Possible urinary biomarkers of lupus nephritis identified in study

Biomarkers could aid in monitoring and allow for faster intervention

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by Lindsey Shapiro |

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An illustration of a person's kidneys, shown from the back, of a person drinking from a glass.

Scientists have identified a number of proteins in the urine with high diagnostic accuracy for identifying kidney involvement in people with systemic lupus erythematosus (SLE).

Such biomarkers may enable the earlier identification of lupus nephritis, a serious manifestation of SLE that can cause kidney failure, thus allowing for faster interventions to prevent kidney function decline.

“These studies have expanded the repertoire of urinary proteins that can be used to monitor renal status in a patient with lupus,” Chandra Mohan, MD, PhD, a professor at the University of Houston, Texas, and the study’s senior author, said in a university press release.

The study, “Proximity extension assay proteomics and renal single cell transcriptomics uncover novel urinary biomarkers for active lupus nephritis,” was published in the Journal of Autoimmunity.

More than half of people with SLE will be affected by lupus nephritis, a serious disease manifestation where there is inflammation and damage to the kidneys. This complication is life-threatening, with about 10%-30% of patients ultimately developing end-stage kidney disease.

There is, thus, a need for better approaches to identify lupus nephritis early on in order to effectively intervene and prevent kidney failure.

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An illustration of a person's kidneys, shown from the back, of a person drinking from a glass.

At-home urine test may allow for earlier lupus nephritis diagnosis

A kidney tissue biopsy is currently the gold standard for detecting kidney involvement in lupus nephritis, but this approach is limited by its invasive and imprecise nature, according to the authors.

As such, there’s a growing interest in identifying predictive biomarkers for lupus nephritis that can be measured from easily collected patient samples, such as urine.

“We and others have reported several urine proteins that can serve as harbingers of renal involvement in lupus,” Mohan said.

In their study, the scientists aimed to identify new urinary biomarkers of lupus nephritis using a highly sensitive technique called proximity extension assay, or PEA, that can detect proteins even at very low levels.

Urine samples were obtained from 87 SLE patients and 30 healthy individuals who served as controls. There were 34 patients with biopsy-established lupus nephritis, 27 with active SLE but no kidney involvement, and 26 with an overall inactive or low disease activity.

A total of 543 proteins in the urine were examined. In general, healthy people and those with inactive disease expressed lower levels of nearly all proteins compared with patients with active SLE or SLE associated with lupus nephritis.

Some new proteins identified along with others previously known

Hundreds of proteins were found to be significantly elevated in the urine of active lupus nephritis patients compared with people with inactive SLE, some of which had been previously identified and some of which were new.

Many of these proteins were found to have very high diagnostic accuracy for distinguishing active lupus nephritis (exceeding 98%), which the researchers noted “contrasts drastically” with traditional SLE biomarkers, such anti-DNA antibodies or the C3 and C4 immune-related proteins.

Certain proteins progressively increased as disease severity worsened over time, many of which were associated with immune system function and signaling.

The top eight altered proteins between lupus nephritis patients and those with inactive disease were then measured in a separate group of patients, with all eight again showing significant elevations in the lupus nephritis group.

The ones ultimately determined to best discriminate lupus nephritis were ICAM-2, FABP4, FASLG, IGFBP-2, SELE, and TNFSF13B/BAFF. The levels of these proteins also correlated strongly with measures of disease activity.

The best-performing marker was ICAM-2, a molecule involved in immune cell trafficking that’s been found to be impaired in SLE patients. Most of the others also are linked in some way to inflammation or immune cell function.

Additional analyses of genetic data obtained from kidney biopsies of lupus nephritis patients identified that the proteins may be released from both immune and nonimmune cell populations.

Now, “longitudinal studies are warranted to assess if these biomarkers can serve as predictive, prognostic or monitoring biomarkers in [lupus nephritis],” the researchers wrote.

They also noted that the profile of these proteins in the urine should be compared with kidney biopsies obtained at the same time to see how they correlate.