Riella, Miguel

Tonelli, Marcello

English

Marcello Tonelli

Miguel Riella

Crossref

Hong Kong Journal of Nephrology

Chronic kidney disease and the aging population

Elsevier - Publisher Connector 

Hong Kong Journal of Nephrology (2014) 16, 2e6Available online at www.sciencedirect.com
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journal homepage: www.hkjn-onl ine.comEDITORIALChronic kidney disease and the aging
populationYouth, which is forgiven everything, forgives itself
nothing: age, which forgives itself everything, is forgiven
nothing.
e George Bernard Shaw
The proportion of older people in the general population is
steadily increasing worldwide, with the most rapid growth
in low- and middle-income countries.1 This demographic
change is to be celebrated, because it is the consequence
of socioeconomic development and better life expectancy.
However, population aging also has important implications
for societydin diverse areas including health systems,
labor markets, public policy, social programs, and family
dynamics.2 A successful response to the aging population
will require capitalizing on the opportunities that this
transition offers, as well as effectively addressing its
challenges.
Chronic kidney disease (CKD) is an important public
health problem that is characterized by poor health out-
comes and very high health care costs. CKD is a major risk
multiplier in patients with diabetes, hypertension, heart
disease, and strokedall of which are key causes of death
and disability in older people.3 Because the prevalence of
CKD is higher in older people, the health impact of popu-
lation aging will depend in part on how the kidney com-
munity responds.
March 13, 2014 will mark the celebration of the 9th
World Kidney Day (WKD), an annual event jointly spon-
sored by the International Society of Nephrology and the
International Federation of Kidney Foundations. Since its
inception in 2006, WKD has become the most successful
effort to raise awareness among policymakers and
the general public about the importance of kidney dis-
ease. The topic for WKD 2014 is “CKD in Older People”.
This article reviews the key links between kidney func-
tion, age, health, and illnessdand discusses the impli-
cations of the aging population for the care of people
with CKD.http://dx.doi.org/10.1016/j.hkjn.2014.02.004
1561-5413/Copyright ª 2014, Hong Kong Society of Nephrology Ltd. PuEpidemiology of aging
The key drivers of population aging are: socioeconomic
development and increasing prosperitydwhich result in
lower perinatal, infant, and childhood mortality; lower risk
of death in early adulthood due to accidents and unsafe
living conditions; and improving survival of middle-aged and
older people with chronic disease. The resulting increases
in life expectancy (together with the lower birth rates that
typically accompany socioeconomic development) mean
that older people account for a larger proportion of the
general population.1 The extent of the resulting changes in
population characteristics can be startling, especially for
developing countries (Fig. 1).
In contrast to the situation even two generations ago,
people can expect to live for many years after the usual
retirement age. For example, in the UK, men and women
aged 65 years in 2030 can expect to live until age 88 years
and 91 years, respectively.4 Predicted life expectancy for
today’s children is controversial, but experts estimate that
50% of UK children born in 2007 will live to at least 103
years.4 Although it is clear that people are living longer, it is
uncertain how much of the increased life expectancy will
translate into years of good health. These demographic
changes have dramatic potential implications for conditions
such as CKD, for which the prevalence increases with age.
CKD is common in older people and its preva-
lence increases in parallel with age
It has been known for decades that estimated glomerular
filtration rate (eGFR) declines in parallel with age.5 The
prevalence of CKD among females in the Chinese general
population increases from 7.4% among those aged 18e39
years to 18.0% and 24.2% among those aged 60e69 years
and 70 years, respectively.6 Relative increases in the
prevalence of CKD with age are equally striking for pop-
ulations in the USA, Canada, and Europe,7e9 although thereblished by Elsevier Taiwan LLC. All rights reserved.
Figure 1 Changing age distribution in the general population of China, 1990e2050. Reproduced from WHO document number
WHO/DCO/WHD/2012.2.
Editorial 3are between-country differences in the absolute
prevalence.
At older ages, an increased proportion of prevalent CKD
cases have low eGFR alone (as compared to albuminuria
alone, or both low eGFR and albuminuria).10 Although this
might suggest that many older people with CKD can expect
lower rates of kidney function loss, available data are
inconclusivedand current knowledge does not allow clini-
cians to distinguish reliably between those whose CKD will
and will not progress.
As for other age groups, the incidence of dialysis-
dependent kidney failure has steadily increased among
older people over the past few decades: in the USA, a 57%
age-adjusted increase in the number of incident octoge-
narians andnonagenarianswas notedbetween 1996 and 2003
alone.11 Despite this increase, patients aged > 80 years are
still less likely to initiate dialysis than those aged 75e79
yearsdalthough a large recent study suggested that the risk
of developing very low eGFR (< 15 mL/minute/1.73 m2) is
similar for older and younger adults.12 It is uncertainwhether
this discrepancy is due to between-age differences in the
true rate of progressive kidney function loss, the risk of death
due to competing causes, patient views about dialysis, or
physician practices.12,13 Regardless of the explanation, theaging population is likely to lead to continued increases in
the number of older people with severe CKD.
CKD is harmful but treatable if patients at risk
are identified
Like younger people, older people with advanced CKD are at
increased risk of death, kidney failure, myocardial infarc-
tion, and stroke compared to otherwise similar people with
normal or mildly reduced eGFR.14,15 Although death is by far
the most common of these adverse outcomes, this does not
mean that older patients with clinically relevant CKD cannot
benefit from timely specialist referral.
With appropriate management, patients with advanced
CKD (regardless of age) may benefit from slower loss of
kidney function (potentially preventing kidney failure),
better control of metabolic consequences such as acidosis,
anemia, and hyperphosphatemia, lower risk of cardiovas-
cular events, and (for those who are interested in renal
replacement) a more informed choice of renal replacement
modality, including timely creation of vascular access.16
The aging population is likely to lead to continued in-
creases in the number of older people who might require
Box 1. Unmet needs for kidney transplantation in older
CKD patients.
 Organ shortage
 Paucity of live donors
 Organ allocation policies that appropriately weight
likelihood of benefit from transplantation as well as
chronological age
 Ensuring appropriate referral of potentially suitable
older recipients for transplantation assessment
 Ethical concerns about offering a kidney to an older
patient versus a younger one
 Optimal immunosuppressive regimen
Note. From “Kidney transplantation in the elderly: it’s
not all gloom and doom,” by V. Mohanlal and M. Weir,
2011, ASN Kidney News, 3, p.15e7. Copyright 2011,
American Society of Nephrology. Adapted with
permission.
Box 2. Meeting the growing demand for kidney trans-
plantation in older CKD patients.
 Preferential transplantation of organs from older
donors to older recipients
 Enlarge the donor pool by accepting expanded
criteria donors: age  60 years or  50 years with
any two of the following conditions: history of hy-
pertension, serum creatinine  1.5 mg/dL or death
due to cerebrovascular accident.
 Transplanting two marginal kidneys instead of one
Note. From “Kidney transplantation in the elderly: it’s
not all gloom and doom,” by V. Mohanlal and M. Weir,
2011, ASN Kidney News, 3, p.15e7. Copyright 2011,
American Society of Nephrology. Adapted with
permission.
4 Editorialsuch referral, which should be considered in assessments of
future nephrology workforce capacity.
Dialysis can benefit older people with kidney
failure
In developed countries, the default management strategy
for older people with kidney failure appears to have shifted
from conservative management to initiation of dialysis.17 On
average, life expectancy after initiation of dialysis is rela-
tively short for older patients: median survival among inci-
dent US dialysis patients aged 80e84 years is 16monthsdand
is only 12 months among those aged 85e89 years.11 At the
same time, these median statistics reflect a bimodal distri-
bution of survival time in older dialysis patients: although a
large proportion die within 6months of commencing dialysis,
a substantial minority may live for years. This heterogeneity
in mortality appears to be driven by differences in baseline
comorbidity. For example, analyses of a small UK cohort of
people with advanced kidney failure suggested that initia-
tion of dialysis was not associated with increased survival for
those aged > 75 years and with two or more comorbid-
ities.18,19 Similarly, the presence of two or three comorbid
conditions in US dialysis patients aged > 65 years was asso-
ciated with substantially increased mortality compared to
those in better health.11 When functional status is lower at
baseline, initiation of dialysis often signals the onset of
further declines: among 3702 nursing home residents initi-
ating dialysis, 58% had died and 87% had experienced addi-
tional loss of function at 1 year.20 Although available data
have limitations, quality of life appears reasonable among
selected older dialysis patientsdand can remain stable
despite moderate or high levels of comorbidity.21,22
These data suggest that dialysis is an appropriate
treatment option for well-informed older patients with
kidney failuredespecially for those with a good baseline
quality of life. However, the very poor outcomes experi-
enced in those with more comorbidity or lower functional
status at baseline clearly demonstrate that dialysis does not
improve clinical outcomes for all older people with kidney
failuredand that good clinical judgment and careful
communication will be increasingly required as the general
population continues to age.
Kidney transplantation can also benefit older
people with kidney failure
It is generally accepted that older age alone does not
preclude kidney transplantation in otherwise suitable can-
didates. However, older patients with kidney failure are
more likely to have absolute and relative contraindications
to transplantation, and are less likely to be placed on the
kidney transplantation waiting list. Unsurprisingly, patient
and graft 5-year survival probabilities are lower among US
kidney transplant recipients aged  65 years as compared
to those aged 35e49 years (patient: 67.2% vs. 89.6%; graft:
60.9% vs. 75.4%, respectively).23 In addition, older people
who are potential kidney transplant recipients face several
potential disadvantages compared to their younger coun-
terparts (Box 1).Nonetheless, transplantation appears to reduce mortal-
ity among patients of all ages. For example, among those
aged 74 years, receiving a deceased donor transplant was
associated with a hazard ratio of mortality of 0.67 (95%
confidence interval, 0.53e0.86) as compared to remaining
on dialysis.23 Use of expanded criteria deceased donors24,25
as well as more liberal use of older living donors26 also
appear to reduce mortality among older people with kidney
failure, as compared to similar patients who remain on the
transplant waiting list (Box 2). These latter two strategies
are especially appealing for use in developing countries,
where growth in the prevalence of older people has been
most pronounced. However, because transplant surgery it-
self temporarily increases the risk of death, the mortality
benefits associated with kidney transplantation (regardless
of donor type) are restricted to those with reasonable
baseline life expectancy and without dramatically
increased perioperative risk.27
Editorial 5Research needs
Although much is known about CKD in older populations, a
great deal remains to be learned. Many trials of therapies
for CKD have excluded older patients28dand most do not
provide guidance on how to manage comorbidities that
often accompany CKD but may lead to competing thera-
peutic priorities. More information is needed on how to
accurately identify people who will progress to kidney
failuredand among these, the subset that can expect
reasonable life expectancy and quality of life if they opt for
dialysis treatment. Future studies should test new ways to
communicate information about the risks and benefits of
dialysis (as compared to conservative management), to
facilitate informed patient decisions. Above all, we need
more studies that demonstrate how to optimize quality of
life and manage symptoms in elderly people with
CKDdincluding those who have chosen conservative
management.
The way forward
The aging of the general population means that older
people now account for a much greater proportion of pa-
tients with or at risk for kidney disease and kidney failure.
The tremendous clinical heterogeneity within this popula-
tion indicates the need for more discerning management.
Chronological age alone will not be sufficient as the basis
for clinical decisions, and a more nuanced approach is
requireddbased on the comorbidities, functional status,
quality of life, and preferences of each individual patient.
Clinicians can be reassured that dialysis and kidney trans-
plantation can increase life expectancydand will allow
reasonable quality of life in selected older people with
kidney failure. Perhaps more importantly, clinicians, pa-
tients, and their families can be comforted by the knowl-
edge that timely specialist evaluation can help to improve
outcomes and reduce symptoms in older people with
advanced kidney diseasedwhether they have selected
conservative management or dialysis as their treatment
plan.
Conflicts of interest
All contributing authors declare no conflicts of interest.
Acknowledgments
Dr Tonelli was supported by a Government of Canada
research chair in the optimal care of people with CKD.
References
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2. Wiener JM, Tilly J. Population aging in the United States of
America: implications for public programmes. Int J Epidemiol
2002;31:776e81.3. Couser WG, Remuzzi G, Mendis S, Tonnelli M. The contribution
of chronic kidney disease to the global burden of major non-
communicable diseases. Kidney Int 2011;80:1258e70.
4. Select Committee on Public Service and Demographic Change.
Ready for Aging? Report. London: House of Lords; 2013.
5. Davies DF, Shock NW. Age changes in glomerular filtration rate,
effective renal plasma flow, and tubular excretory capacity in
adult males. J Clin Invest 1950;29:496e507.
6. Zhang L, Wang F, Wang L, Wang W, Liu B, Liu J, et al. Preva-
lence of chronic kidney disease in China: a cross-sectional
survey. Lancet 2012;379:815e22.
7. Coresh J, Selvin E, Stevens LA, Manzi J, Kusek JW, Eggers P,
et al. Prevalence of chronic kidney disease in the United
States. JAMA 2007;298:2038e47.
8. Zhang QL, Rothenbacher D. Prevalence of chronic kidney dis-
ease in population-based studies: systematic review. BMC
Public Health 2008;8:117.
9. Arora P, Vasa P, Brenner D, Iglar K, McFarlane P, Morrison H,
et al. Prevalence estimates of chronic kidney disease in Can-
ada: results of a nationally representative survey. CMAJ 2013;
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10. James MT, Hemmelgarn BR, Tonelli M. Early recognition and
prevention of chronic kidney disease. Lancet 2010;375:
1296e309.
11. Kurella M, Covinsky KE, Collins AJ, Chertow GM. Octogenarians
and nonagenarians starting dialysis in the United States. Ann
Intern Med 2007;146:177e83.
12. Hemmelgarn BR, James MT, Manns BJ, O’Hare AM, Muntner P,
Ravani P, et al. Rates of treated and untreated kidney failure in
older vs younger adults. JAMA 2012;307:2507e15.
13. Keith DS, Nichols GA, Gullion CM, Brown JB, Smith DH. Longi-
tudinal follow-up and outcomes among a population with
chronic kidney disease in a large managed care organization.
Arch Intern Med 2004;164:659e63.
14. Hemmelgarn BR, Manns BJ, Lloyd A, James MT, Klarenbach S,
Quinn RR, et al. Relation between kidney function, protein-
uria, and adverse outcomes. JAMA 2010;303:423e9.
15. O’Hare AM, Bertenthal D, Covinsky KE, Landefeld CS, Sen S,
Mehta K, et al. Mortality risk stratification in chronic kidney
disease: one size for all ages? J Am Soc Nephrol 2006;17:
846e53.
16. Stevens PE, Levin A, Kidney Disease: Improving Global Out-
comes Chronic Kidney Disease Guideline Development Work
Group M. Evaluation and management of chronic kidney dis-
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comes 2012 clinical practice guideline. Ann Intern Med 2013;
158:825e30.
17. Thorsteinsdottir B, Montori VM, Prokop LJ, Murad MH. Ageism
vs. the technical imperative, applying the GRADE framework to
the evidence on hemodialysis in very elderly patients. Clin
Interv Aging 2013;8:797e807.
18. Chandna SM, Da Silva-Gane M, Marshall C, Warwicker P,
Greenwood RN, Farrington K. Survival of elderly patients with
stage 5 CKD: comparison of conservative management and
renal replacement therapy. Nephrol Dial Transplant 2011;26:
1608e14.
19. Murtagh FE, Marsh JE, Donohoe P, Ekbal NJ, Sheerin NS,
Harris FE. Dialysis or not? A comparative survival study of pa-
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Nephrol Dial Transplant 2007;22:1955e62.
20. Kurella Tamura M, Covinsky KE, Chertow GM, Yaffe K,
Landefeld CS, McCulloch CE. Functional status of elderly adults
before and after initiation of dialysis. N Engl J Med 2009;361:
1539e47.
21. Lamping DL, Constantinovici N, Roderick P, Normand C,
Henderson L, Harris S, et al. Clinical outcomes, quality of life,
and costs in the North Thames Dialysis Study of elderly people
6 Editorialon dialysis: a prospective cohort study. Lancet 2000;356:
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22. Unruh ML, Newman AB, Larive B, Dew MA, Miskulin DC,
Greene T, et al. The influence of age on changes in health-
related quality of life over three years in a cohort undergo-
ing hemodialysis. J Am Geriatr Soc 2008;56:1608e17.
23. Knoll GA. Kidney transplantation in the older adult. Am J
Kidney Dis 2013;61:790e7.
24. Merion RM, Ashby VB, Wolfe RA, Distant DA, Hulbert-
Shearon TE, Metzger RA, et al. Deceased-donor characteristics
and the survival benefit of kidney transplantation. JAMA 2005;
294:2726e33.
25. Cohen B, Smits JM, Haase B, Persijn G, Vanrenterghem Y,
Frei U. Expanding the donor pool to increase renal trans-
plantation. Nephrol Dial Transplant 2005;20:34e41.
26. Gill J, Bunnapradist S, Danovitch GM, Gjertson D, Gill JS,
Cecka M. Outcomes of kidney transplantation from older living
donors to older recipients. Am J Kidney Dis 2008;52:541e52.
27. Gill JS, Tonelli M, Johnson N, Kiberd B, Landsberg D,
Pereira BJ. The impact of waiting time and comorbidconditions on the survival benefit of kidney transplantation.
Kidney Int 2005;68:2345e51.
28. O’Hare AM, Kaufman JS, Covinsky KE, Landefeld CS,
McFarland LV, Larson EB. Current guidelines for using
angiotensin-converting enzyme inhibitors and angiotensin II-
receptor antagonists in chronic kidney disease: is the evi-
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717e24.
Marcello Tonelli*
Department of Medicine, University of Alberta,
Alberta, Canada
Miguel Riella
Department of Medicine, Catholic University of Parana,
Curitiba, Brazil
*Corresponding author.
E-mail address: no_reprints@med.ualberta.ca


Chronic kidney disease and the aging population 

Miguel C. Riella

Kidney International

Brazilian Journal of Nephrology

Journals Portal, Shahid Beheshti University of Medical Sciences

Chronic Kidney Disease and the Aging Population - Tonelli M et alJournal of pediatric nephrology | Volume 2 | Number 1| 2014 15Special ReportJ Ped. Nephrology 2014;2(1):15-20http://journals.sbmu.ac.ir/jpnChronic Kidney Disease and the Aging PopulationMarcello Tonelli,¹* Miguel Riella²How to Cite This Article: Tonelli M, Riella M. Chronic Kidney Disease and the Aging Population.J Ped. Nephrology 2014;2(1):15-20.1University of Alberta. Alberta, Canada2 Catholic University of Parana, Curitiba, Brazil*Corresponding AuthorMarcello Tonelli1University of Alberta. Alberta, CanadaEmail: no_reprints@med.ualberta.caIntroductionYouth, which is forgiven everything, forgives itselfnothing: age, which forgives itself everything, isforgiven nothing.-George Bernard ShawThe proportion of older people in the generalpopulation is steadily increasing worldwide, withthe most rapid growth in low- and middle-incomecountries [1].This demographic change is to becelebrated, because it is the consequence ofsocioeconomic development and better lifeexpectancy. However, population aging also hasimportant implications for society – in diverseareas including health systems, labor markets,public policy, social programs, and familydynamics [2]. A successful response to the agingpopulation will require capitalizing on theopportunities that this transition offers, as well aseffectively addressing its challenges.Chronic kidney disease (CKD) is an importantpublic health problem that is characterized bypoor health outcomes and very high health carecosts. CKD is a major risk multiplier in patientswith diabetes, hypertension, heart disease andstroke – all of which are key causes of death anddisability in older people [3]. Since the prevalenceof CKD is higher in older people, the health impactof population aging will depend in part on how thekidney community responds.March 13, 2014 will mark the celebration of the9th World Kidney Day (WKD), an annual eventjointly sponsored by the International Society ofNephrology and the International Federation ofKidney Foundations. Since its inception in 2006,WKD has become the most successful effort toraise awareness among policymakers and thegeneral public about the importance of kidneydisease. The topic for WKD 2014 is “CKD in olderpeople”. This article reviews the key links betweenkidney function, age, health and illness – anddiscusses the implications of the aging populationfor the care of people with CKD.Epidemiology of agingThe key drivers of population aging aresocioeconomic development and increasingprosperity – which result in lower perinatal, infantand childhood mortality; lower risk of death inearly adulthood due to accidents and unsafe livingconditions; and improving survival of middle-agedand older people due to chronic disease. Theresulting increases in life expectancy (togetherChronic Kidney Disease and the Aging Population - Tonelli M et alJournal of pediatric nephrology | Volume 2 | Number 1| 2014 16with the lower birth rates that typicallyaccompany socioeconomic development) meanthat older people account for a larger proportionof the general population [1]. The extent of theresulting changes in population characteristicscan be startling, especially for developingcountries (Figure 1).In contrast to the situation even two generationsago, people can expect to live for many years afterthe usual retirement age. For example, U.K menand women aged 65 years in 2030 can expect tolive until age 88 and 91 years, respectively [4].Predicted life expectancy for today’s children iscontroversial, but experts estimate that 50% ofU.K children born in 2007 will live to at least 103years [4]. Although it is clear that people are livinglonger, it is uncertain how much of the increasedlife expectancy will translate into years of goodhealth. These demographic changes have dramaticpotential implications for conditions such as CKD,for which the prevalence increases with age.CKD is common in older people and itsprevalence increases in parallel with ageIt has been known for decades that estimatedglomerular filtration rate (eGFR) declines inparallel with age [5]. The prevalence of CKDamong females in the Chinese general populationincreases from 7.4% among those aged 18-39years to 18.0% and 24.2% among those aged 60-69 and 70 years respectively [6]. Relativeincreases in the prevalence of CKD with age areequally striking for populations in the U.S, Canadaand Europe [7-9], although there are between-country differences in the absolute prevalence.At older ages, an increased proportion ofprevalent CKD cases has low eGFR alone (ascompared to albuminuria alone, or both low eGFRand albuminuria) [10]. Although this mightsuggest that many older people with CKD canexpect lower rates of kidney function loss,available data are inconclusive – and currentknowledge does not allow clinicians to reliablydistinguish between those whose CKD will andwill not progress.As for other age groups, the incidence of dialysis-dependent kidney failure has steadily increasedamong older people over the last few decades: inthe U.S, a 57% age-adjusted increase in thenumber of incident octogenarians andnonagenarians was noted between 1996 and 2003alone [11]. Despite this increase, patients aged>80 years are still less likely to initiate dialysisthan those aged 75-79 years – although a largerecent study suggested that the risk of developingvery low eGFR (<15 ml/min/1.73m2) is similar forolder and younger adults [12]. It is uncertainwhether this discrepancy is due to between-agedifferences in the true rate of progressive kidneyfunction loss, the risk of death due to competingcauses, patient views about dialysis, or physicianpractices [13]. Regardless of the explanation, theaging population will likely lead to continuedincreases in the number of older people withsevere CKD.CKD is harmful but treatable if patients at riskare identifiedLike younger people, older people with advancedCKD are at increased risk of death, kidney failure,myocardial infarction and stroke compared tootherwise similar people with normal or mildlyreduced eGFR [14,15]. Although death is by far themost common of these adverse outcomes, thisdoes not mean that older patients with clinicallyrelevant CKD cannot benefit from timely specialistreferral.With appropriate management, patients withadvanced CKD (regardless of age) may benefitfrom slower loss of kidney function (potentiallypreventing kidney failure), better control ofmetabolic consequences such as acidosis, anemiaand hyperphosphatemia, lower risk ofcardiovascular events, and (for those who areinterested in renal replacement) a more informedchoice of renal replacement modality, includingtimely creation of vascular access [16]. The agingpopulation will likely lead to continued increasesin the number of older people who might requiresuch referral, which should be considered inassessments of future nephrology workforcecapacity.Dialysis can benefit older people with kidneyfailureIn developed countries, the default managementstrategy for older people with kidney failureappears to have shifted from conservativemanagement to initiation of dialysis [17]. Onaverage, life expectancy after initiation of dialysisis relatively short for older patients: mediansurvival among incident U.S dialysis patients aged80-84 years is 16 months – and is only 12 monthsamong those aged 85-89 years [18]. At the sametime, these median statistics reflect a bimodaldistribution of survival time in older dialysispatients: although a large proportion die within 6months of commencing dialysis, a substantialminority may live for years. This heterogeneity inmortality appears to be driven by differences inChronic Kidney Disease and the Aging Population - Tonelli M et alJournal of pediatric nephrology | Volume 2 | Number 1| 2014 17baseline comorbidity. For example, analyses of asmall U.K cohort of people with advanced kidneyfailure suggested that initiation of dialysis was notassociated with increased survival for those aged>75 and with two or more comorbidities [19].Similarly, the presence of two to three comorbidconditions in U.S dialysis patients aged >65 yearswas associated with substantially increasedmortality compared to those in better health [11].When functional status is lower at baseline,initiation of dialysis often signals the onset offurther declines: among 3702 nursing homeresidents initiating dialysis, 58% had died and87% had experienced additional loss of function at1 year [20]. Although available data havelimitations, quality of life appears reasonableamong selected older dialysis patients – and canremain stable despite moderate or high levels ofcomorbidity [21,22].These data suggest that dialysis is an appropriatetreatment option for well-informed older patientswith kidney failure – especially for those withgood baseline quality of life. On the other hand,the very poor outcomes experienced in those withmore comorbidity or lower functional status atbaseline clearly demonstrate that dialysis does notimprove clinical outcomes for all older peoplewith kidney failure – and that good clinicaljudgment and careful communication will beincreasingly required as the general populationcontinues to age.Kidney transplantation can also benefit olderpeople with kidney failureIt is generally accepted that older age alone doesnot preclude kidney transplantation in otherwisesuitable candidates. However, older patients withkidney failure are more likely to have absoluteand relative contraindications to transplantation,and are less likely to be placed on the kidneytransplantation waiting list. Unsurprisingly,patient and graft 5-year survival probabilities arelower among U.S kidney transplant recipientsaged ≥65 years as compared to those aged 35-49years (patient: 67.2% vs. 89.6%; graft: 60.9% vs.75.4%, respectively) [23]. In addition, olderpeople who are potential kidney transplantrecipients face several potential disadvantagescompared to their younger counterparts (Box 1).Nonetheless, transplantation appears to reducemortality among patients of all ages. For example,among those aged 74 years, receiving a deceaseddonor transplant was associated with a hazardratio of mortality of 0.67 (95% confidence interval0.53, 0.86) as compared to remaining on dialysis[23]. Use of expanded criteria deceased donors[24,25], as well as more liberal use of older livingdonors [26] also appear to reduce mortalityamong older people with kidney failure, ascompared to similar patients who remain on thetransplant waiting list (Box 2). These latter twostrategies are especially appealing for use indeveloping countries, where growth in theprevalence of older people has been mostpronounced. However, because transplant surgeryitself temporarily increases the risk of death, themortality benefits associated with kidneytransplantation (regardless of donor type) arerestricted to those with reasonable baseline lifeexpectancy and without dramatically increasedperioperative risk [27].Research needsAlthough much is known about chronic kidneydisease in older populations, a great deal remainsto be learned. Many trials of therapies for CKDhave excluded older patients [28] – and most donot provide guidance on how to managecomorbidities that often accompany CKD but maylead to competing therapeutic priorities. Moreinformation is needed on how to accuratelyidentify people who will progress to kidney failure– and among these, the subset that can expectreasonable life expectancy and quality of life ifthey opt for dialysis treatment. Future studiesshould test new ways to communicate informationabout the risks and benefits of dialysis (ascompared to conservative management), tofacilitate informed patient decisions. Above all, weneed more studies that demonstrate how tooptimize quality of life and manage symptoms inelderly people with CKD – including those whohave chosen conservative management.The way forwardThe aging of the general population means thatolder people now account for a much greaterproportion of patients with or at risk for kidneydisease and kidney failure. The tremendousclinical heterogeneity within this populationindicates the need for more discerningmanagement. Chronological age alone will not besufficient as the basis for clinical decisions, and amore nuanced approach is required -- based onthe comorbidities, functional status, quality of lifeand preferences of each individual patient.Clinicians can be reassured that dialysis andkidney transplantation can increase lifeexpectancy – and will allow reasonable quality oflife in selected older people with kidney failure.Chronic Kidney Disease and the Aging Population - Tonelli M et alJournal of pediatric nephrology | Volume 2 | Number 1| 2014 18Perhaps more importantly, clinicians, patients andtheir families can be comforted by the knowledgethat timely specialist evaluation can help toimprove outcomes and reduce symptoms in olderpeople with advanced kidney disease – whetherthey have selected conservative management ordialysis as their treatment plan.AcknowledgementDr. Tonelli was supported by a Government ofCanada research chair in the optimal care ofpeople with chronic kidney disease.Box 1. Unmet needs for kidneytransplantation in older CKD patientsOrgan shortagePaucity of live donorsOrgan allocation policies thatappropriately weight likelihood of benefit fromtransplantation as well as chronological ageEnsuring appropriate referral ofpotentially suitable older recipients fortransplantation assessmentEthical concerns about offering akidney to an older patient versus a younger oneOptimal immunosuppressive regimenAdapted from reference [29].Box 2.  Meeting the growing demand forkidney transplantation in older CKDpatients Preferential transplantation of organsfrom older donors to older recipientsEnlarge the donor pool by acceptingexpanded criteria donors: ≥60 yearsold or ≥ 50 with any of the following 2conditions: history of hypertension,serum creatinine ≥1.5 mg/dl or deathdue to cerebrovascular accident.“Old for old”: preferentially usingkidneys from older living donors forolder recipientsTransplanting two marginal kidneysinstead of oneAdapted from reference [29].This scientific report has been written and sent toJPN on occasion of the world kidney day by the co-chairs of the world kidney day steering committee.www.worldkidneyday.orgReferences1. World Health Organization. Good health adds life toyears: Global brief for World Health Day 2012.Geneva, 2012.2. Wiener JM, Tilly J. Population aging in the UnitedStates of America: implications for publicprogrammes. Int J Epidemiol 2002; 31: 776-781.3. Couser WG, Remuzzi G, Mendis S, et al. Thecontribution of chronic kidney disease to the globalburden of major noncommunicable diseases. KidneyInt 2011; 80: 1258-1270.4. Select Committee on Public Service andDemographic Change. Ready for Aging? Report.House of Lords: London, 2013.5. Davies DF, Shock NW. Age changes in glomerularfiltration rate, effective renal plasma flow, andtubular excretory capacity in adult males. J ClinInvest 1950; 29: 496-507.6. Zhang L, Wang F, Wang L, et al. Prevalence ofchronic kidney disease in China: a cross-sectionalsurvey. Lancet 2012; 379: 815-822.7. Coresh J, Selvin E, Stevens LA, et al. Prevalence ofchronic kidney disease in the United States. JAMA2007; 298: 2038-2047.8. Zhang QL, Rothenbacher D. Prevalence of chronickidney disease in population-based studies:systematic review. BMC Public Health 2008; 8: 117.9. Arora P, Vasa P, Brenner D, et al. Prevalenceestimates of chronic kidney disease in Canada:results of a nationally representative survey. CMAJ2013; 185: E417-423.10. James MT, Hemmelgarn BR, Tonelli M. Earlyrecognition and prevention of chronic kidneydisease. Lancet 2010; 375: 1296-1309.Chronic Kidney Disease and the Aging Population - Tonelli M et alJournal of pediatric nephrology | Volume 2 | Number 1| 2014 1911. Kurella M, Covinsky KE, Collins AJ, et al.Octogenarians and nonagenarians starting dialysisin the United States. Ann Intern Med 2007; 146:177-183.12. Hemmelgarn BR, James MT, Manns BJ, et al. Rates oftreated and untreated kidney failure in older vsyounger adults. JAMA 2012; 307: 2507-2515.13. Keith DS, Nichols GA, Gullion CM, et al. Longitudinalfollow-up and outcomes among a population withchronic kidney disease in a large managed careorganization. Arch Intern Med 2004; 164: 659-663.14. Hemmelgarn BR, Manns BJ, Lloyd A, et al. Relationbetween kidney function, proteinuria, and adverseoutcomes. JAMA 2010; 303: 423-429.15. O'Hare AM, Bertenthal D, Covinsky KE, et al.Mortality risk stratification in chronic kidneydisease: one size for all ages? J Am Soc Nephrol2006; 17: 846-853.16. Stevens PE, Levin A, Kidney Disease: ImprovingGlobal Outcomes Chronic Kidney Disease GuidelineDevelopment Work Group M. Evaluation andmanagement of chronic kidney disease: synopsis ofthe kidney disease: improving global outcomes 2012clinical practice guideline. Ann Intern Med 2013;158: 825-830.17. Thorsteinsdottir B, Montori VM, Prokop LJ, et al.Ageism vs. the technical imperative, applying theGRADE framework to the evidence on hemodialysisin very elderly patients. Clin Interv Aging 2013; 8:797-807.18. Chandna SM, Da Silva-Gane M, Marshall C, et al.Survival of elderly patients with stage 5 CKD:comparison of conservative management and renalreplacement therapy. Nephrol Dial Transplant 2011;26: 1608-1614.19. Murtagh FE, Marsh JE, Donohoe P, et al. Dialysis ornot? A comparative survival study of patients over75 years with chronic kidney disease stage 5.Nephrol Dial Transplant 2007; 22: 1955-1962.20. Kurella Tamura M, Covinsky KE, Chertow GM, et al.Functional status of elderly adults before and afterinitiation of dialysis. N Engl J Med 2009; 361: 1539-1547.21. Lamping DL, Constantinovici N, Roderick P, et al.Clinical outcomes, quality of life, and costs in theNorth Thames Dialysis Study of elderly people ondialysis: a prospective cohort study. Lancet 2000;356: 1543-1550.22. Unruh ML, Newman AB, Larive B, et al. The influenceof age on changes in health-related quality of lifeover three years in a cohort undergoinghemodialysis. J Am Geriatr Soc 2008; 56: 1608-1617.23. Knoll GA. Kidney transplantation in the older adult.Am J Kidney Dis 2013; 61: 790-797.24. Merion RM, Ashby VB, Wolfe RA, et al. Deceased-donor characteristics and the survival benefit ofkidney transplantation. JAMA 2005; 294: 2726-2733.25. Cohen B, Smits JM, Haase B, et al. Expanding thedonor pool to increase renal transplantation.Nephrol Dial Transplant 2005; 20: 34-41.26. Gill J, Bunnapradist S, Danovitch GM, et al. Outcomesof kidney transplantation from older living donorsto older recipients. Am J Kidney Dis 2008; 52: 541-552.27. Gill JS, Tonelli M, Johnson N, et al. The impact ofwaiting time and comorbid conditions on thesurvival benefit of kidney transplantation. KidneyInt 2005; 68: 2345-2351.28. O'Hare AM, Kaufman JS, Covinsky KE, et al. Currentguidelines for using angiotensin-converting enzymeinhibitors and angiotensin II-receptor antagonists inchronic kidney disease: is the evidence base relevantto older adults? Ann Intern Med 2009; 150: 717-724.29. Mohanlal V, Weir M. Kidney Transplantation in theElderly: It’s Not All Gloom and Doom. ASN KidneyNews 2011; 3: 15-17.Chronic Kidney Disease and the Aging Population - Tonelli M et alJournal of pediatric nephrology | Volume 2 | Number 1| 2014 20Figure 1. Changing age distribution in general population of China, 1990-2050

Chronic Kidney Disease and the Aging Population

Current Opinion in Organ Transplantation

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Saudi Journal of Kidney Diseases and Transplantation

The proportion of older people in the general pop‑

ulation is steadily increasing worldwide, with the

most rapid growth in low- and middle-income

countries(1). This demographic change is to be celebrat‑

ed, because it is the consequence of socioeconomic de‑

velopment and better life expectancy. However, popula‑

tion aging also has important implications for society

– in diverse areas including health systems, labor mar‑

kets, public policy, social programs, and family dynam‑

ics(2). A successful response to the aging population will

require capitalizing on the opportunities that this tran‑

sition offers, as well as effectively addressing its chal‑

lenges

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6 African Journal of  Nephrology (2014) 17 (1)Editorialchronic KiDney DiseAse AnD the Aging populAtionMarcello Tonelli (1), Miguel Riella (2)(1) University of  Alberta, Alberta, Canada, (2) Catholic University of  Parana, Curitiba, BrazilYouth, which is forgiven everything, forgives itself  nothing: age, which forgives itself  everything, is forgiven nothing. – George Bernard ShawThe proportion of  older people in the general population is steadily increasing worldwide, with the most rapid growth in low- and middle-income countries [1]. This demographic change is to be celebrated, because it is the consequence of  socio-economic development and a better life expectancy. However, population aging also has important implications on society – in diverse areas including health systems, labour markets, public policy, social programmes, and family dynamics [2]. A successful response to the aging population will require capitalising on opportunities this transition offers, as well as effectively addressing its challenges.Chronic kidney disease (CKD) is an important public health problem, characterised by poor health outcomes and very high healthcare costs. CKD is a major risk multiplier in patients with diabetes, hypertension, heart disease and stroke – all of  which are key causes of  death and disability in older people [3]. Since the prevalence of  CKD is higher in older people, the health impact of  population aging will depend in part on how the kidney community responds. March 13, 2014 marked the celebration of  the 9th World Kidney Day (WKD), an annual event jointly sponsored by the International Society of  Nephrology and the International Federation of  Kidney Foundations. Since its inception in 2006, WKD has become the most successful effort to raise awareness among policymakers and the general public about the importance of  kidney disease. The topic for WKD 2014 was “CKD in older people”. This article reviews the key links between kidney function, age, health and illness – and discusses the implications of  the aging population for the care of  people with CKD.epiDeMiology of AgingThe key drivers of  population aging are socio-economic development and increasing prosperity – which result in lower perinatal, infant and childhood mortality; lower risk of  death in early adulthood due to accidents and unsafe living conditions; and improving survival of  middle-aged and older people due to chronic disease. The resulting increases in life expectancy (together with the lower birth rates that typically accompany socio-economic development) mean that older people account for a larger proportion of  the general population [1]. The extent of  the resulting changes in population characteristics can be startling, especially for developing countries (Figure 1).In contrast to the situation even two generations ago, people can expect to live for many years after the usual retirement age. For example, UK men and women aged 65 years in 2030 can expect to live until age 88 and 91 years respectively [4]. Predicted life expectancy for today’s children is controversial, but experts estimate that 50% of  children born in the UK in 2007 will live to at least 103 years [4]. Although it is clear that people are living longer, it is uncertain how much of  the increased life expectancy will translate into years of  good health. These demographic changes have dramatic potential implications for conditions such as CKD, for which the prevalence increases with age.cKD is coMMon in olDer people AnD its preVAlence increAses in pArAllel With AgeIt has been known for decades that estimated glomerular filtration rate (eGFR) declines in parallel with age [5]. The prevalence of  CKD among females in the Chinese general population increases from 7.4% among those aged 18-39 years to 18.0% and 24.2% among those aged 60-69 and 70 years respectively [6]. Relative increases in the prevalence of  CKD with age are equally striking for populations in the US, Canada and Europe [7-9], although there are between-country differences in the absolute prevalence. At older ages, an increased proportion of  prevalent CKD cases has low eGFR alone (as compared to albuminuria alone, or both low eGFR and albuminuria) [10]. Although this might suggest that many older people with CKD can expect lower rates of  kidney function loss, available data is inconclusive – and current knowledge does not allow clinicians to reliably distinguish between those whose CKD will and will not progress. correspondence to: no_reprints@med.ualberta.ca7Chronic Kidney Disease And The Aging Population African Journal of  Nephrology (2014) 17 (1)As for other age groups, the incidence of  dialysis-dependent kidney failure has steadily increased among older people over the last few decades: in the US, a 57% age-adjusted increase in the number of  incident octogenarians and nonagenarians was noted between 1996 and 2003 alone [11]. Despite this increase, patients aged >80 years are still less likely to initiate dialysis than those aged 75-79 years – although a recent sizeable study suggested that the risk of  developing very low eGFR (<15 ml/min/1.73m2) is similar for older and younger adults [12]. It is uncertain whether this discrepancy is due to between-age differences in the true rate of  progressive kidney function loss, the risk of  death due to competing causes, patient views about dialysis, or physician practices [12, 13]. Regardless of  the explanation, the aging population will likely lead to continued increases in the number of  older people with severe CKD.cKD is hArMful But treAtABle if pAtients At risK Are iDentifieD Like younger people, older people with advanced CKD are at increased risk of  death, kidney failure, myocardial infarction and stroke compared to otherwise similar people with normal or mildly reduced eGFR [14, 15]. Although death is by far the most common of  these adverse outcomes, this does not mean that older patients with clinically relevant CKD cannot benefit from timely specialist referral. With appropriate management, patients with advanced CKD (regardless of  age) may benefit from slower loss of  kidney function (potentially preventing kidney failure), better control of  metabolic consequences such as acidosis, anaemia and hyperphosphatemia, lower risk of  cardiovascular events, and (for those who are interested in renal replacement) a more informed choice of  renal replacement modality, including timely creation of  vascular access [16]. The aging population will likely lead to continued increases in the number of  older people who might require such referral, which should be considered in assessments of  future nephrology workforce capacity.DiAlysis cAn Benefit olDer people With KiDney fAilureIn developed countries, the default management strategy for older people with kidney failure appears to have shifted from conservative management to initiation of  dialysis [17]. On average, life expectancy after initiation of  dialysis is relatively short for older patients: median survival among US dialysis patients aged 80-84 years is 16 months – and is only 12 months for those aged 85-89 years [11]. At the same time, these median statistics reflect a bimodal distribution of  survival time in older dialysis patients: although a large proportion die within six months of  commencing dialysis, a substantial minority may live for years. This heterogeneity in mortality appears to be driven by differences in baseline comorbidity. For example, analyses of  a small UK cohort of  people with advanced kidney failure suggested that initiation of  dialysis was not associated with increased survival for those aged >75 and with two or more comorbidities [18, 19]. Similarly, the presence of  two to three comorbid conditions in US dialysis patients aged >65 years was associated with substantially increased mortality compared to those in better health [11]. When functional status is lower at baseline, initiation of  dialysis often signals the onset of  further declines: among 3,702 nursing home residents initiating dialysis, 58% had died and 87% had experienced additional loss of  function at one year. [20]. Although available data is limited, the quality of  life appears reasonable among selected older dialysis patients – and can remain stable despite moderate or high levels of  comorbidity [21, 22].This data suggests that dialysis is an appropriate treatment option for well-informed older patients with kidney failure – especially for those with good baseline quality of  life. On the other hand, the poor outcomes experienced in those with more comorbidity or lower functional status at baseline clearly demonstrates that dialysis does not improve clinical outcomes for all older people with kidney failure – and that good clinical judgment and careful communication will be increasingly required as the general population continues to age.KiDney trAnsplAntAtion cAn Also Benefit olDer people With KiDney fAilureIt is generally accepted that an older age alone does not preclude kidney transplantation in otherwise suitable candidates. However, older patients with kidney failure are more likely to have absolute and relative contraindications to transplantation, and are less likely to be placed on the kidney transplantation waiting list. Unsurprisingly, patient and graft five-year survival probabilities are lower among US kidney transplant recipients older than 65 years as compared to those aged between 35 and 49 years (patient: 67.2% vs 89.6%; graft: 60.9% vs 75.4%, respectively) [23]. In addition, older people who are possible transplant recipients face several potential disadvantages compared to their younger counterparts (Box 1).Nonetheless, transplantation appears to reduce mortality among patients of  all ages. For example, among those aged 74 years, receiving a deceased donor transplant was associated with a hazard ratio of  mortality of  0.67 (95% confidence interval 0.53, 0.86) as compared to remaining on dialysis [23]. Use of  expanded criteria deceased donors [24, 25] as well as more liberal use of  older living donors [26] also appear to reduce mortality among older people with kidney failure, as compared to similar patients who remain on the transplant waiting list (Box 2). These latter two strategies are especially appealing for use in developing countries, where growth in the prevalence of  older people has been most pronounced. However, because transplant surgery itself  temporarily increases the risk of  death, the mortality benefits associated with kidney transplantation (regardless of  donor type) are restricted to those with reasonable baseline life expectancy and without dramatically increased perioperative risk [27].8Chronic Kidney Disease And The Aging Population African Journal of  Nephrology (2014) 17 (1)reseArch neeDsAlthough much is known about chronic kidney disease in older populations, a great deal remains to be learned. Many trials of  therapies for CKD have excluded older patients [28] – and most do not provide guidance on how to manage comorbidities that often accompany CKD but may lead to competing therapeutic priorities. More information is needed on how to accurately identify people who will progress to kidney failure – and among these, the subset that can expect reasonable life expectancy and quality of  life if  they opt for dialysis treatment. Future studies should test new ways to communicate information about the risks and benefits of  dialysis (as compared to conservative management), to facilitate informed patient decisions. Above all, we need more studies that demonstrate how to optimise quality of  life and manage symptoms in elderly people with CKD – including those who have chosen conservative management. the WAy forWArDThe aging of  the general population means that older people now account for a much greater proportion of  patients with or at risk for kidney disease and kidney failure. The tremendous clinical heterogeneity within this population indicates the need for more discerning management. Chronological age alone will not be sufficient as the basis for clinical decisions, and a more nuanced approach is required – based on the comorbidities, functional status, quality of  life and preferences of  each individual patient. Clinicians can be reassured that dialysis and kidney transplantation can increase life expectancy – and will allow reasonable quality of  life in selected older people with kidney failure. Perhaps more importantly, clinicians, patients and their families can be comforted by the knowledge that timely specialist evaluation can help to improve outcomes and reduce symptoms in older people with advanced kidney disease – whether they have selected conservative management or dialysis as their treatment plan.Acknowledgements: Dr Tonelli was supported by a Government of  Canada research chair in the optimal care of  people with chronic kidney disease.Box 1: unmet needs for kidney transplantation in older cKD patients ● Organ shortage. ● Paucity of  live donors. ● Organ allocation policies that appropriately weight likelihood of  benefit from transplantation as well as chronological age. ● Ensuring appropriate referral of  potentially suitable older recipients for transplantation assessment. ● Ethical concerns about offering a kidney to an older patient versus a younger one. ● Optimal immunosuppressive regimen.Adapted from reference [29].Box 2:  Meeting the growing demand for kidney transplantation in older cKD patients ● Preferential transplantation of  organs from older donors to older recipients. ● Enlarge the donor pool by accepting expanded criteria donors: ≥60 years old or ≥ 50 with any of  the following two conditions: history of  hypertension, serum creatinine ≥1.5 mg/dl or death due to cerebrovascular accident. ● “Old for old”: preferentially using kidneys from older living donors for older recipients. ● Transplanting two marginal kidneys instead of  one.Adapted from reference [29].9Chronic Kidney Disease And The Aging Population African Journal of  Nephrology (2014) 17 (1)Figure 1: Changing age distribution in general population of China, 1990-2050references1. World Health Organization, Good Health Adds Life To Years: Global Brief  For World Health Day 2012, Geneva, 2012.2. Wiener JM, Tilly J, Population Aging In The United States Of  America: Implications For Public Programmes,  International Journal of  Epidemiology, 2002, 31:776-781.3. Couser WG, Remuzzi G, Mendis S, et al, The Contribution Of  Chronic Kidney Disease To The Global Burden Of  Major Noncommunicable Diseases, Kidney International, 2011, 80:1258-1270.4. Select Committee on Public Service and Demographic Change – First Report, Ready For Aging?, House of  Lords: London, 2013.5. Davies DF, Shock NW, Age Changes In Glomerular Filtration Rate, Effective Renal Plasma Flow, And Tubular Excretory Capacity In Adult Males, Journal of  Clinical Investigation, 1950, 29:496-507.6. Zhang L, Wang F, Wang L, et al, Prevalence Of  Chronic Kidney Disease In China: A Cross-Sectional Survey,  The Lancet, 2012, 379:815-822.7. Coresh J, Selvin E, Stevens LA, et al, Prevalence Of  Chronic Kidney Disease In The United States, Journal of  the American Medical Association, 2007, 298:2038-2047.8. Zhang QL, Rothenbacher D, Prevalence Of  Chronic Kidney Disease In Population-Based Studies: Systematic Review, BMC Public Health, 2008, 8:117.9. Arora P, Vasa P, Brenner D, et al, Prevalence Estimates Of  Chronic Kidney Disease In Canada: Results Of  A Nationally Representative Survey, Canadian Medical Association Journal, 2013, 185:E417-423.10Chronic Kidney Disease And The Aging Population African Journal of  Nephrology (2014) 17 (1)10. James MT, Hemmelgarn BR, Tonelli M, Early Recognition And Prevention Of  Chronic Kidney Disease, The Lancet, 2010, 375:1296-1309.11. Kurella M, Covinsky KE, Collins AJ, et al, Octogenarians And Nonagenarians Starting Dialysis In The United States, Annals of  Internal Medicine, 2007, 146:177-183.12. Hemmelgarn BR, James MT, Manns BJ, et al, Rates Of  Treated And Untreated Kidney Failure In Older Vs Younger Adults, Journal of  the American Medical Association,2012, 307:2507-2515.13. Keith DS, Nichols GA, Gullion CM, et al, Longitudinal Follow-Up And Outcomes Among A Population With Chronic Kidney Disease In A Large Managed Care Organisation, Archives of  Internal Medicine, 2004, 164:659-663.14. Hemmelgarn BR, Manns BJ, Lloyd A, et al, Relation Between Kidney Function, Proteinuria, And Adverse Outcomes, Journal of  the American Medical Association, 2010, 303:423-429.15. O’Hare AM, Bertenthal D, Covinsky KE, et al, Mortality Risk Stratification In Chronic Kidney Disease: One Size For All Ages?, Journal of  the American Society of  Nephrology, 2006, 17:846-853.16. Stevens PE, Levin A, Kidney Disease: Improving Global Outcomes Chronic Kidney Disease Guideline Development Work Group M. Evaluation And Management Of  Chronic Kidney Disease: Synopsis Of  The Kidney Disease: Improving Global Outcomes 2012 Clinical Practice Guideline, Annals of  Internal Medicine, 2013, 158:825-830.17. Thorsteinsdottir B, Montori VM, Prokop LJ, et al, Ageism Vs The Technical Imperative, Applying The GRADE Framework To The Evidence On Haemodialysis In Very Elderly Patients, Clinical Interventions in Aging, 2013, 8:797-807.18. Chandna SM, Da Silva-Gane M, Marshall C, et al, Survival Of  Elderly Patients With Stage 5 CKD: Comparison Of  Conservative Management And Renal Replacement Therapy, Nephrology Dialysis Transplantation, 2011, 26:1608-1614.19. Murtagh FE, Marsh JE, Donohoe P, et al, Dialysis Or Not? A Comparative Survival Study Of  Patients Over 75 Years With Chronic Kidney Disease Stage 5, Nephrology Dialysis Transplantation, 2007, 22:1955-1962.20. Kurella Tamura M, Covinsky KE, Chertow GM, et al, Functional Status Of  Elderly Adults Before And After Initiation Of  Dialysis, New England Journal of  Medicine, 2009, 361:1539-1547.21. Lamping DL, Constantinovici N, Roderick P, et al, Clinical Outcomes, Quality Of  Life, And Costs In The North Thames Dialysis Study Of  Elderly People On Dialysis: A Prospective Cohort Study, The Lancet, 2000, 356:1543-1550.22. Unruh ML, Newman AB, Larive B, et al, The Influence Of  Age On Changes In Health-Related Quality Of  Life Over Three Years In A Cohort Undergoing Haemodialysis, Journal of  American Geriatrics Society, 2008, 56:1608-1617.23. Knoll GA, Kidney Transplantation In The Older Adult, American Journal of  Kidney Diseases, 2013, 61:790-797.24. Merion RM, Ashby VB, Wolfe RA, et al, Deceased-Donor Characteristics And The Survival Benefit Of  Kidney Transplantation, Journal of  the American Medical Association, 2005, 294:2726-2733.25. Cohen B, Smits JM, Haase B, et al, Expanding The Donor Pool To Increase Renal Transplantation, Nephrology Dialysis Transplantation, 2005, 20:34-41.26. Gill J, Bunnapradist S, Danovitch GM, et al, Outcomes Of  Kidney Transplantation From Older Living Donors To Older Recipients, American Journal of  Kidney Diseases, 2008, 52:541-552.27. Gill JS, Tonelli M, Johnson N, et al, The Impact Of  Waiting Time And Comorbid Conditions On The Survival Benefit Of  Kidney Transplantation, Kidney International, 2005, 68:2345-2351.28. O’Hare AM, Kaufman JS, Covinsky KE, et al, Current Guidelines For Using Angiotensin-Converting Enzyme Inhibitors And Angiotensin II-Receptor Antagonists In Chronic Kidney Disease: Is The Evidence Base Relevant To Older Adults?, Annals of  Internal Medicine, 2009, 150:717-724.29. Mohanlal V, Weir M, Kidney Transplantation In The Elderly: It’s Not All Gloom And Doom, ASN Kidney News, 2011, 3:15-17.

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