Triple Immunosuppression helps decrease proteinuria in lupus nephritis

In individuals with lupus nephritis (LN) whose proteinuria didn't reply satisfactorily to usual treatment, triple immunosuppression with tacrolimus (TAC) in addition to mycophenolate and prednisolone (PRED) resulted in additional proteinuria decrease and prolonged disease quiescence, says an article published in Kidney International Reports.

The addition of a calcineurin inhibitor (CNI) to corticosteroids and mycophenolate boosted the renal response rate in lupus nephritis due to a reduction in proteinuria, although there is minimal long-term effectiveness and safety evidence on this triple immunosuppressive regimen.

In this study Desmond Y.H. Yap and team examined the outcomes of 22 patients with LN who received TAC titrated according to therapeutic drug monitoring (TDM) after proteinuria did not respond effectively to therapy with PRED and mycophenolate mofetil (MMF). This is a controlled trial of patients with class III/IV/V LN who had proteinuria despite initial conventional treatment with mycophenolate mofetil and prednisolone and who were given tacrolimus (target 12-hour trough TAC plasma levels of 4–6 g/l).

The key findings of this study were as follow:

• A total of 22 patients with LN who were treated with triple immunosuppression were included in the study, with an average follow-up of 61.1±28.1 months.
• TAC and mycophenolic acid (MPA) trough levels were 3.8 to 5.7 g/l and 1.3 to 2.1 mg/l, respectively.
• After 6 months, there was a significant reduction in proteinuria, which lasted for up to 5 years.
• At 12, 24, and 36 months, the complete response (CR) and partial response (PR) rates were 59.1%, 72.7%, and 77.3%, respectively.
• TAC had no effect on the slope of estimated glomerular filtration rate (eGFR) over time.
• Seven patients (31.8%) had progressing chronic renal disease (CKD).
• During the course of the study, two individuals developed end-stage renal disease.
• At -, 3-, and 5-years, the renal survival rate was 100.0%, 95.0%, and 88.7%, respectively.
• After 8.5 0.7 months, two individuals (9.1%) experienced renal recurrence.
• A total of 5 patients (22.7%) had worsening hypertension, while 3 (13.6%) had worsening hyperlipidemia.
• Infection (n = 16, 1 in 7 patient-years) and stomach distress (n = 6) were also significant adverse events.

In conclusion, Long-term TDM therapy with this triple immunosuppressive regimen is typically well tolerated and linked with disease quiescence stability.

Reference:

Yap, D. Y. H., Li, P. H., Tang, C., So, B. Y. F., Kwan, L. P. Y., Chan, G. C. W., Lau, C. S., & Chan, T. M. (2022). Long-Term Results of Triple Immunosuppression With Tacrolimus Added to Mycophenolate and Corticosteroids in the Treatment of Lupus Nephritis. In Kidney International Reports (Vol. 7, Issue 3, pp. 516–525). Elsevier BV. https://doi.org/10.1016/j.ekir.2021.12.005