Long-term ACE Inhibitor/ARB Use Is Associated With Severe Renal Dysfunction and Acute Kidney Injury in Patients With Severe COVID-19: Results From a Referral Center Cohort in the Northeast of France

Abstract

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>In patients with severe coronavirus disease 2019 (COVID-19), data are scarce and conflicting regarding whether chronic use of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) influences disease outcomes. In patients with severe COVID-19, we assessed the association between chronic ACEI/ARB use and the occurrence of kidney, lung, heart, and liver dysfunctions and the severity of the inflammatory reaction as evaluated by biomarkers kinetics, and their association with disease outcomes.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>We performed a retrospective longitudinal cohort study on consecutive patients with newly diagnosed severe COVID-19. Independent predictors were assessed through receiver operating characteristic analysis, time-series analysis, logistic regression analysis, and multilevel modeling for repeated measures.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>On the 149 patients included in the study 30% (44/149) were treated with ACEI/ARB. ACEI/ARB use was independently associated with the following biochemical variations: phosphorus &amp;gt;40 mg/L (odds ratio [OR], 3.35, 95% confidence interval [CI], 1.83–6.14), creatinine &amp;gt;10.1 mg/L (OR, 3.22, 2.28–4.54), and urea nitrogen (UN) &amp;gt;0.52 g/L (OR, 2.65, 95% CI, 1.89–3.73). ACEI/ARB use was independently associated with acute kidney injury stage ≥1 (OR, 3.28, 95% CI, 2.17–4.94). The daily dose of ACEI/ARB was independently associated with altered kidney markers with an increased risk of +25 to +31% per each 10 mg increment of lisinopril-dose equivalent. In multivariable multilevel modeling, UN &amp;gt;0.52 g/L was independently associated with the risk of acute respiratory failure (OR, 3.54, 95% CI, 1.05–11.96).</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>Patients chronically treated with ACEI/ARB who have severe COVID-19 are at increased risk of acute kidney injury. In these patients, the increase in UN associated with ACEI/ARB use could predict the development of acute respiratory failure.</jats:p> </jats:sec>

Adverse impact of renin–angiotensin system blockade on the clinical course in hospitalized patients with severe COVID-19: a retrospective cohort study

“…Some studies did not find any relationship between the use of ACE-I or ARB and the development of AKI 31,32 . Contrary to these results, Oussalah et al reported a harmful effect of long-term ACE-I or ARB use on the renal function and further interaction with the occurrence of AKI and ARDS in 149 patients with severe COVID-19 33 . Our study highlighted the possible association between ACE-I or ARB use and a significant increase in both ARDS and AKI.…”

Pharmacotherapy in COVID-19 patients: a review of ACE2-raising drugs and their clinical safety

“…The evidence for the safety of other ACE2-raising drugs, used alone or in combination, is sparse but the majority of the studies discussed herein suggested that these drugs are not associated with adverse outcomes with exception of one study indicating increased risk of AKI in patients receiving ACEI/ARBs in severe COVID-19 disease [117]. Although the majority of clinical studies examining outcomes on COVID-19 patients have reported results for combined use of ACEIs and ARBs, it should be noted that these two drug classes have divergent cardiovascular effects and outcomes in patients [152], and perhaps future studies should aim to report results for ACEIs and ARBs separately.…”

“…A large body of evidence from clinical observational studies reported thus far, as well as our recalculation of meta-analysis data on all-cause mortality, supports continued use of ACEIs/ARBs in COVID-19 patients. Although these drugs generally appear to be clinically safe, their chronic use in severe COVID-19 patients might increase the risk of acute renal injury [117]. Evidence also exists for the beneficial effects of ACEIs/ARBs in some sub-populations of COVID-19 patients such as in lowering risk of mortality in hypertensive patients or decreasing risk of hospitalisation for COVID-19 patients with diabetes.…”

“…Thus, evidence from the literature reviewed above supports the current guidelines issued by several societies including the recent joint statement of the British Cardiovascular Society together with the British Society for Heart Failure (https://www.britishcardiovascularsociety.org/news/ ACEi-or-ARB-and-COVID-19) that COVID-19 patients can continue with their existing ACEI/ARB therapies. Based on a recent report [117], we suggest that patients with severe COVID-19 on ACEIs or ARBS should be monitored for development of renal dysfunction and AKI. However, for definitive clarity there is still a need for large scale, well-conducted randomised clinical trials as well mechanistic studies investigating the safety of the many ACE2-raising drugs that are routinely used in the clinic in COVID-19 patients.…”

“…The importance of the impact of ACEI/ARB pharmacotherapy and stage of COVID-19 disease was highlighted recently in a study from France. In a retrospective longitudinal cohort study on consecutive patients with newly diagnosed severe COVID-19 [117], chronic use of ACEIs/ARBs in 44 patients was associated with an increased risk of developing acute renal injury (AKI) stage !1 (OR, 3.28, 95% CI, 2.17-4.94). Despite the small number of patients, the authors showed that daily dose of ACEIs/ARBs was independently associated with increased risk of elevated kidney markers, such as urea nitrogen >0.52 g/L (OR, 1.26 [95% CI, 1.13-1.41] with an increased risk of þ25 to þ31% per each 10 mg increment of the lisinopril-dose equivalent.…”