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New Tests for Lupus Kidney Disease?

Wednesday, March 26, 2008

What is the topic?

The kidneys remove impurities from the blood. If the kidneys are damaged, they can lose their ability to filter out those waste products, and serious health complications can occur. Lupus patients can develop inflammation in their kidneys, which is known as lupus nephritis (LN). Rarely, the LN is so severe that all of the function is lost in the kidneys and the patient would need to go on dialysis until they could get a kidney transplant.

What did the researchers hope to learn?

The researchers in this study hoped to learn if the presence of specific antibodies in a patient’s blood could be linked to the more severe kinds of kidney disease. In particular they were interested in anti-dsDNA and anti-nucleosome antibodies.

Who was studied?

The researchers collected information from three different groups of lupus patients in Calgary Canada: 14 LN patients who had received a kidney transplant; 22 patients who had LN stabilized without needing dialysis; and 66 lupus patients without nephritis, to compare with these other groups. The control patients were selected to match the two groups of LN patients as closely as possible in age, sex, and ethnicity.

How was the study conducted?

The researchers obtained blood samples that had previously been taken from the three groups of patients and stored at a serum bank. They also had access to kidney tissue biopsies for the LN patients (12 of 14 transplant patients, 17 of the 22 other LN patients). They compared the antibody profiles for the three different groups, and also looked to see if particular antibodies were associated with the different degrees of kidney damage that showed up on the biopsies.

What did the researchers find?

Ninety-six of the 100 patients had antibodies which are associated with lupus, but there was no significant difference in the frequency of most kinds of antibodies in the three groups of LN patients, except for the anti-nucleosome antibodies. Anti-nucleosome antibodies were observed in much higher frequency (79 percent) and at significantly higher levels in the transplant group than in the other LN patients (18 percent) or the controls (9 percent). In addition, the researchers calculated that lupus patients were seven times more likely to develop lupus nephritis if they had anti-nucleosome antibodies present. They felt that these findings provided strong evidence that the presence of anti-nucleosome antibodies could be a reliable test for picking out people at risk for severe lupus nephritis that might lead to the loss of kidney function without aggressive treatments.

What were the limitations of the study?

There were only 100 patients in this study, so additional research with many more patients will be needed to see if anti-nucleosome antibodies can be used as a good test to predict risk of severe LN. Larger studies will also help researchers see if there are differences in the antibodies in LN in people of different genetic backgrounds. Also, even though 79% of the LN patients who had kidney transplants had anti-nucleosome antibodies, the other 21% of the ESRD patients did not; similarly, there were patients who didn’t develop any lupus nephritis who had anti-nucleosome antibodies in their blood tests: this points out that even when two lupus patients have the same symptoms, different disease activity may be at work—which is why every case of lupus and every lupus patient is unique.

What do the results mean for you?

Doctors find some blood tests useful to help them manage their individual patients’ care. If, as this research suggests, the presence of anti-nucleosome antibodies can identify those patients with higher risk for serious LN, doctors can use this information to provide early and aggressive therapy in hopes of keeping the disease under control before the patient’s kidneys are badly damaged.

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Labels: kidney, lupus neprithis, renal transplantation

Blogged on 5:30 AM

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Are Increased Levels of Nitric Oxide a Sign of Kidney Damage in Lupus?

Monday, March 17, 2008

What is the topic?
Lupus disease activity often occurs without any apparent signs or symptoms. This is especially true when lupus affects the kidneys, which is known as lupus nephritis. It is possible for lupus to cause significant kidney damage even before a patient is diagnosed.

However, though there may be no visible symptoms, there are chemical changes occurring in the cells and tissues that can be measured. Therefore, a major emphasis among lupus researchers is to find simple laboratory tests can be used to detect otherwise silent lupus disease activity. A laboratory test that can be used in this way is called a biomarker. One potential biomarker that is being investigated is nitric oxide (chemical symbol, NO), since NO is one of the chemicals involved in the body’s immune response.

What did the researchers hope to learn?
The researchers wanted to see if there was any relation between the level of NO and lupus, and if increased levels of NO were related to lupus nephritis.

Who was studied?
Eighty-three adult lupus patients and 40 healthy people of similar age and background were recruited for this study. Ninety five percent (95%) of the lupus patients were women; 80% were African American; both percentages were higher than those in the healthy group. The researchers divided the 83 lupus patients into three groups: (1) lupus patients with no history of nephritis; (2) lupus patients with history of nephritis but no active kidney disease; and (3) lupus patients with active kidney disease that required a biopsy (a biopsy involves removing tissue from the kidney and studying it with a microscope and with other special laboratory techniques). Among the 83 lupus patients, 49 either had a history of nephritis or had active nephritis over the course of the study.

How was the study conducted?
At their first visit, all of the patients had blood samples taken, and these blood samples were tested for levels of nitrates and nitrites, which are indications of nitric oxide production; together the nitrates and nitrites are called NOx. The researchers compared the NOx levels of the lupus patients and the controls. They also did further comparisons of the lupus patients’ NOx levels with other standard laboratory measures used to evaluate lupus, such as the presence of certain antibodies and other immune system agents (called complement) in the blood, or protein in the urine. The lupus patients had regularly scheduled visits every 3 months for at least one year (some were seen for as long as two years). During those visits further blood tests were taken to measure NOx levels at that time, and other tests conducted to evaluate their lupus disease.

Patients who had signs of active lupus nephritis had biopsies of their kidneys. Since both smoking tobacco and certain foods can raise the blood levels of NOx, participants in the study agreed not to smoke and to eat only a low-NOx diet 24 hours before each visit.

What did the researchers find?
As expected, the researchers found that the blood levels of NOx in the lupus patients were significantly higher than those without lupus at the first visit. Furthermore, among the lupus patients, those with active lupus nephritis had higher levels than in the other groups. Also, higher levels of NOx were associated with several of the standard laboratory measurements for lupus, including elevated levels of protein in blood and urine (which are signs of kidney disease) and lowered complement, especially the C3 form of complement. Over time, higher NOx levels were associated with greater lupus disease activity.

Turning their attention to the group of patients who had undergone a biopsy for active lupus nephritis, the researchers found that the patients with the highest level of NOx also had the most serious degree of kidney damage. They also looked at how the patients with kidney disease responded to medical treatment; those patients who did not get better (“non-responders”) had higher levels of NOx than those who did respond.

There are two reasons why a chemical can be increased in the bloodstream: either the body is making increased amounts, or the body is not efficiently eliminating the chemical which is being made. The researchers did another series of tests to make sure that the NOx levels were a result of higher production and not because the kidneys were less able to remove the NOx compounds from the blood. Those tests showed that it was, indeed, increased production and this appeared to be related to the activity of C3 complement.

All of these findings led the researchers to conclude that elevated levels of NOx in the blood could be a potential useful marker for lupus disease activity. They also suggested that any medication that aimed to prevent kidney damage in lupus patients might have to limit the production of NO. However, just because something is a marker for disease activity does not necessarily mean that all effective treatments would have to eliminate it. If NO is triggering something else that damages the kidney, then a treatment aimed at that second thing might be effective for nephritis regardless of the NO level.

What were the limitations of the study?
The size of the study group -- 83 lupus patients -- was small, especially considering how different the inflammation of lupus can be from one person to the next. Also, nearly 80% of the lupus patients in the study were African Americans; that is a good aspect of the study, since people of African descent may have worse kidney involvement and have previously not been studied well enough. However this does limit the ability to draw conclusions about people with lupus who might be from different genetic backgrounds.

There are also some limitations to the measurements used. As the researchers themselves pointed out, lupus activity rises and falls over time, and measurements taken at three-month intervals really may not capture important information during the intervening months. Of less concern, but something that should be noted, the researchers didn’t really measure the levels of NO itself, but used the blood levels of nitrate plus nitrite as indicators of NO production. This measurement seems to be useful, but much more could be learned about the specific chemical changes that are going on and in what way they may impact the kidney.

What do the results mean for you?
A number of previous studies had pointed to increased NO production as an important factor in lupus, but those studies were "after the fact"; they only looked back at the records of lupus patients to see if there were any associations. This was the first study to examine the relationship going forward, following lupus patients over time, and gathering information about NO levels in the course of their treatment and evaluation. Thus, it adds strength to the notion that NO may be a useful biomarker for lupus disease activity that could help doctors know what is going on when their patients may not have obvious symptoms.

Their suggestion that limiting NO production might be important to consider for new medications for lupus nephritis is also very intriguing. Both of these points -- the value of NOx as a biomarker and its role as a target for new medications -- are definitely worthy of further studies.

source

Labels: kidney, lupus neprithis, Nitric Oxide, research

Blogged on 7:25 PM

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Kidneys Affected in 40 Percent of People with Lupus

Wednesday, March 05, 2008

March 3, 2008

It is estimated that as many as 40 percent of all people with the autoimmune disease lupus, and as many as two-thirds of all children with lupus, will develop kidney complications that require medical evaluation and treatment. Because there are so few symptoms of kidney disease, significant damage to the kidneys can occur before a person is actually diagnosed with lupus.

Lupus nephritis is the term used when lupus causes inflammation in the kidneys, making them unable to properly remove waste from the blood or control the amount of fluids in the body. Abnormal levels of waste can build up in the blood, and edema (swelling) can develop. Left untreated, nephritis can lead to scarring and permanent damage to the kidneys and possibly end-stage renal disease (ESRD). People with ESRD need regular filtering of their body’s waste done by a machine (dialysis), or a kidney transplant so that at least one kidney is working properly. This occurrence greatly affects the person’s quality of life and life expectancy.

In the early stages of lupus nephritis, there are very few signs that anything is wrong. Often the first symptoms of lupus nephritis are weight gain and puffiness in the feet, ankles, legs, hands, and/or eyelids. This swelling often becomes worse throughout the day. Also, the urine may be foamy or frothy, or have a red color.

Diagnosis
Often the first signs of lupus nephritis show up in clinical laboratory tests on the urine. That is why a urine test, or urinalysis, is an important screening tool. In addition, certain blood tests can provide information about kidney damage and how well the body is filtering waste. A physician also may order a kidney biopsy in which a tiny piece of tissue from one of the kidneys is removed for testing.

Treatments
Even though lupus nephritis is among the more serious complications of lupus, there are effective treatments. Prednisone and other corticosteroids are generally prescribed to stop the inflammation. Immunosuppressive drugs may also be used (with or in place of steroid treatments), such as cyclophosphamide (Cytoxan®), azathioprine (Imuran®), cyclosporin A, and mycophenolate mofetil (CellCept®). Medications developed for other illnesses are also being studied as treatments for lupus nephritis, including rituximab (Rituxan®), eculizuimab (Soliris™), and abetimus sodium (Riquent™).

source

Labels: kidney, lupus neprithis

Blogged on 5:36 PM

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A potential therapy for lupus nephritis when other medications fail

Saturday, September 01, 2007

From Arthritis & Rheumatism, April 2007

Lupus nephritis (kidney disease) is a serious complication of lupus. Researchers in Sweden tested to see if providing rituximab (Rituxan) in combination with cyclophosphamide (CYC) would be a safe and effective therapy for lupus nephritis patients who had previously not responded to CYC. The researchers found that rituximab, in combination with CYC, was effective in treating lupus nephritis in patients who had previously not responded to CYC.
Read more >

Labels: CYC, kidney, lupus neprithis, research, rituximab

Blogged on 7:32 PM

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