Case 1: 27-year-old female with a 5-year history of SLE Richard Furie

A 27-year-old female with a 5-year history of systemic lupus erythematosus (SLE) was admitted to the hospital because of confusion and fever. Past manifestations of SLE included polyarthritis, rash, recurrent episodes of pericarditis, and anaemia (but no nephritis). A flare 2 months prior to admission, consisting of pericarditis, fever, hypocomplementaemia, and a 2-fold rise in anti-DNA antibodies, was successfully treated with prednisone 40 mg/day; prednisone was subsequently tapered. At the time of admission, medicines included hydroxychloroquine 400 mg/day, prednisone 15 mg/day, calcium, and a vitamin.

The patient was given broad-spectrum antibiotics for the treatment of sepsis and/or bacterial meningitis. Methylprednisolone 60 mg/day was also administered. However, the patient’s mental status worsened, and she became comatose. All cultures were sterile. Her creatinine, which was 0.6 mg/dL at baseline, rose 3-fold.

The impression was that of a flare of SLE complicated by anaemia, thrombocytopaenia, nephritis and CNS disease. ‘Pulse’ steroids were administered for 3 days without subsequent improvement. Intravenous gamma-globulin failed to improve the thrombocytopenia, and her creatinine continued to rise.

Discussion points

• Diagnosis and treatment of thrombotic microangiopathy (TMA)

• Proposed modifications to the classification of lupus nephritis

Learning objectives

• Describe the clinical presentation of TMA

• Discuss treatment options of TMA

• Review proposed modifications to the classification of lupus nephritis

Case 2: 16-year-old male with active SLE, trace protein and hematuria Dimitrios Boumpas

A 16-year-old male (60 kg) presents with active SLE (SLEDAI 10). He has active serology with low C3 and C4, anti-DNA is positive at low titer. Normal Cr, albumin and HCT. Urinalysis shows trace protein (300 mg/dL) with 510 RBCs in the urine. He was treated with hydroxychloroquine and prednisone 20 mg/day and was referred to you 4 weeks later. His SLEDAI is now 4 (rash, serology) and urinalysis shows trace protein and hematuria.

Discussion points

• Identify patients at higher risk to develop nephritis and look for renal disease -especially when active- by urinalysis

• Do not underestimate hematuria-especially if active serology and extrarenal lupus. Best to do a biopsy irrespective of the presence or not of proteinuria

• Have a low threshold for renal biopsy. If you think about it, just do it (unless contraindicated)

• Look for crescents/fibrinoid necrosis and tubular atrophy and interstitial fibrosis in the biopsy report

• Stratify according to severity (histologic and clinical factors) and treat accordingly. For most patients mycophenolate mofetil (MMF) is the drug for initial choice based upon its lack of gonadal toxicity

• In patients with chronic disease and scaring in the kidney, or those with nephrotic range proteinuria, may need to wait longer for proteinuria to subside

• Proteinuria is a good prognostic factor (if below 0.7 mg/dl) irrespective of hematuria

• Hematuria/active urine sediment are reliable indicators for activity and flare but not for prognosis

Case 3: 25-year-old woman with arthritis, photosensitive rashes, leukopenia and thrombocytopenia and positive lupus serologies A 25-year-old woman presents with arthritis, photosensitive rashes, leukopenia and thrombocytopenia and positive lupus serologies. Her proteinuria is 1.3 gm/day and she has hematuria, normal serum creatinine and albumin 3.2g/day. Renal biopsy showed focal proliferative lupus nephritis (Class IIIa with AI 7 and CI 0). She was treated with MMF and then with azathioprine because of contemplation of pregnancy reaching remission. Two years later she has nephrotic range proteinuria, increased creatinine to 1.4 mg/dl, and a biopsy consistent with pure membranous lupus nephropathy. No chronicity.

Discussion points

• Membranous nephropathy has a more benign course. Histologic transition may be observed

• Patients with nephrotic range proteinuria and impaired renal function are at greater risk for end stage renal disease and require more aggressive therapy

• Anticoagulant treatment in cases of nephrotic syndrome with serum albumin <20 g/L, presence of antiphospholipid antibodies or other pro-thrombotic conditions

Learning objectives

• Recognise, document and treat renal disease in SLE

• Explain how membranous disease differs from proliferative disease?

• Describe the targets of therapy

• Describe treatment of refractory disease