Author Interview: Dr. Jeffrey Kopp
10 Center Drive, NIH, Bethesda, MD 20892-1268
Kidney Disease Section and Division of Kidney, Urologic and Hematologic Diseases, National Institute of Diabetes and Digestive and Kidney Disease, National Institutes of Health, Bethesda, Maryland
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Publication:
Author Interview: Dr. Jeffrey Kopp
APOL1 Genetic Variants in Focal Segmental Glomerulosclerosis and HIV-Associated Nephropathy.
Kopp JB, Nelson GW, Sampath K, Johnson RC, Genovese G, An P, Friedman D, Briggs W, Dart R, Korbet S, Mokrzycki MH, Kimmel PL, Limou S, Ahuja TS, Berns JS, Fryc J, Simon EE, Smith MC, Trachtman H, Michel DM, Schelling JR, Vlahov D, Pollak M, Winkler CA
J Am Soc Nephrol. 2011 Oct 13. [Epub ahead of print]
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What are the main findings of the study? |
People with two variants of APOL1 have about a 4 percent lifetime risk of getting FSGS – 17 times higher risk than those with no variants. Previous work has shown that the genetic variants appear to have arisen in Africa about 5,000 years ago, and so the mutations are only present in people living in Africa or whose ancestors left Africa after that time. About 12 percent of African-Americans have two variants of APOL1, including 72 percent of African-American FSGS patients.
People with two risk variants tend to get FSGS at a younger age and to progress to end-stage kidney disease faster than people with one or no APOL1 variants.
For people who are HIV-positive and have two variants of APOL1, their risk of a type of kidney disease called HIV-associated nephropathy (HIVAN), becomes 50 percent among those not getting antiviral therapy. However, antiviral therapy appears reasonably effective at preventing HIVAN.
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Were any of the findings unexpected? |
Although the number of subjects was small, the data suggest that people with these two variants respond as well to steroid treatment as their counterparts without two variants, making that a reasonable treatment option.
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What should clinicians and patients take away from this study? |
African-Americans who have diabetes, high blood pressure or a family history of kidney disease should talk to their doctor about being screened for kidney disease. The National Institutes of Health has information about kidney disease on our website, www.nih.gov.
In the future, research may show that getting genetic testing for these variants may be useful for knowing lifetime risk and for making decisions about course of treatment.
At this point, we encourage doctors and other health care providers to consider their patients’ family health history when discussing screening strategies and treatment plans.
If future work indicates that knowing the APOL1 genotype has implications for selection of treatment, such as which drug to use or how aggressively to treat FSGS, then genetic testing might have a role in clinical medicine – but the evidence to support such a role has not been gathered yet.
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What recommendations do you have for nephrology health care providers as a result of your study? |
Clinical trials to learn whether genetic testing in the African-American population makes a difference, whether we should screen young adults with the variant copies for kidney disease at an early stage, and whether prevention or early treatment could affect long-term outcome for these forms of kidney disease.
As well, laboratory studies into how APOL1 variants cause kidney disease might allow researchers to develop new therapies to prevent or treat APOL1-associated kidney disease.
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| Abstract: |
Trypanolytic variants in APOL1, which encodes apolipoprotein L1, associate with kidney disease in African Americans, but whether APOL1-associated glomerular disease has a distinct clinical phenotype is unknown.
Here we determined APOL1 genotypes for 271 African American cases, 168 European American cases, and 939 control subjects. In a recessive model, APOL1 variants conferred seventeenfold higher odds (95% CI 11 to 26) for focal segmental glomerulosclerosis (FSGS) and twenty-nine-fold higher odds (95% CI 13 to 68) for HIV-associated nephropathy (HIVAN). FSGS associated with two APOL1 risk alleles associated with earlier age of onset (P = 0.01) and faster progression to ESRD (P < 0.01) but similar sensitivity to steroids compared with other subjects. Individuals with two APOL1 risk alleles have an estimated 4% lifetime risk for developing FSGS, and untreated HIV-infected individuals have a 50% risk for developing HIVAN.
The effect of carrying two APOL1 risk alleles explains 18% of FSGS and 35% of HIVAN; alternatively, eliminating this effect would reduce FSGS and HIVAN by 67%. A survey of world populations indicated that the APOL1 kidney risk alleles are present only on African chromosomes. In summary, African Americans carrying two APOL1 risk alleles have a greatly increased risk for glomerular disease, and APOL1-associated FSGS occurs earlier and progresses to ESRD more rapidly.
These data add to the evidence base required to determine whether genetic testing for APOL1 has a use in clinical practice.
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| More Author Interview from Hemodialysis.com |
| ASN Press Release: |
(Media-Newswire.com) - African-Americans with two copies of the APOL1 gene have about a 4 percent lifetime risk of developing a form of kidney disease, according to scientists at the National Institutes of Health. The finding brings scientists closer to understanding why African-Americans are four times more likely to develop kidney failure than whites, as they reported in the Oct. 13 online edition of the Journal of the American Society of Nephrology.
Researchers including Jeffrey Kopp, M.D., at the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases and Cheryl Winkler, Ph.D, of the National Cancer Institute have begun tracing the effects of having two variants of the APOL1 gene, which occurs in about 12 percent of African-Americans.
Researchers earlier linked this gene to susceptibility for kidney disease. When a person has kidney disease, the kidneys are unable to fully remove waste products and extra water from the blood. The researchers studied a common kidney disease called focal segmental glomerulosclerosis ( FSGS ), which often progresses to end-stage kidney disease and the need for dialysis or a kidney transplant. The researchers studied FSGS patients who came to the NIH Clinical Center or other collaborating medical centers, and who provided blood samples for genetic studies.
"These findings explain nearly all of the excess risk of non-diabetic kidney failure in African-Americans. African-Americans with no variant or one variant have about the same risk of end-stage kidney disease as their white counterparts," Winkler said. "People with two APOL1 variants have greatly increased risk of particular kidney diseases — by 17- to 30-fold."
The researchers found that African-Americans with two copies of the APOL1 variants have about a 4 percent lifetime risk of developing FSGS. Those who develop kidney disease tend to do so at younger ages than other FSGS patients, with 70 percent diagnosed with FSGS between age 15 and 39, compared to 42 percent in that age group for people with one or no APOL1 variants.
Possessing two APOL1 variants also raises the risk for African-Americans with HIV of developing HIV-associated nephropathy ( HIVAN ) — a type of kidney disease that develops in some people with human immunodeficiency virus — to 50 percent among those not getting anti-viral therapy. Anti-viral therapy appears fairly effective at preventing HIVAN.
"The much higher risk of kidney disease in patients with HIV suggests that a second hit with a virus or other unknown factor is necessary for kidney injury in people who have two APOL1 variants," Winkler said. This may be why most people with two APOL1 variants do not develop kidney disease.
FSGS patients with two APOL1 variants respond as well to steroid treatments as their counterparts who don’t have the variants, making steroids a viable treatment option, the researchers found. Further, they found that kidney disease progresses more rapidly in patients with two APOL1 variants, and they hypothesize that aggressive therapy may be advisable.
"In the future, knowing that you have these gene variants and are at increased risk of developing kidney disease may tell you when to start screening for the disease and how to choose therapy," Kopp said. "However, more research is needed, including clinical trials that test whether early genetic testing in the African-American population makes a difference, whether screening tests for young adults with the variant copies detects kidney disease at an early stage, and whether early treatment affects long-term outcome."
This research builds on earlier advances in understanding the role of genetics in kidney disease. In 2008, Kopp, Winkler and other researchers found that variants in the MYH9 gene on chromosome 22 are linked to susceptibility to various forms of kidney disease.
In 2010, working with researchers at Harvard Medical School, among others, Kopp and Winkler found some kidney disease risk is due to variants APOLI, a gene adjacent to MYH9. These variants appear to have evolved about 5,000 years ago in some regions of sub-Saharan Africa to protect against trypanosomal infection, also called African sleeping sickness, a degenerative and potentially fatal disease affecting tens of thousands of people in those regions. People from other continents do not have the APOL1 variants.
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Home Dialysis Summit Recommends Policy Changes to Increase Home Dialysis Usage
WASHINGTON, April 25, 2012 /PRNewswire -- On the heels of the first National Summit on Home Dialysis Policy, Summit organizers released a report reflecting the views of the delegates -- leaders in the kidney disease patient, clinician, facility and industry communities -- on federal policy steps to improve utilization of home dialysis for patients who can benefit from this often advantageous form of treatment. Many of the organizers also announced they have formed a new alliance, called the Alliance for Home Dialysis, to advance the recommendations identified at the Summit.
The Summit's "Report of the Delegates" highlights key findings from a March 29th meeting in Washington, DC where experts probed why, despite widely accepted and well-documented benefits of home dialysis -- improved outcomes, enhanced patient satisfaction, improved quality of life, and lower costs-- fewer than ten percent of the more than 390,000 current U.S. dialysis patients receive treatment at home. Current rates of home dialysis utilization reflect a steep decline from the 1970s, when almost 40% of U.S. dialysis patients were treated in-home.
Specifically, delegates found that policymakers should work with stakeholders in the dialysis community to confront three areas:
Accessibility: Patients and clinicians face array of hurdles in education, training, and infrastructure that hinder equalized access to home dialysis.
Accountability: Utilization of home dialysis can be improved through measures within government programs that are designed to recognize and support excellence in the delivery of home dialysis services.
Aligning Incentives: Reimbursement policies, regulation of new technologies and other policy incentives can be realigned to better support federal policy goals of expanding access to home dialysis.
The Report includes 15 recommendations to serve these goals, including that federal policymakers should:
Maintain parity for home and in-center dialysis in Medicare reimbursement;
Support home dialysis mentoring programs, particularly those that use existing patients as mentors; and
Align federal and state regulatory requirements for home therapies, such as revising the Centers for Medicare and Medicaid Services Conditions for Coverage requirements, to reflect differences in home and in-center dialysis.
Summit supporters will begin work through the new Alliance to dialogue with federal policymakers and advance policy improvements in the three consensus areas that emerged at the Summit.
SOURCE National Summit on Home Dialysis Policy
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National Kidney Foundation's Top 10 Things Every Dialysis Patient Should Know.
- You have treatment choices. Options exist for how, where and when you dialyze. Dialysis can be done in a hospital, in a dialysis unit that is not part of a hospital, or at home. You and your doctor will decide which place is best, based on your medical condition and your wishes. There are different types of dialysis - peritoneal and hemodialysis. Work with your health care team to determine a treatment plan that makes you feel comfortable. Recent studies show that the majority of patients beginning in-center hemodialysis (HD) know very little, if anything, about the option to dialyze at home. Once informed, 40% or more of patients are interested in this treatment option, and yet less than 10% actually begin home dialysis. If you're dissatisfied with the type of dialysis treatment that you're receiving, ask your healthcare team if another type of dialysis treatment would be better.
- You can compare in-center dialysis facilities online. Information on over 5,600 US-based dialysis centers is available online through the Medicare website. To help you make choices about your care, you can compare different facilities side-by-side and evaluate each facility based upon clinic characteristics and quality measures. You can search for dialysis facilities by name or geographic proximity. After completing an initial facility comparison to determine which facilities best meet your needs - such as the number of hemodialysis stations at a particular location and whether there are evening shifts available - visit the facilities that you're most interested in. Talk to the staff and other patients, as well as your doctor to ensure that this dialysis facility is a good fit for you.
- There are ways to prepare ahead for an emergency. Ask your dialysis facility about their emergency plan in case of a snow storm, fire, power outage or other natural disaster. As back up, make sure you have the names, locations and phone numbers of other dialysis units and hospitals in your area. Since regular community transportation services may not be working in an emergency, be prepared to make other arrangements for getting to dialysis. You may need to contact the police and Emergency Medical Services (EMS) for assistance. If you dialyze at home, make sure you have at least two weeks' worth of unexpired supplies on hand. If you have to miss a dialysis treatment, begin your emergency meal plan.
- There is an easy way to transfer patient records between clinics. There is an easy, secure way for your health care team to transfer your treatment records online. In 2009, the Centers for Medicare and Medicaid Services (CMS) created a centralized web-based data collection system called CROWNWeb to help reduce and eliminate patient treatment interruptions. This central system helps to streamline patient care regardless of the reason for changing dialysis centers. For example, if you've been admitted to the hospital, or if you needed to relocate during an emergency evacuation, your doctors and health care team can access up-to-date information about your dialysis so that you continue to receive appropriate care no matter where you are.
- You can travel while on dialysis.
Dialysis centers are located in every part of the United States and in many foreign countries. The treatment is standardized, but you need to plan ahead by making an appointment for dialysis at another center before you go. The staff at your center may help you make these appointments.
- You can be your own best advocate. Know what key questions to ask your doctor or other healthcare professionals. Take notes so that you can refer back to them later. Partner with your doctor and decide on a treatment plan together. Advocate for yourself and share how you're feeling.
- You have many rights. You as a patient have a great deal of control over your treatments. Patients have a bill of rights which includes receiving quality care, counseling about your medical information, and an expectation of privacy.
You also have responsibilities. Once you decide on a course of treatment, it's important to follow the recommendations of your health care team. If you decide to receive in-center dialysis, arrive at dialysis on time so that you can receive the full treatment without delays.
- You can receive insurance coverage. If you have end stage renal failure, you are likely eligible for Medicare insurance coverage. Speak with your health care team and social worker for help filling out insurance paperwork.
- You may need to follow a special diet. When your kidneys are not working properly, you may not be able to eat everything you like, and you may need to limit how much you drink. Your diet may vary according to the type of dialysis you receive. It is important to speak with a renal dietitian so that you are able to understand what you can and cannot eat based on your full health history.
- Dialysis patients can work. Many dialysis patients can go back to work or school after they have gotten used to dialysis. After establishing a dialysis routine, many patients have more energy and find that they are able to time to work around this new schedule. Some patients even find creative ways to work remotely from dialysis with the use of a laptop or cell phone, depending on their field of expertise.
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New Book to Help Educate Patients with Chronic Kidney Disease who may be facing Dialysis or Hemodialysis: |
Help, I Need Dialysis!
How to have a good future with kidney disease
By Dori Schatell, MS and Dr. John Agar
An internationally known nephrologist and life-long kidney patient educator explain how dialysis works, each of the ways to do it, and how your treatment choice may affect your diet, energy level, work, travel, sexuality and fertility, sleep, and survival. Comprehensive and fully referenced, this book is a must-read if you face the life-changing choices that come with kidney failure. |
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