OBJECTIVES

• NOT TO BE A NEPHROLOGIST

• TO UNDERSTAND LUPUS NEPHRITIS AS A PRIMARY CARE PHYSICIAN .

OBJECTIVES

• Define nephrotic syndrome and glomerulonephritis

• Identify the Diagnostic criteria for SLE • Antibodies markers in SLE• Prognostic markers in SLE• Classification of lupus nephritis • Indications and contraindications of renal biopsy• Common side effects of medicine used in lupus

nephritis

GLOMERULAR DISEASE

NEPHRITIC

FOCAL NEPHRITIC

DIFFUSE NEPHRITIC

NEPHROTIC Heavy protienuria (>3.5gm/day)

LipiduriaEdema

Hyperlipidemia

FOCAL NEPHRITIC

• URINALYSIS Red cells ( usually

dysmorphic ) Red cell cast Mild proteinuria (<1.5gm

/day)• Findings of more severe

disease are usually absent

DIFFUSE NEPHRITIC

• URINALYSIS Similar to focal disease but

heavy proteinuria (which may be in nephrotic range)

Edema Hypertension + Renal Insufficiency

Why Dr Reed’s Top Differential was Lupus ?

Why did he order anti-dsDNA and anti-SM antibody?

What is the role of complement level in lupus nephritis?

Serologic test

• ANA's are a highly sensitive screen for SLE, being found in more than 90% of untreated patients, but they are not specific for SLE.

• anti-dsDNA are a more specific but less sensitive marker of SLE and are found in almost three fourths of untreated patients with active SLE(97% specificity).

• Titers of anti-dsDNA antibodies often fluctuate with disease activity.

• Anti-Sm antibodies, although very specific for SLE are found in only about 25% of lupus patients.

MONITORING CLINICAL DISEASE

• There is controversy regarding the value of a declining C3 and C4 level and a rising anti-DNA antibody titer in predicting a clinical flare of SLE or active renal disease.clearly these are the most widely used serologic tests to monitor SLE activity.

• Nonspecific:ESR /CRP

• SO IF A PATIENT HAS POSITIVE SEROLOGIC MARKERS FOR LUPUS WHICH CORRELATE

WITH CLINICAL FINDINGS DO THEY STILL NEED A RENAL BIOPSY ? AND WHY?

CLASSIFICATION OF LUPUS NEPHRITIS

• 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 )• CLASSVI (Advanced sclerosing lupus nephritis)

International Society of Nephrology/Renal Pathology Society (2003) Classification of Lupus Nephritis

• 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% of glomeruli) Diffuse segmental (IV-S) or global (IV-γ) 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) .

Indications and contraindications of Renal Biopsy

• INDICATIONS: Persistent proteinuria (especially if >3.5gm/24hrs) not due to

diabetes. Persistent glomerular hematuria(especially if accompained by

RBC cast) Unexplained acute renal failure

RENAL BIOPSY

• CONTRAINDICATIONS: Coagulation Disorders Thrombocytopenia Uremic Platelet Dysfunction(relative contraindication) Uncontrolled hypertension(relative risk, maintain B.P<140/90) Solitary Kidney (open biopsy is procedure of choice) Advanced age and Pregnancy are NOT a contraindication

RENAL BIOPSY

• COMPLICATIONS:Intrarenal Renal and perinephric

Hematomas(60-80%)Bleeding causing hypotension(1-2%),requiring

transfusion (6%)AV fistula (4-18%)Perirenal Soft Tissue Infection(0.2%).

Treatment of Lupus Nephritis

• IMMUNOSUPPRESIVE THERAPY:

Cyclophosphamide

PREDNISONE

Mycophenolate mofetil (MMF)

Other Drugs Azathioprine Cyclosporine Rituximab

Side effects of medication .

• Cyclophosphamide: Pancytopenia (to check cbc every two weeks) Predispose to infection by bonemarrow depression Premature amenorrhea,Permanent infertility Increases the risk of malignancy Bladder toxicity Hyponatremia due to SIADH

• Mycophenolate mofetil (MMF)It is substantially more expensive then other

drugsCytopenias: cbc first 2 weeks then every 6

weeksAssociation with developing CNS lymphoma.Antacids and Iron Supplements decrease

absorption of MMF

• AZATHIOPRINE :• Bone Marrow Suppression • Infection• Malignancy