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Benefits of Atrasentan on Albuminuria and Blood Pressure in Type 2 Diabetic Patients

Endothelin inhibitors may have synergistic role in combating diabetes-related complication…. 

In a new study, researchers at the University Medical Center Groningen investigated whether additional treatment with atrasentan — a selective endothelin A receptor antagonist — would further reduce albuminuria. A total of 211 type 2 diabetes patients with chronic kidney disease (CKD) stages 1 and 2 were evaluated in a parallel, multinational, double blind study.

Each individual was randomly assigned into 1 of 3 cohorts. Group 1 consisted of 78 patients who received 0.75 mg/day; group 2- 83 patients received 1.25 mg/day; and 50 received a placebo; for a total of 12 weeks.

At baseline, participants had estimated glomerular filtration rates ranging from 30 mL/minute/1.73 m2 to 75 mL/minute/1.73 m², and urine albumin-to-creatinine ratios ranging from 300 to 3,500 mg/g. Study participants were also receiving maximum tolerated doses of renin-angiotensin-system inhibitors.

Patient data collected during biweekly visits included; blood pressure, weight and presence of edema. Researchers also collected 3 morning urine samples during visits after the first week, along with 24-hour ambulatory blood pressure measurements and blood samples.

Compared to placebo, patients who received 0.75 mg and 1.25 mg of atrasentan experienced an average 35% reduction in urine albumin-to-creatinine ratios (CI 95%, 24 to 45) and 38% (CI 95%, 28 to 47), respectively – in addition to a ≥30% reduction in albuminuria in 51% and 55% of patients, respectively.

In all groups, no change was observed in regards to estimated glomerular filtration rates and office blood pressure however significant decreases in 24-hour systolic and diastolic were seen in those who received 0.75 mg atrasentan 0.75 (–4.5 mmHg, P=0.026) and 1.25 mg (–5.4 mmHg, P=0.01). Further, those who received 0.75 mg atrasentan experienced a significantly lower total cholesterol level (16.8 mg/dL, P<0.001) and 1.25 mg (18.6 mg/dL, P<0.001).

Practice Pearls:
  • Atrasentan was found to improve urine albumin-to-creatinine ratios in patients with diabetic nephropathy on maximum tolerable dose of renin-angiotensin-system inhibitors
  • Endothelin inhibitors may be a potential new tool for treating diabetic nephropathy
  • More studies are needed to assess safety and efficacy outcomes

De zeeuw D, Coll B, Andress D, et al. The Endothelin Antagonist Atrasentan Lowers Residual Albuminuria in Patients with Type 2 Diabetic Nephropathy. J Am Soc Nephrol. 2014; http://jasn.asnjournals.org/content/early/2014/04/09/ASN.2014020174.full