Minimizing Glucocorticoid Administration in Patients With Proliferative Lupus Nephritis

After an initial screening phase during which a first kidney biopsy is performed, all patients that meet the inclusion criteria will be randomized to one of the treatment arms:

• EUROLUPUS regimen: 3 daily pulses of 750 mg of intravenous Methylprednisolone, followed by oral corticosteroid therapy starting with a dose of 0.5 mg / kg / day for 4 weeks, then decreased by 2.5 mg of Prednisolone / day each 2 weeks. A low dose of glucocorticoid (5-7.5 mg / day) is maintained until 24 months after enrollment. All patients will receive Cyclophosphamide intravenously starting day 1, 6 pulses at a fixed dose of 500 mg given at 2 weeks. After 3 months, Azathioprine (2 mg / kg / day) is initiated 2 weeks after the last administration of Cyclophosphamide and maintained for the next 21 months.
• RITUXILUP regimen: 2 doses of Rituximab 1 g and Methylprednisolone 500 mg on days 1 and 15. Patients will receive Mycophenolate Mofetil, initially 500 mg twice daily, titrated to a maximum of 1.5 g twice daily, depending on leukocyte count and digestive tolerance, which will be maintained 24 months.

Second kidney biopsy will be performed 6 months after the start of the treatment phase.

Inclusion criteria

• Age of the patient between 18 and 80 years,
• Patients diagnosed with systemic lupus erythematosus according to ACR 1997 or SLICC-2012 criteria
• Diagnosis of proliferative lupus nephritis class III, IV +/- V (confirmed by renal biopsy and classified according to ISN / RPS);
• Estimated glomerular filtration rate by CKD-EPI> 30 ml / min / 1.73 sqm
• Estimated glomerular filtration rate by CKD-EPI <30 ml / min / 1.73 sqm but> 15 ml / min / 1.73 sqm with chronicity index (according to NIH score) <6
• Absence of contraindications to the use of Methylprednisolone, Mycophenolate mofetil, oral corticosteroids or Rituximab
• Ability to provide informed consent

Exclusion criteria

• The patient's age under 18 years
• Patients with life-threatening complications (e.g. Cerebritis)
• Estimated glomerular filtration rate by CKD-EPI <30 ml / min / 1.73 sqm
• Estimated glomerular filtration rate by CKD-EPI <30 ml / min / 1.73 sqm but> 15 ml / min / 1.73 sqm with chronicity index (according to NIH score)> 6
• Presence of pregnancy / lactation
• Patients who have received more than 2 g of Methylprednisolone intravenously in the last 4 weeks
• Use in the last 3 months of biological therapy
• Use of intravenous immunoglobulins / plasmapheresis in the last 6 months
• The presence of an active infection
• History of neoplasia
• Comorbidities requiring systemic corticosteroid therapy
• Non-adhesion