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Link Between Hypertension, Kidney Complications in Patients with COVID-19 Not Well Understood

Nephrologists raise key questions about virus, role of RAS inhibitors, and kidney risk

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The kidney complications of COVID-19 have been cited frequently in early research highlighting a link between patients with hypertension and the risk of kidney failure or injury following infection with SARS-CoV-2.

But several nephrologists and clinical researchers suggest in recent commentaries that more study is needed to understand the relationship between the virus and renin-angiotensin system (RAS) inhibitors. The editorials emphasize that the risk attributable to hypertension and other comorbidities cited in early COVID-19 data—chronic kidney disease (CKD), cardiovascular disease (CVD), and diabetes mellitus (DM)—requires further research and is not confirmed.

Duke nephrologist and researcher Matthew A. Sparks, MD, is the lead author of a perspective published in April in the Clinical Journal of American Society of Nephrology. The article points out the need for social and traditional media to take a step back and consider known evidence before making quick decisions about RAS inhibition with commonly used medications and the drugs’ interaction with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

“It is becoming increasingly important for the research community to do a better job at looking at kidney indices in patients with COVID-19,” says Sparks, "We are beginning to see more data that focuses on kidney disease, but the key points are trickling out quite slowly.”

Sparks and Duke nephrologist Daniel Edmonston, MD, were among five contributors who penned a second commentary in Nature Reviews Nephrology focusing on the virus’ entry into host cells via angiotensin-converting enzyme 2 (ACE2). This entry point, the authors suggested, highlights the need to better understand the relationship between the virus, the RAS, and whether RAS inhibition is harmful or protective.

Matthew Sparks, MD
It is becoming increasingly important for the research community to do a better job at looking at kidney indices in patients with COVID-19. We are beginning to see more data that focuses on kidney disease, but the key points are trickling out quite slowly.
Matthew A. Sparks, MD, Duke nephrologist and researcher

Consideration of age as potential confounder raises questions

Early reports suggested that patients with severe COVID-19 were more likely to have a history of hypertension, CKD, CVD, or DM than those with milder disease. One of the authors’ chief concerns, Sparks says, was the fact that the preliminary findings did not account for potential sources of bias and confounding, including age, sex, baseline pulmonary disease, co-morbid conditions, or baseline medication use.

“It’s clear that consideration of age as a potential confounder is particularly important because the prevalence of hypertension increases dramatically with age,” Sparks says. The mechanisms underlying the suggested association between COVID-19 severity and hypertension are not clear, he says, but some evidence points towards a potential link with the RAS because it is associated with both viral transmission and hypertension. However, it is quite possible that use of these medications is protective.

More targeted studies will offer greater insights into the impact of the virus on the RAS, Sparks says, and will have important implications for clinical management. “We also need to be cautious not to draw inappropriate conclusions from observational studies and welcome rapid initiation of new clinical trials.” Sparks and Duke nephrology colleagues are encouraging patients to enroll in a trial related to the coronavirus that is active at Duke Health.

Sparks was also a contributor to another perspective article published in May in the Journal of the American Society of Nephrology that highlighted the importance of assessing, defining, and reporting the course of acute kidney injury (AKI) as a complication of COVID-19. Data on AKI is not thorough enough in early published research to define the pathophysiology of the condition in patients with COVID-19.