Lupus Nephritis

Definition
• Lupus nephritis is histologically evident in most
patients with SLE.
• Systemic lupus erythematosus is an
autoimmune disease in which organs and cells
undergo damage initially mediated by tissue
binding autoantibodies and immune
complexes.
• One of the most serious manifestations of SLE.
• Usually arises within 5 years of diagnosis.
 Epidemiology
• It usually found in more than 30% of
patients who are diagnosed with SLE.
• LES can be found at any age, but most often at
the age of 15-45 years and 90% of sufferers
are women
• The incidence ratio of LES in women
compared to men increases with age, with a
ratio of 2: 1 in children and 9: 1 in young
adults
 Etiology
• Lupus nephritis is a common manifestation of
SLE
• There are multiple susceptibility factors, which
result in abnormal immune responses, which
vary among different patients.
These factors include:
• Genetic factors
• Immunologic factors
• Environmental factors
Genetic predisposition plays an important role in the development of both
SLE and lupus nephritis. Multiple genes, many of which are not yet identified,
mediate this genetic predisposition [Human leukocyte antigen (HLA) class II
genes, Complement genes, FcγR genes and others]
IMMUNOLOGIC FACTORS
Patients with SLE have poor clearance mechanisms for cellular debris. Nuclear
debris from apoptotic cells induces plasmacytoid dendritic cells to produce
interferon-α, which is a potent inducer of the immune system and
autoimmunity.
• Autoreactive B lymphocytes, which are normally inactive, become active
in SLE because of a malfunction of normal homeostatic mechanisms,
resulting in escape from tolerance. This leads to the production of
autoantibodies.
• Anti-dsDNA antibodies, develop through a process of epitope
spreading.
ENVIRONMENTAL FACTOR
• UV light
• EBV
• Smoking
• Alcohol
• Silica dust
 Pathofisiollogy

Autoimmunity plays a major role in the

pathogenesis of lupus nephritis.
 Autoantibodies

Form pathogenic immune Bind to antigens already

complexes intravascularly located in the glomerular
basement membrane

Immune complexes Immune complexes in situ

deposited in glomeruli

Activating complement and attracting inflammatory cells, including

lymphocytes, macrophages, and neutrophils

Promote an inflammatory
response

The histologic type of lupus nephritis that develops depends on

numerous factors, including the antigen specificity and other
properties of the autoantibodies and the type of inflammatory
response that is determined by other host factors.
 Clinical symptoms
1. Asymptomatic
2. Symptoms of active systemic lupus erythematosus (SLE), including fatigue,
fever, rash, arthritis, serositis, or central nervous system (CNS) disease.
3. Symptoms related to active nephritis may include peripheral edema secondary
to hypertension or hypoalbuminemia.
4. Other symptoms directly related to hypertension that are commonly associated
with diffuse lupus nephritis include headache, dizziness, visual disturbances, and
signs of cardiac decompensation.
5. Focal and diffuse lupus nephritis: evidence of generalized active SLE with the
presence of a rash, oral or nasal ulcers, synovitis, or serositis. Signs of active
nephritis are also common.
6. Active lupus nephritis: hypertension, peripheral edema, and, occasionally, cardiac
decompensation.
7. Membranous lupus nephritis: signs of an isolated nephrotic syndrome are
common. These include peripheral edema, ascites, and pleural and pericardial
effusions without hypertension.
 Investigations

Evaluating renal function

• To detect any renal involvement early.

Renal biopsy
• Classification is based on light microscopy,
immunofluorescence, and electron microscopy
findings from renal biopsy specimens.
 Features %
Proteinuria 100
Miroscopic hematuria 80
Tubular abnormalities 60-80
Reduced renal function 40-80
Nephrotic syndrome 45-65
Granular casts 30
Rapidly declining renal function 30
Hypertension 15-50
Hyperkalemia 15
Macroscopic hematuria 1-2
Acute renal failure 1-2
International Society of Nephrology/Renal Pathology Society 2003 classification
of LN
Class I Minimal mesangial LN
Class II Mesangial proliferative LN
Class III Focal LN (50% of glomeruli)
III (A): active lesions
III (A/C): active and chronic lesions
III (C): chronic lesions
Class IV Diffuse LN (50% glomeruli)
Diffuse segmental (IV-S) or global (IV-G)
LN
IV (A): active lesions
IV (A/C): active and chronic lesions
IV (C): chronic lesions
Class V Membranous LN
Class VI Advanced sclerosing LN (90% globally
sclerosed glomeruli without residual
activity)
 Treatment
The principal goal of therapy in lupus nephritis is to normalize
renal function or, at least, to prevent the progressive loss of renal
function. Therapy differs depending on the pathologic lesion. It is
important to treat extrarenal manifestations and other variables
that may affect the kidneys.

• Adjunctive Treatments
• Primary disease management by immunosuppressive agents
• Induction Therapy
• Maintenance Therapy
• Lifestyle Changes
 ADJUNCTIVE TREATMENTS
Drugs
Hydroxychloroquine
[Max 6–6.5 mg/kg body weight]
ACEi/ARBs
Antihypertensive
Statin therapy
Calcium supplementation
Cause
All SLE patients with; unless there is a
contraindication:
• Lower rates of Flare
• Reduced renal damage
• Less clotting events
Patients with proteinuria >0.5 gm/day
• Reduces proteinuria by 30%, and
• Significantly delays doubling of serum
creatinine
• Delays progression to ESRD
Target of ≤130/80 mmHg
• Significant delay in progression of
renal disease
Patients with LDL >100 mg/dl
• As GFR<60ml/min/1.73m2 & SLE itself
accelerated atherosclerosis
Prevent osteoporosis if the patient is on
long-term corticosteroid therapy