Long-term data on tacrolimus treatment in lupus nephritis

Rheumatology (Oxford). 2014 Dec;53(12):2232-7. doi: 10.1093/rheumatology/keu265. Epub 2014 Jul 4.

Abstract

Objective: Calcineurin inhibitors are effective immunosuppressants. They also reduce proteinuria in glomerular diseases but are potentially nephrotoxic. Short-term data suggest that tacrolimus (TAC) combined with corticosteroids is effective in LN, but long-term data are lacking. This study examined the long-term outcomes and tolerability of TAC for the treatment of LN.

Methods: We retrospectively reviewed 29 LN patients who received TAC treatment for 46.9 months (s.d. 37.9).

Results: In 17 patients with class III/IV or V LN and persistent proteinuria >2 g/day despite induction immunosuppression, response rates after 12 and 24 months of add-on TAC treatment were 66.7% and 80.0%, respectively. In 10 patients with nephrotic syndrome due to class V LN who were given prednisolone and TAC as initial treatment, the response rate was 60.0% and 90.0% after 12 and 24 months, respectively. TAC facilitated steroid minimization in two patients with lupus podocytopathy. As a group, proteinuria decreased from 3.6 g/day (s.d. 2.6) to 1.0 (s.d. 1.1) (P < 0.05). Four patients developed end-stage renal failure, with 3-, 5- and 8-year renal survival rates of 93%, 83% and 83%, respectively. In the remaining patients, serum creatinine and estimated GFR remained stable after 36 months. One patient with pre-existing chronic renal failure developed TAC nephrotoxicity. Four renal flares occurred, all associated with low TAC blood levels. Six patients (20.1%) had deterioration of hypertension and one patient (3.4%) had new-onset diabetes mellitus. Six patients (20.1%) had infections that required hospitalization. Two deaths occurred: one due to pneumonia and one to breast cancer.

Conclusion: The results suggest efficacy of TAC in LN, especially in reducing proteinuria, and its role as a long-term maintenance agent warrants further investigation.

Keywords: long-term; lupus; nephritis; tacrolimus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Creatinine / blood
  • Drug Evaluation / methods
  • Drug Therapy, Combination
  • Female
  • Glomerular Filtration Rate / drug effects
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / therapeutic use*
  • Lupus Nephritis / blood
  • Lupus Nephritis / complications
  • Lupus Nephritis / drug therapy*
  • Lupus Nephritis / physiopathology
  • Male
  • Middle Aged
  • Prednisolone / therapeutic use
  • Proteinuria / drug therapy
  • Proteinuria / etiology
  • Proteinuria / physiopathology
  • Retrospective Studies
  • Tacrolimus / adverse effects
  • Tacrolimus / therapeutic use*
  • Treatment Outcome

Substances

  • Glucocorticoids
  • Immunosuppressive Agents
  • Prednisolone
  • Creatinine
  • Tacrolimus