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Could urine tests predict kidney injury and mortality in COVID-19?
A team of scientists from the Columbia University, New York, has recently identified a potential biomarker to predict acute kidney injury in coronavirus disease 2019 (COVID-19) patients. By analyzing urine samples of 444 COVID-19 patients, they have revealed that the urinary level of neutrophil gelatinase-associated lipocalin (NGAL) can be used to determine the severity and duration of acute kidney and tubular injuries, as well as to predict the risk of mortality in acute COVID-19 patients. The study is currently available on the medRxiv* preprint server.
Background
Elevated serum level of creatinine is a commonly used marker to predict acute kidney function loss in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, it is not a reliable maker to diagnose subtotal kidney damage or kidney injuries in the early stages. Moreover, the anatomical and physiological causes of kidney function loss cannot be predicted by serum creatinine levels.
According to the literature, urinary NGAL and kidney injury marker-1 (KIM-1) are two sensitive markers for detecting kidney and tubular injuries. Since these two molecules are derived from different segments of the kidney, they can accurately differentiate between volume depletion and acute tubular injury in real-time.
Given these observations, the scientists from the Columbia University have investigated whether urinary levels of NGAL and KIM-1 can detect acute kidney and tubular injuries in COVID-19 patients, as well as predict the clinical consequences of the disease.
Study design
The scientists collected urine and blood samples from 444 patients who tested positive for SARS-CoV-2 via reverse transcription-polymerase chain reaction (RT-PCR). The samples were collected immediately after hospital admission and within 1 day of a positive viral test in 70% of patients.
In the urine samples, NGAL, KIM-1, and proteinuria were measured, and the levels were correlated with the clinical data. The baseline serum creatinine was determined for each patient by assessing previously available data. A more than 50% increase in serum creatinine from the baseline was interpreted as a loss of kidney excretory function (acute kidney injury).
The stages of acute kidney injury were determined using serum creatinine kinetics. From the baseline, 1.5 to 2-fold, 2 to 3-fold, and more than 3-fold increase in serum creatinine levels were considered as stage 1, stage 2, and stage 3 acute kidney injury, respectively.
Important observations
At admission, the COVID-19 patients with acute kidney injury or sustained acute kidney injury exhibited significantly higher urinary levels of NGAL compared to those without kidney injury. A positive correlation was also observed between the NGAL levels and increasing stages of acute kidney injury. Specifically, the analysis revealed that NGAL had 80% specificity and 75% sensitivity to diagnose higher stages of acute kidney injury.
Furthermore, urinary NGAL as a predictive marker for acute kidney injury was independent of the patient’s age, sex, ethnicity, baseline creatinine level, proteinuria, and pre-existing health conditions.
Regarding clinical consequences of COVID-19, urinary NGAL quantitatively predicted the risk of in-hospital mortality, duration of hospital stay, shock, and acute dialysis. Per standard deviation of NGAL, the risk of death increased by 73% in COVID-19 patients. Specifically, in patients with the highest urinary NGAL, about 25% mortality was observed within 20 days of hospital admission. This risk prediction was independent of the patient’s demographic features, comorbidities, proteinuria, and baseline creatinine level.
Unlike urinary NGAL, the levels of urinary KIM-1 failed to significantly detect the duration and severity of acute kidney injury and predict the clinical outcomes in COVID-19 patients.
In a separate set of examinations on 13 COVID-19 patients and 4 non-COVID patients with acute tubular injury, the transcriptomic analysis of NGAL and KIM-1 was conducted in different segments of the nephron. The findings revealed that in both COVID and non-COVID patients, KIM-1 and NGAL were predominantly expressed in the proximal tubule and in the limbs of Henle and collecting ducts, respectively.
In COVID-19 patients with maximum acute kidney injury, KIM-1 and NGAL were expressed in 27% and 66% of tubules, respectively, indicating a widespread distribution of NGAL compared to KIM-1. Moreover, an extensive co-expression of NGAL with KIM-1 was observed in the proximal tubule. Importantly, a significant correlation was observed between the NGAL – KIM-1 co-expression and degree of acute kidney injury.
To further investigate the NGAL distribution, the expression of NGAL at the RNA level was determined in mice with renal ischemia reperfusion injury. The NGAL RNA was found to express in the cortico-medullary junction, medulla, and papilla. Moreover, an overlap between NGAL and KIM-1 was observed in the proximal tubule.
Study significance
The study identifies urinary NGAL as a potential marker for determining the duration and severity of acute kidney injury, as well as predicting clinical outcomes in COVID-19 patients.
*Important notice
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.
The original article was written by AVE Science & Technology Co. Ltd.
COVID-19: How a new blood test could help speed up vaccine development and population screening
In an interview with Medical News Today, James Hindley, Ph.D., from Indoor Biotechnologies explains how his company is developing a new T cell test during the COVID-19 pandemic. He also reveals why this test is a much-needed tool for those designing new vaccines and studying immune responses to the new coronavirus.
Image credit: James Hindley, Ph.D.
All data and statistics are based on publicly available data at the time of publication. Some information may be out of date. Visit our coronavirus hub and follow our live updates page for the most recent information on the COVID-19 outbreak.
Since the COVID-19 pandemic began, scientists across disciplines and geographical locations have collaborated in unprecedented ways.
The speed at which diagnostic tests went from conception to reality was astounding, as were the global efforts to test new and repurposed drugs to find treatments for those with the disease.
However, effective treatments are only tentatively emerging. Diagnostic testing capabilities have been slow to ramp up to the scales needed to keep the pandemic at bay.
Many questions remain about how the virus causes catastrophic deterioration in some but leaves many others relatively unscathed.
Undeterred, investigators continue to research and develop new arsenals in this global fight.
Medical News Today spoke to one such scientist, who recently began a new project with a grant from the British government’s Innovate UK fund.
James Hindley, Ph.D., is the Executive Director at Indoor Biotechnologies in Cardiff in Wales, and the work is underway in collaboration with Martin Scurr, Ph.D., a research associate at Cardiff University’s School of Medicine.
Working with the team at Indoor Biotechnologies, Dr. Hindley and Dr. Scurr are developing a new type of test that can show if someone has developed specific T cells to SARS-CoV-2.
T cells are a type of white blood cell. They play a key role in how our bodies fight off viral pathogens, such as SARS-CoV-2, the new coronavirus.
Stay informed with live updates on the current COVID-19 outbreak and visit our coronavirus hub for more advice on prevention and treatment.
‘Need for a simple T cell test’
MNT: Why is there a need to develop a new T cell test?
Dr. James Hindley: The current focus for testing immunity to the SARS-CoV-2 virus is based on the assessment of antibodies.
These are an undoubtedly important part of our memory immune response to viruses. However, another critical component of our immune response to viruses is the T cell. These also provide memory immune responses and may even be more sensitive than antibodies.
The challenge with T cells is that, unlike antibodies, measuring them is not simple.
As such, there is a need for a simple T cell test, that could enable testing for virus-specific T cells to be done routinely.
MNT: What will the test results show?
Dr. Hindley: The test we have developed can provide quantitative results measuring the magnitude of an individual’s T cell response to the SARS-CoV-2 virus.
We can also run in parallel the same test for other human coronaviruses and viruses, such as influenza. This allows us to establish a person’s immune status. Like antibodies, whether a positive T cell test is protective against future infection remains to be determined.
MNT: Who will benefit from your test, and who can administer it?
Dr. Hindley: At first, we believe the primary use of this test will be for vaccine development, to determine whether a T cell response to the vaccine has been generated and whether that is adequate to be protective from infection.
Such testing would be done in laboratories, alongside other tests needed for the vaccine trial.
We also believe this test will enable public health bodies to perform much wider screenings of the population. Again, this would be carried out by laboratories in conjunction with antibody testing to determine what constitutes protective immunity.
Once this is proven, the assessment could then be made available to the wider public, but it is likely to remain as a test performed in a laboratory.