Lupus Nephritis

Question 1

systemic lupus erythematosus (SLE)

Answer 1

*severe, multisystem autoimmune disorder
*variable symptoms and prognosis depending on severity and organ involvement
*diagnosed by a combination of clinical and laboratory features
*production of several auto-antibodies directed at one or more nuclear components (nuclear antigens, dsDNA, histones, RNP)

Question 2

diagnostic criteria for SLE

Answer 2

DOPAMINE RASH:
D - discoid rash
O - oral ulcers
P - photosensitivity
A - arthritis
M - malar rash
I - immuno markers (anti-smith, anti-dsDNA)
N - neuro changes (psychosis, seizures)
E - elevated ESR

R - renal
A - + ANA
S - serositis (pleurisy, pericarditis)
H - hematologic (hemolytic anemia, thrombocytopenia, leukopenia)

Question 3

immunologic tests for SLE

Answer 3

*ANA
*anti-dsDNA
*anti-smith antibodies
*low complement levels

Question 4

lupus nephritis - overview

Answer 4

*results from immune complex-mediated damage to glomeruli
*the pattern of injury is directly related to the SITE of immune deposit formation
*ALL classes of lupus nephritis have “full house” appearance of all immunoglobulins on immunofluorescence (IgG, IgA, IgM, C1q, and C3)

Question 5

class I lupus nephritis - clinical findings

Answer 5

*aka minimal mesangial LN
*no evidence of renal disease; urinalysis typically normal
*represents the earliest and mildest form of glomerular involvement
*prognosis excellent

Question 6

class I (minimal mesangial) lupus nephritis - pathology

Answer 6

*LM: normal
*IF/EM: mesangial immune deposits, “full house”

Question 7

class I (minimal mesangial) lupus nephritis - treatment

Answer 7

*no immunosuppressive therapy indicated
*ACEi/ARB for BP/proteinuria
*lipid and CV risk management
*follow-up

Question 8

class II lupus nephritis - clinical findings

Answer 8

*aka mesangial proliferative LN
*microscopic hematuria +/- proteinuria
*HTN is NOT common
*nephrotic syndrome/renal insufficiency are virtually never seen
*prognosis excellent

Question 9

class II (mesangial proliferative) lupus nephritis - pathology

Answer 9

*LM: mesangial hypercellularity or matrix expansion
*IF/EM: few subepithelial/subendothelial deposits, “full house”

Question 10

class II (mesangial proliferative) lupus nephritis - treatment

Answer 10

*no immunosuppressive therapy is indicated
*treat as class I (ACEi/ARB, lipid and CV risk management, follow-up)

Question 11

class III lupus nephritis - clinical findings

Answer 11

*aka focal proliferative LN
*hematuria & proteinuria (almost all patients)
*some with nephrotic-range proteinuria, HTN, and elevated sCr

Question 12

class III (focal proliferative) lupus nephritis - renal prognosis

Answer 12

*variable depending on extent of involvement:
-less than 25% glomerular involvement and segmental proliferation is less commonly associated with progressive renal dysfunction
-40 to 50% glomerular involvement & necrosis/crescent formation/nephrotic-range proteinuria/HTN is associated with poorer prognosis

Question 13

class III (focal proliferative) lupus nephritis - pathology

Answer 13

*LM: < 50% of glomeruli affected
-segmental or global, active or chronic
-endocapillary or extracapillary proliferative lesions
-subendothelial deposits
-some mesangial changes may be present
*IF: uniform involvement of IgG, IgA, IgM, C3, and C1q = “full house”
*EM: deposits in subendothelial/mesangial space

Question 14

class III (focal proliferative) lupus nephritis - treatment

Answer 14

*prednisone + cytotoxic agents (immunosuppression)
*essentially, treat as class IV

Question 15

class IV lupus nephritis - clinical findings

Answer 15

*aka diffuse proliferative LN
*most common and most SEVERE form of LN
*hematuria & proteinuria (all patients)
*frequently with nephrotic-range proteinuria, HTN, and elevated Cr
*significant hypocomplementemia and elevated anti-dsDNA levels (esp. during active disease)

Question 16

class IV (diffuse proliferative) lupus nephritis - pathology

Answer 16

*LM: > 50% of glomeruli involvement
-segmental or global, active or chronic
-endocapillary or extracapillary proliferative lesions
-subendothelial deposits (during active phase)
-some mesangial changes may be present
-diffuse wire loop deposits +/- little glomerular proliferation
*IF: “full house”
*EM: subendothelial/mesangial deposits

Question 17

class IV (diffuse proliferative) lupus nephritis - treatment

Answer 17

*prednisone + cytotoxic agents (immunosuppression)
*despite effective immunosuppression, progressive scarring can still occur

Question 18

class V lupus nephritis - clinical findings

Answer 18

*aka membranous LN
*signs of NEPHROTIC SYNDROME
*microscopic hematuria + HTN may also be seen
*plasma Cr is usually normal or slightly elevated
*affects 10-20% of LN patients
*predisposed to thrombotic complications (renal vein thrombosis, pulmonary embolism)

Question 19

class V (membranous) lupus nephritis - pathology

Answer 19

*LM:
-segmental or global
-diffuse basement membrane thickening
-subendothelial deposits
*IF/EM: full house subepithelial immune deposits

Question 20

class V (membranous) lupus nephritis - treatment

Answer 20

*depends on degree of proteinuria and renal insufficiency
1. nonimmunosuppressive therapy (ACEi/ARB, HTN control)
2. immunosuppressives: prednisone +/- cytotoxic agents if proteinuria > 4g

Question 21

class VI (advanced sclerosing) lupus nephritis

Answer 21

*global sclerosis > 90% of glomeruli
*represents scarring or prior inflammatory injury as well as chronic class III, IV, V
*progressive renal dysfunction
*relatively bland urine sediment
*unlikely to respond to immunosuppressive therapy