Related Experiment Video
Updated: Jun 25, 2025
Genetic Analysis of Hereditary Transthyretin Ala97Ser Related Amyloidosis
Published on: June 9, 2018
Effect of Tafamidis on Renal Function in Patients With Transthyretin Amyloid Cardiomyopathy in ATTR-ACT
Brett W Sperry1, Marla B Sultan2, Balarama Gundapaneni3
1Saint Luke's Mid America Heart Institute, Kansas City, Missouri, USA.
Insights
Tafamidis treatment in transthyretin amyloid cardiomyopathy (ATTR-CM) patients slowed kidney function decline and improved chronic kidney disease (CKD) staging over 30 months compared to placebo. This suggests a renal benefit for tafamidis in ATTR-CM.
Area of Science:
- Cardiology
- Nephrology
- Pharmacology
Background:
- Chronic kidney disease (CKD) is a common comorbidity in patients with amyloid cardiomyopathy.
- Tafamidis is approved for treating transthyretin amyloid cardiomyopathy (ATTR-CM), a condition often associated with renal impairment.
- The ATTR-ACT trial provided efficacy and safety data for tafamidis in ATTR-CM patients.
Purpose of the Study:
- To conduct a post hoc analysis of the ATTR-ACT trial to evaluate the impact of tafamidis on renal function in ATTR-CM patients.
- To assess changes in estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD) staging over 30 months.
- To analyze the composite renal endpoint in patients treated with tafamidis versus placebo.
Main Methods:
- Patients with ATTR-CM were randomized to receive tafamidis (pooled 20 mg and 80 mg doses) or placebo for 30 months.
- Changes in eGFR from baseline were compared between treatment groups over the study duration.
- A composite renal endpoint (all-cause death, dialysis, kidney transplant, or ≥30% eGFR decline) was analyzed for time to first event.
Main Results:
- Tafamidis treatment was associated with a significantly smaller decline in eGFR compared to placebo (mean difference of 3.99 mL/min/1.73 m²; P=0.004).
- Improvement in CKD staging was observed more frequently in the tafamidis group (17.7%) versus the placebo group (7.2%; P=0.034).
- A lower proportion of patients receiving tafamidis reached the composite renal endpoint (34.5%) compared to placebo (44.1%; P=0.040).
Conclusions:
- Renal function naturally deteriorates in patients with ATTR-CM.
- Tafamidis treatment demonstrated a significant reduction in the decline of renal function over 30 months.
- Tafamidis therapy was associated with a higher incidence of improved eGFR and CKD staging compared to placebo in ATTR-CM patients.
Background:
Chronic kidney disease (CKD) is common among patients with amyloid cardiomyopathy. Tafamidis was approved for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) based on findings from ATTR-ACT (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy).
Objectives:
This post hoc analysis evaluated changes in renal function among patients with ATTR-CM in ATTR-ACT.
Methods:
Patients were randomized to receive tafamidis (20 mg and 80 mg pooled) or placebo for 30 months. The change from baseline in the estimated glomerular filtration rate (eGFR) was compared over time. A composite endpoint of all-cause death, dialysis, kidney transplant, or ≥30% decline in eGFR from baseline was analyzed based on the time to first event.
Results:
The mean baseline eGFR was 57.5 ± 17.3 and 55.6 ± 16.8 mL/min/1.73 m2 in the tafamidis (n = 264) and placebo (n = 177) groups, respectively. At 30 months, patients treated with tafamidis had a significantly smaller decline in eGFR compared with placebo (least squares mean difference = 3.99 mL/min/1.73 m2; 95% CI: 1.31-6.68; P = 0.004). In patients who completed ATTR-ACT, improvement in CKD staging was more common with tafamidis vs placebo treatment (17.7% vs 7.2%; OR: 2.75; 95% CI: 1.10-6.90; P = 0.034). A lower proportion of tafamidis-treated patients reached the composite renal endpoint (crude rates 34.5% vs 44.1%; HR: 0.73, 95% CI: 0.54-0.99; P = 0.040).
Conclusions:
Renal function deteriorates over time in patients with ATTR-CM, and tafamidis treatment was associated with a reduction in this deterioration, and a higher incidence of improved eGFR and CKD staging over 30 months compared with placebo. (Safety and Efficacy of Tafamidis in Patients With Transthyretin Cardiomyopathy [ATTR-ACT] NCT01994889).
Related Concept Videos
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:11Renal Failure: Dose Adjustments
Reduced renal clearance and elimination rate are common outcomes of renal impairment. These alterations lead to a prolonged elimination half-life and an altered apparent volume of distribution for drugs. As a result, dosage adjustments are typically necessary to maintain optimal drug levels in the body.
However, dosage adjustments...
01:17Factors Affecting Renal Clearance: Renal Impairment
One condition associated with renal failure is uremia. Uremia is characterized by impaired glomerular filtration and fluid accumulation in the body. This condition hinders the renal clearance of drugs, resulting in drug accumulation and potential...