Prevention of microalbuminuria using early intervention with renin-angiotensin system inhibitors in patients with type 2 diabetes: a systematic review
Open accessAbstract
Hypothesis/objectives: Early prevention of diabetic nephropathy by way of blocking the renin-angiotensin system (RAS) in patients with normoalbuminuria seems rational, but trials have so far shown conflicting results. The present meta-analysis was undertaken to investigate if such treatment can prevent development of microalbuminuria. Materials and methods: We searched MEDLINE, EMBASE and the Cochrane Library (2 June 2014) for randomised controlled trials, with a population of patients with type 2 diabetes and normoalbuminuria, comparing angiotensin-converting enzyme inhibitors (ACEis) or angiotensin receptor blockers (ARBs) to placebo. Studies had to have at least 50 participants in each arm and one year of follow-up. Random and fixed effect models were performed as well as trial sequential analysis. Results: Six trials were included in the analysis ( n=16,921). Overall risk of bias was variable. In a fixed model analysis ACE or ARB treatment was superior to placebo in relation to prevention of development of microalbuminuria, risk ratio 0.84 (95% confidence interval (CI) 0.79–0.88) p<0.001, I 2 =23%, similar to random model results. Treatment also showed a trend towards a reduction in all-cause mortality( p=0.07). Conclusions: We conclude that in patients with type 2 diabetes and normoalbuminuria, early intervention with ACEis or ARBs reduces the risk for development of microalbuminuria.
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Available data suggest that ACEi and ARB treatments are not beneficial for patients with neither albuminuria nor elevated blood pressure.
“Available data suggest that ACEi and ARB treatments are not bene fi cial for patients with neither albuminuria nor elevated blood pressure.”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [60]
The Discussion reports that ACEi/ARB treatment reduced microalbuminuria in normoalbuminuric patients with type 2 diabetes. It says the authors could not analyze normotensive patients separately and could not rule out a similar benefit in them. The paper therefore does not suggest that treatment is unbeneficial for patients without albuminuria or elevated blood pressure. (LLM, conf=0.85)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredA review found 6 studies in normoalbuminuric T2D patients showing benefit on albuminuria progression by RAS blockade, but most patients had hypertension.
“A review found 6 studies in normoalbuminuric T2D patients showing bene fi t on albuminuria progression by RAS blockade, but most patients had hypertension. 60”
From KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (2022) · cites this paper as [60]
There is clinical inertia in treating residual hypertension among people with type 2 diabetes.
“There appears to be inertia to treat residual hypertension in persons with T2D, and pharmacotherapy should be intensified when needed to achieve BP goals.”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [251]
The Discussion recommends considering ACE inhibitors or ARBs for people with type 2 diabetes, including for hypertension, but does not assess whether clinicians fail to treat residual hypertension. The Results report baseline hypertension status, not treatment inertia. Searches for clinical inertia, residual hypertension, and treatment intensification found no passage addressing that claim. (LLM, conf=0.74)
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Self-citationThe Second Gaddum Lecture: its origins and outcomes
Bakhle, Y. S. (2019) · British Journal of Pharmacology · doi:10.1111/bph.14928 · Cited by 2 · see citing works
Hirukawa, H., Kamei, S., Kimura, T., Obata, A., Kohara, K., Tatsumi, F., Shimoda, M., Nakanishi, S., Mune, T., Kaku, K., et al. (2018) · Journal of Diabetes Research · doi:10.1155/2018/9435401 · Cited by 2 · see citing works
Rhode, H., Tautkus, B., Weigel, F., Schitke, J., Metzing, O., Boeckhaus, J., Kieß, W., Groß, O., Dost, A., & John-Kroegel, U. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25179320 · Cited by 1 · see citing works
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Diabetic Kidney Disease: Identification, Prevention, and Treatment
Caramori, M. L., & Rossing, P. R. (2022) · Springer eBooks · doi:10.1007/978-3-030-98927-9_7 · Cited by 1 · see citing works
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Proteinuria and hypertension with and without type 2 dibetes mellitus: an update
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Elliott, W. J. (2022) · Springer eBooks · doi:10.1007/978-3-030-86020-2_23
Proteinuria and Hypertension with and without Type 2 Diabetes Mellitus: 2021 Update
(2021) · The Singapore Family Physician · doi:10.33591/sfp.47.1.u1
Proteinuria and Hypertension with and without Type 2 Diabetes Mellitus: 2022 Update
(2022) · The Singapore Family Physician · doi:10.33591/sfp.48.1.u1
Cai, J., Li, Y., & Han, Y. (2026) · Cardiac Research · doi:10.1097/re9.0000000000000008
Bannuru, R. R., Fazioli, K., de Boer, I. H., Earley, A., ElSayed, N. A., Fioretto, P., Khunti, K. K., Navaneethan, S. D., Noble, M., Richardson, C., et al. (2026) · Diabetes Obesity and Cardiometabolic CARE · doi:10.2337/doci25-0014
Self-citation
- Authors
- Persson, F., Lindhardt, M., Rossing, P., & Parving, H.-H.
- Affiliations
- Steno Diabetes Centers (DK)
- University of Copenhagen (DK)
- Aarhus University (DK)
- Corresponding author
- Persson, Frederik
- Venue
- Journal of the Renin-Angiotensin-Aldosterone System
- Publisher
- SAGE Publications
- Published
- 2016-07
- Volume
- 17
- Issue
- 3
- ISSN
- 1470-3203 (ISSN-L)
- 1752-8976
- PMC
- PMC5843870
- OpenAlex
- W2488756905
- Cited by
- 54
- References
- 50
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2022: 6 · 2021: 10 · 2020: 9 · 2019: 5 · 2018: 11 · 2017: 4 · 2016: 2
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Journal of the Renin-Angiotensin-Aldosterone System (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by-nc)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- American Society of Nephrology
- Novo Nordisk
- European Association for the Study of Diabetes
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- microalbuminuria, type 2 diabetes, renin-angiotensin system inhibitors, ACE inhibitors, angiotensin receptor blockers, diabetic nephropathy prevention, normoalbuminuria, early intervention, all-cause mortality
- MeSH terms
- Albuminuria, Angiotensin-Converting Enzyme Inhibitors, Blood Pressure, Clinical Trials as Topic, Diabetes Mellitus, Type 2, Humans, Hypertension, Renin-Angiotensin System, Publication Bias
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