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Anti-TGF-β1 Antibody Therapy in Patients with Diabetic Nephropathy. J Am Soc Nephrol 2017 Mar;28(3):953-962

Date

09/21/2016

Pubmed ID

27647855

Pubmed Central ID

PMC5328150

DOI

10.1681/ASN.2015111230

Scopus ID

2-s2.0-85021850104 (requires institutional sign-in at Scopus site)   226 Citations

Abstract

TGF-β has been implicated as a major pathogenic factor in diabetic nephropathy. This randomized, double-blind, phase 2 study assessed whether modulating TGF-β1 activity with a TGF-β1-specific, humanized, neutralizing monoclonal antibody (TGF-β1 mAb) is safe and more effective than placebo in slowing renal function loss in patients with diabetic nephropathy on chronic stable renin-angiotensin system inhibitor treatment. We randomized 416 patients aged ≥25 years with type 1 or type 2 diabetes, a serum creatinine (SCr) level of 1.3-3.3 mg/dl for women and 1.5-3.5 mg/dl for men (or eGFR of 20-60 ml/min per 1.73 m2), and a 24-hour urine protein-to-creatinine ratio ≥800 mg/g to TGF-β1 mAb (2-, 10-, or 50-mg monthly subcutaneous dosing for 12 months) or placebo. We assessed a change in SCr from baseline to 12 months as the primary efficacy variable. Although the Data Monitoring Committee did not identify safety issues, we terminated the trial 4 months early for futility on the basis of their recommendation. The placebo group had a mean±SD change in SCr from baseline to end of treatment of 0.33±0.67 mg/dl. Least squares mean percentage change in SCr from baseline to end of treatment did not differ between placebo (14%; 95% confidence interval [95% CI], 9.7% to 18.2%) and TGF-β1 mAb treatments (20% [95% CI, 15.3% to 24.3%], 19% [95% CI, 14.2% to 23.0%], and 19% [95% CI, 14.0% to 23.3%] for 2-, 10-, and 50-mg doses, respectively). Thus, TGF-β1 mAb added to renin-angiotensin system inhibitors did not slow progression of diabetic nephropathy.

Author List

Voelker J, Berg PH, Sheetz M, Duffin K, Shen T, Moser B, Greene T, Blumenthal SS, Rychlik I, Yagil Y, Zaoui P, Lewis JB

Author

Samuel S. Blumenthal MD Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Antibodies, Monoclonal
Diabetic Nephropathies
Double-Blind Method
Female
Humans
Male
Middle Aged
Transforming Growth Factor beta1