Tacrolimus Linked to Long-Term eGFR Decline in Lupus Nephritis

Full access

Among patients with lupus nephritis, exposure to the calcineurin inhibitor (CNI) tacrolimus is associated with greater long-term reduction in kidney function, reports a study in Nephrology Dialysis Transplantation.

The retrospective cohort study included 219 patients with lupus nephritis treated at the authors’ center between 2010 and 2023. Of these, 43 patients were exposed to tacrolimus, and 176 had never been treated with any CNI. Renal outcomes, diabetes status, cardiovascular events, and risk factors were compared between groups at a median follow-up of 7.1 years.

The median follow-up was 80.6 months in the tacrolimus group and 88.9 months in those with no CNI exposure. The median duration of tacrolimus exposure was 17.7 months. Disease flares were the most common indication for tacrolimus therapy, followed by pregnancy and side effects of previous immunosuppression.

Patients receiving tacrolimus had a greater decline in the estimated glomerular filtration rate (eGFR): median, −6.8 mL/min/1.73 m2 compared with −0.8 mL/min/1.73 m2 in the nonexposed group. The median annual eGFR slope was 1.1 for the tacrolimus group versus 0.1 mL/min/1.73 m2 for the group without CNI. The rate of eGFR decline was related to the duration of tacrolimus treatment. Three patients in the tacrolimus group progressed to kidney failure, all during active tacrolimus treatment.

After adjustment for potential confounders, tacrolimus exposure was associated with a −14.7-mL/min/1.73 m2 decline in eGFR. On the sensitivity analysis, the tacrolimus-associated change in eGFR was greater in patients without a major disease flare: −20.0 mL/min/1.73 m2.

Tacrolimus exposure was also associated with higher hemoglobin A1c: 37.4 mmol/mol versus 33.6 mmol/mol. Cardiovascular events and cardiovascular risk factors were not significantly different between groups.

Tacrolimus, in combination with mycophenolate and corticosteroids, is an effective treatment option for patients with active lupus nephritis. CNIs have known renal and cardiovascular adverse effects in kidney transplant recipients. However, in the absence of long-term follow-up data, there are persistent concerns about the safety of tacrolimus in lupus nephritis.

The new study shows “clinically meaningful” long-term declines in kidney function associated with tacrolimus treatment in patients with lupus nephritis. The effect on an eGFR decline is greater with longer duration of treatment but appears independent of indications of tacrolimus therapy. The researchers conclude: “[O]ur study supports the need for increased vigilance [toward] tacrolimus treatment, especially in [patients with lupus nephritis] with an increased risk of developing ESKD [end stage kidney disease]” [van Schaik M, et al. Long-term renal and cardiovascular risks of tacrolimus in patients with lupus nephritis. Nephrol Dial Transpl, published online May 20, 2024. doi: 10.1093/ndt/gfae113].