Pirfenidone for diabetic nephropathy

Kumar Sharma, Joachim H. Ix, Anna V. Mathew, Monique Cho, Axel Pflueger, Stephen R. Dunn, Barbara Francos, Shoba Sharma, Bonita Falkner, Tracy A. McGowan, Michael Donohue, Satish RamachandraRao, Ronghui Xu, Fernando C. Fervenza, Jeffrey B. Kopp

Research output: Contribution to journalArticle

163 Citations (Scopus)

Abstract

Pirfenidone is an oral antifibrotic agent that benefits diabetic nephropathy in animal models, but whether it is effective for human diabetic nephropathy is unknown. We conducted a randomized, double-blind, placebo-controlled study in 77 subjects with diabetic nephropathy who had elevated albuminuria and reduced estimated GFR (eGFR) (20 to 75 ml/min per 1.73 m2). The prespecified primary outcome was a change in eGFR after 1 year of therapy. We randomly assigned 26 subjects to placebo, 26 to pirfenidone at 1200 mg/d, and 25 to pirfenidone at 2400 mg/d. Among the 52 subjects who completed the study, the mean eGFR increased in the pirfenidone 1200-mg/d group (-3.3 ± 8.5 ml/min per 1.73 m2) whereas the mean eGFR decreased in the placebo group (-2.2 ± 4.8 ml/min per 1.73 m2; P = 0.026 versus pirfenidone at 1200 mg/d). The dropout rate was high (11 of 25) in the pirfenidone 2400-mg/d group, and the change in eGFR was not significantly different from placebo (-1.9 ± 6.7 ml/min per 1.73 m 2). Of the 77 subjects, 4 initiated hemodialysis in the placebo group, 1 in the pirfenidone 2400-mg/d group, and none in the pirfenidone 1200-mg/d group during the study (P = 0.25). Baseline levels of plasma biomarkers of inflammation and fibrosis significantly correlated with baseline eGFR but did not predict response to therapy. In conclusion, these results suggest that pirfenidone is a promising agent for individuals with overt diabetic nephropathy.

Original languageEnglish (US)
Pages (from-to)1144-1151
Number of pages8
JournalJournal of the American Society of Nephrology
Volume22
Issue number6
DOIs
StatePublished - Jun 1 2011
Externally publishedYes

Fingerprint

Diabetic Nephropathies
Placebos
pirfenidone
Albuminuria
Renal Dialysis
Fibrosis
Animal Models
Biomarkers
Inflammation
Therapeutics

ASJC Scopus subject areas

  • Nephrology

Cite this

Sharma, K., Ix, J. H., Mathew, A. V., Cho, M., Pflueger, A., Dunn, S. R., ... Kopp, J. B. (2011). Pirfenidone for diabetic nephropathy. Journal of the American Society of Nephrology, 22(6), 1144-1151. https://doi.org/10.1681/ASN.2010101049

Pirfenidone for diabetic nephropathy. / Sharma, Kumar; Ix, Joachim H.; Mathew, Anna V.; Cho, Monique; Pflueger, Axel; Dunn, Stephen R.; Francos, Barbara; Sharma, Shoba; Falkner, Bonita; McGowan, Tracy A.; Donohue, Michael; RamachandraRao, Satish; Xu, Ronghui; Fervenza, Fernando C.; Kopp, Jeffrey B.

In: Journal of the American Society of Nephrology, Vol. 22, No. 6, 01.06.2011, p. 1144-1151.

Research output: Contribution to journalArticle

Sharma, K, Ix, JH, Mathew, AV, Cho, M, Pflueger, A, Dunn, SR, Francos, B, Sharma, S, Falkner, B, McGowan, TA, Donohue, M, RamachandraRao, S, Xu, R, Fervenza, FC & Kopp, JB 2011, 'Pirfenidone for diabetic nephropathy', Journal of the American Society of Nephrology, vol. 22, no. 6, pp. 1144-1151. https://doi.org/10.1681/ASN.2010101049
Sharma K, Ix JH, Mathew AV, Cho M, Pflueger A, Dunn SR et al. Pirfenidone for diabetic nephropathy. Journal of the American Society of Nephrology. 2011 Jun 1;22(6):1144-1151. https://doi.org/10.1681/ASN.2010101049
Sharma, Kumar ; Ix, Joachim H. ; Mathew, Anna V. ; Cho, Monique ; Pflueger, Axel ; Dunn, Stephen R. ; Francos, Barbara ; Sharma, Shoba ; Falkner, Bonita ; McGowan, Tracy A. ; Donohue, Michael ; RamachandraRao, Satish ; Xu, Ronghui ; Fervenza, Fernando C. ; Kopp, Jeffrey B. / Pirfenidone for diabetic nephropathy. In: Journal of the American Society of Nephrology. 2011 ; Vol. 22, No. 6. pp. 1144-1151.
@article{e09c52f645c543b0bfe063ce0a04b14a,
title = "Pirfenidone for diabetic nephropathy",
abstract = "Pirfenidone is an oral antifibrotic agent that benefits diabetic nephropathy in animal models, but whether it is effective for human diabetic nephropathy is unknown. We conducted a randomized, double-blind, placebo-controlled study in 77 subjects with diabetic nephropathy who had elevated albuminuria and reduced estimated GFR (eGFR) (20 to 75 ml/min per 1.73 m2). The prespecified primary outcome was a change in eGFR after 1 year of therapy. We randomly assigned 26 subjects to placebo, 26 to pirfenidone at 1200 mg/d, and 25 to pirfenidone at 2400 mg/d. Among the 52 subjects who completed the study, the mean eGFR increased in the pirfenidone 1200-mg/d group (-3.3 ± 8.5 ml/min per 1.73 m2) whereas the mean eGFR decreased in the placebo group (-2.2 ± 4.8 ml/min per 1.73 m2; P = 0.026 versus pirfenidone at 1200 mg/d). The dropout rate was high (11 of 25) in the pirfenidone 2400-mg/d group, and the change in eGFR was not significantly different from placebo (-1.9 ± 6.7 ml/min per 1.73 m 2). Of the 77 subjects, 4 initiated hemodialysis in the placebo group, 1 in the pirfenidone 2400-mg/d group, and none in the pirfenidone 1200-mg/d group during the study (P = 0.25). Baseline levels of plasma biomarkers of inflammation and fibrosis significantly correlated with baseline eGFR but did not predict response to therapy. In conclusion, these results suggest that pirfenidone is a promising agent for individuals with overt diabetic nephropathy.",
author = "Kumar Sharma and Ix, {Joachim H.} and Mathew, {Anna V.} and Monique Cho and Axel Pflueger and Dunn, {Stephen R.} and Barbara Francos and Shoba Sharma and Bonita Falkner and McGowan, {Tracy A.} and Michael Donohue and Satish RamachandraRao and Ronghui Xu and Fervenza, {Fernando C.} and Kopp, {Jeffrey B.}",
year = "2011",
month = "6",
day = "1",
doi = "10.1681/ASN.2010101049",
language = "English (US)",
volume = "22",
pages = "1144--1151",
journal = "Journal of the American Society of Nephrology",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "6",

}

TY - JOUR

T1 - Pirfenidone for diabetic nephropathy

AU - Sharma, Kumar

AU - Ix, Joachim H.

AU - Mathew, Anna V.

AU - Cho, Monique

AU - Pflueger, Axel

AU - Dunn, Stephen R.

AU - Francos, Barbara

AU - Sharma, Shoba

AU - Falkner, Bonita

AU - McGowan, Tracy A.

AU - Donohue, Michael

AU - RamachandraRao, Satish

AU - Xu, Ronghui

AU - Fervenza, Fernando C.

AU - Kopp, Jeffrey B.

PY - 2011/6/1

Y1 - 2011/6/1

N2 - Pirfenidone is an oral antifibrotic agent that benefits diabetic nephropathy in animal models, but whether it is effective for human diabetic nephropathy is unknown. We conducted a randomized, double-blind, placebo-controlled study in 77 subjects with diabetic nephropathy who had elevated albuminuria and reduced estimated GFR (eGFR) (20 to 75 ml/min per 1.73 m2). The prespecified primary outcome was a change in eGFR after 1 year of therapy. We randomly assigned 26 subjects to placebo, 26 to pirfenidone at 1200 mg/d, and 25 to pirfenidone at 2400 mg/d. Among the 52 subjects who completed the study, the mean eGFR increased in the pirfenidone 1200-mg/d group (-3.3 ± 8.5 ml/min per 1.73 m2) whereas the mean eGFR decreased in the placebo group (-2.2 ± 4.8 ml/min per 1.73 m2; P = 0.026 versus pirfenidone at 1200 mg/d). The dropout rate was high (11 of 25) in the pirfenidone 2400-mg/d group, and the change in eGFR was not significantly different from placebo (-1.9 ± 6.7 ml/min per 1.73 m 2). Of the 77 subjects, 4 initiated hemodialysis in the placebo group, 1 in the pirfenidone 2400-mg/d group, and none in the pirfenidone 1200-mg/d group during the study (P = 0.25). Baseline levels of plasma biomarkers of inflammation and fibrosis significantly correlated with baseline eGFR but did not predict response to therapy. In conclusion, these results suggest that pirfenidone is a promising agent for individuals with overt diabetic nephropathy.

AB - Pirfenidone is an oral antifibrotic agent that benefits diabetic nephropathy in animal models, but whether it is effective for human diabetic nephropathy is unknown. We conducted a randomized, double-blind, placebo-controlled study in 77 subjects with diabetic nephropathy who had elevated albuminuria and reduced estimated GFR (eGFR) (20 to 75 ml/min per 1.73 m2). The prespecified primary outcome was a change in eGFR after 1 year of therapy. We randomly assigned 26 subjects to placebo, 26 to pirfenidone at 1200 mg/d, and 25 to pirfenidone at 2400 mg/d. Among the 52 subjects who completed the study, the mean eGFR increased in the pirfenidone 1200-mg/d group (-3.3 ± 8.5 ml/min per 1.73 m2) whereas the mean eGFR decreased in the placebo group (-2.2 ± 4.8 ml/min per 1.73 m2; P = 0.026 versus pirfenidone at 1200 mg/d). The dropout rate was high (11 of 25) in the pirfenidone 2400-mg/d group, and the change in eGFR was not significantly different from placebo (-1.9 ± 6.7 ml/min per 1.73 m 2). Of the 77 subjects, 4 initiated hemodialysis in the placebo group, 1 in the pirfenidone 2400-mg/d group, and none in the pirfenidone 1200-mg/d group during the study (P = 0.25). Baseline levels of plasma biomarkers of inflammation and fibrosis significantly correlated with baseline eGFR but did not predict response to therapy. In conclusion, these results suggest that pirfenidone is a promising agent for individuals with overt diabetic nephropathy.

UR - http://www.scopus.com/inward/record.url?scp=79957670746&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79957670746&partnerID=8YFLogxK

U2 - 10.1681/ASN.2010101049

DO - 10.1681/ASN.2010101049

M3 - Article

VL - 22

SP - 1144

EP - 1151

JO - Journal of the American Society of Nephrology

JF - Journal of the American Society of Nephrology

SN - 1046-6673

IS - 6

ER -