Adding the calcineurin inhibitor tacrolimus to standard immunosuppression may further reduce proteinuria in patients with lupus nephritis who have suboptimal response, a new study finds.

Investigators administered tacrolimus to 16 patients with class 3/4 with or without class 5 disease and 6 patients with pure class 5 lupus nephritis who had persistent proteinuria of 2 g/d or more despite standard therapy with mycophenolate mofetil (MMF) and prednisolone. The target 12-hour trough tacrolimus plasma level was 4 to 6 μg/L. The patients had a mean follow-up of 61.1 months.

Tacrolimus achieved trough levels of 3.8 to 5.7 μg /L and mycophenolic acid (MPA) 1.3 to 2.1 mg/L.

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Proteinuria significantly declined from a baseline urinary protein excretion rate of 5.4 g/d to 2.1 g/d after 6 months and was maintained up to 5 years, Tak Mao Chan, MD, of The University of Hong Kong, and colleagues reported in Kidney International Reports. Combined complete and partial response rates at 12, 24, and 36 months were 59.1%, 72.7%, and 77.3%, respectively.

Tacrolimus did not accelerate decline in estimated glomerular filtration rate (eGFR). However, 7 patients (31.8%) had chronic kidney disease progression, including 2 who had kidney failure. The renal survival rate at 0, 3, and 5 years was 100.0%, 95.0%, and 88.7%, respectively. Two patients (9.1%) had renal relapse after 8.5 months. No acute kidney injury related to calcineurin inhibitor nephrotoxicity occurred possibly because tacrolimus was added after the early treatment phase and with therapeutic drug monitoring. New-onset diabetes also did not occur.

Hypertension worsened in 5 patients (22.7%) and hyperlipidemia in 3 (13.6%). There were 16 infection episodes (at a rate of 1 in 7 patient-years) and 6 gastrointestinal upset episodes.

“Long-term treatment with this triple immunosuppressive regimen, with [therapeutic drug monitoring], is generally well-tolerated and associated with stability of disease quiescence,” according to Dr Chan’s team.

The investigators suggested tacrolimus acts on podocytes and thereby reduces proteinuria, while its immunosuppressive action contributes to disease quiescence.


Yap DYH, Li PH, Tang C, et al. Long-term results of triple immunosuppression with tacrolimus added to mycophenolate and corticosteroids in the treatment of lupus nephritis. Kidney Int Rep. Published online December 14, 2021.doi:10.1016/j.ekir.2021.12.005