title: Tacrolimus versus cyclophosphamide as treatment for diffuse proliferative or membranous lupus nephritis: a non-randomized prospective cohort study.
abstract: Treatment of lupus nephritis (LN) with cyclophosphamide (CYC) is effective but retains a certain severe adverse effect. Tacrolimus (TAC) may be a suitable treatment for LN. Forty patients with diffuse proliferative or membranous LN were recruited for this non-randomized open-label study - 67.5% (27/40) had nephrotic proteinuria (>3.5 g/day) and 50.0% (20/40) had low estimated glomerular filtration rate (eGFR) (<60 mL/min/1.73m(2)). We compared the efficacy and adverse effects of TAC (0.04-0.08 mg/kg/d)/prednisone for 12 months (TAC group, n = 20) with intravenous CYC (750 mg/m(2) per month)/prednisone for six months followed by azathioprine (Aza) (100 mg/day)/prednisone for six months (CYC group, n = 20). The TAC target concentration was 6-8 ng/mL or 4-6 ng/mL, respectively, when induction or maintenance therapy was required and 4.0 ng/mL for patient with renal insufficiency. In the TAC group, mean urinary protein excretion decreased significantly from 5.00 ± 1.91 g/day at baseline to 2.54 ± 1.68 g/day after two weeks of therapy (P < 0.001), compared with the CYC group (4.9 ± 19.4 g/day), P = 0.001, and 65.0% (13/20) achieved partial remission at one month, compared with the CYC group (0/20), P < 0.001. The incidence of complete remission (CR) was significantly higher in the TAC group than in the CYC group (55.0% vs.15.0% by five months, P = 0.008, and 75.0% vs.40.0% by 12 months, P = 0.025, respectively). The significant improvement in serum anti-dsDNA and systemic lupus erythematosus (SLE) disease activity index (DAI) was in the TAC group relative to the CYC group at 12 months (P = 0.031, P = 0.003, respectively). The eGFR improved in the TAC group from 59.90 ± 23.64 mL/min/1.73m(2) at baseline to 93.75 ± 28.52 mL/min/1.73m(2) after 12 months, P = 0.001. In the CYC group, two patients developed end-stage renal disease (ESRD), three patients experienced serious pneumonia, and one patient died. Our preliminary study showed TAC is a safe and effective treatment for LN with severe renal disease, and with less-severe adverse events compared with CYC followed Aza therapy. Further larger sample studies are needed to confirm our conclusion.
authors.affiliation: Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, People's Republic of China.
authors.forename: S
authors.initials: S
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Qu
authors.forename: R
authors.initials: R
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: Q
authors.initials: Q
authors.lastname: Li
authors.forename: X
authors.initials: X
authors.lastname: He
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.forename: J
authors.initials: J
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008181:Lupus Nephritis / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D003520:Cyclophosphamide; D016559:Tacrolimus