A report of five patients with focal segmental glomerulosclerosis (FSGS) showed that the drug abatacept (Orencia), already approved as a treatment for rheumatoid arthritis, induced partial or complete remission of proteinuria in persons with the kidney disease.

“We identified abatacept as the first personalized, targeted treatment for kidney disease and specifically for FSGS, a devastating and largely untreatable disease,” affirmed Peter Mundel, MD, of the Division of Nephrology at Massachusetts General Hospital in Boston, in a statement issued by the facility. “We also identified a biomarker that helps us discern which patients are most likely to benefit from therapy with abatacept.”

Dr. Mundel was the senior author of The New England Journal of Medicine report describing the abatacept findings. As he and his team explained, this immunomodulator is an inhibitor of the T-cell co-stimulatory molecule B7-1 (CD80); podocyte B7-1 expression is found in patients with certain glomerular diseases, but not in healthy human kidneys.

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FSGS, which is characterized by the formation of scar tissue in the glomeruli, affects millions of patients worldwide and often leads to end-stage renal disease (ESRD).

“In particular, primary FSGS as well as recurrent FSGS after kidney transplantation remain largely untreatable, leading to ESRD and, after transplantation, to allograft loss,” Dr. Mundel and colleagues wrote.

After observing B7-1 immunostaining in 13 of 21 randomly selected biopsy specimens from patients with proteinuric kidney disease and in every biopsy specimen from patients with recurrent FSGS, Dr. Mundel’s group treated five FSGS patients with abatacept. Four of the patients had rituximab-resistant recurrent FSGS after transplantation, and one had glucocorticoid-resistant primary FSGS.

Abatacept therapy induced remission of FSGS-caused proteinuria in all five patients. At the time the study findings were released, two of the patients with recurrent disease had been in remission for three and four years after receiving a single dose of the drug. The other two patients with recurrent disease had been in remission for 10 and 12 months, after receiving a second dose of abatacept when proteinuria reappeared a few weeks after administration of the first dose.

The patient with primary FSGS receives monthly doses of abatacept, has been in remission for a year, and no longer needs high-dose steroids and immunosuppressive drugs.

“Our clinical and in vitro data, taken together, indicate that podocyte B7-1 induction in primary and recurrent FSGS offers a rationale for using abatacept to treat a subgroup of patients with proteinuric kidney diseases,” Dr. Mundel and co-investigators concluded.