Researchers identify gene variants that may cause kidney problems in lupus patients

Findings may lead to improved diagnosis and treatment

2013-08-23

(Press-News.org) Washington, DC (August 22, 2013) — Variants in a particular gene are linked with an increased risk for kidney complications in patients with lupus, according to a study appearing in an upcoming issue of the Journal of the American Society of Nephrology (JASN). The findings could lead to better treatments to protect the kidney health of patients with the disease.

Lupus is an autoimmune disease that affects many different body systems, including the central nervous system, joints, skin, heart, lungs, and kidneys. Kidney involvement—termed lupus nephritis—occurs in about 50% to 75% of patients, and up to 30% of those patients develop kidney failure. Currently, experts do not understand what makes some lupus patients susceptible to lupus nephritis.

David Powell, PhD, Dawn Caster, MD, and Erik Korte, MS (University of Louisville School of Medicine) led a team that looked at the role of a particular gene that may be involved. Their previous research conducted in collaboration with investigators in Scotland revealed that mice with an inactive form of the ABIN1 protein develop lupus-like disease and have enhanced activation of the NF-kappaB pathway. This pathway is involved with the control of inflammation.

In their current study, the researchers found that mice with inactive ABIN1 develop progressive kidney problems similar to lupus nephritis in humans. The investigators then sequenced the gene encoding ABIN1 in human samples. Comparing cases of lupus with nephritis and cases of lupus without nephritis revealed strong associations of lupus nephritis with a genetic variant called rs7708392 in European Americans and a variant called rs4958881 in African Americans. Comparing cases of lupus with nephritis and healthy controls revealed a stronger association at rs7708392 in European Americans, but not at rs4958881 in African Americans.

The findings suggest that variants in the gene that encodes ABIN1 are linked with an increased risk for lupus nephritis and could be mechanistically involved in disease development through aberrant regulation of NF-kappaB.

"Our studies identify genes of the NF-kappaB pathway as a focus for future work understanding the pathogenesis and therapy of lupus nephritis," said Dr. Powell. "Understanding the role of genes in the NF-kappaB pathway in the development and severity of lupus nephritis provides the hope that personalized therapy for the condition may be possible," he added. Current treatments for lupus nephritis consist of immunosuppressive drugs, which are effective in only about 50% of patients and are associated with undesirable short- and long-term side effects.

### Highlights Variants in the gene that encodes ABIN1—which is involved in the control of inflammation—are linked with an increased risk for kidney complications in patients with lupus. The finding may point to improved treatments for kidney complications in patients with the disease.

Study co-authors include Sambit K. Nanda, Kenneth R. McLeish, Rebecca K. Oliver, Rachel T. G′Sell, Ryan M. Sheehan, Darrell W. Freeman, Susan C. Coventry, Jennifer A. Kelly, Joel M. Guthridge, Judith A. James, Kathy L. Sivils, Marta E. Alarcon-Riquelme, R. Hal Scofield, Indra Adrianto, Patrick M.Gaffney, Anne M. Stevens, Barry I. Freedman, Carl D. Langefeld, Betty P. Tsao, Bernardo A. Pons-Este0, Chaim O. Jacob, Diane L. Kamen, Gary S. Gilkeson, Elizabeth E. Brown, Graciela S. Alarcon, Jeffrey C. Edberg, Robert P. Kimberly, Javier Martin, Joan T. Merrill, John B. Harley, Kenneth M. Kaufman, John D. Reveille, Juan-Manuel Anaya, Lindsey A. Criswell, Luis M. Vila, Michelle Petri, Rosalind Ramsey-Goldman, Sang-Cheol Bae, Susan A. Boackle, Timothy J. Vyse, Timothy B. Niewold, and Philip Cohen.

Disclosures: The authors reported no financial disclosures.

The article, entitled "ABIN1 Dysfunction as a Genetic Basis for Lupus Nephritis," will appear online at http://jasn.asnjournals.org/ on August 22, 2013, doi: 10.1681/ASN.2013020148.

The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies.

Founded in 1966, and with more than 14,000 members, the American Society of Nephrology (ASN) leads the fight against kidney disease by educating health professionals, sharing new knowledge, advancing research, and advocating the highest quality care for patients.

ELSE PRESS RELEASES FROM THIS DATE:

Exercise effective and safe in patients with moderate kidney disease

2013-08-23

Washington, DC (August 22, 2013) — A structured exercise and lifestyle program can improve fitness, body composition, and heart function in patients with kidney disease, according to a study appearing in an upcoming issue of the Clinical Journal of the American Society of Nephrology (CJASN). The findings suggest that patients with kidney disease can benefit from greater physical activity and can do so safely even though they may have other medical problems. Approximately 60 million people globally have chronic kidney disease (CKD). These individuals have a high risk of ...

New risk model sheds light on arsenic risk in China's groundwater

2013-08-23

This news release is available in French, Italian and German. Since the 1960s, it has been known that groundwater resources in certain provinces of China are contaminated with arsenic. Estimates of the numbers of affected people have risen year by year. In the most recent survey – conducted by the Chinese Ministry of Health between 2001 and 2005 – more than 20,000 (5%) of the 445,000 wells tested showed arsenic concentrations higher than 50 µg/L. According to official estimates, almost 6 million people consume drinking water with an arsenic content of more than 50 ...

In mild strokes, ultra-early treatment may eliminate risk of disability

2013-08-23

DALLAS, August 22, 2013 — In the case of mild or moderate strokes, getting treatment ultra-fast – within 90 minutes of experiencing symptoms – greatly reduces the risk of suffering disability, according to a new study reported in the American Heart Association's journal Stoke. The American Heart Association/American Stroke Association recommends getting to a hospital within three hours of the onset of stroke symptoms. According to guidelines, clot-busting drugs may be given to treat stroke up to 4.5 hours after the onset of symptoms. The study found that survivors ...

Stroke risk similar among men and women smokers worldwide

2013-08-23

DALLAS, Aug. 22, 2013 — Smoking cigarettes may cause similar stroke risks for men and women, but women smokers may be at greater risk for a more deadly and uncommon type of stroke, according to new research in the American Heart Association journal Stroke. When compared to non-smokers of the same gender, smoking increases the risk of having any type of stroke by 60 to 80 percent in women and men. Researchers said the finding is intriguing because other studies have found strong evidence that smoking conveys a much higher risk of heart disease – which shares a common ...

Go on, volunteer -- it could be good for you!

2013-08-23

Volunteering may be good for your health, reveals a large systematic review and meta-analysis led by the University of Exeter Medical School. Volunteering can improve mental health and help you live longer, finds the study which is published in the open access journal BMC Public Health. The research pools and compares data from multiple experimental trials and longitudinal cohort studies. Some observational evidence points to around a 20 per cent reduction in mortality among volunteers compared to non-volunteers in cohort studies. Volunteers also reported lower levels ...

Morphing manganese

2013-08-23

An often-overlooked form of manganese, an element critical to many life processes, is far more prevalent in ocean environments than previously known, according to a study led by University of Delaware researchers that was published this week in "Science." The discovery alters understanding of the chemistry that moves manganese and other elements, like oxygen and carbon, through the natural world. Manganese is an essential nutrient for most organisms and helps plants produce oxygen during photosynthesis. "You wouldn't think manganese is that important, but without manganese, ...

Drug used for blood cancers may stop spread of breast cancer cells, Mayo Clinic finds

2013-08-23

JACKSONVILLE, Fla. — A drug used to treat blood cancers may also stop the spread of invasive breast cancer, researchers at Mayo Clinic in Florida have discovered. Their study, published online in Breast Cancer Research, found that in the lab and in animals, the drug decitabine turns on a gene coding for protein kinase D1 (PRKD1) that halts the ability of cancer cells to separate from a tumor and spread to distant organs. "Treatment with low doses of decitabine in an animal model of breast cancer restored PRKD1 expression, reduced tumor size, and blocked metastasis to ...

Protein-based urine test predicts kidney transplant outcomes

2013-08-23

Levels of a protein in the urine of kidney transplant recipients can distinguish those at low risk of developing kidney injury from those at high risk, a study suggests. The results also suggest that low levels of this protein, called CXCL9, can rule out rejection as a cause of kidney injury. The study appears online Aug. 22 in the American Journal of Transplantation. The work was funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. To prevent rejection, kidney transplant recipients typically take immunosuppressive ...

Astronomers use Hubble images for movies featuring space slinky

2013-08-23

Astronomers have assembled, from more than 13 years of observations from NASA's Hubble Space Telescope, a series of time-lapse movies showing a jet of superheated gas -- 5,000 light-years long -- as it is ejected from a supermassive black hole. The movies promise to give astronomers a better understanding of how black holes shape galaxy evolution. "Central, supermassive black holes are a key component in all big galaxies," said Eileen T. Meyer of the Space Telescope Science Institute in Baltimore, Md. "Most of these black holes are believed to have gone through an active ...

Researchers figure out why gold nanoparticles can penetrate cell walls

2013-08-23

CAMBRIDGE, Mass-- Cells are very good at protecting their precious contents — and as a result, it's very difficult to penetrate their membrane walls to deliver drugs, nutrients or biosensors without damaging or destroying the cell. One effective way of doing so, discovered in 2008, is to use nanoparticles of pure gold, coated with a thin layer of a special polymer. But nobody knew exactly why this combination worked so well, or how it made it through the cell wall. Now, researchers at MIT and the Ecole Polytechnique de Lausanne in Switzerland have figured out how the ...

Researchers identify gene variants that may cause kidney problems in lupus patients

ELSE PRESS RELEASES FROM THIS DATE:

LAST 30 PRESS RELEASES: