Eprodisate slows kidney decline in amyloid A amyloidosis

Amyloid A amyloidosis is a rare complication of chronic inflammatory diseases and chronic infections. In this condition, a proteolytic fragment of serum amyloid A protein—an acute phase reactant produced in the liver—is deposited extracellularly in the tissues as insoluble fibrils. Such deposition causes progressive dysfunction of organs and, eventually, death. A new drug, eprodisate, inhibits polymerisation of amyloid fibrils and their deposition in tissues, and it seems to slow down the decline in kidney function seen in people who have nephropathy associated with amyloid A amyloidosis.

A recent multicentre randomised trial that included 183 people with amyloid A amyloidosis compared eprodisate with placebo. After two years, disease had worsened (concentrations of serum creatinine had at least doubled or creatinine clearance had declined by 50% or more) in 27% of patients randomised to eprodisate, compared with 40% of those who received placebo. The difference, however, did not reach statistical significance (P=0.06). Furthermore, the decline in creatinine clearance was 10.9 ml per minute per 1.73 m² of body surface area in patients randomised to eprodisate, compared with 15.6 m² of body surface area in those randomised to placebo (P=0.02). Eprodisate had no effect on progression to end stage kidney disease or the risk of death (hazard ratio 0.54, P=0.20).

Almost all participants in the trial had at least one adverse event, and more than a third had at least one serious adverse event. The incidence of adverse events was similar in the two study groups.

The authors conclude that eprodisate delays the progression of renal disease associated with amyloid A amyloidosis, and they suggest that this drug might be useful in other types of amyloidosis, including familial amyloidosis and Alzheimer's disease.