A significant proportion of patients with systemic lupus erythematosus develop renal disease, which has a major impact on the course of the disease. In 2012, the European League Against Rheumatism (EULAR) and European Renal Association–European Dialysis and Transplant Association (ERA-EDTA) developed joint recommendations for the management of lupus nephritis (LN), involving a multidisciplinary panel of physicians. Because of the emergence of new data since the original publication, the objective was to update the 2012 EULAR/ERA-EDTA recommendations for the management of LN, again with the participation of physicians from different disciplines, as well as nurses and patient representatives.
To this end, the standardised operating procedures for the publication of EULAR-endorsed treatment recommendations were followed. Expert meeting and application of Delphi-based methodology led to 15 questions for the systematic literature review, which covered essentially all aspects of LN; the systematic literature review was undertaken by three fellows.
The main recommendations are as follows:1 therapy in LN should aim for a complete renal response (proteinuria <0.5–0.7 g/24hours with [near-]normal glomerular filtration rate) by 12 months, although this time point can be extended in patients with significant, nephrotic-range proteinuria at baseline. Hydroxychloroquine is recommended in all patients, at a dose not exceeding 5 mg/kg/day, with regular ophthalmological monitoring. In active proliferative LN, initial treatment with mycophenolate mofetil ([MMF] 2–3 g/day, or mycophenolic acid at equivalent dose) or low-dose intravenous cyclophosphamide (500 mg x6 biweekly doses), both combined with glucocorticoids (pulses of intravenous methylprednisolone, then oral prednisone 0.3-0.5 mg/kg/day) is recommended. Alternative choices include either combination of MMF with a calcineurin inhibitor (especially tacrolimus) or high-dose cyclophosphamide, for patients with nephrotic-range proteinuria or prognostic factors for adverse long-term outcome at baseline, respectively. Subsequent, maintenance treatment with MMF or azathioprine should follow for the long-term, with glucocorticoid use minimised to the lowest possible dose (<7.5 mg/day prednisone equivalent). The choice between MMF and azathioprine will depend on the initial regimen and potential plans for pregnancy. In patients who do not respond to the recommended therapy, a switch to an alternative induction regimen or rituximab are recommended. In Class V LN, immunosuppressive therapy is indicated from the beginning in patients with nephrotic-range proteinuria or patients in whom proteinuria remains >1 g/24hours despite renin–angiotensin–aldosterone blockade; in these circumstances, MMF in combination with glucocorticoids is preferred as first choice. A repeat kidney biopsy should be considered in cases of incomplete response or nephritic flares. Belimumab may be considered as add-on treatment, in order to facilitate glucocorticoid sparing, control extra-renal lupus activity, and decrease the risk for flares. In end-stage renal disease, transplantation is the preferred kidney replacement option because of its better graft- and patient-survival rates. Relapse of LN in the transplanted kidney is rarely clinically significant.
In conclusion, the 2019 updated EULAR/ERA-EDTA recommendations serve as a guideline to inform rheumatologists, nephrologists, patient organisations, and regulators about the treatment of LN based on combined evidenced-based and expert opinion.