Triple immunosuppression results in better proteinuria reduction in lupus nephritis: Study

Hong Kong: A recent study found that in patients with lupus nephritis (LN) whose proteinuria did not react well to usual therapy, triple immunosuppression with tacrolimus (TAC) in addition to mycophenolate and prednisolone (PRED) resulted in even more proteinuria reduction and long-term disease quiescence. The findings of this study were published in Kidney International Reports.

Because proteinuria was reduced when a calcineurin inhibitor (CNI) was added to corticosteroids and mycophenolate, the renal response rate in LN improved, although there is not much known about the long-term efficacy and safety data on the use of this triple immunosuppressive regimen.

Tak Mao Chan, The University of Hong Kong, Hong Kong, and colleagues conducted a cohort study of patients with class III/IV/V LN who had proteinuria despite usual treatment with mycophenolate mofetil (MMF) and prednisolone (PRED), and who were given tacrolimus (TAC) (target 12-hour trough TAC plasma levels of 4–6 g/l).

The key findings of this study are as follow:

1. There were 22 patients with LN who were treated with triple immunosuppression, with a mean follow-up of 61.1 28.1 months.

2. TAC and mycophenolic acid (MPA) trough levels were 3.8 to 5.7 g/l and 1.3 to 2.1 mg/l, respectively.

3. After 6 months, there was a significant reduction in proteinuria, which lasted for up to 5 years.

4. At 12, 24, and 36 months, the complete response (CR) and partial response (PR) rates were 59.1%, 72.7%, and 77.3 percent, respectively.

5. TAC had no effect on the slope of the estimated glomerular filtration rate (eGFR) over time.

6. A total of 7 patients (31.8%) had a chronic renal disease that was progressing (CKD).

7. During follow-up, two individuals had end-stage kidney disease. At -, 3-, and 5-years, the renal survival rate was 100.0%, 95.0%, and 88.7%, respectively.

8. After 8.5 0.7 months, two individuals (9.1%) experienced renal recurrence.

9. A total of 5 patients (22.7%) had deteriorating hypertension, whereas 3 (13.6%) had worsening hyperlipidemia. Infection (n = 16, 1 in 7 patient-years) and stomach distress (n = 6) were two other major adverse events.

In conclusion, in patients with poor proteinuria reduction after conventional therapy with PRED and MMF, triple immunosuppressive treatment with the addition of TAC resulted in significant proteinuria reduction in 77.3 percent of patients. Long-term treatment with TDM, a triple immunosuppressive regimen, is generally well tolerated and linked to disease quiescence stability.

Reference:

Yap, Desmond & Li, Philip & Tang, Colin & So, Benjamin & Kwan, Lorraine & Chan, Gary & Lau, Chak & Chan, Tak. (2021). Long-Term Results of Triple Immunosuppression With Tacrolimus Added to Mycophenolate and Corticosteroids in the Treatment of Lupus Nephritis. Kidney International Reports. 10.1016/j.ekir.2021.12.005.