Tacrolimus versus mycophenolate mofetil for induction therapy of lupus nephritis: a randomised controlled trial and long-term follow-up.

OBJECTIVE: To compare the efficacy of tacrolimus (TAC) and mycophenolate mofetil (MMF) for the initial therapy of lupus nephritis (LN). STUDY DESIGN: This is an open randomised controlled parallel group study. METHODS: Adult patients with biopsy-confirmed active LN (class III/IV/V) were randomised to receive prednisolone (0.6 mg/kg/day for 6 weeks and tapered) in combination with either TAC (0.06-0.1 mg/kg/day) or MMF (2-3 g/day) for 6 months. Good responders were shifted to azathioprine for maintenance. The primary outcome was the rate of complete renal response (CR) at 6 months and the secondary outcomes included partial renal response, renal flares and decline of renal function over time. RESULTS: 150 patients (92% women; aged 35.5±12.8 years; 81% class III/IV) were randomised (76 MMF, 74 TAC). At month 6, the rate of CR was 59% in the MMF and 62% in the TAC group (treatment difference: 3.0% (-12%, 18%); p=0.71). Major infective episodes occurred in 9.2% patients treated with MMF and in 5.4% patients treated with TAC (p=0.53). Maintenance therapy with azathioprine was given to 79% patients. After 60.8±26 months, proteinuric and nephritic renal flares developed in 24% and 18% of patients in the MMF group and 35% (p=0.12) and 27% (p=0.21) in the TAC group, respectively. The cumulative incidence of a composite outcome of decline of creatinine clearance by ≥30%, development of chronic kidney disease stage 4/5 or death was 21% in the MMF and 22% in the TAC group of patients (p=0.35). CONCLUSIONS: TAC is non-inferior to MMF, when combined with prednisolone, for induction therapy of active LN. With azathioprine maintenance for 5 years, a non-significant trend of higher incidence of renal flares and renal function decline is observed with the TAC regimen. TRIAL REGISTRATION NUMBER: Hospital Authority Research Ethics Committee Clinical Trial Registry (HARECCTR0500018; Hong Kong) and US ClinicalTrials.gov (NCT00371319).

Risk and predictors of arterial thrombosis in lupus and non-lupus primary glomerulonephritis: a comparative study.

We conducted the current study to compare the incidence and risk factors of arterial thrombosis in lupus and non-lupus primary glomerulonephritis. We identified patients in whom lupus nephritis and non-lupus primary glomerulonephritis were diagnosed between 1993 and 2003 using our lupus cohort database and pathology registry. We analyzed the cumulative incidence of new arterial thromboembolic events since diagnosis by Kaplan-Meier plot, and studied risk factors by multivariate analysis. We studied 162 patients with lupus and 181 patients with non-lupus primary glomerulonephritis. After a mean observation of 8.1 years, 47 (14%) patients died, 23 (7%) were lost to follow-up, and 38 (11%) developed 42 arterial events (incidence, 15.1/1000 patient-years). Although patients with lupus nephritis were younger and had a significantly lower frequency of smoking, hypertension, obesity, and renal dysfunction, their cumulative risk of arterial event at 5 years was not significantly lower than that of patients with primary non-lupus glomerulonephritis (6.3% vs. 6.6%, p = 0.96). In a Cox regression model, lupus was found to be an independent risk factor for arterial thrombosis (hazard ratio 3.57 [1.07-11.9]; p = 0.04), in addition to increasing age (hazard ratio 1.04 per year; p = 0.02), low-density lipoprotein > or =2.6 mmol/L (hazard ratio 4.46; p = 0.002), and glomerular filtration rate <30 mL/min (hazard ratio 2.67; p = 0.04). We concluded that in immune-mediated glomerulonephritis, having systemic lupus increased the risk of arterial thromboembolism after adjustment for age, renal insufficiency, and other traditional risk factors.

Tacrolimus for induction therapy of diffuse proliferative lupus nephritis: an open-labeled pilot study.

BACKGROUND: Tacrolimus is a relatively new calcineurin inhibitor that has been increasingly used in transplant medicine. The objective of the current work is to report our preliminary experience with tacrolimus in the treatment of diffuse proliferative glomerulonephritis in systemic lupus erythematosus (SLE). METHODS: Nine consecutive patients who fulfilled the American College of Rheumatology criteria for SLE and with biopsy-proven diffuse proliferative glomerulonephritis were recruited for an open-labeled trial with prednisolone and oral tacrolimus (0.1 mg/kg/day for 2 months, followed by 0.06 mg/kg/day). Prospective data on renal response and serologic lupus activity were collected. The efficacy and safety of this regimen was reported. RESULTS: Baseline characteristics of the patients were: mean age 33.3 +/- 12 years, women to men ratio 2:1, serum creatinine 94.2 +/- 46 micromol/L, daily proteinuria 4.56 +/- 2.4 g, seven (78%) patients were nephrotic, three (33%) were hypertensive, and four (44%) had elevated serum creatinine at the time of renal biopsy. At 6 months of therapy, complete and partial renal response was achieved in six (67%) and two (22%) patients, respectively. Significant improvement in proteinuria, hemoglobin, serum albumin, and C3 levels was observed in comparison with baseline values, starting at the second month. Tacrolimus was generally well tolerated, except for two patients who developed transient hyperglycemia. Infective complications, amenorrhea, hypertrichosis, gingivitis, new-onset hypertension, and significant increase in serum creatinine were not reported. CONCLUSION: Tacrolimus is an effective option for induction treatment of SLE-diffuse proliferative glomerulonephritis. Further trials are necessary to determine the optimal dosage and duration of therapy, and its efficacy in comparison to standard regimens.