Case 1: A 27-year-old female with lupus nephritis

A 27-year-old Caucasian female was diagnosed with systemic lupus erythematosus (SLE) in 2016 based on arthralgias, high fever, malar rash, leukopenia, anemia, ANA, anti-SM, anti-RNP, anti-dsDNA, and anti-C1q positivity. Renal function and urinalysis were normal. She was treated with prednisone 8 mg/day, hydroxychloroquine 300 mg/day and mycophenolate mofetil (MMF) 1.5 g/day.

In April 2018, urinalysis showed proteinuria 1.1 g/day and active urinary sediment with dysmorphic erythrocytes and erythrocyte casts, and normal renal function.

The patient underwent kidney biopsy. Despite the mild renal lab’ alterations, kidney biopsy showed a severe intra- and extra-capillary glomerulonephritis Class IV ISN/RPS with an activity index of 15 and chronicity index of 1. Due to the severity of the histology, cyclophosphamide was suggested, but the patient refused and was treated with the methylprednisolone pulses and rituximab 2 g 15 days apart, and MMF at higher dose than originally prescribed. Twelve months later urinary manifestations were clearly improved, however, to prove that also histological lesions had also improved, a second kidney biopsy was performed. The second biopsy revealed the persistence of active lesions though of lesser severity compared to previous biopsy but an increase in the chronicity index. Based on this result, immunosuppressive therapy was strengthened.

Learning Objectives

• Describe the discrepancies between clinical and histological data

• Explain the importance of kidney biopsy and of activity and chronicity indexes particularly in cases of mild clinical renal presentation.

• Explain why the approach to lupus nephritis cannot be standardised

• Describe the new therapeutic approaches of lupus nephritis

• Explain of the importance of repeated kidney biopsy to evaluate the response to therapy

Learning Objectives Case 2: A 28-year-old pregnant Caucasian woman

This is the case of a 28-year-old Caucasian woman at her second pregnancy. The patient experienced a deep venous thrombosis in the lower limbs at 19 years and a miscarriage at 26 years. ANA:1/160 was found during an immunological screening performed after the miscarriage.

At the 32nd week of the second pregnancy the patient developed arterial hypertension, severe proteinuria and 15 kg body weight increase. Preeclampsia was diagnosed, C-section was performed, giving birth to a 2.45 kg male child.

Six months later proteinuria persisted and reached nephrotic range (proteinuria 8 g/24 h, serum protein 5.1 g/dl, albumin 2.8 g/dl). Renal function was normal and urinary sediment showed only lipid casts and fat oval bodies. Immunological screening confirmed ANA positivity 1/160 only. A kidney biopsy allowed the diagnosis of membranous lupus nephropathy due to the presence of mesangial proliferation at light microscopy, ‘full house’ immune deposits at immunofluorescence and presence of fingerprints in endothelial cells at electron microscopy.

The patient was treated with three methylprednisolone pulses of 0.5 g/each followed by prednisone 0.5 mg/kg/day and mycophenolate mofetil (MMF) 2 g/day, hydroxychloroquine 200 mg/day and ACE-inhibitors. MMF was increased at 2.5 g/day after 3 months due to persistent nephrotic syndrome.

Six months later, due to the persistence of nephrotic syndrome, tacrolimus 4 mg/day was added and MMF reduced to 1.5 g/day.

Learning Objectives

• Explain that membranous lupus nephritis can be the first and the only manifestations of lupus nephritis

• Describe the importance of kidney biopsy in the differential diagnosis between idiopathic and lupus membranous nephropathy

• Describe the treatment of membranous lupus nephritis based on the international recommendations and on the results of the randomized studies

• Explain why the approach to lupus nephritis cannot be standardised

• Discuss the therapeutical approaches for resistant cases of lupus nephritis, particularly severe proteinuria