Faculty Collaboration Database

Pyridorin in type 2 diabetic nephropathy. J Am Soc Nephrol 2012 Jan;23(1):131-6

Date

10/29/2011

Pubmed ID

22034637

Pubmed Central ID

PMC3269925

DOI

10.1681/ASN.2011030272

Scopus ID

2-s2.0-84863393388 (requires institutional sign-in at Scopus site)   126 Citations

Abstract

Pyridoxamine dihydrochloride (Pyridorin, NephroGenex) inhibits formation of advanced glycation end products and scavenges reactive oxygen species and toxic carbonyls, but whether these actions translate into renoprotective effects is unknown. In this double-blind, randomized, placebo-controlled trial, we randomly assigned 317 patients with proteinuric type 2 diabetic nephropathy to twice-daily placebo; Pyridorin, 150 mg twice daily; or Pyridorin, 300 mg twice daily, for 52 weeks. At baseline, the mean age ± SD was 63.9±9.5 years, and the mean duration of diabetes was 17.6±8.5 years; the mean serum creatinine level was 2.2±0.6 mg/dl, and the mean protein-to-creatinine ratio was 2973±1932 mg/g. Regarding the primary end point, a statistically significant change in serum creatinine from baseline to 52 weeks was not evident in either Pyridorin group compared with placebo. However, analysis of covariance suggested that the magnitude of the treatment effect differed by baseline renal function. Among patients in the lowest tertile of baseline serum creatinine concentration, treatment with Pyridorin associated with a lower average change in serum creatinine concentration at 52 weeks (0.28, 0.07, and 0.14 mg/dl for placebo, Pyridorin 150 mg, and Pyridorin 300 mg, respectively; P=0.05 for either Pyridorin dose versus placebo); there was no evidence of a significant treatment effect in the middle or upper tertiles. In conclusion, this trial failed to detect an effect of Pyridorin on the progression of serum creatinine at 1 year, although it suggests that patients with less renal impairment might benefit.

Author List

Lewis EJ, Greene T, Spitalewiz S, Blumenthal S, Berl T, Hunsicker LG, Pohl MA, Rohde RD, Raz I, Yerushalmy Y, Yagil Y, Herskovits T, Atkins RC, Reutens AT, Packham DK, Lewis JB, Collaborative Study Group

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

Aged
Creatinine
Cystatin C
Diabetes Mellitus, Type 2
Diabetic Nephropathies
Double-Blind Method
Female
Glomerular Filtration Rate
Humans
Male
Middle Aged
Proteinuria
Pyridoxal Phosphate
Pyridoxamine