Mar. 23, 2010

Urine May Help Track Kidney Disease and Predict Treatment Success in People With Lupus

Urinary FOXP3 mRNA in patients with lupus nephritis – relation with disease activity and treatment response. 
Authors: Wang G, Lai FM, Tam LS, Li EK, Kwan BC, Chow KM, Li PK, and Szeto CC. (2009).
Rheumatology, 48: 755-760.

What is the topic?
Lupus nephritis (LN) - inflammation of the kidney - can damage the kidney’s ability to remove waste from the body. Currently, the best way to diagnose kidney inflammation is with a biopsy, an invasive procedure that can sometimes have serious side effects. Researchers have been working to develop specific tests that could be done on urine that could evaluate kidney disease without a biopsy, something that could be a major advance for people with lupus.

One kind of white blood cell is called a regulatory T cell. A gene called "forkhead box P3" (FOXP3) regulates the activity of these cells, and may affect how active the immune system becomes.

Genes are the blueprints for making proteins in the body. When the FOXP3 gene is activated, it makes messenger RNA (mRNA), which is like a mold for how a cell will make a specific protein. It is possible that levels of mRNA for FOXP3 in the urine might reflect lupus kidney disease.

What did the researchers hope to learn?
The researchers hoped to learn whether mRNA in urine samples for the protein made by the FOXP3 gene could be related to lupus kidney disease activity or response to treatment.

Who was studied?
A total of 49 people participated in the study. Of these, 25 had active LN and needed kidney biopsies. Also included were 17 patients who had LN in the past, but not for at least six months. Another seven healthy people also participated.

How was the study conducted?
Patients with active LN provided a urine sample on the same day they had a kidney biopsy in order to compare the study results to the biopsy.

The patients with active LN were treated with various medications including either cyclophosphamide (Cytoxan®) or mycophenolate mofetil (Cellcept®). After 12 weeks of treatment, patients with active disease were classified as being in "complete remission," "partial remission," or having "no response to treatment," based on blood tests and total protein in the urine, which are the usual current measurements.

Most patients were followed for at least one year.

What did the researchers find?
The researchers found that levels of mRNA for FOXP3 protein in the urine were increased in patients with active LN (especially in cases of “proliferative LN”) compared to those with inactive disease and to healthy people. Levels of mRNA for FOXP3 were also increased in patients who were spilling more total protein in the urine but were similar between people with inactive disease and healthy people. In addition, levels of mRNA for FOXP3 were related to total lupus disease activity (including but not limited to LN) and to levels of antibodies to double-stranded DNA, another disease marker of lupus.

Patients who had a complete remission after treatment had higher levels of mRNA for FOXP3 (at the beginning of the 12 weeks of drug treatment) than those who did not get better with treatment.

What were the limitations of the study?
The number of patients studied here was small. They also had different kinds of kidney involvement and were being treated by different kinds of drugs. All of these factors could have affected the results of the study.

Also, the researchers did not study levels of mRNA for FOXP3 in people without lupus who had protein in their urine. This could have helped to clarify whether levels of mRNA for FOXP3 may just indicate levels of protein in the urine.

What do the results mean for you?
Levels of mRNA for FOXP3 could potentially become a test that can be done on simple urine samples to help figure out what is going on in the kidney and to help predict responses to current treatments for people with lupus. It may be that someday, if these results hold up in larger studies, a test like this could inform doctors not to use our current treatments (or to use them longer); or a new treatment might come along that works better for those patients. By having tests like this, it is more likely that such improvements in treatment might happen as time goes on. If enough tests like this are put together, then it might be possible someday to avoid kidney biopsies altogether.

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