• Proportion of subjects that achieve a complete response (defined as: stabilization or improvement of estimated glomerular filtration rate, urine protein-to-creatinine ratio <0.5, prednisone dose tapered to <=10 mg/day) [ Time Frame: week 24 ] [ Designated as safety issue: No ]
  

• Proportion of participants who achieve a partial response [ Time Frame: week 24 ] [ Designated as safety issue: No ]
  
• Proportion of participants who achieve a complete response and who have maintained that complete response [ Time Frame: weeks 24 and 52 ] [ Designated as safety issue: No ]
  
• Time to complete or partial response [ Time Frame: 0 ] [ Designated as safety issue: No ]
  
• Lupus disease activity assessed by multiple measures [ Time Frame: various, up to 104 weeks ] [ Designated as safety issue: No ]
  
• Frequency of adverse events [ Time Frame: 0 ] [ Designated as safety issue: Yes ]
  

Lupus nephritis is a kind of kidney inflammation that occurs in patients with systemic lupus erythematosus (SLE). It is caused by the immune system attacking the kidney. It is among the most serious complications of SLE, and left untreated it can cause long term damage to the kidneys or, in some cases, result in kidney failure. One of the more common treatments for lupus nephritis is the "Euro-lupus" therapy. In this therapy, patients receive three different drugs - cyclophosphamide, azathioprine and prednisone - over the course of several months. However, some patients do not respond to this therapy and many only show some improvement. In the ACCESS trial for lupus nephritis, an experimental medication known as abatacept will be added to the Euro-lupus therapy to find out if it works better than Euro-lupus therapy alone. Abatacept is a man-made protein that suppresses parts of the immune system that can cause autoimmune disease. While abatacept is experimental for lupus, it has been approved by the FDA to treat rheumatoid arthritis. It is also being studied for use in other autoimmune diseases, like multiple sclerosis and type 1 diabetes. Participants in the ACCESS trial for lupus nephritis will receive bi-weekly intravenous infusions of cyclophosphamide for 3 months, then will take azathioprine tablets daily for at least 3 months more. Abatacept or a placebo will be administered every 2 weeks at first, then every 4 weeks for at least the first 6 months. Treatment of abatacept or placebo and azathioprine may continue for the remainder of the year. All subjects will take prednisone tablets daily during the whole study. Because the ACCESS trial is a randomized, controlled study, each participant has a 50-50 chance (like flipping a coin) of receiving abatacept. Others will receive an inactive, placebo form of the drug. Note however, that all participants will receive the Euro-lupus therapy. As a blinded study, neither participants nor study physicians will know to which group a person has been assigned.

All participants will undergo regular physical examinations, medical history and various blood and urine tests. Many of these tests will be repeated throughout the study. Participants will be asked to attend 18 study visits in the first year, and one study visit at the end of the second year.

The study will reimburse participants for certain expenses incurred as part of the study.