Lupus Nephritis
Conditions
Keywords
glomerulonephritis, systemic lupus erythematosus
Brief summary
Glomerulonephritis is one of the major disease manifestations of systemic lupus erythematosus (SLE). Around one-third of the patients, however, do not respond to conventional immunosuppressive therapy, and they have a high risk of progressing to dialysis-dependent renal failure. Recent studies suggest that immunosuppressive therapy targeted against the calcineurin pathway of T-helper cell, for example, tacrolimus, may be effective in the treatment of primary glomerulonephritis. The investigators plan to an open-label single-arm study the efficacy and safety of long-acting tacrolimus in the treatment of treatment-resistant lupus nephritis. Twenty-five patients with biopsy-proven lupus nephritis will be recruited. They will be treated with oral prednisolone and long-acting tacrolimus for 6 months, followed by 6 months of maintenance steroid and azathioprine. Proteinuria, renal function, clinical and serologic lupus activity will be monitored. This study will explore the potential role of long-acting tacrolimus in resistant lupus nephritis, which has a poor prognosis and no effective treatment at the moment.
Interventions
DRUGLong-acting tacrolimus (Advagraf, Astellas Pharma)
Long-acting tacrolimus (Advagraf, Astellas Pharma) will be started at single daily dose of 0.15-0.2 mg/kg/day for 6 months.
Sponsors
Chinese University of Hong Kong
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age over 18 with informed consent. * Fulfill the revised American College of Rheumatology criteria for SLE * Biopsy-proven class III, IV, or V lupus nephritis within the past 24 months. * Could not achieve complete remission after at least 4 months of conventional therapy (oral steroid plus cyclosphosphamide or mycophenolate mofetil). * NB. Complete response is defined as proteinuria less than 0.5 g/day, with normal urinary sediment, a normal serum albumin concentration, and serum creatinine \<15% above the base-line value. * Female patients of child-bearing age and male patients agree to maintain effective birth control practice during the study.
Exclusion criteria
* Abnormal liver function tests * Hepatitis B surface antigen or hepatitis C antibody positive * Diabetic * Receiving NSAID or other agents known to influence urinary * Protein excretion * Allergic or intolerant to macrolide antibiotics or tacrolimus
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| overall clinical response | 6 months | complete response is defined as urinary protein \< 0.5 g/day, with normal urinary sediment, normal serum albumin, and serum creatinine \< 15% above the base-line value. Partial response is defined as urinary protein between 0.6 and 2.9 g/day, with a serum albumin \> 30 g/dL, and stable renal function. No response is defined as urinary protein \> 3 g/day or a value of 0.6 to 2.9 g/day but serum albumin \< 30 g/dL, an increase in serum creatinine ≥ 50 µmol/l or 15% above the base-line value, or the discontinuation of treatment due to side effects. |
Secondary
| Measure | Time frame |
|---|---|
| change in SLEDAI score | 6 months |
| 24-hour urinary protein excretion | 6 months |
| renal function | 6 months |
| development of lupus flare (renal or non-renal) | 6 months |
Countries
Hong Kong
Outcome results
None listed