Association of Treatment Effects on Early Change in Urine Protein and Treatment Effects on GFR Slope in IgA Nephropathy: An Individual Participant Meta-analysis.
GFR slope
Glomerular filtration rate (GFR)
IgA nephropathy (IgAN)
end-stage renal disease (ESRD)
kidney disease progression
meta-analysis
proteinuria
regulatory approval
renal function
surrogate end point
treatment effect
trial design
urine protein
Journal
American journal of kidney diseases : the official journal of the National Kidney Foundation
ISSN: 1523-6838
Titre abrégé: Am J Kidney Dis
Pays: United States
ID NLM: 8110075
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
received:
21
08
2020
accepted:
03
03
2021
pubmed:
30
3
2021
medline:
14
9
2021
entrez:
29
3
2021
Statut:
ppublish
Résumé
An early change in proteinuria is considered a reasonably likely surrogate end point in immunoglobulin A nephropathy (IgAN) and can be used as a basis for accelerated approval of therapies, with verification in a postmarketing confirmatory trial. Glomerular filtration rate (GFR) slope is a recently validated surrogate end point for chronic kidney disease progression and may be considered as the end point used for verification. We undertook a meta-analysis of clinical trials in IgAN to compare treatment effects on change in proteinuria versus change in estimated GFR (eGFR) slope. Individual patient-level meta-analysis. Individual data of 1,037 patients from 12 randomized trials. Randomized trials of IgAN with proteinuria measurements at baseline and 6 (range, 2.5-14) months and at least a further 1 year of follow-up for the clinical outcome. For each trial, we estimated the treatment effects on proteinuria and on the eGFR slope, computed as the total slope starting at baseline or the chronic slope starting 3 months after randomization. We used a Bayesian mixed-effects analysis to relate the treatment effects on proteinuria to effects on GFR slope across these studies and developed a prediction model for the treatment effect on the GFR slope based on the effect on proteinuria. Across all studies, treatment effects on proteinuria accurately predicted treatment effects on the total slope at 3 years (median R Study population restricted to 12 trials of small sample size, leading to wide BCIs. There was heterogeneity among trials with respect to study design and interventions. These results provide new evidence supporting that early reduction in proteinuria can be used as a surrogate end point for studies of chronic kidney disease progression in IgAN.
Identifiants
pubmed: 33775708
pii: S0272-6386(21)00502-3
doi: 10.1053/j.ajkd.2021.03.007
pmc: PMC8384669
mid: NIHMS1707566
pii:
doi:
Substances chimiques
Creatinine
AYI8EX34EU
Types de publication
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
340-349.e1Subventions
Organisme : NCATS NIH HHS
ID : UL1 TR002538
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002544
Pays : United States
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
Références
J Am Soc Nephrol. 2019 Sep;30(9):1735-1745
pubmed: 31292197
J Nephrol. 2013 Jan-Feb;26(1):86-93
pubmed: 22460183
J Am Soc Nephrol. 2019 Sep;30(9):1756-1769
pubmed: 31292198
Semin Nephrol. 2004 May;24(3):179-96
pubmed: 15156525
Nephrol Dial Transplant. 2009 Dec;24(12):3694-701
pubmed: 19628647
J Am Soc Nephrol. 2003 Jun;14(6):1578-83
pubmed: 12761258
Kidney Int Rep. 2019 Aug 19;4(11):1633-1637
pubmed: 31891005
Am J Kidney Dis. 2014 Dec;64(6):821-35
pubmed: 25441437
Am J Kidney Dis. 2006 May;47(5):751-60
pubmed: 16632013
Lancet. 1999 Mar 13;353(9156):883-7
pubmed: 10093981
Lancet Diabetes Endocrinol. 2019 Feb;7(2):128-139
pubmed: 30635226
Am J Kidney Dis. 2016 Sep;68(3):392-401
pubmed: 27032886
Am J Kidney Dis. 2012 Jun;59(6):865-73
pubmed: 22497792
J Am Soc Nephrol. 2001 Apr;12(4):791-799
pubmed: 11274240
Nephrol Dial Transplant. 2002 Jul;17(7):1197-203
pubmed: 12105241
Am J Kidney Dis. 2003 May;41(5):972-83
pubmed: 12722031
Clin J Am Soc Nephrol. 2019 Mar 7;14(3):469-481
pubmed: 30635299
Am J Kidney Dis. 2020 Jan;75(1):4-5
pubmed: 31672253
Am J Kidney Dis. 2014 Dec;64(6):848-59
pubmed: 25441438
J Am Soc Nephrol. 2007 Dec;18(12):3177-83
pubmed: 17978307
J Am Soc Nephrol. 1999 Aug;10(8):1772-7
pubmed: 10446945
Nephrol Dial Transplant. 2005 Oct;20(10):2139-45
pubmed: 16030050
Stat Med. 2019 Sep 30;38(22):4218-4239
pubmed: 31338848
Am J Kidney Dis. 2014 Jul;64(1):74-85
pubmed: 24787763
J Am Soc Nephrol. 2004 Jan;15(1):157-63
pubmed: 14694168
Kidney Int. 2014 Oct;86(4):828-36
pubmed: 24694989
J Am Soc Nephrol. 2003 Jul;14(7 Suppl 2):S154-65
pubmed: 12819322
Kidney Int. 2004 May;65(5):1842-9
pubmed: 15086925
Kidney Int. 2009 Sep;76(5):534-45
pubmed: 19571791
Nephrol Dial Transplant. 1997 Dec;12(12):2569-75
pubmed: 9430853
Ann Intern Med. 2009 May 5;150(9):604-12
pubmed: 19414839
Clin Lab. 2014;60(10):1709-15
pubmed: 25651718
Am J Kidney Dis. 2020 Jan;75(1):6-8
pubmed: 31672251
JAMA. 2017 Aug 1;318(5):432-442
pubmed: 28763548
Pediatr Nephrol. 2015 Jun;30(6):961-7
pubmed: 25487669
Clin Exp Nephrol. 2013 Aug;17(4):555-62
pubmed: 23224025
J Am Soc Nephrol. 2010 Oct;21(10):1783-90
pubmed: 20634300
J Am Soc Nephrol. 2019 Sep;30(9):1746-1755
pubmed: 31292199
Ren Fail. 2001 May-Jul;23(3-4):495-505
pubmed: 11499564
Clin Exp Nephrol. 2012 Dec;16(6):883-91
pubmed: 22618296
JAMA. 2014 Jun 25;311(24):2518-2531
pubmed: 24892770
N Engl J Med. 2012 Dec 20;367(25):2407-18
pubmed: 23121377
N Engl J Med. 2015 Dec 3;373(23):2225-36
pubmed: 26630142