LUPUS NEPHRITIS• Mrs G.G, 27 yr old female

• referred from Northdale Hosp & admitted on 29/1/02 to Greys Hosp via renal unit

• Presenting complaints : 1.Diarrhoea, vomiting 2.haematuria

3.swelling of feet and abdomen

• Past Medical History - seen at Derm Clinic(Greys) for eczematous rash since March 2001. Skin biopsy: feats of acute inflammatory ulcer involving the full thickness of the epidermis. Stains for fungi and

AFB were negative. Pt treated for eczema.

• GYNAE HX : Hyperemesis gravidarum in May 2000 Had NVDs in 1996 and 2000. No complications.

• SURG HX : Nil

• FAMILY HX : Nil of note

• SOCIAL HX : Works with computrs. Married with 2 children. No smoking or alcohol intake.

• DRUG HX : Emolient cream, Phenergan 10mg bd (Derm)

EXAMINATION

• Patient was comfortable and not in distress.

• Generalised mild swelling of body assoc with facial swelling. BP = PR =

• Pallour present No lymphadenopathy

• Chest : No resp distress. RR = 20/min. Mild bilatral crepitations auscultated at bases.

• CVS : JVP increased to 5cm. Heart sounds normal. No murmurs auscultated. Apex beat undisplaced.

• Abd : Mild ascites. Not tense. No organomegaly. Kidneys not ballotable

• CNS : GCS = 15/15. No focal signs.

SUMMARY

• 27 yr old female presenting with diarr, vomiting, and haematuria x 1 day with elevated urea and creatinine levels of

• Examination revealed generalised swelling of the face and body with ascites and crepitations of the chest - in keeping with hypervolaemia.

• Hypertension also present with findings of blood +++ in urine dipstix and protein?

INVESTIGATIONS• FBC: Hb = 8,4 Normochromic normocytic anaemia

WCC = 4,2 Plt = 99

• U and E : 136/ 4,5/ 104/ 17/ 32/ 730

• LFT : ALP = 120 Tot bili = 14 Tot prot = Albumin= ALT = Gamma GT =

• Cal = 2,10 Phos = 1,7 Mg = 0.8

• Specimens for complement screen, ANF, ANCA were taken and results were pending.

• 24 hr urine protein = 2g/l Red cell casts present.

• Renal biopsy - results pending

RADILOGICAL INVESTIGATIONS

• CXR : Globular shaped heart with bilateral pleural effusions and features of pulm oedema

• ULTRASOUND KIDNEYS : Dense kidneys bilaterally

• ECHO : Pericardial effusion present of about 9mm with no tamponade effect present.

DIFFERENTIAL DIAGNOSIS

• ACUTE RENAL FAILURE

• ? Rapidly progessive GN (RPGN) or Acute Nephritic Syn 1. Secondary glomerulopathy - Collagen vasc dx eg. SLE, Cryoglobulinaemia 2. Post Streptococcal GN 3. Ig A Nephropathy

INITIAL MANAGEMENT• IV LASIX 40MG BD, HAEMATINICS

.

• RESULTS 1. ANF - POSITIVE AT 1:3200 . ANTI HEP 2 CELLS POSITIVE . ANTI DNA AB NEG 2. COMPLEMENT C3 - 0.22 (L) . COMPLEMENT C4 - 0.05 (L) . COMPLEMENT FACTOR B - 0.27 3. RENAL BIOPSY - NON-REPRESENTATIVE SAMPLE.

• FINAL DIAGNOSIS : SLE NEPHRITIS IN ARF

• FOLLOW UP MX 1. SOLUMEDROL 1G IVI DAILY X 3/7 2. CYCLOPHOSPHAMIDE 750mg MONTHLY IVI 3. CONTINUED ON PREDNISONE 60mg DAILY 4. INH PROPHYLAXIS, TITRALAC, PREGAMEL, VIT C, LASIX IV

• 01/03/02 - DIALYSIS COMMENCED - STARTED RECEIVING HAEMODIALYSIS ABOUT 2-3 x / WEEK

LUPUS NEPHRITIS

HISTORY

- The term “lupus” is latin for wolf - used in the 18th century to describe a variety of skin conditions.

- In 1872, Kaposi described the systemic nature of lupus erythematosis.

- Descriptions of lupus nephropathy were initially repoted bt Keith and Rowntree in 1922.

• DEFINITION - SLE is a disease of unknown aetiology in which tissues and cells are damaged by pathogenic autoantibodies and immune complexes.

• EPIDEMIOLOGY - 90% of cases are in women - usually child-bearing age. - Children, men and elderly can be affected - Prevalence in the U.S varies from 15 to 50 per 100000 and is more common amongst blacks than whites. Asian and Hispanic populations are also susceptible.

CRITERIA FOR CLASSIFICATION OF SLE

• IF 4 OF THESE CRITERIA ARE PRESENT AT ANY TIME DURING THE COURSE OF THE DX, A DIAG OF SLE CAN BE MADE WITH 98% SPECIFICITY AND 97% SENSITIVITY 1. Malar rash 2. Discoid rash 3. Photosensitivity 4. Oral ulcers 5. Arthritis 6. Serositis 7. Renal disorder 8. Neurological disorder 9. Haematological disorder 10. Immunological disorder 11. Anti-nuclear Abs

• CLINICAL MANIFESTATIONS OF RENAL DX - Only one half have clinical nephritis defined by proteinuria. - Early in disease, most are asymptomatic, although some develop the oedema of nephrotic syndrome. - Urinanalysis shows haematuria, cylinduria and proteinuria - The revised criteria for the classification of SLE recognizes proteinuria of > 0.5g per 24hrs (or >3+ if quantitative evaluation is not done) or the presence of casts as evidence of renal disease. - In addition, the presence of haematuria (>5RBC/ high power field) and/or pyuria in the absence of infection, and the detection of an elevated serum creatinine has been recognized as evidence for clinical renal disease.

• PATHOGENESIS- The pathogenesis of lupus nephritis is thought to be similar to that of chronic immune complex glomerulonephritis. - The current paradigm for the pathogenesis of tissue injury in SLE including lupus nephropathy involves two linked components. - The first component involved production of autoantibodies and the deposition of pre-formed antibody-antigen complexes in situ. These complexes acivate the complement cascade and result in neutrophil ifiltration and activation. - The second component is characterized by cell proliferation, necrosis and thrombus formation secondary to factors released by infiltrating cells and platelets.

THE ROLE OF RENAL BIOPSY

• Clinical value is controversial

• Helps to direct management - in a subset of pts with circulating anti-coagulants, the renal pathology may be dominated by microvascular thrombosis. Corticosteroids may have adverse effects on these pts. - Value of renal biopsy is greater if obtained early in dx.

• CLASSIFICATION OF LUPUS NEPHRITIS 1. CLASS I - Renal biopsy reveals an essentially normal kidney by light, electron and immunofluorescence microscopy . - Patients usually do not have clinical disease. . 2. CLASS II - Class IIa - have minimal or no significant changes by light microscopy although there may be immunoflourescent evidence of immune deposits confined to the mesangium and/or dense deposits by EM. - Class IIb - shows definite glomerular mesangial hypercellularity by light microscopy, which is confined to the centrilobular regions away from the vascular pole. Clinically, these patients have mild to moderate evidence of renal involvement and in general have a good prognosis.

3. CLASS III - Focal segmental proliferative lupus nephritis with necrosis or sclerosis affecting fewer than 50% of glomeruli. - Up to one third of patients have nephrotic syndrome and glomerular filtration is impaired in 15-25%. . 4. CLASS IV - Characterized by diffuse proliferative GN. - Most glomeruli show cell proliferation often with crescent formation and sometimes nuclear debris represented by “haematoxylin” bodies. - By EM, the characteristic findings are subendothelial deposits and mesangial deposits. Sometimes, there may be sub-epithelial and intramembranous deposits. - Patients have a relatively severe clinical picture with nephrotic-range proteinuria and an active sediment. A high percentage progress to renal failure

•5. CLASS V - represented by diffuse membranous GN. - On Light microscopy, thickening of the GBM is evident. - EM reveals predominantly subepithelial deposits. - Most (90%) of pts present with a nephrotic syndrome but significant impairment of the GFR is unusual. . 6. CLASS VI - represents the end stages of proliferative lupus nephritis and is characterized by diffuse glomerulo-sclerosisand advanced tubulo-interstitial disease. - Patients are often hypertensive, may have nephrotic syndrome, and usually have impaired GFR.

• SILENT LUPUS NEPHRITIS- Although the renal lesion is mild in the majority of patients with clinically silent lupus nephritis, several reports have described severe proliferative GN in the absence of proteinuria or abnorm of urinary sediment. - Clinical Mx of these pts is uncertain.

• CLINICAL COURSE OF SLE IN ESRD AND AFTERTRANSPLANTATION - Several reports indicate that even though pts may have severe systemic dx and serological abnormalities at the time renal dx progresses to RF, within a few months clinical activity of non-renal SLE markedly decreases. - A reduction in systemic manifestations and lack of evidence of recurrent lupus nephritis have been characteristic features of lupus pts treadted with renal transplantation.

MANAGEMENT• Principle goals of therapy is to improve or prevent loss of

renal fxn and treatment must do the pt as little harm poss 1. Renal biopsy - if no contra-indications 2. Diet 3. Loop diuretics - to decrease oedema 4. Evaluate renal activity : urine sediment appearance, serum creatinine, creat clearance, BP, serum alb, 24hr urine prot, c3 complement, anti-DNA, urine dipstix. 5. Monitoring toxicity of steroids, diuretics and cytotoxic agents : FBC, K+, gluc, chol, LFTs. 6. Aggressive Rx of Hypertension 7. Discourage pregnancy - increased risk of renal failure 8. Antimalarials if have active skin dx.

TREATMENT• 1. GLUCOCORTICOIDS• 2. PULSE STEROID THERAPY• 3. CYTOTOXIC DRUGS• 4. PLASMAPHARESIS• 5. ANCROD• 6. TOTAL LYMPHOID IRRADIATION

• 7. IMMUNOTHERAPY

•• PROGNOSIS - poor indicators

-Nephrotic synd - Class IV lxes - High chronicity indices - HPT - Childhood onset of nephritis

FOLLOW UP OF PT

• Initially improved dramatically on Rx and haemodialysis

• Subsequently developed Nosocomial PseudomonasPneum sensitive to Ciprobay

• Developed Pulm TB - proven on sputum AFB in April

• Patient demised on 26/5/02

• REFERENCES1. Nephropathy of SLE - Hayslett, Kashgarian 2. Dubois Lupus Erythematosis 3. Harrisons Principles of Int Medicine