Primary FSGS with Nephrotic Syndrome — What to Do When Calcineurin Inhibitor Therapy Has Not Achieved Remission

Adults with steroid-resistant primary FSGS and nephrotic syndrome face a challenging clinical situation when a calcineurin inhibitor course — the standard second-line approach — fails to produce the expected reduction in proteinuria and remission. This protocol addresses that specific next step.

Clinical scenario

Adults with primary FSGS presenting with nephrotic syndrome, without relative contraindications or intolerance to glucocorticoids, in whom progression to calcineurin inhibitor therapy was required but has not yielded adequate response.

Previous treatment — failure condition triggering this protocol

This protocol is indicated after calcineurin inhibitor therapy (cyclosporine or tacrolimus, continued for at least 6 months) has not achieved the primary goals of remission and reduction of proteinuria. Because remissions under calcineurin inhibitors may emerge slowly — sometimes taking up to 4–6 months — this failure threshold accounts for adequate treatment duration before escalation is warranted.

Next-step approach (partial overview)

Adults with steroid-resistant primary FSGS who have not responded to, or cannot tolerate, calcineurin inhibitors should be considered for referral to a specialised nephrology centre — where rebiopsy, enrolment in a clinical trial, or consideration of an alternative treatment approach becomes available. A specific combination treatment option exists for patients in whom all other therapeutic avenues have been exhausted — the full structured regimen is accessible via the link below.

Instant Access to Structured Evidence-Based Regimens

References

We recommend that high-dose oral glucocorticoids be used as the first-line immunosuppressive treatment for primary FSGS (1D).

In adults with relative contraindications or intolerance to glucocorticoids, alternative immunosuppression with CNIs should be considered as the initial therapy in patients with primary FSGS (Figure 54).

Adults who have steroid-resistant primary FSGS with resistance to or intolerance of CNIs should be referred to specialized centers for consideration of rebiopsy, alternative treatment, or enrollment in a clinical trial (Figure 55).

In considering these issues, the KDIGO 2021 Work Group agreed that it would be more appropriate to remove the use of MMF and high-dose dexamethasone as a clinical recommendation and consider this as an alternative treatment possibility when other therapeutic options have failed.

View source ↗