Strong immune response underlies acute kidney injury linked to COVID-19

ROCHESTER, Minn. – Researchers at the Mayo Clinic have found that acute kidney injury associated with COVID-19 resembles kidney injury caused by sepsis, and the immune response triggered by the infection plays a central role.

The conclusions, published in Proceedings of the Mayo Clinic, also suggest that mitochondrial dysfunction – a loss of function in the production of cellular energy – is commonly seen in kidney damage linked to COVID-19. More than a third of hospitalized COVID-19 patients report acute kidney failure, and sudden kidney failure is a risk factor for in-hospital mortality, according to studies published last year.

“These results suggest that COVID-19 may induce a robust immune response in patients that contributes to kidney injury, and kidney supportive treatments should be initiated early for these patients,” says Mariam Alexander, MD, renal pathologist at the Mayo Clinic and the lead author of the study. “Our data indicate that mitochondrial damage is a potential target for therapies, some of which have recently been developed and tested in preclinical models.”

Severe COVID-19 disease is known to be associated with a systemic inflammatory response, as well as inflammation of the heart and lungs. Little research is available on the immune response in the kidneys, and molecular studies on renal pathology in COVID-19 patients have been limited.

“To our knowledge, this is the first comprehensive study examining the molecular and cellular changes observed in kidney damage associated with COVID-19,” said Dr. Alexander.

The Mayo Clinic study evaluated the kidneys of 17 adults who died from COVID-19 and underwent an autopsy in Mayo between April 2020 and October 2020. Researchers described the pathological spectrum of COVID-19-related kidney injury and characterized its molecular profile, relative to injuries associated with sepsis.

According to the study, the morphological and molecular profile of severe kidney damage from COVID-19 resembles kidney damage from sepsis, including microvascular dysfunction, inflammation, and metabolic reprogramming.

“The acute kidney injury seen in COVID-19 is likely secondary to activation of the immune system, similar to what is seen in patients with sepsis,” says Dr. Alexander. “COVID-19 kidneys are inflamed and have an increased rate of cell death, including more mitochondrial damage, compared to kidneys with non-COVID-19 damage.” Mitochondria are cellular structures that generate much of the chemical energy necessary for cells to function properly.

Of COVID-19 patients admitted to hospital intensive care units, 76% have acute kidney failure. According to data published in the Journal of the American Society of Nephrology, COVID-19 hospital patients with secondary acute kidney disease have an almost 50% risk of death, compared to 8% among those without kidney failure.

The 17 patients in the Mayo Clinic study had a median age of 78 and 15 were men. Most had been hospitalized more than five days before death and 53% reported hypertension as a comorbidity. The other main comorbidities included diabetes and cardiovascular disease.

“The complex integrated imaging and molecular tests used in this study pave the way for performing similar molecular analyzes in different diseases to study immune-mediated kidney damage in native and transplant settings,” says Timucin Taner , MD, Ph.D., a Mayo Clinic transplant surgeon, immunologist and senior author. “We currently have several projects using this approach, with the aim of identifying the underlying mechanisms of different diseases, so that we can help doctors treat these conditions more effectively.”

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About Proceedings of the Mayo Clinic

Proceedings of the Mayo Clinic is a peer-reviewed monthly journal that publishes original articles and journals in clinical and laboratory medicine, clinical research, basic scientific research, and clinical epidemiology. Proceedings of the Mayo Clinic is sponsored by the Mayo Foundation for Medical Education and Research as part of its commitment to physician education. The journal has been published since 1926 and has a circulation of 127,000 copies.

About the Mayo Clinic

Mayo Clinic is a non-profit organization committed to innovation in clinical practice, education, and research, and providing compassion, expertise, and answers to all in need of healing. Visit the Mayo Clinic News Network for more information on the Mayo Clinic. For more information on COVID-19, including the Mayo Clinic Coronavirus Map Tracker, which has 14-day forecasts of case trends nationwide, visit the Resource Center Mayo Clinic COVID-19.

Media contact:

Bob Nellis, Mayo Clinic Public Affairs, [email protected]

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