# Extracorporeal SuPAR Extraction to Prevent COVID-19-associated Acute Kidney Injury

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $326,710

## Abstract

Abstract
Acute kidney injury (AKI) is a global problem that affects one in five hospitalized adults worldwide. It has a
major impact on morbidity and healthcare utilization, with small changes in kidney function shown to be
associated with both short and long-term complications. AKI is a characteristic feature of the disease caused
by the SARS-CoV-2 virus, coronavirus disease 19 (COVID-19), with close to 50% of hospitalized patients
developing acute kidney injury (AKI) and 20% of patients requiring dialysis. The pathophysiology of AKI is
complex and dependent on both intrinsic factors (age, co-morbid diabetes, hypertension, pre-existing kidney
disease) and extrinsic factors (nephrotoxic drugs, hypovolemia, intra-arterial contrast, infections). Inflammation
is an under-explored but crucial link between intrinsic and extrinsic factors in the pathogenesis of AKI. We have
identified soluble urokinase plasminogen activator receptor (suPAR) as an immune-derived mediator of kidney
injury. The expression of suPAR by immune cells is heavily induced by various stimuli, notably RNA viruses
such as SARS-CoV-2. High levels of suPAR in circulation are strongly predictive of kidney dysfunction, with
prolonged exposure directly affecting the kidneys by pathologic activation of αvβ3 integrins expressed on
podocytes, resulting in activation of GTPase, podocyte effacement and subsequent proteinuria. We have
recently shown high suPAR levels predisposes patients to AKI in various clinical scenarios including the
critically ill, likely by modulating mitochondrial respiration and inducing reactive oxygen species generation in
proximal tubular cells, sensitizing them to additional insults. Most importantly, effects of suPAR on the kidneys
were abrogated using anti-suPAR in experimental models, suggesting suPAR is a promising therapeutic target
to mitigate AKI. We have found that suPAR is dramatically elevated in COVID-19 and independently predictive
of AKI. Despite the significant burden of AKI overall and specifically in COVID-19, there has been little
progress in the prevention and treatment of AKI. We hypothesize that suPAR extraction early in the
hospitalization of patients with COVID-19 may decrease the risk of moderate to severe AKI. To that end we
have planned a phase 1 clinical trial randomizing adult patients hospitalized for COVID-19 who have high
suPAR levels to daily extracorporeal extraction of suPAR by apheresis using a suPAR-specific adsorber, or
sham treatment for a total of 5 days. The primary outcome of the trial is the occurrence of treatment-related
serious adverse events. Exploratory outcomes include the incidence of AKI, respiratory failure, and in-hospital
mortality. We will assess the kinetics of suPAR extraction by measuring daily levels prior to and post-treatment,
in addition to its impact on markers of inflammation and kidney function. The proposed work is innovative in
that it is the first trial targeting an immune-derived factor for prevent...

## Key facts

- **NIH application ID:** 10362860
- **Project number:** 1R01DK128012-01A1
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Salim Hayek
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $326,710
- **Award type:** 1
- **Project period:** 2021-09-20 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10362860

## Citation

> US National Institutes of Health, RePORTER application 10362860, Extracorporeal SuPAR Extraction to Prevent COVID-19-associated Acute Kidney Injury (1R01DK128012-01A1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10362860. Licensed CC0.

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