New Ways to Detect Lupus Nephritis?
- Elevated Urinary VCAM-1, P-Selectin, Soluble TNF Receptor-1, and CXC Chemokine Ligand 16 in Multiple Murine Lupus Strains and Human Lupus Nephritis
Journal of Immunology, Volume 179, Number 10, November 15, 2007, pp. 7166-7175
What is the topic?
Lupus nephritis, which is inflammation of the kidneys, is one of the most serious complications of lupus. It is especially of concern because significant kidney damage can occur without any visible symptoms, even before a person has been diagnosed with lupus. Kidney disease is diagnosed through a series of laboratory tests, and usually confirmed through biopsy. Biopsy -- in which kidney tissue is removed via insertion of a needle through the person’s back and then examined under a microscope -- is the most accurate way to discover the amount of damage that has occurred from lupus disease activity. However this procedure, which typically takes place in a hospital, can be expensive, can have side effects, and would only be done after kidney disease is suspected. For these reasons, less invasive and less expensive ways to routinely measure inflammation in the kidneys and disease progression would be of great benefit. Since the kidneys produce urine to help carry off waste products from the body’s cells, researchers have focused their attention on a number of proteins that show up in the urine to see if changes in their levels bear any relationship to active kidney disease and could serve as markers in place of more invasive and expensive tests.
What did the researchers hope to learn?
In this study, the researchers hoped to learn whether one or more of four proteins found in urine and in the blood could be used as a sign of potentially damaging lupus activity in the kidneys. The four proteins were VCAM-1, P-Selectin, TNFR-1, and CXCL16. Each of these proteins plays an important role in the immune system.
Who was studied?
The researchers first studied mice that develop lupus-like symptoms similar to those in humans. They found a relationship between an increase in the level of the four proteins in the urine and lupus activity in the mice. They then analyzed urine and blood samples from 55 volunteers (54 women and one man): 34 with lupus, six with rheumatoid arthritis (RA), and 15 with no disease. The majority of the participants were either Hispanic or African American. The 34 people with lupus showed varying degrees of lupus activity; with 23 showing high levels of activity. Of the 23 with serious active lupus, 18 had kidney involvement (lupus nephritis) and five did not.
How were the studies conducted?
The initial work with the mice provided valuable information about the four proteins, all of which were higher in the urine of mice with lupus than in the urine of healthy mice. In addition, the researchers were able to examine kidney tissue from the mice and found evidence that these four proteins were being produced at higher levels in the kidneys of the mice with lupus. These findings led the researchers to conclude that, at least in mice, higher levels of these proteins in the urine were not only a sign of lupus activity, but also could be traced, at least in part, to kidney inflammation, and it was guessed that the proteins might play a role in causing kidney damage in lupus.
The researchers then analyzed the blood and the urine of the 55 volunteers, comparing the levels of VCAM-1, P-Selectin, TNFR-1, and CXCL16 between the different groups and comparing these proteins to other factors that are being considered as possible markers for lupus nephritis.
What did the researchers find?
Urine from the study participants with lupus had significantly higher concentrations of all four proteins than the urine from the healthy volunteers or those with RA. Those with lupus nephritis had the highest levels of the proteins in their urine, particularly VCAM-1 and CXLC16, which were higher even than the levels found in those with active lupus but no lupus nephritis. This suggests that high levels of these proteins in the urine might be a diagnostic test for lupus involvement in the kidneys.
All of the participants with active lupus had higher blood levels of the four proteins as compared to those with inactive lupus. This raises the possibility that these proteins, when found in the blood, could indicate lupus activity in other tissues besides the kidneys. Furthermore, the people with active lupus nephritis not only had higher levels of the proteins in the blood, but the protein levels in their urine were so much more greatly increased than in the people without kidney disease that the researchers speculated these compounds might be directly contributing to kidney inflammation.
When compared to other potential markers for lupus and lupus nephritis, measurement of VCAM-1, P-Selectin, CXLC16, and TNFR-1 in urine all appeared to be better indicators of kidney disease than the others, some of which barely showed up in urine at all.
What were the limitations of the studies?
This study involved a very small number of participants. In addition, the volunteers were predominantly Hispanic or African American. Similar studies with many more participants, including people of ethnic backgrounds not represented in this study (such as Asian, Native American, and Caucasian) will be needed before definite conclusions can be made about the range of these proteins as diagnostic tests for lupus nephritis.
What do the results mean for you?
The earlier lupus nephritis is discovered and treated, the better the long-term prognosis will be, in terms of limiting damage to the kidneys. However, early treatment depends on knowing that inflammation is taking place in the kidneys, and this may go unnoticed because of the lack of observable symptoms. Markers that reveal the existence of kidney disease are therefore critical in limiting damage from inflammation due to lupus nephritis. This study points to several proteins, VCAM-1 and CXLC16 in particular, that seem to hold promise in this regard, especially since they can be measured in a urine sample that can easily and inexpensively provided and tested.