Lisinopril versus lisinopril and losartan for mild childhood IgA nephropathy: a randomized controlled trial (JSKDC01 study).
Adolescent
Child
Child, Preschool
Drug Therapy, Combination
/ adverse effects
Female
Glomerulonephritis, IGA
/ complications
Humans
Kidney Glomerulus
/ pathology
Lisinopril
/ administration & dosage
Losartan
/ administration & dosage
Male
Prospective Studies
Proteinuria
/ diagnosis
Severity of Illness Index
Treatment Outcome
Children
IgA nephropathy
Lisinopril
Losartan
Randomized controlled trial
Journal
Pediatric nephrology (Berlin, Germany)
ISSN: 1432-198X
Titre abrégé: Pediatr Nephrol
Pays: Germany
ID NLM: 8708728
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
26
06
2018
accepted:
24
09
2018
revised:
23
09
2018
pubmed:
5
10
2018
medline:
6
5
2020
entrez:
5
10
2018
Statut:
ppublish
Résumé
Persistent proteinuria seems to be a risk factor for progression of renal disease. Its reduction by angiotensin-converting inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) is renoprotective. Our previous pilot study showed that 2-year lisinopril therapy is effective and safe for children with mild IgA nephropathy. When combined with ACEI and ARB, reported results are of greater decrease in proteinuria than monotherapy in chronic glomerulonephritis, including IgA nephropathy. To date, however, there have been no randomized controlled trials in children. This is an open-label, multicenter, prospective, and randomized phase II controlled trial of 63 children with biopsy-proven proteinuric mild IgA nephropathy. We compared efficacy and safety between patients undergoing lisinopril monotherapy and patients undergoing combination therapy of lisinopril and losartan to determine better treatment for childhood proteinuric mild IgA nephropathy. There was no difference in proteinuria disappearance rate (primary endpoint) between the two groups (cumulative disappearance rate of proteinuria at 24 months: 89.3% vs 89% [combination vs monotherapy]). Moreover, there were no significant differences in side effects between the two groups. We propose lisinopril monotherapy as treatment for childhood proteinuric mild IgA nephropathy as there are no advantages of combination therapy. Clinical trial registry, UMIN ID C000000006, https://www.umin.ac.jp .
Sections du résumé
BACKGROUND
Persistent proteinuria seems to be a risk factor for progression of renal disease. Its reduction by angiotensin-converting inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) is renoprotective. Our previous pilot study showed that 2-year lisinopril therapy is effective and safe for children with mild IgA nephropathy. When combined with ACEI and ARB, reported results are of greater decrease in proteinuria than monotherapy in chronic glomerulonephritis, including IgA nephropathy. To date, however, there have been no randomized controlled trials in children.
METHODS
This is an open-label, multicenter, prospective, and randomized phase II controlled trial of 63 children with biopsy-proven proteinuric mild IgA nephropathy. We compared efficacy and safety between patients undergoing lisinopril monotherapy and patients undergoing combination therapy of lisinopril and losartan to determine better treatment for childhood proteinuric mild IgA nephropathy.
RESULTS
There was no difference in proteinuria disappearance rate (primary endpoint) between the two groups (cumulative disappearance rate of proteinuria at 24 months: 89.3% vs 89% [combination vs monotherapy]). Moreover, there were no significant differences in side effects between the two groups.
CONCLUSIONS
We propose lisinopril monotherapy as treatment for childhood proteinuric mild IgA nephropathy as there are no advantages of combination therapy.
CLINICAL TRIAL REGISTRATION
Clinical trial registry, UMIN ID C000000006, https://www.umin.ac.jp .
Identifiants
pubmed: 30284023
doi: 10.1007/s00467-018-4099-8
pii: 10.1007/s00467-018-4099-8
doi:
Substances chimiques
Lisinopril
E7199S1YWR
Losartan
JMS50MPO89
Banques de données
UMIN-CTR
['C000000006']
Types de publication
Clinical Trial, Phase II
Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
837-846Commentaires et corrections
Type : CommentIn
Références
Pediatrics. 2000 Jun;105(6):1242-9
pubmed: 10835064
Pediatr Nephrol. 2008 Jun;23(6):905-12
pubmed: 18224344
Semin Nephrol. 2004 Mar;24(2):158-67
pubmed: 15017528
Semin Nephrol. 1997 Sep;17(5):431-40
pubmed: 9316211
Hypertens Res. 2004 Dec;27(12):963-70
pubmed: 15894837
Pediatr Nephrol. 2009 Apr;24(4):845-9
pubmed: 18825420
J Am Soc Nephrol. 2003 Jun;14(6):1578-83
pubmed: 12761258
N Engl J Med. 1996 Apr 11;334(15):939-45
pubmed: 8596594
N Engl J Med. 2002 Sep 5;347(10):738-48
pubmed: 12213946
Am J Med. 2001 Apr 15;110(6):434-7
pubmed: 11331053
Kidney Int. 2004 Jan;65(1):341-55
pubmed: 14675076
BMJ Open. 2017 Apr 7;7(4):e012674
pubmed: 28389482
Clin Nephrol. 2005 Jul;64(1):35-40
pubmed: 16047643
Int J Clin Pract. 2012 Oct;66(10):917-23
pubmed: 22994326
Ren Fail. 2007;29(4):441-6
pubmed: 17497466
Stat Med. 2001 Apr 15;20(7):1051-60
pubmed: 11276035
Kidney Int. 2018 Feb;93(2):460-469
pubmed: 28927644
BMJ Open. 2016 Dec 21;6(12):e012690
pubmed: 28003286
J Am Soc Nephrol. 2003 Nov;14(11):2861-72
pubmed: 14569096
Lancet. 2008 Aug 16;372(9638):547-53
pubmed: 18707986
Clin J Am Soc Nephrol. 2015 Dec 7;10(12):2159-69
pubmed: 26482258
J Clin Invest. 1988 Jul;82(1):322-30
pubmed: 3392211
Circulation. 2001 Oct 16;104(16):1985-91
pubmed: 11602506
J Pediatr. 1987 Apr;110(4):555-60
pubmed: 3550023
J Am Soc Nephrol. 2007 Jun;18(6):1880-8
pubmed: 17513327
Semin Nephrol. 2001 Nov;21(6):544-53
pubmed: 11709802
Cancer Treat Rep. 1985 Dec;69(12):1375-81
pubmed: 4075313
Am J Kidney Dis. 2006 May;47(5):751-60
pubmed: 16632013
Am J Kidney Dis. 2001 Jul;38(1):18-25
pubmed: 11431176