The use of lupus biomarkers, such as those present in the blood or urine, to help predict and/or manage lupus nephritis over time could be very useful. The results of this study highlight the potential feasibility of using lupus biomarkers to differentiate between acute and chronic kidney disease activity-related changes.
Blood Test May Indicate Lupus Nephritis Activity
Prospective assessment of C4d deposits on circulating cells and renal tissues in lupus nephritis: a pilot study
Batal I, Liang K, Bastacky S, Kiss LP, McHale T, Wilson NL, Paul B, Lertratanakul A, Ahearn JM, Manzi SM, and Kao AH. Lupus. 2011 Oct 17. [epub ahead of print]
What is the topic?
Many people with lupus experience a complication known as lupus nephritis (LN), or inflammation of the kidney. LN is one of the more severe manifestations of lupus, but an accurate determination of the type and severity of LN if often limited to confirmation by a kidney “biopsy” (removal of a piece of kidney tissue for microscopic evaluation). Since a kidney biopsy is an invasive procedure, the possibility of studying blood components, instead, as a means to diagnose and monitor LN is of great clinical interest.
What did the researchers hope to learn?
The researchers hoped to learn about whether a protein in the blood called C4d could serve as an indicator of LN activity in people with lupus. Specifically, the researchers were interested in measuring levels of C4d bound to the surface of various blood cells and to kidney tissue, and to determine whether these C4d levels are associated with LN activity.
Who was studied?
Three groups of patients were included in the study: a) 15 lupus patients with LN (“LN group”); b) 239 lupus patients without LN (“lupus group”); and c) 13 non-lupus patients with kidney disease (“kidney group”).
How was the study conducted?
The researchers studied patients who visited the University of Pittsburgh between May 2008 and December 2009. Levels of C4d circulating on blood cells were measured in all patients. Kidney biopsies were performed on patients in the LN and kidney groups, but not the lupus group (without LN).
Levels of C4d bound to portions of “glomeruli” (structures within the kidney which act as filters to remove waste products from the blood) or to specific blood cells (“erythrocytes” or mature red blood cells, “reticulocytes” or immature red blood cells, and “platelets” or blood cells involved in clotting) were measured using laboratory techniques. C4d levels in the kidneys and on the various blood cells were then compared among the three groups of patients and analyzed for association with LN activity.
What did the researchers find?
People in the LN group were younger and more likely to be African-American than those in the kidney group or the lupus group. Patients in the LN group were also more likely to be female than those in the kidney group. Blood levels of creatinine (which may indicate kidney damage) were significantly higher for those in the LN group than in the lupus group, but were lower than in the kidney group. In addition, more people in the LN group had antibodies to double-stranded DNA (an indicator of increased lupus disease activity) and reduced levels of complement proteins in the blood (which may indicate inflammation and increased lupus disease activity) than did those in the lupus group.
Levels of C4d on erythrocytes and reticulocytes were greater in the LN group than in either the kidney or the lupus group. Levels of C4d bound to platelets were greater in the LN group than in the kidney group. Additionally, levels of C4d bound to glomeruli in the kidneys were greater in the LN group than in the kidney group. Finally, in the LN group, the levels of C4d bound to erythrocytes were correlated with kidney disease activity as measured by the NIH activity index from the kidney biopsy.
What were the limitations of the study?
This study included a small number of lupus patients with LN and non-lupus patients with kidney disease. Also, the kidney group may have had worse kidney disease than the LN group. Prognosis was not evaluated in this study. The investigators intend to conduct follow-up studies which will include larger samples of LN patients with varying classes of LN, and non-lupus patients with different types of kidney disease.
What do the results means for you?
This is the first study to evaluate the association of C4d levels bound to various blood cells and within specific compartments of the kidney among lupus patients with LN, non-lupus patients with kidney disease, and lupus patients without kidney disease. More research is needed to validate whether this test could become of use to detect and monitor LN presence and activity at earlier stages, allowing physicians to treat LN more efficiently. At present, however, this blood test is not widely available and additional studies will be needed to verify these results and assess their relevance in clinical practice.
Current treatments for lupus nephritis in children are toxic and sometimes ineffective. New tests for proteins that might be abnormal in lupus nephritis could help make the diagnosis earlier and might also point to new ways of treating the disease.