Chronic Lesions Versus Active Lesions in Lupus Nephritis
- Revised classification of lupus nephritis is valuable in predicting renal outcome with an indication of the proportion of glomeruli affected by chronic lesions
Rheumatology, Volume 47, Number 5, May 2008, pp. 702-707
What is the topic?
For many years doctors have classified lupus nephritis (LN) by the extent of inflammation and where it occurs in the kidney. They determine this by removing small pieces of kidney tissue with a needle (a process called a kidney biopsy) and looking at the tissue under a microscope.
Under the original classification system developed in 1974 by the World Health Organization (WHO), there were six categories, or classes, of lupus nephritis, reflecting different ways in which inflammation could affect the kidney tissue. Class III and Class IV indicate the extent and pattern of damage cause by inflammation caused by lupus disease activity. This inflammation can affect the part of the kidney that acts as a filter to remove waste products from the blood. Each filter is called a glomerulus, (plural: glomeruli), and each kidney has about one million glomeruli. . Class III refers to damage that involves fewer than half of the total number of glomeruli in a tissue sample; Class IV refers to damage that involves more than half.
In 2003, changes to these WHO classifications were proposed. Class IV was divided into segmental (Class IV-S) and global (Class IV-G). These sub-divisions refer to the extent of inflammation within each glomerulus.
Class III, Class IV-S, and Class IV-G were then divided to differentiate between active lesions (A) and chronic lesions (C). This is an important distinction, since it is thought that active lesions should be treated with aggressive immune suppression. Tissue damage that appears to be long-standing, or chronic, may indicate previous damage that is unlikely to improve from immunosuppressive treatments. Of course, a kidney affected by lupus nephritis can show both active and chronic disease, which suggests that the nephritis is serious and has already damaged the kidney. However, in many cases there may be a good justification for immune suppression because it could still make a difference in how that kidney will function in the future.
What did the researchers hope to learn?
The researchers wanted to see if the new classifications could be used to predict how LN would progress, and whether it would respond to treatment.
Who was studied?
The researchers reviewed the medical records and samples of kidney tissue of 92 patients who were treated for lupus nephritis over a period of 17 years at a university clinic in Japan. Seventy-eight (85%) of the patients studied were women, 14 (15%) were men. The average length of follow-up after the diagnosis was seven years.
How was the study conducted?
The researchers re-classified each of the 92 cases of kidney disease using the new divisions for Class III (A), Class III (C), Class IV-S (A), Class IV-S (C), Class IV-G (A), and Class IV-G (C). They compared the outcomes for each of the patients depending on the new classifications, noting those whose kidney disease had progressed and those who had responded to treatment and remained well.
What did the researchers find?
Overall the researchers noted that most of the patients with LN—93%—responded very well to treatment, with no or only mild loss of kidney function at the time of their last follow-up visit. This was true for patients who had been diagnosed with Class I, II, III, and IV-S.
Those in Class IV-G had the most severe kidney inflammation at the time of the biopsy, and the poorest kidney function at the time of their last follow-up visit. However, the sub-division between those in this group who had active lesions, Class IV-G (A), and those who had chronic lesions as well as active lesions, Class IV-G (A/C), showed important differences in their outcomes: those with only active lesions responded to medical therapy, even if they had severe inflammation at the time of their biopsy, and none of them showed progression of LN to the point of impaired kidney function. On the other hand, Class IV-G patients with both active and chronic lesions did not fare so well; a number of them had significant kidney damage at their last follow-up visit.
The researchers then further examined the outcomes of Class IV-G (A/C) patients, depending on the percentage of chronic lesions as part of the total number of lesions identified. They concluded that the greater the percentage of chronic lesions, the higher the risk for loss of kidney function.
What were the limitations of the study?
Because this was an observational study based on a review of past records, the researchers were not able to factor in other clinical conditions that could affect kidney outcomes, such as high blood pressure or the amount of protein spillage and the speed with which proteinuria could be controlled. Differences in treatment methods among the patients, or how much time had elapsed between their lupus diagnosis and the initial biopsy, also could have affected the outcomes.
What do the results mean for you?
This research suggests that the new revised classification for lupus nephritis, and the focus on the percentage of chronic lesions, may be able to identify patients who are at greater risk for serious kidney damage. If so, those patients could be treated more aggressively with combinations of medications or new biologic therapies that have shown promise in preliminary studies. It would also be important to be able to predict the degree of damage at which it is no longer worth subjecting a patient to potentially toxic treatments, if they would not be effective. Perhaps someday, some types of treatment could be studied with the potential to stop or even reverse certain types of damage, such as the tissue scarring that can be triggered by inflammation; this kind of approach might also be better advanced by further study and more sophisticated interpretation of a kidney biopsy.