Effect of sodium–glucose cotransporter-2 inhibitors on aldosterone-to-renin ratio in diabetic patients with hypertension: a retrospective observational study

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Abstract

Background

Plasma aldosterone-to-renin ratio (ARR) is popularly used for screening primary aldosteronism (PA). Some medications, including diuretics, are known to have an effect on ARR and cause false-negative and false-positive results in PA screening. Currently, there are no studies on the effects of sodium–glucose cotransporter-2 (SGLT2) inhibitors, which are known to have diuretic effects, on ARR. We aimed to investigate the effects of SGLT2 inhibitors on ARR.

Methods

We employed a retrospective design; the study was conducted from April 2016 to December 2018 and carried out in three hospitals. Forty patients with diabetes and hypertension were administered SGLT2 inhibitors. ARR was evaluated before 2 to 6 months after the administration of SGLT2 inhibitors to determine their effects on ARR.

Results

No significant changes in the levels of ARR (90.9 ± 51.6 vs. 81.4 ± 62.9) were found. Body mass index, diastolic blood pressure, heart rate, fasting plasma glucose, and hemoglobin A1c were significantly decreased by SGLT2 inhibitors. Serum creatinine was significantly increased.

Conclusion

SGLT2 inhibitor administration yielded minimal effects on ARR and did not increase false-negative results in PA screening in patients with diabetes and hypertension more than 2 months after administration.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12902-020-00656-8.

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Most cited references 45

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The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline.

John Funder, Robert Carey, Franco Mantero … (2016)

To develop clinical practice guidelines for the management of patients with primary aldosteronism.

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Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes Mellitus: Cardiovascular and Kidney Effects, Potential Mechanisms, and Clinical Applications.

Hiddo J.L. Heerspink, Bruce A. Perkins, David H. Fitchett … (2016)

Sodium-glucose cotransporter-2 (SGLT2) inhibitors, including empagliflozin, dapagliflozin, and canagliflozin, are now widely approved antihyperglycemic therapies. Because of their unique glycosuric mechanism, SGLT2 inhibitors also reduce weight. Perhaps more important are the osmotic diuretic and natriuretic effects contributing to plasma volume contraction, and decreases in systolic and diastolic blood pressures by 4 to 6 and 1 to 2 mm Hg, respectively, which may underlie cardiovascular and kidney benefits. SGLT2 inhibition also is associated with an acute, dose-dependent reduction in estimated glomerular filtration rate by ≈5 mL·min(-1)·1.73 m(-2) and ≈30% to 40% reduction in albuminuria. These effects mirror preclinical observations suggesting that proximal tubular natriuresis activates renal tubuloglomerular feedback through increased macula densa sodium and chloride delivery, leading to afferent vasoconstriction. On the basis of reduced glomerular filtration, glycosuric and weight loss effects are attenuated in patients with chronic kidney disease (estimated glomerular filtration rate 30% reductions in cardiovascular mortality, overall mortality, and heart failure hospitalizations associated with empagliflozin, even though, by design, the hemoglobin A1c difference between the randomized groups was marginal. Aside from an increased risk of mycotic genital infections, empagliflozin-treated patients had fewer serious adverse events, including a lower risk of acute kidney injury. In light of the EMPA-REG OUTCOME results, some diabetes clinical practice guidelines now recommend that SGLT2 inhibitors with proven cardiovascular benefit be prioritized in patients with type 2 diabetes mellitus who have not achieved glycemic targets and who have prevalent atherosclerotic cardiovascular disease. With additional cardiorenal protection trials underway, sodium-related physiological effects of SGLT2 inhibitors and clinical correlates of natriuresis, such as the impact on blood pressure, heart failure, kidney protection, and mortality, will be a major management focus.

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Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus.

Vesta Lai, Nima Soleymanlou, Alana Lee … (2014)

The primary objective of this mechanistic open-label, stratified clinical trial was to determine the effect of 8 weeks' sodium glucose cotransporter 2 inhibition with empagliflozin 25 mg QD on renal hyperfiltration in subjects with type 1 diabetes mellitus (T1D). Inulin (glomerular filtration rate; GFR) and paraaminohippurate (effective renal plasma flow) clearances were measured in individuals stratified based on having hyperfiltration (T1D-H, GFR ≥ 135 mL/min/1.73m(2), n=27) or normal GFR (T1D-N, GFR 90-134 mL/min/1.73m(2), n=13) at baseline. Renal function and circulating levels of renin-angiotensin-aldosterone system mediators and NO were measured under clamped euglycemic (4-6 mmol/L) and hyperglycemic (9-11 mmol/L) conditions at baseline and end of treatment. During clamped euglycemia, hyperfiltration was attenuated by -33 mL/min/1.73m(2) with empagliflozin in T1D-H, (GFR 172±23-139±25 mL/min/1.73 m(2), P<0.01). This effect was accompanied by declines in plasma NO and effective renal plasma flow and an increase in renal vascular resistance (all P<0.01). Similar significant effects on GFR and renal function parameters were observed during clamped hyperglycemia. In T1D-N, GFR, other renal function parameters, and plasma NO were not altered by empagliflozin. Empagliflozin reduced hemoglobin A1c significantly in both groups, despite lower insulin doses in each group (P≤0.04). In conclusion, short-term treatment with the sodium glucose cotransporter 2 inhibitor empagliflozin attenuated renal hyperfiltration in subjects with T1D, likely by affecting tubular-glomerular feedback mechanisms. http://www.clinicaltrials.gov. Unique identifier: NCT01392560.

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Author and article information

Contributors

Toshitaka Sawamura: sawaa4211@gmail.com

Shigehiro Karashima:

ORCID: http://orcid.org/0000-0002-4084-9653

skarashima@staff.kanazawa-u.ac.jp

Satoshi Nagase: kenzi@stu.kanazawa-u.ac.jp

Hidetaka Nambo: nambo@blitz.ec.t.kanazawa-u.ac.jp

Eiko Shimizu: pleasefor1979@gmail.com

Takuya Higashitani: popfunfun@yahoo.co.jp

Daisuke Aono: daisukeaono2007@yahoo.co.jp

Azusa Ohbatake: azusa_k_23@yahoo.co.jp

Mitsuhiro Kometani: kometankomekome@yahoo.co.jp

Masashi Demura: m-demura@med.kanazawa-u.ac.jp

Kenji Furukawa: kenjif-knz@umin.ac.jp

Yoshiyu Takeda: takeday@med.kanazawa-u.ac.jp

Takashi Yoneda: endocrin@med.kanazawa-u.ac.jp

Journal

Journal ID (nlm-ta): BMC Endocr Disord

Journal ID (iso-abbrev): BMC Endocr Disord

Title: BMC Endocrine Disorders

Publisher: BioMed Central (London )

ISSN (Electronic): 1472-6823

Publication date (Electronic): 30 November 2020

Publication date PMC-release: 30 November 2020

Publication date Collection: 2020

Volume: 20

Electronic Location Identifier: 177

Affiliations

[1 ]GRID grid.9707.9, ISNI 0000 0001 2308 3329, Division of Endocrine and Diabetes, Department of Internal Medicine, , Kanazawa University Graduate School of Medicine, ; 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641 Japan

[2 ]GRID grid.415124.7, ISNI 0000 0001 0115 304X, Division Department of Diabetes and Endocrinology and Internal Medicine, , Fukui Prefectural Hospital, ; 2-8-1 Yotsui, Fukui, Fukui 910-8526 Japan

[3 ]GRID grid.9707.9, ISNI 0000 0001 2308 3329, Department of Laboratory Sciences, Faculty of Health Sciences, , Kanazawa University, ; Kanazawa, Japan

[4 ]GRID grid.9707.9, ISNI 0000 0001 2308 3329, School of Electrical, Information and Communication Engineering, College of Science and Engineering, Kanazawa University, ; Kanazawa, Japan

[5 ]GRID grid.9707.9, ISNI 0000 0001 2308 3329, Department of Hygiene, , Kanazawa University Graduate School of Medicine, ; 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641 Japan

[6 ]GRID grid.444515.5, ISNI 0000 0004 1762 2236, Health Care Center, , Japan Advanced Institute of Science and Technology, ; 1-1 Asahidai, Nomi, Ishikawa 923-1292 Japan

[7 ]Division Department of Internal Medicine, Houju memorial hospital, 11-71 Midorigaoka, Nomi, Ishikawa 923-1226 Japan

[8 ]GRID grid.9707.9, ISNI 0000 0001 2308 3329, Institute of Liberal Arts and Science, Kanazawa University, ; 13-1 Takara-machi, Kanazawa, Ishikawa 920-8641 Japan

[9 ]GRID grid.9707.9, ISNI 0000 0001 2308 3329, Department of Health Promotion and Medicine of the Future, , Kanazawa University, ; 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641 Japan

Author information

Shigehiro Karashima http://orcid.org/0000-0002-4084-9653

Article

Publisher ID: 656

DOI: 10.1186/s12902-020-00656-8

PMC ID: 7706199

PubMed ID: 33256676

SO-VID: f548e4ec-a7fa-4e6a-b9b0-00e9d2d1fa83

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 28 June 2020

Date accepted : 20 November 2020

Custom metadata

ScienceOpen disciplines: Endocrinology & Diabetes

Keywords: sglt2 inhibitor,aldosterone-to-renin ratio,renin-angiotensin-aldosterone system,primary aldosteronism,diabetes,hypertension

Data availability:

ScienceOpen disciplines: Endocrinology & Diabetes

Keywords: sglt2 inhibitor, aldosterone-to-renin ratio, renin-angiotensin-aldosterone system, primary aldosteronism, diabetes, hypertension

Effect of sodium–glucose cotransporter-2 inhibitors on aldosterone-to-renin ratio in diabetic patients with hypertension: a retrospective observational study

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Abstract

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Methods

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Supplementary Information

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Bioscientifica Open Endocrinology

Most cited references 45

The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline.

Sodium Glucose Cotransporter 2 Inhibitors in the Treatment of Diabetes Mellitus: Cardiovascular and Kidney Effects, Potential Mechanisms, and Clinical Applications.

Renal hemodynamic effect of sodium-glucose cotransporter 2 inhibition in patients with type 1 diabetes mellitus.

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