Continuous B-cell Depletion in Nephrotic Syndrome: Latest on Rituximab

Tejas P. Desai, MD


February 27, 2019

FR, SD, and SR Nephrotic Syndrome: A Therapeutic Challenge

Nearly two decades into the 21st century and steroids remain the first-line agent for many glomerulonephritides. In particular, steroids continue to have a dominant therapeutic role in treating either minimal change disease or focal glomerulosclerosis.

For a sizable portion of patients, however, steroids are a disappointing solution to a significant problem. Patients who have a suboptimal response to steroids are conveniently grouped into one of three categories: frequently relapsing (FR), steroid-dependent (SD), or steroid resistant (SR).

In many of these challenging cases, calcineurin inhibitors are used as a second-line therapeutic, but the results are often underwhelming. Currently, rituximab is being studied as a potential savior to treat patients with challenging disease. As a B-cell-depleting agent, rituximab is often dosed when CD19 or CD20 cells reconstitute. This strategy creates an inconsistent dosing schedule that could result in disease relapse if B cells reconstitute earlier than expected.

In a small study, published in Clinical Kidney Journal, a nearly fixed frequency of rituximab was administered to FR, SD, or SR adult patients with either minimal change disease or focal glomerulosclerosis to determine treatment efficacy.[1]


Twenty patients from a single center in the United States were analyzed. After achieving a suboptimal result using steroids, these patients were exposed to two doses 1000 mg of rituximab each over a 2- to 4-week period. Physician discretion determined whether a patient continued with rituximab monotherapy or was exposed to both rituximab and a lower dose of an oral steroid. Each patient was scheduled to receive a fixed dose of rituximab every 4 months; those with earlier B-cell reconstitution were given rituximab every 3 months. After 2 years of therapy, the frequency of rituximab was changed to every 6 months. The outcomes calculated were complete or partial remission, based on proteinuria levels.


In this retrospective review, every patient achieved partial remission (defined as a 50% or more reduction in proteinuria and an absolute proteinuria value < 3.5 g/g). The sole frequently relapsing patient and the majority of steroid-dependent patients achieved complete remission. Nearly all of the steroid-resistant patients achieved only a partial remission at best.

Where Does This Study Leave Us?

While this study is extremely small and does not have a comparator arm, it raises two interesting points of discussion. The first is that in patients with suboptimal steroid responses, rituximab may have an important redeeming role. Of even greater value is to know whether rituximab has the required efficacy to displace calcineurin inhibitors in the hierarchy of treatment. Second, the magnitude and frequency of dosing might make administration easier and more likely to sustain a depleted B-cell response. By decreasing the likelihood of B-cell reconstitution, a fixed frequency of rituximab dosing could help patients avoid a relapse in disease.

For either of these points to have a realistic chance of being true, larger and better-designed studies are needed. In the interim, small, retrospective studies like these have a limited role in changing the course of care. Tell us what you think about this and similar studies in the comments section below.

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