Diabetic nephropathy may not just slow but may actually improve with the novel antifibrotic agent pirfenidone (Esbriet).…
Kidney function continued to drop in diabetic kidney disease patients without treatment, but rose significantly with a low dose of pirfenidone over one year.
Mean estimated glomerular filtration rate (eGFR) rose by an average 3.3 ml/min per 1.73 m2 with 1,200-mg pirfenidone, but fell by 2.2 ml/min per 1.73 m2 with placebo in the study (P=0.026). This kind of improvement hasn’t been seen with the current standard of care with renin-angiotensin system (RAS) blockers, the researchers noted, calling the results promising.
“Even when maximized, [RAS blockers] may decrease rate of progression, but they do not arrest or reverse diabetic nephropathy,” wrote Dr. Sharma, of the University of California San Diego and VA Medical Center in La Jolla.
When diabetes patients develop even low levels of kidney disease, their risk of cardiovascular and other complications requiring hospitalization goes up, Sharma explained.
Pirfenidone is under development for treatment of idiopathic pulmonary fibrosis. An FDA advisory panel gave the thumbs up to the drug early last year, but the agency ultimately turned it down, citing the need for further efficacy data.
But since fibrosis and inflammation play a role in progression of diabetic kidney damage as well, Sharma’s group did an exploratory study in 77 patients with Type 1 or Type 2 diabetes and established nephropathy marked by elevated albuminuria and eGFR of 20 to 75 ml/min per 1.73 m2.
The double-blind, placebo-controlled, dose-ranging protocol randomized patients to placebo or pirfenidone at either 1,200 or 2,400 mg per day on top of their stable regimen; study participants had both their diabetes and their blood pressure under good control.
During the study, no patient in the low-dose pirfenidone group was put on dialysis by their primary provider, whereas four placebo-group patients initiated dialysis, as did one in the 2,400-mg pirfenidone group.
However, a larger study is needed to validate any difference in rates of progression to dialysis, Sharma warned. The paper also noted that a larger study was needed to replicate these results.
Change in urine albumin-to-creatinine ratio did not differ significantly among groups. Nor did the researchers find any biomarkers that could predict benefit from pirfenidone.
Sharma said his group is actively looking for such biomarkers and noted that their exploratory study is just one step on the way to a larger-scale trial to validate the benefits for diabetic nephropathy.
- Explain that an exploratory study found that 54 weeks of 1200 mg of the new antifibrotic drug, pirfenidone, improved the mean estimated glomerular filtration rate (eGFR) in patients with existing diabetic nephropathy due to Type 1 or Type 2 diabetes.
- Note that the eGFR after one year was not significantly different between those receiving 2400 mg of the drug and placebo and the study had a high drop-out rate.
Journal of the American Society of Nephrology, April 2011.