Acute kidney injury (AKI) among patients hospitalized with COVID-19 portends severe disease, major adverse cardiac events (MACEs), and death, even outside of the ICU, a new study finds.

“Our large study that includes multiple US health centers confirms a strong connection between the presence of AKI and mortality in COVID‐19,” James de Lemos, MD, of the University of Texas Southwestern Medical Center in Dallas, Texas, and colleagues stated in the Journal of the American Heart Association.

The investigators analyzed data from 8574 patients with COVID-19 from 88 US hospitals within The American Heart Association COVID‐19 Cardiovascular Disease Registry. Based on admission or in-patient serum creatinine values meeting modified Kidney Disease Improving Global Outcomes guideline definitions, 16% of the cohort had AKI.

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AKI stage 1, 2, and 3 significantly correlated with 1.7-, 1.8-, and 1.7-fold increased risks for all-cause mortality, respectively, the investigators reported. In a novel finding, AKI stage 1, 2, and 3 also significantly correlated with 2.2-, 2.7-, and 3.1-fold increased risks, respectively, for a secondary MACE endpoint, including cardiovascular death, nonfatal stroke or myocardial infarction, new-onset heart failure, and cardiogenic shock.

Results remained robust even after the researchers stratified and adjusted the data by in‐hospital complications that may cause AKI, such as shock, cardiac arrest, and respiratory failure requiring mechanical ventilation. They also adjusted the multivariate model for age, sex, race/ethnicity, insurance status, smoking, diabetes mellitus, hypertension, prior cardiovascular disease, and chronic kidney disease (CKD). AKI did not independently associate with thromboembolic complications.

Patients with CKD and end‐stage kidney disease (ESKD) did not have significantly increased risks for all-cause mortality and MACE after adjustments. Due to the lack of pre-admission creatinine measurements, some patients with CKD may have been misclassified as having AKI, the researchers acknowledged. Data on proteinuria, hematuria, and urine sediment were also lacking.

The timing of AKI in patients with COVID‐19 was not captured. The investigators suggested that “AKI in patients with COVID‐19 may be both an outcome of critical illness and an exposure that contributes to adverse outcomes.”

Dr de Lemos’ team discussed possible direct and indirect mechanisms linking COVID-19, AKI, and adverse events. SARS‐CoV‐2 may enter cells via the angiotensin‐converting enzyme 2 (ACE2) receptor. The virus may downregulate the function of ACE2, permitting angiotensin II to accumulate and leading to vasoconstriction and inflammation. “These broad pernicious effects of SARS‐CoV‐2 on ACE2 may thus contribute both to AKI and the higher rates of MACEs among patients with AKI observed in our study,” the investigators wrote. They also noted that common causes of AKI in hospitalized patients appear to play a role in the development of AKI in patients with COVID‐19 and may contribute to MACEs and death.

Dr de Lemos’ team believes their study findings have potential clinical implications for patients hospitalized with COVID‐19.

“First, the significant association between AKI and mortality in stratified analyses of patients without major complications suggests that kidney injury is an important marker of future adverse outcomes in COVID‐19 and is not merely a manifestation of higher disease acuity,” they wrote. “Second, the novel findings regarding MACEs suggest that when AKI is detected, heightened awareness for cardiovascular complications is warranted.”

According to the investigators, clinicians should closely monitor infected patients for hemodynamic fluctuations, maintain fluid homeostasis, and avoid nephrotoxins, such as iodinated contrast and nonsteroidal anti‐inflammatory drugs. They noted that patients with AKI, CKD, or ESKD were more likely to present with confusion as a COVID-19 symptom, and less likely to report headache, anosmia, myalgias, nasal congestion, sore throat, and nausea.

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures. 


Rao A, Ranka S, Ayers C, et al. Association of kidney disease with outcomes in COVID-19: results from the American Heart Association COVID-19 cardiovascular disease registry. J Am Heart Assoc. Published online June 10, 2021. doi:10.1161/JAHA.121.020910