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Simpler Measures for Predicting Kidney Function May Be Useful

Tuesday, September 12, 2006

Simpler Measures for Predicting Kidney Function May Be Useful


In order to measure how well the kidneys are functioning, doctors frequently use a measurement called the creatinine clearance (CrCl). Creatinine is a breakdown product of creatine, a component of muscles in the body. The way that the kidney eliminates creatinine reflects how well the kidneys are working.

The CrCl test compares the level of creatinine in the urine with the creatinine level in the blood. The classic way of doing this takes measurements on a sample of urine that has been collected over a 24-hour period, and compares this to a blood sample drawn at the end of that time. Because creatinine is freely filtered through a well-functioning kidney and not reabsorbed into the bloodstream the way some other proteins are, creatinine clearance can be used to estimate how fast the kidney is filtering out wastes from the body (known as the glomerular filtration rate (or GFR). This is the gold standard by which kidney function is assessed. As kidneys become damaged, the GFR goes down and less creatinine is filtered out, leaving more creatinine in the bloodstream, along with other potentially toxic waste products.

Researchers wanted to know whether creatinine clearance (CrCl) that is estimated by different, easier methods agreed with the CrCl measured, using a 24-hour collection of urine. Forty-three lupus patients with mild to moderate kidney disease were studied. For this study, the methods used to estimated creatinine clearances were (1) the Cockcroft-Gault (CG) equation, (2) the Modification of Diet in Renal Disease (MDRD) study equation, and (3) the abbreviated MDRD (aMDRD) study equation. These methods each were compared to the measured CrCl by 24-hour urine collection.

The results were that the MDRD and aMDRD methods seemed more accurate than the CG equation. However, there seemed to be a tendency for the MDRD and aMDRD study equations to underestimate CrCl, making the kidneys appear to be functioning more poorly that was indicated using the 24-hour urine collection data. Some, however, would argue that there are some inaccuracies in all of the methods, including the 24-hour urine collection. The take-home message from these studies is that easier methods for measuring kidney function, although not perfect, are reasonably reliable. They certainly can be used and understood in evaluating how patients with kidney disease are doing and in examining the progress over time of people undergoing treatments. This could be of significant benefit in treating patients and also in running clinical trials of new medications.

Read the Abstract:
http://www.ingentaconnect.com/content/sage/lu/2006/00000015/00000005/art00004

Leung, Y.Y.; Lo, K.M.; Tam, L.S.; Szeto, C.C.; Li, E.K.; Kun, E.W.

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Blogged on 12:43 AM

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Smoking May Be Related to Increased Risk for Developing Lupus

Monday, September 11, 2006

Smoking May Be Related to Increased Risk for Developing Lupus

That exposure to tobacco smoke is hazardous to health is by no means breaking news, but what may come as a surprise is that smoking has been associated with a number of autoimmune diseases, including rheumatoid arthritis, multiple sclerosis, and autoimmune thyroid disease – and may actually increase a person’s susceptibility to lupus. One current idea is that smoking-related damage to the genetic material in a cell (DNA) will lead to the formation of antibodies to double-stranded DNA (dsDNA), which may in turn have a role in the development of lupus.

To examine the relationship between smoking and dsDNA, researchers at the University of California at San Francisco (UCSF) looked at the medical records of 410 lupus patients which had been collected for a large genetics study. These records included a complete self-report of each person’s smoking history and showed the antibodies that had been detected in these patients. The people in this study were all Caucasian. 91 percent were women (reflecting the percentage of lupus patients who are women).

Participants were identified as “never smokers” (who had smoked fewer than 100 cigarettes in their lifetime), “former smokers” (who had smoked at least 100 cigarettes in their lifetime, but none in the year during which the antibody testing was performed), and “current smokers” (who had smoked at least 100 cigarettes in their lifetime and had smoked within the calendar year during which the dsDNA testing was performed). The combined group of “former smokers” and “current smokers” was also tagged as “ever smokers.”

Antibodies to dsDNA were found in people from all groups, but current smokers had a higher rate (73%) of dsDNA autoantibodies than never smokers (54%) and former smokers (52%). The cumulative amount of smoking did not affect whether these antibodies were seen, nor did the age at which the “ever smokers” first began using tobacco.

Since the current smokers in this study appeared to have more dsDNA antibody than former smokers, the researchers suggested that the mechanism by which tobacco smoke alters DNA could be an important factor in what causes these antibodies to be made. Tobacco smoke causes changes in DNA structure, and these altered DNA molecules — called DNA adducts — tend to trigger immune response activity more than “native” (unaltered) DNA. However, unless they are replenished, the DNA adducts eventually will disappear and are usually 50 percent gone after only 9–13 weeks, which means that the former smokers, having been tobacco-free for one year or more, would seem more like never smokers than current smokers. Knowing that at least some of the negative impact of smoking diminishes once a person stops using tobacco sends a strong message in support of programs to quit smoking.

Interestingly, lupus patients have higher levels of DNA adducts than people who don’t have lupus, regardless of their smoking history. The findings of this study, though dealing with the relation between smoking and dsDNA autoantibodies, may therefore have implications for understanding what causes lupus in general.

Read the Abstract:
http://ard.bmjjournals.com/cgi/content/abstract/65/5/581


Freemer, M.; King Jr., T.; Criswell, L., Annals of the Rheumatic Diseases 2006; 65: 581-584

Blogged on 10:23 PM

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Open-Label Study of Epratuzumab Shows Promise for Lupus

Open-Label Study of Epratuzumab Shows Promise for Lupus

Epratuzumab, under development by Immunomedics, Inc., is a treatment that interferes with B cells, a type of white blood cell that is important in lupus. This small, preliminary study tested epratuzumab in 14 patients with moderately active lupus. This study, like many preliminary studies, was an “open label” study. This means that the patient, physician and study team all know for sure that the patient is receiving the treatment and what the dose is.

The results are considered preliminary because they are not as scientific as “double-blind” studies in which patients are randomly selected to get the real treatment or a “dummy” treatment (placebo), and the patients and study team do not know which one they are getting. Double-blind studies make it a lot less likely that improvements in symptoms are from wishful thinking.

Patients were given epratuzumab every 2 weeks for 18 weeks. The activity of their lupus was measured using a special index measure called the BILAG (which stands for British Isles Lupus Assessment Group). High BILAG scores reflect that a person has a lot of active inflammation or significant symptoms from lupus in one or more organ.

In this study the BILAG scores decreased by 50 percent or more in all 14 patients at some point during the study. Almost all patients experienced improvements in disease activity after 6, 10 and 18 weeks of treatment, and 3 patients had no disease activity at all by 18 weeks. Also, it did look as if the drug managed to affect its intended target, since B cell levels decreased by an average of 35 percent at 18 weeks and remained low when measured 6 months after treatment.

In this study, patients with mild to moderate active lupus tolerated epratuzumab well and showed some preliminary evidence of clinical improvement after the first dose. Further studies of epratuzumab are now underway. These studies will be larger and more scientific and will help to determine whether this drug is safe and effective.

Click here to read the abstract.

Thomas Dörner, Joerg Kaufmann, William A. Wegener, Nick Teoh, David M. Goldenberg, and Gerd R. Burmester, Arthritis Research & Therapy 2006;8:R74

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Blogged on 9:44 PM

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First National Study Shows Need to Monitor Lupus Pregnancies More Closely

First National Study Shows Need to Monitor Lupus Pregnancies More Closely

Researchers compared pregnancy outcomes in women with lupus and rheumatoid arthritis (RA) to pregnancy outcomes in women with diabetes and in healthy women. The researchers used a large collection of information from the 2002 Nationwide Inpatient Sample of the Healthcare Cost and Utilization Project to compare the number of pregnancies among women in these groups around the nation. They also compared the length of time people in each group were hospitalized, the numbers of women who developed high blood pressure or related complications during pregnancy, such as preeclampsia (toxemia), how many women developed premature rupture of membranes, and how many pregnancies in each group led to poor growth of the baby in the mother’s womb.

Women with lupus, RA, and diabetes had significantly increased rates of high blood pressure complications compared with the general healthy group, as well as longer hospital stays and significantly higher risk of needing a cesarean section (surgical delivery of the baby). Because women with lupus and RA also have more pregnancy complications, close monitoring of these pregnancies is highly recommended.

Click here to read the abstract.

Eliza F. Chakravarty, Lorene Nelson, and Eswar Krishnan, Arthritis & Rheumatism 54;3:899-907

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Blogged on 9:37 PM

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Lupus Vasculitis Underlies Skin Denervation

Lupus Vasculitis Underlies Skin Denervation

To better understand why some lupus patients develop a loss of nerves in the skin, the researchers of this study measured density of nerve fibers within the skin and looked at the relationship of nerve density to lupus activity, the sensitivity of nerves to touch, and the electric activity associated with the use of different parts of the body.

There were 45 lupus patients in the study (4 men and 41 women). Compared with healthy people of the same age and gender, the density of the nerves in the lupus patients was lower. Eleven patients (24.4%) were found to have a kind of inflammation of the blood vessels in the skin (cutaneous vasculitis) which is often found in lupus patients, and the severity and extent of this vasculitis seemed to be associated with lower nerve density. In addition, patients with active lupus had lower nerve density in the skin than those with inactive lupus.

Loss of nerve density was found not only in the patients with skin symptoms, but also in the patients with symptoms that affected brain function. In the lupus patients, the sense of touch was less sensitive to the perception of warmth and coldness compared to healthy people. This loss of sensitivity to heat and cold was also associated with reduced nerve densities.

In conclusion, blood vessel inflammation in the skin (cutaneous vasculitis) may lead to the loss of nerves in the skin in lupus patients, and this might lead to dysfunction in the perception of heat and cold. This suggests the importance of treating some symptoms of lupus that may otherwise be regarded as low grade and less important in some quarters.

Click here to read the abstract.

Ming-Tsung Tseng, Song-Chou Hsieh, Chia-Tung Shun, Kuang-Lun Lee, Chun-Liang Pan, Whei-Min Lin, Yea-Hui Lin, Chia-Li Yu, and Sung-Tsang Hsieh
Brain 2006;129(4):977-985

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Blogged on 9:28 PM

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Study Suggests Cyclophosphamide May Be More Effective in Treating CNS Lupus Compared to Methylprednisolone

Study Suggests Cyclophosphamide May Be More Effective in Treating CNS Lupus Compared to Methylprednisolone

The authors of this paper conducted a systematic review of the scientific literature to assess the safety and effectiveness of cyclophosphamide compared to methylprednisolone to treat neuropsychiatric lupus (lupus that affects the central nervous system). They identified one study which involved thirty two patients that were randomly divided into two groups. One group was treated with cyclophosphamide by IV (intravenous or through a vein) and the other group was treated with steroids (methylprednisolone by IV). All participants were on oral steroids (prednisone) at the beginning of the study and their dose was decreased over the two-year duration of the study.

Study results showed that more of the IV cyclophosphamide patients improved than did the patients on methylprednisolone. Eighteen of 19 patients (95 percent) on cyclophosphamide had at least a 20 percent improvement in their symptoms, compared to only six of 13 patients (46 percent) on methylprednisolone. Disease activity, seizures and central nervous system damage also decreased more among patients receiving cyclophosphamide.

After six months of treatment, the patients on cyclophosphamide took less prednisone than the patients on methylprednisolone. Side effects, such as infections, high blood sugar and high blood pressure occurred about the same amount in people who took cyclophosphamide or methylprednisolone.

The results of this small study suggest that cyclophosphamide may improve symptoms of central nervous system lupus more than methylprednisolone. However, due to the limitations of the study, these results must be confirmed by additional studies involving a larger number of patients.

Click here to read the abstract.

V.F. Trevisani, A.A. Castro, J.F. Neves Neto, A.N. Atallah, Cochrane Database System Review, 2006, April 19;(2) CD002265

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Blogged on 9:17 PM

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