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Diabetes Metab J : Diabetes & Metabolism Journal



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Use of Renin-Angiotensin-Aldosterone System Inhibitors and Severe COVID-19 Outcomes in Patients with Hypertension: A Nationwide Cohort Study
Jae Hyun Bae, Sun Kyu Choi, Nam Hoon Kim, Juneyoung Lee, Sin Gon Kim
Diabetes Metab J. 2021;45(3):430-438.   Published online February 22, 2021
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  • 3 Crossref
Graphical AbstractGraphical Abstract AbstractAbstract PDFSupplementary MaterialPubReader   ePub   
Angiotensin-converting enzyme 2 facilitates the entry of severe acute respiratory syndrome coronavirus 2 into the human body. We investigated the association of renin-angiotensin-aldosterone system (RAAS) inhibitor use with severe coronavirus disease 2019 (COVID-19) outcomes in hypertensive patients.
We identified hypertensive patients with confirmed COVID-19 from the Korean Health Insurance Review and Assessment Service from inception to May 15, 2020. The primary outcome was the composite of intensive care unit (ICU) admission, invasive mechanical ventilation (IMV), continuous renal replacement therapy (CRRT), extracorporeal membrane oxygenation (ECMO), and death from COVID-19. The individual components were evaluated as secondary outcomes.
Of 1,374 hypertensive patients with COVID-19, 1,076 (78.3%) and 298 (21.7%) were users and never-users of RAAS inhibitors, respectively. The RAAS inhibitor users were not associated with the risk of the primary outcome (adjusted odds ratio [aOR], 0.72; 95% confidence interval [CI], 0.46 to 1.10). The risk of ICU admission was significantly lower in the users than the never-users (aOR, 0.44; 95% CI, 0.24 to 0.84). The RAAS inhibitors were beneficial only in ICU admissions that did not require IMV (aOR, 0.28; 95% CI, 0.14 to 0.58). The risk of death from COVID-19 was comparable between the groups (aOR, 1.09; 95% CI, 0.64 to 1.85). We could not evaluate the risks of CRRT and ECMO owing to the small number of events.
RAAS inhibitor use was not associated with the composite of severe outcomes in the hypertensive patients with COVID-19 but significantly lowered the risk of ICU admission, particularly in patients who did not require IMV.


Citations to this article as recorded by  
  • Systematic review and meta-analysis of the clinical outcomes of ACEI/ARB in East-Asian patients with COVID-19
    Nancy Xurui Huang, Qi Yuan, Fang Fang, Bryan P. Yan, John E. Sanderson, Masaki Mogi
    PLOS ONE.2023; 18(1): e0280280.     CrossRef
  • Renin‐Angiotensin Aldosterone System Inhibitors and COVID‐19: A Systematic Review and Meta‐Analysis Revealing Critical Bias Across a Body of Observational Research
    Jordan Loader, Frances C. Taylor, Erik Lampa, Johan Sundström
    Journal of the American Heart Association.2022;[Epub]     CrossRef
  • Renin-angiotensin-aldosterone system blockers in Bulgarian COVID-19 patients with or without chronic kidney disease
    Rumen Filev, Lionel Rostaing, Mila Lyubomirova, Boris Bogov, Krassimir Kalinov, Dobrin Svinarov
    Medicine.2022; 101(48): e31988.     CrossRef
Differential Activation of the Renal Renin-Angiotensin System Components in Diabetic Rats.
Woon Jung Kim, Mi Young Lee, Tae Hyung Kim, Eun Kyoung Yang, Won Jung Lee
Korean Diabetes J. 1998;22(2):218-230.   Published online January 1, 2001
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The renin-angiotensin system(RAS) plays an important role in the physiologic regulation of the renal microcirculation and may contribute to the imbalance of resistances present at the preglomerular and postglomerular sites whirh are responsible for glomerular capillary hypertension, a major injurious factor in the diabetic kidney. Blockade of angiotensin(Ang II) with angiotensin converting enzyme(ACE) inhibitor or Ang II receptor antagonists reduces glomerular injury. However, the relationship between diabetes and the RAS is unclear. METHOD: To investigate changes of gene expression of the renal renin-angiotensin system in diabetic nephropathy, mRNA levels of the RAS components were determined with the methods of Northern blot and RT-PCR in streptozotocin-induced diabetic(STZ-D) rats. Sprague-Dawley rats(240~260 g) were made diabetic by double i.p. injections of 45 mg/kg STZ. Result: Plasma renin concentration increased significantly at the onset of diabetes, and then suppressed at 4 and 8 week sof diabetes. Changes in renal renin content and mRNA levels were in parallel with plasma renin concentration during 8 weeks of diabetes. Renal angiotensinogen mRNA levels of the STZ-D rats decreased initially and then returned to the baseline with the progression of diabetes. Gene expression of angiotensin II-AT1 receptor subtypes, AT1a and AT1b, was not significantly changed during 8 wk of diabetes. Plasma and renal ACE activity increased significantly at 4 and 8 wk of diabetes. CONCLUSION: Results of the present study show a marked decrease in renal renin mRNA levels and renin concentration, but significant increase in ACE activity in chronic diabetic rats. When considering renoprotective effect of ACE inhibitors and AT receptor antagonists, the present result may suggest an increased intrarenal generation of Ang II and its pathophysiologic role in diabetic nephropathy. However, further studies are required to clarify meanings of the differential activation of the renal renin-angiotensin system components in diabetic rats.

Diabetes Metab J : Diabetes & Metabolism Journal