Diffuse global proliferative and sclerosing lupus nephritis

Class IV-S (C)

Chronic inactive lesions with scars - Diffuse segmental sclerosing lupus nephritis

Class IV-G (C)

Chronic inactive lesions with scars - Diffuse global sclerosing lupus nephritis

Light microscopy findings

Active or inactive diffuse, segmental or global glomerulonephritis involving = 50% of all glomeruli; subdivided into diffuse segmental (class IV-S) when = 50% of involved glomeruli have segmental lesions (involving less than half of glomerular tuft) and diffuse global (class IV-G) when = 50% of involved glomeruli have global lesions

Immunofluorescence electron microscopy findings

Subendothelial immune deposits

Clinical manifestations

Clinical evidence of renal disease including hypertension, edema, active urinary sediment, worsening renal function, and nephrotic range proteinuria in most cases; active extrarenal SLE in many patients

Class V

Membranous lupus nephritis

Light microscopy findings

Diffuse thickening of glomerular basement membrane without inflammatory infiltrate; possibly, subepithelial deposits and surrounding basement membrane spikes on special stains, including silver and trichrome; may occur in combination with class II or IV; may show advanced sclerosis

Immunofluorescence electron microscopy findings

Subepithelial and intramembranous immune deposits; subendothelial deposits present only when associated proliferative component is present

Clinical manifestations

Clinical and laboratory features of nephrotic syndrome, usually without manifestations of active SLE

Class VI

Advanced sclerosis lupus nephritis

Light microscopy findings

Advanced glomerular sclerosis involving = 90% of glomeruli, interstitial fibrosis, and tubular atrophy, all morphological manifestations of irreversible renal injury

Clinical manifestations

Significant renal insufficiency or end-stage renal disease in most cases; unlikely to respond to medical therapy

SLE = systemic lupus erythematosus.

In addition to the pathologic classification, activity and chronicity indices are scored pathologically and predict the renal prognosis—that is, the progression of renal disease (see Table 3 below). The activity index reflects the state of active inflammation observed at biopsy, which may be reversible with medical therapy. The chronicity index reflects the amount of fibrosis and scarring, which are unlikely to respond to therapy. Renal lesions with a high activity index are more likely to respond to aggressive therapy, whereas renal lesions with high chronicity are not.

These indices in the table below serve as a prognostic tool and a general guide to therapy. Signs of activity justify aggressive medical therapy because such therapy may arrest or reverse the pathologic changes. Signs of chronicity suggest irreversibility, and aggressive therapy is less likely to affect the outcome. The activity and chronicity indices are evaluated at a single point in time, and renal lesions may transform from one class to another either spontaneously or as a result of treatment.

Table 3. Active and Chronic Glomerular Lesions (Open Table in a new window)

Activity Index

Chronicity Index

• Endocapillary hypercellularity with or without leukocyte infiltration; luminal reduction

• Karyorrhexis

• Fibrinoid necrosis

• Rupture of glomerular basement membrane

• Cellular or fibrocellular crescents

• Subendothelial deposits on light microscopy

• Intraluminal immune aggregates

• Glomerular sclerosis; segmental, global

• Fibrous adhesion

• Fibrous crescents

See the images below.

Mesangial proliferative lupus nephritis with moder Mesangial proliferative lupus nephritis with moderate mesangial hypercellularity. International Society of Nephrology/Renal Pathology Society 2003 class II (×200, hematoxylin-eosin).
Focal lupus nephritis. International Society of Ne Focal lupus nephritis. International Society of Nephrology/Renal Pathology Society 2003 class III (×100, hematoxylin-eosin).
Focal lupus nephritis. International Society of Ne Focal lupus nephritis. International Society of Nephrology/Renal Pathology Society 2003 class III (×200, immunofluorescence).
Diffuse lupus nephritis with hypertensive vascular Diffuse lupus nephritis with hypertensive vascular changes. International Society of Nephrology/Renal Pathology Society 2003 class IV (×200, hematoxylin-eosin).
Diffuse lupus nephritis with early crescent format Diffuse lupus nephritis with early crescent formation. International Society of Nephrology/Renal Pathology Society 2003 class IV (×200, hematoxylin-eosin).
Diffuse lupus nephritis with extensive crescent fo Diffuse lupus nephritis with extensive crescent formation (rapidly progressive glomerulonephritis). International Society of Nephrology/Renal Pathology Society 2003 class IV (×200, hematoxylin-eosin).
Membranous lupus nephritis. International Society Membranous lupus nephritis. International Society of Nephrology/Renal Pathology Society 2003 class V (×200, hematoxylin-eosin).
Membranous lupus nephritis showing thickened glome Membranous lupus nephritis showing thickened glomerular basement membrane. International Society of Nephrology/Renal Pathology Society 2003 class V (×200, silver stain).

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