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Soluble Urokinase Receptor (SuPAR) in COVID-19–Related AKI
Quick Takes
- There is an association between suPAR and AKI in patients hospitalized for COVID-19, with admission suPAR levels being a strong predictor of in-hospital AKI.
- Mechanistically, high suPAR levels modulate mitochondrial respiration and induce the generation of reactive oxygen species in proximal tubular cells, sensitizing them to additional insults.
- Targeting suPAR may be a useful strategy to mitigate AKI in COVID-19 and other patient populations at high risk of AKI, but needs to be prospectively tested.
Study Questions:
What is the association between admission soluble urokinase plasminogen activator receptor (suPAR) levels and incident acute kidney injury (AKI) in patients hospitalized for coronavirus disease 2019 (COVID-19)?
Methods:
The investigators measured suPAR levels in plasma samples from 352 adult patients that had been collected within 48 hours of admission in a multinational observational study of adult patients hospitalized for COVID-19. They examined the association between suPAR levels and incident in-hospital AKI. The primary outcome was incident AKI during the hospitalization, defined on the basis of the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Logistic regression with AKI as the binary dependent variable in models that incorporated age, sex, race, country of enrollment, body mass index, diabetes mellitus, hypertension, coronary artery disease, congestive heart failure, oxygen saturation on admission, and estimated glomerular filtration rate derived from serum creatinine level obtained from the sample in which suPAR was measured was used to identify determinants of in-hospital AKI.
Results:
Of the 352 patients (57.4% were male, 13.9% were black, and mean age was 61 years), 91 (25.9%) developed AKI during their hospitalization, of whom 25 (27.4%) required dialysis. The median suPAR level was 5.61 ng/ml. AKI incidence rose with increasing suPAR tertiles, from a 6.0% incidence in patients with suPAR <4.60 ng/ml (first tertile) to a 45.8% incidence of AKI in patients with suPAR levels >6.86 ng/ml (third tertile). None of the patients with suPAR <4.60 ng/ml required dialysis during their hospitalization. In multivariable analysis, the highest suPAR tertile was associated with a 9.15-fold increase in the odds of AKI (95% confidence interval [CI], 3.64-22.93) and a 22.86-fold increase in the odds of requiring dialysis (95% CI, 2.77-188.75). The association was independent of inflammatory markers and persisted across subgroups.
Conclusions:
The authors concluded that admission suPAR levels in patients hospitalized for COVID-19 are predictive of in-hospital AKI and the need for dialysis.
Perspective:
This study reports an association between suPAR and AKI in a multinational cohort of patients hospitalized for COVID-19. Furthermore, admission suPAR levels in these patients were found to be a strong predictor of in-hospital AKI. Mechanistically, high suPAR levels modulate mitochondrial respiration and induce the generation of reactive oxygen species in proximal tubular cells, sensitizing them to additional insults. If suPAR is confirmed as an immune-mediator of kidney injury in additional prospective studies, targeting suPAR may be a useful strategy to mitigate AKI in COVID-19 and other patient populations at high risk of AKI.
Clinical Topics: COVID-19 Hub, Diabetes and Cardiometabolic Disease, Dyslipidemia, Prevention, Lipid Metabolism, Novel Agents
Keywords: Acute Kidney Injury, Coronavirus, COVID-19, Creatinine, Dialysis, Glomerular Filtration Rate, Inflammation, Kidney Diseases, Metabolic Syndrome, Primary Prevention, Receptors, Urokinase Plasminogen Activator, Renal Dialysis, Renal Replacement Therapy, Urokinase-Type Plasminogen Activator
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