1. OBJECTIVES NOT TO BE A NEPHROLOGIST
TO UNDERSTAND LUPUS NEPHRITIS AS A PRIMARY CARE PHYSICIAN .

2. 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

3. GLOMERULAR DISEASE NEPHRITIC Heavy protienuria (>3.5gm/day)
FOCAL NEPHRITIC
DIFFUSE NEPHRITIC
NEPHROTIC
Heavy protienuria (>3.5gm/day)
Lipiduria
Edema
Hyperlipidemia

4. FOCAL NEPHRITIC
DIFFUSE NEPHRITIC
URINALYSIS
Red cells ( usually dysmorphic )
Red cell cast
Mild proteinuria (<1.5gm /day)
Findings of more severe disease are usually absent
URINALYSIS
Similar to focal disease but heavy proteinuria (which may be in nephrotic range)
Edema
Hypertension
+ Renal Insufficiency

6. Why Dr Reed’s Top Differential was Lupus ?

7. Development of 4 of the 11 criteria over a lifetime gives 96% sensitivity and specificity for sle .

9. Why did he order anti-dsDNA and anti-SM antibody?
What is the role of complement level in lupus nephritis?

10. 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.

11. 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
COURSE OF LUPUS NEPHRITIS EXTREMELY VARIED

12. SO IF A PATIENT HAS POSITIVE SEROLOGIC MARKERS FOR LUPUS WHICH CORRELATE WITH CLINICAL FINDINGS DO THEY STILL NEED A RENAL BIOPSY ? AND WHY?

14. 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)

15.   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) .

16. Indications and contraindications of Renal Biopsy
Persistent proteinuria (especially if >3.5gm/24hrs) not due to diabetes.
Persistent glomerular hematuria(especially if accompained by RBC cast)
Unexplained acute renal failure

17. 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

18. 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%).

19. Treatment of Lupus Nephritis
IMMUNOSUPPRESIVE THERAPY:
Cyclophosphamide
PREDNISONE
 Mycophenolate mofetil (MMF)
Other Drugs
Azathioprine
Cyclosporine
Rituximab

20. 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

21.  Mycophenolate  mofetil (MMF)
It is substantially more expensive then other drugs
Cytopenias: cbc first 2 weeks then every 6 weeks
Association with developing CNS lymphoma.
Antacids and Iron Supplements decrease absorption of MMF

22. AZATHIOPRINE :
Bone Marrow Suppression
Infection
Malignancy