Kidney News May 2012, 4#5 : Page 1

May 2012 | Vol. 4, Number 5 Does Living Donor Age Matter in Kidney Transplantation? Recent study results should encourage more donor paired exchanges By Tracy Hampton Inside 6 Racial disparities in kidney care is focus of congressional brieﬁ ng A 7 many will die before a suitable organ becomes available. Th e shortage is ex-pected to worsen. Such living donor chains and simpler closed-loop paired exchanges, which in-volve two pairs of donors and recipients, assume that kidneys from living donors are of comparable quality and antici-pated longevity. But how true is this assumption? Potential recipients often wonder, will the kidney received from a stranger—particularly an older one—be as good as a kidney donated by a loved one? “In a proposed kidney paired dona-tion match, if an old donor–recipient pair is matched to a young donor–re-cipient pair, the young recipient may feel disadvantaged and may not be will-Continued on page 2 cross the globe, numerous kid-ney transplant candidates and donors are linking up in often complicated ways to facilitate more transplants through exchange pro-grams, or swaps. Th e largest swap so far, which was orchestrated by the National Kidney Registry (NKR) and involved 60 lives and 30 kid-neys, was described recently in Th e New York Times (http://www. nytimes.com/2012/02/19/health/ lives-forever-linked-through-kid-ney-transplant-chain-124.html?_ r=2). Also, in early February the NKR announced that it had facilitated its 400th exchange transplant. Th ese ef-forts by the NKR and other programs could not come at a better time. Nearly 90,000 people in the United States are waiting for a kidney transplant, and National Quality Forum endorses 12 measures for renal care 9 Overwhelmed with information? Looking for new ways to connect with your peers, we can help. Kidney 2.0 14 Journal View Trading life expectancy to avoid dialysis 18 Medical Education Research Antiplatelet Therapy in Patients with Chronic Kidney Disease: Is It Safe? By Tracy Hampton ntiplatelet therapy that inhibits blood clotting can be life-saving for individuals at high risk for cardiovascular disease or stroke. At fi rst glance, this should apply to patients with chronic kidney disease (CKD), who are more likely to die of cardiovas-cular disease than of any other cause. Help others learn from your experiences 20 Policy Update A But nonatherosclerotic conditions such as cardiac failure, sudden cardiac death, and arrhythmia are more com-mon causes of cardiovascular events in individuals with CKD than in the gen-eral population, and the bleeding risk of antiplatelet agents may be greater among people with CKD because of impaired hemostasis. Investigators recently published a re-view in the Annals of Internal Medicine on the benefi ts and harms of antiplate-let agents in these patients, focusing on cardiovascular events, mortality, and bleeding. “Until now, data from studies done in the general population were extrap-olated to people with chronic kidney disease,” said senior author Giovanni Strippoli, MD, PhD, who holds titles at the school of public health at the University of Sydney in Australia, the Mario Negri Sud Consortium in Italy, Continued on page 4 NIH research, immunosuppressive coverage, and changes to Medicare ESRD program among topics discussed with legislators on ASN Hill Day

Does Living Donor Age Matter In Kidney Transplantation?

Tracy Hampton

Recent study results should encourage more donor paired exchanges Across the globe, numerous kidney transplant candidates and donors are linking up in often complicated ways to facilitate more transplants through exchange programs, or swaps. The largest swap so far, which was orchestrated by the National Kidney Registry (NKR) and involved 60 lives and 30 kidneys, was described recently in The New York Times (http://www. Nytimes.com/2012/02/19/health/ lives-forever-linked-through-kidney- transplant-chain-124.html?_ r=2). Also, in early February the NKR announced that it had facilitated its 400th exchange transplant. These efforts by the NKR and other programs could not come at a better time. Nearly 90,000 people in the United States are waiting for a kidney transplant, and many will die before a suitable organ becomes available. The shortage is expected to worsen. Such living donor chains and simpler closed-loop paired exchanges, which involve two pairs of donors and recipients, assume that kidneys from living donors are of comparable quality and anticipated longevity. But how true is this assumption? Potential recipients often wonder, will the kidney received from a stranger—particularly an older one—be as good as a kidney donated by a loved one? “In a proposed kidney paired donation match, if an old donor–recipient pair is matched to a young donor–recipient pair, the young recipient may feel disadvantaged and may not be will ing to trade with an older donor,” said Paolo Ferrari, MD, director of Australia’s national registry for paired kidney exchanges. “Refusal to participate in an exchange could break the chain of potential matches identified after a match run and could limit the success of a kidney paired donation program.” A recent study by John Gill, MD, and his colleagues, of the University of British Columbia, in Vancouver, Canada, that appears in the Clinical Journal of the American Society of Nephrology investigates this issue. The researchers analyzed the survival of kidneys from donors of different age groups that were transplanted into recipients of different age groups. Their study included data from all adult kidney transplants from living donors that were performed in the United States from January 1988 to December 2003, with follow-up through September 2007. Age not an issue The investigators found that except for recipients aged 18 to 39, who benefited the most when they received kidneys from donors aged 18 to 39, donor age between 18 and 64 had a minimal effect on the survival of transplanted kidneys. Specifically, the researchers noted a difference of only 1 to 2 years in allograft half-life, with no graded association, among different donor age groups. “These findings show that in contrast to deceased donor transplantation, the age of a living donor has little impact on transplant survival,” Gill said. “This information should help increase participation and efficiency of living donor paired exchange programs because it alleviates patient concerns about receiving a kidney from an older aged living do- nor that currently limits acceptance of a proposed transplant in paired exchange programs.” More experience is needed to determine the outcome of transplants from living donors aged 65 and older relative to younger living donors, Gill said. In addition to expanding participation in exchange programs by blood group and tissue-incompatible donor– recipient pairs, the results may also encourage participation of more compatible donor–recipient pairs. Finally, the information should prompt exchange programs to reexamine any matching algorithms that emphasize donor–recipient age matching. “This study’s observation supports data from the Australian registry, where 13. 8 percent of live donors were aged 60 years or older, showing that live donor– recipient age difference does not impact graft or patient survival,” said Ferrari, who was not involved with the study by Gill and his associates. Those findings were published by Ferrari and his colleagues in 2011 in Nephrology Dialysis Transplantation. “Taken together, these findings of the two registry data are of major relevance for policy and decision making in kidney paired donation,” Ferrari said. They reinforce the view that it is acceptable to ignore donor–donor or donor–recipient age differences as a scoring parameter in ranking match combinations.” Weighing options Gill and his team also juxtaposed their results against the probabilities that wait-listed patients would receive a kidney from a deceased donor and their risk of being excluded from transplantation during the study because of death or permanent removal from the wait-list. The probability of deceased donor transplantation after 3 years of waitlisting ranged from 21 percent to 66 percent depending on patients’ blood type and antibody levels, whereas the probability of being excluded from transplantation ranged from 6 percent to 27 percent by age, race, and type of kidney disease. Gill noted that when patients consider these probabilities, many will likely find that participating in living donor paired exchanges—and possibly receiving a kidney from an older donor—is a better option than continuing to wait for a deceased donor transplant. Yet the study included relatively few living donors aged 60 and older, the authors said, noting that there may be certain patient subgroups who tolerate dialysis relatively well, so that waiting while they continue to receive dialysis would be a reasonable consideration. Also, they were unable to evaluate the effect of other important donor factors that may affect transplant survival and confound the results, including predonation kidney function, donor blood pressure, and diabetes in the donor. The authors stressed that their find-Ings should not be interpreted as a dismissal of the importance of living donor age on transplant outcomes. Most recipient age groups with living donors between 40 and 64 had a small but statistically signifi-cant increased risk of allograft loss compared with those whose living donors were 18 to 39 years old, and in all recipient age groups, the greatest donor age-associated risk of allograft loss was among recipients from living donors aged 65 and older. This increased risk of allograft failure with older donor age is consistent with results from a recent single-center American Journal of Transplantation publication from the Mayo Clinic that showed an association between living donor age and the risk of death-censored graft loss. that study did not show an association between living donor age and patient death. Although questions still remain about the comparable quality of different donors’ organs, the results shown by Gill and his team provide valuable information to transplant candidates and potential donors who are weighing their options. Study co-authors include Peter Chang, MD, Jagbir Gill, MD, James Dong, Caren Rose, Howard Yan, MD, David Landsberg, MD (University of British Columbia, in Vancouver, Canada); and Edward Cole, MD (University of Toronto, in Canada). Disclosures: The authors reported no financial disclosures. The article “Living donor age and kidney allograft half-life: implications for living donor paired exchange programs,” appeared online at http://cjasn.asnjournals. org/ in March 2012, doi: 10.2215/ CJN.09990911. “

Antiplatelet Therapy In Patients With Chronic Kidney Disease: Is It Safe?

Tracy Hampton

Antiplatelet therapy that inhibits blood clotting can be life-saving for individuals at high risk for cardiovascular disease or stroke. At first glance, this should apply to patients with chronic kidney disease (CKD), who are more likely to die of cardiovascular disease than of any other cause. But nonatherosclerotic conditions such as cardiac failure, sudden cardiac death, and arrhythmia are more common causes of cardiovascular events in individuals with CKD than in the general population, and the bleeding risk of antiplatelet agents may be greater among people with CKD because of impaired hemostasis. Investigators recently published a review in the Annals of Internal Medicine on the benefits and harms of antiplatelet agents in these patients, focusing on cardiovascular events, mortality, and bleeding. “Until now, data from studies done in the general population were extrapolated to people with chronic kidney disease,” said senior author Giovanni Strippoli, MD, PhD, who holds titles at the school of public health at the University of Sydney in Australia, the Mario Negri Sud Consortium in Italy and Diaverum in Sweden. “Previous research from our group and others has shown that such extrapolations could be very dangerous, and interventions that may be very good in the general population may have no effect or even be harmful in people with chronic kidney disease Paying particular attention to patients with CKD while conducting clinical trials will only become more important. Approximately 10 percent to 15 percent of the adult population worldwide have the disease, and its prevalence is on the rise because of increasing rates of diabetes and obesity. Analyzing available data Mining Embase and Cochrane databases from 1980 through November 2011 without language restriction, Strippoli and his colleagues selected randomized trials that included adults with CKD and compared antiplatelet agents with standard care, placebo, or no treatment. “Nephrology is lagging behind all other disciplines of internal medicine when it comes to randomized trials, and a strong effort is needed to do more trials and to summarize existing knowledge from the few small existing trials that have been published,” said Strippoli. Many of the trials in the analysis were not performed to study issues specifically in kidney disease but included a small portion of people with the condition. Nine trials (9969 participants) provided information on antiplatelet treatment among persons with CKD who had acute coronary syndrome or were undergoing coronary artery intervention and were considered at high risk for subsequent vessel closure. All data for these trials were post hoc analyses for subgroups of participants with CKD from larger trials. The trials provided data for glycoprotein Iib/IIIa inhibitors (abciximab, eptifibatide, or tirofiban) or clopidogrel (two trials, 4498 participants), and all involved coadministration of aspirin with or without heparin. The median follow-up time was 12 months. Another 31 trials provided data on 11,701 persons with stable or no cardiovascular disease who received antiplatelet therapy. Twelve trials studied antiplatelet effects on mortality, progression of kidney disease, or safety in patients who had glomerulonephritis, diabetic nephropathy, or an impaired GFR regardless of cause. The agents administered included aspirin, dipyridamole, aspirin and dipyridamole, or a thienopyridine (clopidogrel or ticlopidine), and the median follow-up time was 12 months. Seventeen of the trials provided shorter-term data (median of 6 months of follow-up) for a variety of antiplatelet treatments in persons who were receiving or would soon require dialysis. Four trials administered antiplatelet therapy to kidney transplant recipients. Pros and cons of anticlotting drugs In general, the investigators found that the available information on antiplatelet therapy in patients with CKD is of low or very low quality, with considerable variation in trial duration, heterogeneity in the definitions and assessment of bleeding outcomes, reliance on subgroup data from major trials, and substantial methodologic limitations in data for patients with stable cardiovascular disease. The researchers reported low-quality evidence that in people with acute coronary syndromes, glycoprotein Iib/IIIa inhibitors or clopidogrel plus standard care had little or no effect compared with standard care alone on all-cause or cardiovascular mortality or on myocardial infarction, but the treatments increased serious bleeding by up to 40 percent. Also according to generally low-quality evidence, antiplatelet therapy prevented myocardial infarction (lowering the risk by about 34 percent) but caused uncertain effects on mortality and increased minor bleeding by approximately 70 percent compared with placebo or no treatment in persons with stable or no cardiovascular disease. These findings indicate that any benefits of antiplatelet therapy for people with CKD are uncertain and are potentially outweighed by bleeding hazards. “All in all, these drugs should be used with care and attention, as all doctors do, and we should always think before we prescribe,” said Strippoli. Also, he and his coauthors noted that many patients would not be likely to accept the risk for major bleeding to reduce their risk for myocardial infarction without proven reductions in death or the need for coronary revascularization. “This systematic review and metaanalyses primarily highlight the rather limited evidence from existing randomized trials about the efficacy and safety of antiplatelet agents for preventing cardiovascular events and death across the spectrum of chronic kidney disease and in those receiving dialysis or a renal transplant,” said Alan Go, MD, who is the director of the comprehensive clinical research unit and the regional medical director for clinical trials at Kaiser Permanente Northern California and who was not involved with the research. Given the low quality of the available evidence, the investigators advocate for specific trials evaluating antiplatelet therapies, including newer agents, in individuals with CKD and coexisting acute or stable cardiovascular disease. They also note that no data are currently available on antiplatelet use in dialysis patients or kidney transplant recipients who have acute coronary syndromes or require coronary artery revascularization. “Given the risks of bleeding associated with these agents, additional studies are needed to delineate the net clinical benefit or harm at different levels of renal function through randomized trials as well as studies done in large, diverse clinical practice populations that are more representative,” said Go.

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