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Journal article

Effects of sacubitril/valsartan vs irbesartan on urine tubular biomarkers in CKD: findings from the UK HARP III trial

Alternative title:
Urine tubular biomarkers in UK HARP III
Abstract:
Introduction:
Sacubitril/valsartan shows benefits in heart failure and may have kidney protective effects. Its impact on kidney tubular health in chronic kidney disease (CKD) remains unclear. We evaluated the effects of sacubitril/valsartan on urinary markers of tubular dysfunction and injury in UK Heart and Renal Protection-III (HARP III, ISRCTN:11958993).
Methods:
Urine tubular biomarkers were measured at baseline, 3 and 6 months using first morning void or spot urine samples among 411 participants from UK HARP III. A mixed model repeated measures approach was used to quantify the study average effect of treatment on the urine biomarkers.
Results:
Compared to allocation to irbesartan, allocation to sacubitril/valsartan reduced neutrophil-gelatinase associated lipocalin (NGAL), a marker secreted in the distal tubules after ischemia and reperfusion, by 18% (95% CI: -32% to -1%). No significant changes were observed for the other biomarkers, and there was no evidence of effect modification by key baseline characteristics across all biomarkers studied. 
Conclusion:
In UK HARP-III, sacubitril/valsartan reduced urinary NGAL compared with irbesartan but did not affect other tubular biomarkers of injury, ischemia and fibrosis, suggesting limited tubular benefits, consistent with no observed effect on kidney function.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1159/000552348

Authors

More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Nuffield Department of Population Health
Sub department:
Clinical Trial Service Unit
Role:
Author
ORCID:
0000-0002-6093-5575
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Nuffield Department of Population Health
Sub department:
Clinical Trial Service Unit
Oxford college:
St Edmund Hall
Role:
Author
ORCID:
0000-0002-7940-386X
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Nuffield Department of Population Health
Sub department:
Clinical Trial Service Unit
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Nuffield Department of Population Health
Sub department:
Clinical Trial Service Unit
Role:
Author


More from this funder
Funder identifier:
https://ror.org/0187kwz08
Grant:
17/140/02
Programme:
Health Technology Assessment (HTA)
More from this funder
Funder identifier:
https://ror.org/0415cr103
More from this funder
Funder identifier:
https://ror.org/052gg0110
More from this funder
Funder identifier:
https://ror.org/02wdwnk04
More from this funder
Funder identifier:
https://ror.org/04rtjaj74


Publisher:
Karger Publishers
Journal:
American Journal of Nephrology More from this journal
Publication date:
2026-05-07
Acceptance date:
2026-04-28
DOI:
EISSN:
1421-9670
ISSN:
0250-8095


Language:
English
Keywords:
Pubs id:
2412793
Local pid:
pubs:2412793
Deposit date:
2026-04-30
ARK identifier:

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