Age and treatment of kidney failure

REVIEW C URRENT OPINION Age and treatment of kidney failure Meghan J. Elliott a, Helen Tam-Tham b, Brenda R. Hemmelgarn a,b, for the Alberta Kidney Disease Network Purpose of review This review discusses issues related to treatment of chronic kidney disease, and kidney failure in particular, among older adults. Recent findings A substantial proportion of older adults have chronic kidney disease and progress to kidney failure. There is considerable variability in treatment practices for advanced kidney disease among older adults, and evidence that treatment decisions such as dialysis initiation may be made without adequate preparation. When initiated, survival among older adults on chronic dialysis remains poor, and is associated with a significant decline in functional status. There is also evidence to suggest that dialysis initiation may not reflect overall treatment goals of elderly patients, but rather a lack of clear communication between patients and health practitioners, and underdeveloped conservative care programs in many centers. Summary Kidney failure is common among older adults. When considering treatment options for kidney failure, patient priorities, preferences, and symptoms should be taken into account, using a shared decision-making approach. Keywords age, chronic kidney disease, kidney failure INTRODUCTION Although chronic kidney disease (CKD) progressing to kidney failure is a significant public health issue for patients of all ages, there is a limited body of literature addressing treatment of kidney failure among older adults. However, most healthcare practitioners would agree that caring for older patients with CKD, and in particular those with kidney failure, presents unique challenges because of the substantial differences between older and younger patients with this condition. In this article, we will review the literature regarding age and treatment of kidney failure, and in particular focus on the unique issues facing older adults with kidney failure. We begin by presenting age-related changes in estimated glomerular filtration rate (egfr), discuss treatment considerations (including dialysis options) for older adults with CKD, review the outcomes for older adults initiating dialysis, and end by discussing the need for shared decision-making and the options for comprehensive conservative management as a treatment option. PREVALENCE OF CHRONIC KIDNEY DISEASE AND AGE-RELATED CHANGES IN ESTIMATED GLOMERULAR FILTRATION RATE CKD, defined as egfr less than 60 ml/min per 1.73 m 2 for greater than 3 months, is common with a prevalence in the adult population of 8%, a rate that increases to almost 45% among individuals 70 years of age and older [1]. Whether these changes in egfr with age, and the resultant increased prevalence of CKD among older adults, are natural has been hotly debated in the literature [2]. The fact that there is a single staging system for CKD, irrespective of age, inherently implies a Department of Medicine and b Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada Correspondence to Brenda R. Hemmelgarn, MD, PhD, Division of Nephrology, Foothills Medical Centre, 1403 29th Street NW, Calgary, AB T2N 2T9, Canada. Tel: +1 403 944 2745; fax: +1 403 944 2876; e-mail: brenda.hemmelgarn@albertahealthservices.ca Curr Opin Nephrol Hypertens 2013, 22:344 350 DOI:10.1097/MNH.0b013e32835fe540 www.co-nephrolhypertens.com Volume 22 Number 3 May 2013

Age and treatment of kidney failure Elliott et al. KEY POINTS Chronic kidney disease and progression to kidney failure is common among older adults. Chronic kidney disease and end-stage renal disease are associated with high morbidity, mortality, and healthcare costs, particularly in the very old population. There is considerable variability in treatment practices for elderly patients with advanced kidney disease, many of whom are not referred to a nephrologist. Treatment considerations for older adults with kidney failure are complex and should be individualized according to patient priorities, preferences, and symptoms in a shared decision-making process. that there are no age-related changes in egfr, and that risk for outcomes by CKD stage is similar across age groups. Prior studies, however, question these assumptions. Rule et al. [3] in an evaluation of 365 health potential kidney donors demonstrated a reduction in GFR (using iothalamate measurements the gold standard for assessing kidney function) of 4.6 ml/min per decade in men and 7.1 ml/min per decade in women. It has been argued that this decline in GFR with age is natural and not a pathological phenomenon, and that these reductions begin from about the age of 30 years [4]. REDUCED ESTIMATED GLOMERULAR FILTRATION RATE AND ADVERSE OUTCOMES BY AGE Regardless of whether changes in egfr with age are natural, reduced egfr is associated with adverse outcomes among older adults, although the risks appear to vary compared with younger adults. Although it may be associated with aging, this well recognized decline in kidney function with age is not a benign phenomenon. Older adults with mild reductions in egfr have similar risk of death compared to those of similar age but with higher egfr, and have a less than 1% chance per year of progressing to end-stage renal disease (ESRD; kidney failure) [5]. However, more severe reductions in egfr have consistently been shown to be associated with worse outcomes. Compared to the younger population, among older adults the relative risk of death associated with a given level of egfr is attenuated [6,7]. The agedependent effects of CKD on ESRD and death are evident in Fig. 1 [5], in that the relative frequency of these outcomes among patients with a comparable level of egfr varies considerably by age. Older individuals, especially those more than 75 years of age, are much more likely to die than develop ESRD, even when their egfr is severely reduced. Although the relative risk may be attenuated, the absolute mortality risk has been shown to be increased in older adults. A recent study from the CKD Prognosis Consortium [8] provides further Threshold egfr 60 50 40 Risk of death>risk of ESRD 30 20 10 Risk of ESRD>risk of death 0 18 44 45 54 55 64 65 74 75 84 85 100 Age group FIGURE 1. Baseline estimated glomerular filtration rate threshold below which risk for end-stage renal disease exceeded risk for death for each age group. Adapted from figure 2 of [5]. egfr, estimated glomerular filtration rate; ESRD, end-stage renal disease. 1062-4821 ß 2013 Wolters Kluwer Health Lippincott Williams & Wilkins www.co-nephrolhypertens.com 345

Epidemiology and prevention evidence of the importance of CKD in older adults. In this large collaborative meta-analysis of more than 2 million participants from 46 cohorts, CKD was associated with excess mortality risks among older adults that were as high as, or higher, than the excess risk observed among middle-aged adults. The risk of ESRD (receipt of renal replacement therapy) was similar to that in prior reports, with an attenuation of risk among older compared with younger participants. Importantly, the authors demonstrated that both egfr and albuminuria were strongly associated with both mortality and ESRD across the full age range. Although previous studies report that elderly patients are less likely to develop ESRD compared with younger patients, and are more likely to die than progress to kidney failure, these studies are limited in that they have defined kidney failure by receipt of long-term dialysis, which reflects both disease progression and a treatment decision. Using a population-based cohort of more than 1.8 million adults from the province of Alberta, Canada, we have reported that the rate of progression to treated kidney failure (initiation of long-term dialysis or receipt of a kidney transplant) and untreated kidney failure (progression to a sustained egfr <15 ml/min per 1.73 m 2 ) varied substantially by age [9 & ]. Whereas both the absolute and relative risks of treated kidney failure were highest among younger participants, the rate of progression to untreated kidney failure was considerably higher among older people. These results suggest that kidney disease does progress in older adults. Further, the results suggest that the true incidence of progressive CKD may be underestimated when defined by receipt of renal replacement therapy alone. TREATMENT CONSIDERATIONS FOR OLDER ADULTS WITH CHRONIC KIDNEY DISEASE Given the significant morbidity, mortality, and healthcare costs associated with CKD, its early recognition can permit timely implementation of treatment strategies aimed at slowing CKD progression and reducing associated cardiovascular disease burden [10,11]. Further, prompt identification of CKD provides earlier opportunities for patient education and preparedness for the expected disease trajectory. According to the Kidney Disease Improving Global Outcomes 2012 CKD Clinical Practice Guidelines, all patients with GFR less than 30 ml/min should be referred to a nephrologist, with consideration for earlier referral in patients at higher risk, such as those with acute kidney injury or abrupt sustained fall in egfr, hypertension refractory to treatment, or significant proteinuria [12]. However, in practice, physicians may be less likely to refer patients of advanced age and with significant comorbidities to a nephrologist, even in the presence of advanced CKD [13,14]. For example, in one retrospective study of patients followed at an outpatient geriatrics clinic, only 8.8% of those with identified CKD (egfr <60 ml/min per 1.73 m 2 )were referred to a nephrologist [14]. Several studies have clearly documented that delayed referral to a nephrologist (defined as a first nephrology visit <90 days before the onset of renal replacement therapy) was highly associated with older age [15,16]. Possible reasons for underreferral of the elderly with CKD include competing comorbidities, functional loss, or cognitive impairment, although these factors have not been well studied [17]. However, even with early detection of CKD and surveillance of egfr, traditional treatment approaches that focus on slowing disease progression and managing associated complications and comorbidities may not be suitable for the very old with early or stable CKD. Rather than a care delivery model focused on disease as a specific entity, management of the elderly with complex comorbidities should be individualized according to patient priorities, preferences, and symptoms in addition to the disease process itself (Table 1) [18]. As O Hare [19] describes, such integrated care plans emphasize individual risk and modifiable processes in the context of patient perceptions and overall care goals. INDIVIDUALIZING TREATMENT OF KIDNEY FAILURE IN OLDER ADULTS This individualized care planning becomes particularly relevant in patients with advanced CKD approaching the need for renal replacement therapy. Given the aging population and increasing prevalence of CKD, decisions surrounding dialysis initiation will have major implications at both the patient and health system levels. Chronic dialysis represents a substantial proportion of total Medicare spending, with increasing ESRD costs upward of $80 000 annually per patient [20,21]. Further, dialysis initiation may not reflect overall treatment goals of elderly patients, but rather a lack of clear communication between patients and health practitioners and underdeveloped conservative care programs in many centers [22]. A survey conducted at a Canadian university-based renal program found that almost two thirds of 295 patients receiving chronic dialysis for a mean duration of 27.3 months regretted their decision to start dialysis [23]. In this survey, 51.9% reported choosing dialysis over conservative care because it was their physician s 346 www.co-nephrolhypertens.com Volume 22 Number 3 May 2013

Age and treatment of kidney failure Elliott et al. Table 1. Characteristics of two models of medical care Disease-oriented model Clinical decision-making is focused primarily on diagnosis, prevention, and treatment of individual diseases. Discrete pathology is believed to cause disease; psychological, social, cultural, environmental, and other factors are secondary factors, not primary determinants of disease. Treatment is targeted at the pathophysiologic mechanisms thought to cause the disease(s). Symptoms and impairments are best addressed by diagnosing and treating causative disease(s). Relevant clinical outcomes are determined by the disease(s). Survival is the usual primary focus of disease prevention and treatment. Integrated, individually tailored model Clinical decision-making is focused primarily on the priorities and preferences of individual patients. Health conditions are believed to result from the complex interplay of genetic, environmental, psychological, social, and other factors. Treatment is targeted at the modifiable factors contributing to the health conditions impeding the patient s health goals. Symptoms and impairments are the primary foci of treatment even if they cannot be ascribed to a discrete disease. Relevant clinical outcomes are determined by individual patient preference. Survival is one of several competing goals. Data from table 1 of [18]. wish, and 13.9% stated they felt it was their family s wish. Further, population data suggest that approximately one third of ESRD patients above the age of 75 years ultimately withdraw from dialysis prior to dying [24]. There is also considerable geographic variability in treatment practices, and evidence that treatment decisions such as dialysis initiation may be made hastily in certain situations, for older adults with kidney failure [25]. In this study, older adults receiving higher intensity care toward the end-of-life as defined by Medicare expenditures were more likely to initiate dialysis but were less prepared for ESRD and were less likely to discontinue dialysis before death. Further, almost one third of patients in the cohort were not under the care of a nephrologist before the onset of ESRD. These results suggest that higher intensity-of-care regions have a greater willingness to initiate dialysis and that these patients may not be adequately prepared for dialysis, denoting potential opportunities for advanced care planning and shared decision-making related to ESRD, and further highlighting the importance of comprehensive, individualized care for these patients. The issue of dialysis initiation was recently discussed as part of the Choosing Wisely campaign, an initiative that aims to identify excessively or inappropriately used medical tests, procedures, and therapies that can contribute to unnecessary health spending and patient harm [26]. As part of this campaign, the American Society of Nephrology (ASN) recommended that dialysis be initiated only following a shared decision-making process among patients, family members, and healthcare providers [27 & ]. Similarly to individualized treatment plans as described above, such shared decision-making processes rely on frank discussions between healthcare providers and patients on the details of therapy, including its benefits and harms, and anticipated prognosis. Discussions should also incorporate the individual patient s goals, expectations, and preferences in order to reach a mutual decision. Finally, the patient should be supported in their decision, recognizing that treatment goals and preferences are not static but often change with time as new health issues arise and social circumstances change. DIALYSIS INITIATION IN OLDER ADULTS Over the past 20 years, there has been a trend of increasing egfr at initiation of dialysis, with up to 20% starting dialysis at an egfr of at least 15 ml/min [28]. The Initiating Dialysis Early and Late study, which is the only randomized, controlled trial to date examining timing of dialysis initiation, demonstrated that patients who started dialysis later (mean egfr 9.8 ml/min by Cockcroft Gault formula) had similar mortality risk as those who started dialysis earlier (mean egfr 12.0 ml/min) [29]. In addition, timing of dialysis initiation did not influence quality-of-life measures, which were generally low in both groups throughout the study [30]. There has also been a significant increase in the number of octogenarians and nonagenarians initiating dialysis over the past decade, with an average annual increase in dialysis initiation of 9.8% in this age group [31]. Similarly to the general population, the mean egfr at dialysis initiation in this elderly cohort also increased from 8.3 to 10.5 ml/min per 1.73 m 2 during the same time frame. Approximately half of patients over the age of 75 years initiating dialysis do so at an egfr of at least 1062-4821 ß 2013 Wolters Kluwer Health Lippincott Williams & Wilkins www.co-nephrolhypertens.com 347

Epidemiology and prevention 10 ml/min per 1.73 m 2 [32]. Frequently cited explanations for the trends in dialysis initiation at a higher GFR include malnutrition, perceived uremic symptoms, heart failure, and overestimation of the true GFR by estimation equations, all of which are generally more common among the elderly population. However, even the signs and symptoms associated with dialysis initiation at an egfr of at least 15 ml/min per 1.73 m 2 in nursing home residents explained less than one third of the cases of early dialysis [33]. OUTCOMES IN THE ELDERLY ON DIALYSIS Despite the increasing octogenarian and nonagenarian incident dialysis population, survival after initiating dialysis remains quite poor in this age group, with only 54% of the cohort remaining alive at 1 year [31]. This is significantly lower than survival of the age-matched general population as well as that of the younger ESRD population. A Canadian study using data from a national dialysis registry reported similarly limited life expectancy in patients starting dialysis over the age of 65 years, although survival overall seemed to have improved over the decade of study [34]. Initiation of dialysis has also been associated with a significant decline in functional status in nursing home residents independent of age, sex, race, and functional-status trajectory before starting dialysis, with only 13% of patients having maintained their predialysis functional status at 1 year (Fig. 2) [35]. Whereas the majority of patients aged 80 years or older were living independently at home at the time of dialysis initiation in one retrospective study, more than 30% experienced functional loss requiring caregiver support or transfer to nursing home within 6 months [36]. Dialysis initiation in older patients with CKD has not clearly been shown to improve survival, and in fact observational evidence suggests that life expectancy on dialysis may be similar to that of patients managed conservatively [37,38]. This is evident particularly among patients with higher degree of comorbidity including diabetes and ischemic heart disease. One study suggested improved survival on dialysis compared with conservative care; however, any gains in life expectancy may be mitigated by higher hospitalization rates experienced by those on dialysis [39]. Although patients receiving dialysis survived longer in this study (median 37.8 months), those receiving conservative management still had a substantial life expectancy (median 13.9 months). COMPREHENSIVE CONSERVATIVE CARE For patients who choose not to initiate dialysis, comprehensive conservative care is a treatment option that relies on coordinated efforts of a multidisciplinary team, including healthcare providers from diverse areas of expertise. In addition to the primary nephrologist, team members typically include social workers, dieticians, pharmacists, spiritual care providers, home care providers, and palliative care nurses and physicians among others. In addition to management of end-of-life Died Functional status decreased Functional status maintained Months since initiation of dialysis 3 6 9 12 0 20 40 60 80 100 Residents (%) FIGURE 2. Change in functional status after initiation of dialysis. Data were missing for 549 nursing home residents at 3 months, 696 residents at 6 months, 823 residents at 9 months, and 787 residents at 12 months from the full analytic cohort of 3702 residents. Adapted from figure 2 of [35]. 348 www.co-nephrolhypertens.com Volume 22 Number 3 May 2013

Age and treatment of kidney failure Elliott et al. symptoms, this comprehensive team provides physical, emotional, and spiritual support to patients, families, and caregivers. The focus is to maintain the patient s independence and comfort at home in accordance with his or her wishes. In circumstances in which symptoms are complex and the patient s needs cannot be met in the home setting, and/or life expectancy is limited (i.e., less than 1 month), transfer to a specialized palliative care unit or hospice may be appropriate. The use of hospice care has increased among ESRD patients over the past several years in the United States, from 12% in 2000 to almost 19% in 2006 [24]. Similarly, hospice care among patients who withdraw from dialysis has increased from 39.2 to 54.8% over the same time frame. Given the significant impact on patients and families, the decision to undergo comprehensive conservative care or dialysis initiation in ESRD patients must be individualized and take into account the estimation of survival, expected quality of life, and patient values and preferences [19,31]. CONCLUSION CKD and progression to kidney failure is common among older adults; however, treatment considerations for this patient population are complex. Management of the elderly with complex comorbidities including kidney failure should be individualized according to patient priorities, preferences, and symptoms. The use of such integrated care plans that emphasize individual risk along with patient perceptions and preferences will ensure an informed decision-making approach regarding treatment options for kidney failure among elderly patients. Acknowledgements This work was supported by the Canadian Institute of Health Research (CIHR) and by an interdisciplinary team grant from Alberta Innovates Health Solutions (AI-HS). B.R.H. is supported by the Roy and Vi Baay Chair in Kidney Research. Conflicts of interest There are no conflicts of interest. REFERENCES AND RECOMMENDED READING Papers of particular interest, published within the annual period of review, have been highlighted as: & of special interest && of outstanding interest Additional references related to this topic can also be found in the Current World Literature section in this issue (p. 366). 1. Coresh J, Selvin E, Stevens LA, et al. Prevalence of chronic kidney disease in the United States. JAMA 2007; 298:2038 2047. 2. Glassock RJ, Rule AD. The implications of anatomical and functional changes of the aging kidney: with an emphasis on the glomeruli. Kidney Int 2012; 82:270 277. 3. Rule AD, Gussak HM, Pond GR, et al. 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