Urine Levels of G3BP Protein May Show Lupus Nephritis in SLE Patients

Study supports easier, noninvasive way of determining kidney involvement

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by Margarida Maia |

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A test of galectin-3-binding protein (G3BP) levels in the urine is an easy way to distinguish lupus nephritis, an inflammation of the kidneys caused by systemic lupus erythematosus (SLE), from other forms of lupus where the kidneys are not affected, a study suggested.

Researchers also observed that protein levels could help in determining disease activity or a person’s response to treatment.

Overall, findings support G3BP “as a non-invasive urinary biomarker to help [detect] and … monitor renal involvement in SLE patients,” the researchers wrote.

The study, “Urine galectin-3 binding protein reflects nephritis activity in systemic lupus erythematosus,” was published by an international team of researchers in the journal Lupus.

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An easier way of diagnosing lupus nephritis via a protein’s levels in urine

SLE is an autoimmune disease that occurs when the immune system becomes overactive for a combination of reasons, some of which are yet unclear. It is not always easy to diagnose lupus, because its symptoms vary among patients and can overlap with those of other conditions.

Disease symptoms are due to inflammation in various organs and tissues, including the heart, the lungs,  muscles, and the joints. Inflammation that affects the kidneys is known as lupus nephritis, and it damages these organs.

Diagnosing lupus nephritis typically requires taking a small sample of kidney tissue in a biopsy. However, this procedure is invasive and uncomfortable for patients, and it can lead to complications.

“In this context, it is highly desirable to identify new non-invasive biomarkers that may reflect the type of kidney involvement, reflect the degree of histological [tissue] activity and damage, predict [lupus nephritis] flares and be useful for assessing treatment response,” the researchers wrote.

G3BP is a protein that helps in the process by which a cell interacts with neighboring cells. It also triggers inflammation.

Previous work has shown that G3BP levels in the urine may be a biomarker of disease activity in people with SLE who develop lupus nephritis.

Researchers, led by those at the Karolinska Institute in Sweden, tested the protein’s usefulness in distinguishing SLE patients with lupus nephritis from those with SLE without kidney involvement and others with inactive SLE.

Their study involved 270 people, including 86 with lupus nephritis. Patients with lupus nephritis had a mean age of 35.5 and most (89.5%) were women. In almost half (43%) of them, the symptoms of lupus nephritis started around the same time as the onset of SLE. Almost three-quarters (73.2%) were being treated with prednisolone, a corticosteroid, and almost half (45.3%) were on antimalarials.

Also included for comparison were 63 people with active SLE but no kidney involvement, 73 people with inactive SLE, and 48 healthy individuals matched by age and sex as a control group.

Those with inactive SLE were a mean of 15.5 years older than those with lupus nephritis, and their disease’s duration was a mean of five years longer than those with lupus nephritis (eight vs. two years). Their disease’s duration was a mean of three years longer than for active SLE patients with no kidney involvement (eight vs. 5 years).

The amount of G3BP in the urine was determined and normalized to the levels of creatinine, a common waste product that is flushed out in urine.

G3BP at significantly higher levels in lupus nephritis patients

Normalized G3BP urine levels were significantly higher in people with lupus nephritis relative to each of the other groups.

Kidney biopsy tissues were available for most of the lupus nephritis patients. Examination showed 47 of them had proliferative lupus nephritis, a severe form of the condition that may cause scars to form in the kidneys and lead to end-stage kidney disease. Another 26 patients had membranous lupus nephritis, a milder disease form that may present with no other SLE manifestations. Twelve people with inactive SLE were found to have mesangial lupus nephritis, a form that usually causes minimal damage to the kidneys.

G3BP urine levels were higher in patients with proliferative or membranous lupus nephritis than in those with the mesangial form.

In proliferative lupus nephritis, G3BP urine levels correlated positively with disease activity measured using the SLE Disease Activity Index 2000 (SLEDAI-2K). This means that higher levels of G3BP in the urine were associated with greater disease activity in the kidneys.

The use of oral corticosteroids, but not of antimalarials or immunosuppressants, appeared to be linked to a lower G3BP level in the urine among all with SLE. No correlation was seen between protein levels and a patient’s daily corticosteroid dose, the researchers added.

Urine samples and kidney biopsies for 10 lupus nephritis patients were available before and a median of 7.5 months after induction therapy with immunosuppressants, an SLE treatment for these people. The protein’s urine levels dropped significantly after induction therapy.

Study results support G3BP levels in the urine as “a good marker of renal disease in SLE,” the researchers concluded.

They also are useful in determining “the type of renal inflammation and level of activity, both by showing elevated levels during active disease, and by declining following immunosuppressive treatment,” the team added.