The multifaceted aspects of refractory lupus nephritis

Abstract

The term refractory lupus nephritis is generally used to indicate cases that do not respond to traditional treatment. However, the clinical presentation of lupus nephritis is variable and the time to response depends on the typology of the underlying renal syndrome. The criteria and the time for response are different in lupus patients with nephritic flares, in those with nephrotic syndrome, and in those with asymptomatic renal disease. In this paper, we will focus on the clinical characteristics, the consequences, and the possible therapeutic approaches for patients with different forms of refractory lupus nephritis, defined on the basis of renal syndrome at presentation.

Keywords:

• lupus nephritis
• nephritic flares
• nephrotic syndrome
• refractory nephritis
• systemic lupus erythematosus

Financial & competing interests disclosure

In the last 2 years, C Ponticelli has received honoraria from Janssen Cilag, Novartis and Astellas. The authors have no other relevant affiliations or financial involvement with organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Lupus nephritis may be associated with a high rate of morbidity and mortality. Its clinical course is characterized by a period of quiescence alternated with flares of exacerbation.

• The current treatment of lupus nephritis rests on an aggressive induction treatment aimed to achieve remission, followed by a maintenance therapy aimed to prevent flares and silent progression of renal disease.

• Although there is no formal definition of refractory lupus nephritis, this term is usually employed to define cases not responding to standard treatment. However, the time of response should be included in the definition, since it can be variable in the different clinical setting of lupus nephritis.

• When refractory lupus nephritis is identified, reinforcement of treatment is recommended in order to prevent irreversible progression of the disease or severe extra-renal complications.

• Based on the available data, rituximab seems to be the best therapeutic options for treating refractory nephritic flares. Tacrolimus or cyclosporine, alone or in association with mycophenolate salts, may be suggested for patients with resistant nephrotic syndrome and for those with normal or subnormal renal function.

• Poor response to treatment is a risk factor for flares and renal function deterioration. Timely diagnosis of refractory form is of paramount importance as a delay in the intervention is associated with a poor outcome, while an early and an unnecessary increase in the immunosuppressive therapy causes increased morbidity.