Lupus Nephritis

Abinash Yadav
Alisha Gurung
Om Sahani
 Introduction
• Lupus nephritis- one of the most serious
manifestations of  systemic lupus
erythematous (SLE)
• Systemic lupus erythematosus (SLE) is an
autoimmune disease in which organs, tissues, and
cells undergo damage mediated by tissue-binding
autoantibodies and immune complexes
• Approximately 10 to 30 % of patients with lupus
nephritis progress to end-stage renal disease
(ESRD)
 Epidemiology
• Around 90% of affected individuals are
women (F:M= 9:1)
• Peak Age at onset is between 20-40 years,
children with SLE have higher risk
• Mortality within 5 years of diagnosis is usually
due to organ failure or overwhelming sepsis
 Pathophysiology
• Deposition of circulating immune complexes
against cellular antigens particularly anti-dsDNA
in glomeruli.
• Complement cascade activation leading to:
– complement-mediated damage
– leukocyte infiltration
– release of various cytokines
 Pathophysiology
Other pathogenic mechanisms:
– Infarction of glomerular segments
– Thrombotic microangiopathy
– Vasculitis
– Glomerular sclerosis

• Humoral response are main effective mediators, IgE autoantibodies,

basophils and type 2 helper cells are involved

• IgE containing immune complex trigger circulating basophils get

into secondary lymphoid organs activated basophils secret IL-4
TH2 cell differentiation B-cell differentiation production of auto
reactive antibodies.
 Classification of Lupus Nephritis
(International Society of Nephrology and
Renal Pathology Society)
• Class I- Minimal mesangial lupus nephritis
• Class II- Mesangial proliferative lupus nephritis
• Class III- Focal lupus nephritis
• Class IV- Diffuse lupus nephritis
• Class V- Membranous lupus nephritis
• Class VI- Advanced sclerotic lupus nephritis
 Classifications
1. Minimal mesangial lupus nephritis
– Normal glomeruli  on light microscopy
– Minimal mesangial immune deposits  immuno-
fluorescent or electron microscopy
– Asymptomatic

2. Mesangial proliferative lupus nephritis

– With Mesangial hyper-cellularity and matrix expansion
– Clinically mild renal disease
 Classifications
3. Focal lupus nephritis
– Involving <50% of all glomeruli
– Sub-epithelial immune deposits seen
– Clinically: haematuria, proteinuria
– 10-20% of all LN

4. Diffuse lupus nephritis

– Involving >50% of all glomeruli
– Segmental and global lesions
– Subendothelial immune deposits present
– Clinically progression to: Nephrotic syndrome, HTN, Renal
insufficiency
– Most common and severe form of LN
 Classifications
5. Membranous lupus nephritis
– Affects 10-20% of patients
– Can occur in combination with class III or IV lesions
– Good prognosis

6. Advanced sclerotic lupus nephritis

– >90% of glomeruli globally sclerosed without residual activity
– Represents advanced stages of the above
– Immunosuppressive therapy is unlikely to help as it is inactive
– Progressive CKD
 Clinical manifestations
• Symptoms of active SLE: including arthralgia,
fatigue, fever, malar rash, oral or nasal ulcers,
arthritis, serositis, or central nervous system
disease
• Hypertension (headache, dizziness, visual
disturbances)
• Peripheral edema
• Pleural and pericardial effusions
• Ascites
• Proteinuria
 Investigations
• Subclinical renal involvement, with low-level haematuria
and proteinuria but minimally impaired or normal renal
function, is common in SLE

• Evaluating renal function in patients with SLE is important

because early detection and treatment can significantly
improve renal outcome

• Renal biopsy should be considered in any patient with SLE

who has clinical or laboratory evidence of active nephritis
 Investigations
• Full blood count,
• Blood urea nitrogen (BUN) testing
• Serum creatinine assessment
• Urinalysis (to check for protein, red blood cells , and
cellular casts): proteinuria, dysmorphic RBCs and RBC
casts
• A 24-hour urine test for creatinine clearance and protein
excretion
• Autoantibodies and serum complement C3 and C4 levels:
ANA, Anti ds DNA Ab & hypo complementemia
• Renal biopsy & Immunofluroscence +ve for IgG, IgA,
IgM,C1q,C3&C4
 Management
Medications used to treat SLE manifestations include
the following:
• Biologic DMARDs (disease-modifying antirheumatic
drugs): Belimumab, rituximab, IV immune globulin
• Nonbiologic DMARDS: Cyclophosphamide,
methotrexate, azathioprine, mycophenolate,
cyclosporine
• Nonsteroidal anti-inflammatory drugs (NSAIDS; eg,
ibuprofen, naproxen)
• Corticosteroids (eg, methylprednisolone, prednisone)
• Antimalarials (eg, hydroxychloroquine)
 Management
• Initial treatment depends on clinical presentation but Hypertension
and oedema should always be treated
• Definite histopathological diagnosis required (Renal biopsy)
• Type I requires no treatment
• Type II usually runs a benign course but some are treated with
steroids
• A number of clinical trials with immunosuppressive agents have
been trialed in types III, IV and V (most severe forms)
• Steroids and high dose IV cyclophosphamide or mycophenolate
mofetil (MMF) usually used for induction
• Mycophenolate mofetil and azathioprine for maintenance therapy
• B cell depletion with rituximab (anti-CD20) shown to be effective
 Management
• Class II lupus nephritis may require treatment if
proteinuria is greater than 1000 mg/day
– Predniosolone (20-40 mg/day) for 1-3 months with
subsequent tapering

• Class III and IV

– Prednisone 1 mg/kg/day for at least 4 weeks
– Taper it gradually to a daily maintenance dose of 5-
10 mg/day for approximately 2 years
 Management
Class V
• Prednisolone for 1-3 months, tapering for 1-2
years if response occurs

ESRD
• Hemodialysis
• Renal transplantation
 Prognosis
• Treatment leading to normalization of
proteinuria, HTN and renal dysfunction
indicates good prognosis

• Prognosis better in patient with types I, II and V

Lupus nephritis

• Glomerulosclerosis (type VI) predicts end-stage

renal disease
 References
• Harrison’s Principle of Internal Medicine, 19 th
edition
• Davidson’s principle and practice of medicine,
22nd edition
• Kumar and Clark's clinical medicine, 8th edition
Thank You