Patients who contract COVID-19 are at increased risk for pulmonary and extrapulmonary complications following their acute illness, a condition referred to as “long COVID.” Adverse kidney outcomes are a critical component of long COVID, so post-acute COVID-19 care should involve close attention to kidney problems, according to investigators.
A study of 1,726,683 US veterans identified from March 1, 2020 to March 15, 2021, showed that after the acute phase of COVID-19, 30-day survivors exhibited higher risks for acute kidney injury (AKI), a steep decline in established glomerular filtration rate (eGFR), end-stage kidney disease (ESKD), and major adverse kidney events (MAKE).
“The most surprising finding was that the risk was evident even among people whose acute COVID disease was mild and did not necessitate hospitalization,” said senior study author Ziyad Al-Aly, MD, director of the Clinical Epidemiology Center and chief of the Research and Education Service at the Veterans Affairs St. Louis Health Care System in Missouri. “This represents the lion’s share of people with COVID-19.”
Dr Al-Aly’s team published their findings in the Journal of the American Society of Nephrology.
The study cohort included 89,216 30-day COVID-19 survivors and 1,637,467 uninfected controls. Patients were categorized by care setting into non-hospitalized and hospitalized patients and those admitted to an intensive care unit (ICU). The COVID-19 patients in the study were mostly men in their late 60s. However, the researchers also analyzed data from 151,289 women (8,817 with COVID-19) and adults of all ages. Among the COVID-19 patients, 12,376 (13.9%) required hospitalization, including 4146 (4.6%) who were admitted to ICUs. The researchers adjusted for predefined demographic and health characteristics, and algorithmically selected high dimensional covariates that included diagnoses, medications, and laboratory test results.
Renal Risks by COVID-19 Severity
The median follow-up time was 164 days for the COVID-19 group and 172 days for the control group. After the initial 30 days of COVID-19 infection, 4,757 (5.3%) patients experienced an eGFR decrease of 30% or more. Compared with uninfected controls, patients who had milder COVID-19 cases (that is, not hospitalized) had a 9% increased risk for an eGFR decline of 30% or more compared with uninfected controls. The risk for an eGFR decrease of 30% or more increased 2-fold and 3-fold for hospitalized patients not in ICUs and those admitted to ICUs, respectively.
Patients who had COVID-19 that did not require hospitalization had a significant 30%, 15%, and 215% higher risks for AKI, MAKE, and ESKD, respectively. The risk increased for patients hospitalized for COVID-19, especially for those admitted to an ICU. ICU patients had significant, 8-fold, 7-fold, and 13-fold higher risks for AKI, MAKE, and ESKD, respectively, compared with controls.
More than 40 million people in the US have been diagnosed with COVID-19 since the pandemic started in early 2020. Based on the new findings, Dr Al-Aly and colleagues estimate that 510,000 of those individuals could have kidney injury or disease.
Early Detection Important
“People who had COVID will need care and attention to ensure early detection and recognition of kidney disease and care strategies to mitigate further loss of kidney function and to avoid further progression of kidney disease,” Dr Al-Aly said. “We think that post-acute COVID care clinics should certainly integrate a kidney care component.”
“The main limitation is that findings from our VA data may not be generalizable to other populations,” Dr Al-Aly said. “The strengths are the large size — in fact the largest kidney study to date — the long follow-up, and the use of advanced statistical methods to estimate risks and burdens of kidney disease in COVID-19.”
Commenting on the new findings, Anupam Agarwal, MD, professor of nephrology and director of the Division of Nephrology at the University of Alabama at Birmingham School of Medicine, said the new study highlights the significant risk of not only AKI, but the long-term reduction in kidney function presenting either as chronic kidney disease or ESKD following COVID-19 infection. “While common knowledge portrays the lung, heart and other organs as key targets for the long-term sequelae of COVID-19, this work clearly attests to the kidney-related complications after COVID-19 infection,” said Dr Agarwal, who is a past president of the American Society of Nephrology.
“I think it is important to understand the mechanisms of kidney injury in COVID-19 to implement specific treatments,” said Gabriela Garcia, MD, from the Division of Renal Diseases at the University of Colorado Anschutz Medical Campus in Aurora.
She and her colleagues have conducted research, published recently in Kidney International, showing that both mRNA and protein expression of ACE2 is reduced in models of inflammation targeting glomeruli and tubulointerstitium compared to a normal kidney.2 They hypothesize that downregulation of the ACE2/angiotensin 1-7 pathway may account for higher kidney complications in these patients.
“Our hypothesis is in line with reports suggesting inflammation (cytokine storm syndrome) as a mechanism of kidney damage in COVID19 infection,” Dr Garcia said.
Jochen Reiser, MD, PhD, professor and chairman of medicine at RUSH University Medical Center in Chicago, Illinois, pointed out that patients discharged from the hospital after having had some degree of AKI may improve, but they may not necessarily come back to the same hospital and may be lost to follow-up. “Even so, it’s not entirely clear what happens to these patients’ kidney function over a longer period of time,” Dr Reiser said. “We will need to create better system for follow-up of patients with COVID and kidney problems.” Nephrologists will need to adapt to ensure that adequate surveillance protocols are in place.
Anjay Rastogi, MD, professor and clinical chief of nephrology at the UCLA’s David Geffen School of Medicine in Los Angeles, California, said the most notable finding from the study is that even patients with mild COVID-19 cases may have long-term kidney dysfunction. Planning is underway at his institution to implement surveillance of these patients by their healthcare providers, Dr Rastogi said. “This is about primary prevention.”
Through electronic health records it will be easy to flag and monitor all these individuals with blood and urine tests. “Patients should be counseled on keeping their kidneys as healthy as possible by implementing and adopting appropriate life style changes among other things. There is also an age dependent decline in kidney function so you can counsel them on how to slow down the decline,” Dr Rastogi said. “This is an evolving field.”
- Bowe B, Xie Y, Xu E, et al. Kidney outcomes in long COVID. J Am Soc Nephrol. Published online September 1, 2021. doi:10.1681/ASN.2021060734
- Garcia GE, Truong LD, and Johnson RJ. ACE2 decreased expression during kidney inflammatory diseases: Implications to predisposing to COVID 19 kidney complications. Kidney Int. Published online August 30, 2021. doi:10.1016/j.kint.2021.08.016