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Cited by 108Chronic Kidney Disease and DiabetesRenal Diseases and GlomerulopathiesAcute Kidney Injury Research

Effect of Losartan on Prevention and Progression of Early Diabetic Nephropathy in American Indians With Type 2 Diabetes

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Weil, E. Jennifer, Fufaa, Gudeta, Jones, Lois I., Lovato, Tracy, Lemley, Kevin V., Hanson, Robert L., Knowler, William C., Bennett, Peter H. +3 more·2013·Diabetes
DOI 10.2337/db12-1512PMC PMC3749332
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Abstract

Angiotensin receptor blockers are renoprotective in hypertensive azotemic patients with type 2 diabetes, but their efficacy in early diabetic kidney disease is uncertain. We performed a 6-year randomized clinical trial in 169 American Indians with type 2 diabetes and normoalbuminuria (albumin/creatinine ratio [ACR] <30 mg/g; n = 91) or microalbuminuria (ACR 30–299 mg/g; n = 78) at baseline. The primary outcome was decline in glomerular filtration rate (GFR) to ≤60 mL/min or to half the baseline value in subjects who entered with GFR <120 mL/min. Another outcome was differences in glomerular structure at end of treatment. Subjects received 100 mg losartan or placebo daily. GFR was measured annually; 111 subjects underwent kidney biopsies. Only nine subjects reached the GFR outcome, and the unadjusted hazard ratio (losartan vs. placebo) was 0.50 (95% CI, 0.12–1.99). Differences in mesangial fractional volume were not estimated in the combined albuminuria groups because of an interaction with treatment assignment. In separate analyses, mesangial fractional volume was lower in subjects treated with losartan in the microalbuminuria group (18.8 vs. 25.6%; P = 0.02), but not in the normoalbuminuria group (19.6 vs. 17.8%; P = 0.86). Treatment with losartan may preserve some features of kidney structure in American Indians with type 2 diabetes and microalbuminuria.

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  • Among people with type 1 or 2 diabetes with established CKD (eGFR <60 mL/min/1.73m2 and UACR >=300 mg/g creatinine), ACE inhibitor or ARB therapy reduces the risk of progression to ESKD.

    “Antihypertensive therapy reduces the risk of albuminuria (67)(68)(69)(70), and among people with type 1 or 2 diabetes with established CKD (eGFR <60 mL/min/1.73m 2 and UACR $300 mg/g creatinine), ACE inhibitor or ARB therapy reduces the risk of progression to ESKD (71)(72)(73)(74)(75)(76)(77)(78)(79)(80).”

    From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [79]

    The introductory passage in our copy states that ARBs reduce diabetic kidney disease progression in hypertensive, azotemic patients with type 2 diabetes. It does not establish reduced progression to ESKD with ACE inhibitors or ARBs across both diabetes types in people meeting the specified eGFR and UACR thresholds. The study itself enrolled people with normoalbuminuria or microalbuminuria and measured GFR and structural outcomes, not progression to ESKD. (LLM, conf=0.85)

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  • Two long-term, double-blind studies demonstrated no renoprotective effect of either ACE inhibitors or ARBs among people with type 1 and type 2 diabetes who were normotensive with or without high albuminuria (30-299 mg/g creatinine).

    “Moreover, two long-term, double-blind studies demonstrated no renoprotective effect of either ACE inhibitors or ARBs among people with type 1 and type 2 diabetes who were normotensive with or without high albuminuria (formerly microalbuminuria, 30-299 mg/g creatinine) (78,79).”

    From 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2025 (2025) · cites this paper as [79]

    The Discussion (Conclusions; page not provided) says losartan offered no benefit for primary prevention in normoalbuminuric patients. But the Abstract reports a possible kidney-structural benefit in patients with type 2 diabetes and microalbuminuria (30–299 mg/g), so the blanket claim of no renoprotective effect with or without elevated albuminuria overstates this study. This trial tested an ARB in type 2 diabetes, not an ACE inhibitor in type 1 diabetes. (LLM, conf=0.90)

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Research works printed but not linked: 23

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Authors
Weil, E. J., Fufaa, G., Jones, L. I., Lovato, T., Lemley, K. V., Hanson, R. L., Knowler, W. C., Bennett, P. H., Yee, B., Myers, B. D., & Nelson, R. G.
Affiliations
  • National Institute of Diabetes and Digestive and Kidney Diseases (US)
  • Children's Hospital Los Angeles (US)
  • Southwest Kidney Institute (US)
  • Stanford Medicine (US)
Corresponding author
Nelson, Robert G.
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
2013-08-15
Volume
62
Issue
9
Pages
3224-3231
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/db12-1512
PMC
PMC3749332
OpenAlex
W2149450389
Cited by
108
References
3
Citations by year
2026: 2 · 2025: 5 · 2024: 6 · 2023: 16 · 2022: 10 · 2021: 12 · 2020: 10 · 2019: 6 · 2018: 5 · 2017: 7 · 2016: 12 · 2015: 5 · 2014: 6 · 2013: 6
FWCI
7.33
Type
journal article
Language
en
Update notices
correction (2018-03-01)
Open access
Licence
Locations
  • Diabetes (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
National Institutes of Health
Topics
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
  • Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
  • Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
Keywords
losartan, diabetic nephropathy, type 2 diabetes, Native Americans, angiotensin receptor blockers, microalbuminuria, normoalbuminuria, glomerular filtration rate decline, renal biopsy, renal protection, early diabetic nephropathy
MeSH terms
Adult, Aged, Diabetes Mellitus, Type 2, Diabetic Nephropathies, Female, Humans, Indians, North American, Male, Middle Aged, Losartan, Young Adult

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