The Relevance of Geriatric Impairments in Patients Starting Dialysis: A Systematic Review : Clinical Journal of the American Society of Nephrology

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Original Articles: Geriatric Nephrology

The Relevance of Geriatric Impairments in Patients Starting Dialysis: A Systematic Review

van Loon, Ismay N.*,†,‡; Wouters, Tom R.; Boereboom, Franciscus T.J.*,†; Bots, Michiel L.§; Verhaar, Marianne C.; Hamaker, Marije E.

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Clinical Journal of the American Society of Nephrology 11(7):p 1245-1259, July 2016. | DOI: 10.2215/CJN.06660615
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The ESRD population is aging rapidly. A significant percentage of patients accepted for RRT is now >75 years old, ranging from 17% to 45% (1). In addition, patients with ESRD are prone to accelerated aging (2). Underlying mechanisms, such as inflammation and microvascular damage, contribute to both decline of kidney function and development of impairment across other physiologic domains. Consequently, a high prevalence of impairment in physical and psychosocial domains, such as dependency in activities of daily living (ADLs), cognitive impairment, depression, and malnutrition, can be found in the dialysis population in both young (3) and older patients (4). There may be considerable interaction between various domains. For instance, elderly patients are at higher risk for malnutrition because of dentition loss and gastrointestinal symptoms, but mood and social circumstances may additionally compromise nutritional status (5). Accumulation and interaction of impairment of multiple domains may contribute to increased vulnerability to external stressors, also referred to as the (renal) frailty phenotype (6). This complicates treatment decisions in vulnerable and elderly patients with ESRD. Conservative care has become an accepted alternative for dialysis to discuss with selected patients with ESRD who may not benefit from dialysis (7). There is general consensus that chronologic age is not a useful selection criterion here, because ageing is a heterogeneous process (8). However, a systematic and evidence-based way to guide treatment decisions is currently lacking.

In other research fields, a systematic geriatric assessment (GA) was shown to fill this knowledge gap (8,9). A GA is defined as a multidimensional, interdisciplinary diagnostic process focusing on determining an older person’s medical, psychosocial, and functional capabilities to develop a coordinated and integrated plan for treatment and long–term follow-up (10). Such a GA has been shown to successfully identify patients at risk for poor outcome in geriatric oncology (11) and improve outcomes in older patients admitted to the emergency department (9), and it is increasingly recommended as being the standard of care in the treatment decision–making process in elderly patients (8). The aim of this review is to give an overview of all currently available evidence regarding the relation of geriatric impairments and the accumulation of impairment across these domains at initiation of dialysis with mortality and dialysis-related complications.

Materials and Methods

Search Strategy and Article Selection

We identified cohort studies investigating the relation between impairment in geriatric domains and outcome in incident patients on dialysis. Studies were included that investigated patients directly before or within 3 months of dialysis initiation. Geriatric impairment was defined as being an impairment in one or more of the following distinct domains generally considered part of a GA (6,8): cognitive function, mood, performance status or the ability to perform ADLs and instrumental ADLs, mobility (including falls), social environment, and nutritional status (12). In addition, an assessment addressing frailty was considered to be part of the assessment of geriatric impairments, because frailty may incorporate aspects of several geriatric domains (13). Studies on nutritional status were only included if a systematic assessment tool was used containing features of alimentation and physical examination. Studies only assessing body mass index, which could reflect a stable condition rather than malnutrition, or albumin, which may also reflect inflammation, were not included (12). Polypharmacy was not included, because most patients on dialysis meet the criteria for polypharmacy, and the relation with outcome would be hard to establish. Comorbidity was not included, because its relation with mortality has already been well established (14,15).

Outcome was defined as mortality or hospitalizations: duration of hospitalization, hospitalization rate, time to first hospitalization, or a combined outcome mortality and hospitalizations. A preliminary search including an age limit (≥70 years old) resulted in only a handful of publications. We, therefore, decided not to apply an age limit. In addition, we only found a few articles that included a systematic and validated assessment to determine the presence of one or more geriatric impairments. We, therefore, broadened the scope of our search and included all studies on the basis of chart review as well. We conducted a literature search in both Medline and Embase on December 1, 2015 using a combination of dialysis or renal disease with synonyms of each of the geriatric impairments or GA itself and outcomes as listed above (Supplemental Table 1). No limits in publication date were applied to the search. One investigator (I.N.v.L.) assessed the titles and abstracts of all studies retrieved by the search to determine which studies would be eligible for additional investigation. All potentially relevant articles were subsequently screened as full text by two authors (I.N.v.L. and T.W.). Studies were excluded if the primary focus was not kidney disease, patients suffered from acute kidney failure, the patient population consisted of kidney transplant recipients, or the studies focused on conservative management without dialysis. Studies with children or animals were also excluded. We distinguished between a systematic screening modality and a nonsystematic screening modality. A systematic screening modality to determine the presence of one or more geriatric impairments was defined as a validated screening tool, a validated subscale of a more elaborate screening tool, or an approximation of these screening tools on the basis of available clinical data. Only full text reports were included. Crossreferencing of the remaining articles was done to retrieve any additional relevant citations.

Data Extraction

Data regarding study design and results were independently extracted by two investigators (I.N.v.L. and T.W.) for each eligible study. Studies were subdivided into those performing the screening for geriatric impairments directly before or within 7 days after initiation of dialysis and those in which screening was performed within the first 3 months after initiation of dialysis. For each of the studies included, the following items were extracted: study design, study population (age and dialysis type), moment of inclusion (as described above), acute or planned start of dialysis, geriatric impairment of interest, assessment tools used, prevalence of geriatric impairments, length of follow-up, outcome measures examined, and the reported results on the relation between GAs and the outcome measures. In case of insufficient data in the original manuscript, an attempt was made to contact the authors for additional information.

Quality Assessment

The methodologic quality of each of the eligible studies was independently assessed by two reviewers (I.N.v.L. and T.W.) using the Newcastle–Ottawa Scale (16) for cohort studies adapted to this topic (Supplemental Table 2). Disagreement among the reviewers was discussed during a consensus meeting, and in case of persisting disagreement, the assistance of a third reviewer (M.E.H.) was enlisted.

Data Synthesis and Analyses

As a result of the heterogeneity of patient populations, the wide variety of methods of assessing the presence of geriatric impairments, and the heterogeneity in outcome measures, a meta-analysis was not considered to be feasible. Therefore, we summarized the individual study results to describe our main outcomes of interest.

Where necessary for good comparability of the effect size of the outcomes, we computed reciprocal hazard ratios (HRs) or reciprocal odds ratios (ORs). Where lacking, ORs were calculated on the basis of the presented data for optimizing comparability of the data (calculator Vassar College) (5).


Characteristics of Included Studies

The literature search resulted in 19,622 citations (8121 from Medline and 11,501 from Embase), of which 6433 articles were duplicates (Figure 1). Of the remaining publications, 13,083 were excluded for reasons listed in Figure 1; 106 potentially relevant articles were subsequently screened as full text. Ultimately, 27 full-text publications were considered relevant to our search (Table 1) (17–43). Crossreferencing did not yield any additional relevant studies. The studies were published between 1991 and 2015. Eight studies focused on hemodialysis (27,28,31,33,35–38), and three studies focused on peritoneal dialysis only (24,29,43). Fifteen studies performed the screening for impairments at dialysis initiation, and 12 studies performed the screening for impairments within 3 months after initiation. The sample size ranged from 40 to 272,024 patients, and the mean age ranged from 53 to 82 years old. Seven studies focused exclusively on elderly patients (mean age ranging from 67 to 82 years old) (18,25,26,29,33,34,42), and one study performed a subgroup analysis of elderly patients (31).

Figure 1.:
Flow chart.
Table 1. - Baseline characteristics and geriatric impairments
Baseline Characteristics Study Setting and Design Geriatric Impairments Assessed
Authors Year of Publication No. of Patients Age, yr (SD/range) Dialysis Modality Setting Planned Start Only Exclusion Criteria P/R Median/Mean Follow-Up, mo a Cognition Mood ADL Performance Mobility Nutrition Frailty
Inclusion at initiation of dialysis
 Alfaadhel et al. (17) 2015 390 63 (15) HD, PD Monocenter AKI, dialysis <1 wk in own dialysis center P 20 (11–34) b +
 Arai et al. (18) 2014 202 80 (4) HD, PD Monocenter None R 6 c +
 Chandna et al. (22) 1999 292 61 (18–92) HD, PD Monocenter AKI P +
 Churchill et al. (43) 1996 680 54 (18–82) PD Multicenter x Early deaths/transplant (<6 mo), HIV, hepatitis B positive, active inflammatory disease P 24 c + +
 Couchoud et al. (25) d , e 2009 2500 81 (4) HD, PD Database (REIN 2002–2006) Acute renal failure, <75 yr old R 6 c + +
 Couchoud et al. (26) d 2015 12,500 81 (?) HD, PD Database (REIN 2005–2012) Acute renal failure, <75 yr old R 3 c + +
 Doi et al. (28) 2015 688 69 (59–77) HD Multicenter (UMINCTR) x No predialysis care, withdrawal within 1 yr, eGFR>10 at start of dialysis R 12 c +
 Genestier et al. (29) 2009 122 81 (4) PD Monocenter x ≤75 yr old R 18 (?) + + + +
 Jassal et al. (31) 1996 99 65 (41–90) HD Monocenter AKI P ? + + + +
 Joly et al. (33) f 2003 107 82 (3) HD Monocenter Patients <80 yr old, AKI P 100 c +
 Kim et al. (34) g 2014 410 72 (5) HD, PD Database (CRC for ESRD) AKI, <65 yr R 60 c + +
 Mauri et al. (38) d 2008 3455 65 (14) HD Database (RMRC) No minimum follow-up of 1 yr R 12 c +
 Rakowski et al. (40) 2006 272,024 63(?) HD, PD Database (USRDS 1995–1999) None R 24 c + +
 Soucie et al. (41) d 1996 15,245 57 (16) HD, PD Database (Network 6) Nonwhite or black patients R 3 c + +
 Thamer et al. (42) 2015 52,796 77 (7) HD, PD Database (USRDS 2009–2010) Did not have 2-yr previous Medicare claims history, <67 yr old R 6 c +
Inclusion after initiation of dialysis
 Bao et al. (19) 2012 1576 60 (14) HD, PD Database USRDS 2005–2007 AKI R 35 (?) +
 Boulware et al. (20) 2006 917 ? (19–95) HD, PD Database (CHOICE Study) x None R 18 (2–24) b +
 Chilcot et al. (23) 2011 160 57 (16) HD, PD Three centers x No visual, physical, or cognitive (MMSE<22) impairment P 17 (2–34) + +
 Chan et al. (21) 2012 167 65 (14) HD, PD Monocenter x AKI, early transplant, early transfer other unit R 53 (23–83) +
 Chung et al. (24) 2009 219 54(13) PD Monocenter x None P 23 (±10) +
 Diefenthaeler et al. (27) 2008 40 55 (15) HD Monocenter x MMSE<18, blindness, illiteracy P 11 (5–22) +
 Honda et al. (30) 2007 328 53 (12) HD, PD Monocenter x ≥70 yr old, overt infection, acute vasculitis, liver disease P 21 (1–72) +
 Johansen et al. (32) 2007 2275 58 (16) HD, PD Database (Dialysis Wave II Study) None R 12 c +
 Lacson et al. (35) 2012 6415 62 (15) HD Multicenter (FMCNA) None R 12 c +
 Lacson et al. (36) h 2013 8776 62 (15) HD Multicenter (FMCNA) None R 12 c +
 Lopez Revuelta et al. (37) 2004 318 60 (?) HD Multicenter AKI, severe physical or psychiatric impairments P 26 (0–42) +
 McClellan et al. (39) 1991 294 57 (15) HD, PD Multicenter None P 16 (1–19) + +
P, prospective cohort study; R, retrospective cohort study; ADL, activity of daily living; HD, hemodialysis; PD, peritoneal dialysis; +, addressing this geriatric impairment; REIN, Ramipril Efficacy in Nephropathy; ?, not reported; UMINCTR, University Hospital Medical Information Network Clinical Trials Registry; CRC for ESRD, Clinical Research Center for End Stage Renal Disease; RMRC, Registre de Malalts Renals de Catalunya; USRDS, US Renal Database System; CHOICE, Choices for Healthy Outcomes in Caring for; MMSE, Mini Mental State Examination; FMCNA, Fresenius Medical Care North America.
aIf mean is reported, SD is in parentheses; if median is reported, range is in parentheses.
bInterquartile range instead of range.
cTotal study follow-up.
dData of development/training cohort only.
eSmall overlap of patients of the two cohorts in works by Couchoud et al. (25,26) (years 2005–2006, with a maximum potentially overlap of 20%).
fData of the dialysis cohort only.
gData of the ≥65 years old cohort only. Early deaths (unless otherwise described) are <3 months.
hImportant overlap of the two cohorts in the works by Lacson et al. (35,36).

Quality Assessment

Results of the quality assessment of included studies are summarized in Figure 2; details per study can be found in Supplemental Table 3. The agreement between the two reviewers in this paper was >95% for all aspects. The quality of three of 27 studies was good according to all of the established quality criteria (17,22); the remainder of studies was (somewhat) compromised. In 15 studies (56%), the representativeness of the exposed cohort was (somewhat) compromised, because the population proved to be either selected (not black or white race [41] or not ≥2 years Medicare follow-up before entering the study) or highly selected (exclusion of elderly patients [30], early deaths [43], and one study included 17% prevalent patients who were on chronic hemodialysis before peritoneal dialysis was initiated [24]). The remaining studies applied baseline assessment of geriatric impairments ≥7 days after the start of dialysis. Ascertainment of exposure was potentially compromised in seven studies (26%), because no systematic assessment was applied. In ten studies (37%), loss to follow-up was >10%, or the percentage of participants lost to follow-up was not adequately described.

Figure 2.:
Quality assessment of the included studies.

Assessment and Prevalence of Geriatric Impairments

Most studies focused on one or two geriatric domains only, whereas two studies assessed multiple impairments (Table 1) (29,31). The domain most frequently assessed was performance status, which was described in 12 of the 27 included studies, followed by depression (seven of 27), nutrition (five of 27), and cognition (five of 27). Table 2 shows the prevalence of the various impairments and lists the various tests and cutoff values used. Performance status was assessed with the Karnofsky Index, the World Health Organization scale, or a national performance scale (Supplemental Table 4), and two studies focused specifically on aspects of ADLs, of which one study used a systematic ADL screening test (29). Severely impaired performance status ranged from 13% to 33%. Depressive symptoms were present in 24%–55% of patients in the studies that applied a systematic assessment (20,23,27,35), whereas the prevalence of the International Statistical Classification of Diseases diagnosis depression ranged from 4% to 28% (23,29,39,41). Prevalence of cognitive impairment ranged from 6% to 13% in general (25,26,29,31,40) and was 41% in the very old (18). No studies assessed the relation between falls or social environment and poor outcome in the incident dialysis population.

Table 2. - Prevalence of geriatric impairments
Impairment and Authors Test Prevalence, % Cutoff Scale Test Elderly
Mood disturbance
 Diefenthaeler et al. (27) BDI 55 ≥14 0–63 S
 Lacson et al. (35,36) Depression score 41 >2 0–6 P
 Genestier et al. (29) Depression ICD 28 R x
 Chilcot et al. (23) BDI 26 ≥16 0–63 S
 Chilcot et al. (23) Depression ICD 15 R
 Boulware et al. (20) MHI SF-36 24 ≤52 0–100 P
 Soucie et al. (41) Depression ICD 18 R
 Thamer et al. (42) Depression ICD 10 R x
 McClellan et al. (39) Depression ICD 4 R
Cognitive impairment
 Arai et al. (18) Dementia ICD 41 R x
 Jassal et al. (31) Mental score 36 a ; 7 b <8 0–10 S x
 Genestier et al. (29) Dementia ICD 13 R x
 Rakowski et al. (40) Dementia ICD c 12 R
 Thamer et al. (42) Dementia ICD 6 R x
 Couchoud et al. (25) Behavioral disorders d 5 R x
 Couchoud et al. (26) Behavioral disorders d 4 R x
 Arai et al. (18) Japanese criteria 33 ≥3 1–8 S x
 Couchoud et al. (25) Assistance for transfers 25 R x
 Couchoud et al. (25) Dependent for transfers 7 R x
 Couchoud et al. (26) Assistance for transfers 22 R x
 Couchoud et al. (26) Dependent for transfers 8 R x
 Rakowski et al. (40) Unable to ambulate 5 R
 Rakowski et al. (40) Unable to transfer 2 R
 Genestier et al. (29) ADL scale 30 ≥7 0–12 S x
 Thamer et al. (42) ADL: dependent 21 R x
 Bao et al. (19) Modified Fried score 73 ≥2 0–3 P
 Johansen et al. (32) Modified Fried score 68 ≥3 0–5 P
 Alfaadhel et al. (17) Clinical frailty score 26 ≥5 1–7 P
 Churchill et al. (43) SGA (mild to severe) 55 ≤5 7–0 S
 Chan et al. (21) SGA (idem) 52 B and C A–C S
 Chung et al. (24) SGA (idem) 47 ≤5 7–0 S
 Kim et al. (34) SGA (idem) 42 ≤5 7–0 S x
 Honda et al. (30) SGA (idem) 32 ≥2 1–4 S
Test Mild to Severe Prevalence Cutoff Severe Prevalence Cutoff Scale Test Elderly
% Νο. % Νο.
Impaired performance
 Joly et al. (33) Karnofsky 69 ≤70 22 ≤40 10–100 S x
 Chandna et al. (22) Karnofsky 54 ≤70 33 ≤40 10–100 C
 Churchill et al. (43) Karnofsky 41 ≤70 10–100 S
 Soucie et al. (41) Karnofsky e 49 <7 18 <6 1–10 S
 Mauri et al. (38) Karnofsky e 42 <80 13 <70 10–100 C
 McClellan et al. (39) Karnofsky e 37 <7 20 <6 1–10 S
 Kim et al. (34) Karnofsky 24 ≤70 10–100 S x
 Chilcot et al. (23) Karnofsky 15 <70 10–100 S
 Genestier et al. (29) AGGIR 48 ≤4 28 ≤2 1–6 S
 Doi et al. (28) WHO scale 23 ≥3 0–4 C
Prevalence of impairment. If necessary for comparison, the combined prevalence of two separate categories is shown (e.g., severely dependent and dependent for ADLs). Of all of the studies that applied a systematic assessment, the scale and cutoff values are reported. BDI, Beck Depression Inventory, S, applied by staff; P, patient self-report; ICD, International Statistical Classification of Diseases; R, review of medical chart; x, analysis includes elderly patients exclusively; MHI SF-36, Mental Health Inventory Short Form 36; ADL, activity of daily living; SGA, Subjective Global Assessment; A, well nourished; B, mild-moderately malnourished; C, severely malnourished; —, not mentioned; AGGIR, Autonomie Gérontologique Groupes Iso-Ressources; WHO, World Health Organization.
aAge ≥65 years old.
bAge <65 years old.
cAlzheimer disease, vascular dementia, dementia not otherwise specified, or presenile dementia.
dDementia, psychosis, or severe neurosis that may affect patient dependence or compliance with treatment.
eModification of the Karnofsky Index (39).

Relation of Geriatric Impairments and Outcome

The relations between geriatric impairments, mortality, and hospitalization are shown in Table 3. Table 3 also shows studies that focused on elderly patients. Details and effect sizes are shown in Tables 4 and 5.

Table 3. - Geriatric impairments related to outcome
Geriatric Impairment No. of Studies Associations a
Univariate Multivariate
No. % No. %
 Depressive symptoms (20,23,27,29,31,35,41) 7 5/7 71 3/7 43
 Cognitive impairment (25,26,29,31,40) 5 4/5 80 3/5 60
 ADL dependency (29,31,42) 3 3/3 100 2/3 67
 Mobility impairment (18,25,26,40) 4 4/4 100 3/4 75
 Performance (22,23,28,29,31,33,34,37–39–,41,43) 12 8/12 67 7/12 55
 Frailty (17,19,32) 3 3/3 100 3/3 100
 Malnutrition (21,24,30,34,43) 5 4/5 80 4/5 80
 Performance (37,43) 2 2/2 100 1/2 50
 Malnutrition (43) 1 1/1 100 1/1 100
 Depression (36) 1 1/1 100 1/1 100
Mortality in Elderly Patients
 Depressive symptoms (29,31) 2 0/2 0 0/2 0
 Cognitive impairment (25,26,29,31) 4 3/4 75 2/4 50
 ADL dependency (29,31,42) 3 3/3 100 2/3 67
 Mobility impairment (18,25,26) 3 3/3 100 2/3 67
 Performance (29,31,33,34) 4 2/4 50 2/4 50
 Malnutrition (34) 1 0/1 0 0/1 0
ADL, activity of daily living.
aThe number of studies addressing an impairment that is significantly related to adverse outcomes.

Table 4. - The relation of geriatric impairment with mortality
Geriatric Impairments and Authors Relation with Mortality Adjusted for in Multivariate Analysis (if Applicable)
Univariate Multivariate
HR/OR (95% CI) P Value HR/OR (95% CI) P Value
 Boulware et al. (20) 1.19 (0.88 to 1.61) >0.05 1.24 (0.81 to 1.89) >0.05 Age, sex, race, marital status, education, coexistent illness, dialysis modality, use of antidepressant therapy, history of CVD risk factors, systolic and diastolic BP, CRP, IL-6, WBC count, hematocrit, creatinine, albumin, calcium, phosphorus
 Chilcot et al. (23) 2.58 (1.19 to 5.63) 0.02 2.70 (1.06 to 6.80) 0.04 Albumin, hemoglobin, dialysis vintage, Davies comorbidity score, CRP, KPS<70
 Diefenthaeler et al. (27) 4.50 (1.10 to 17.7) 0.03 6.50 (0.80 to 55.0) 0.09 Age, hypertension, DM
 Genestier et al. (29) >0.05
 Jassal et al. (31) >0.05
 Lacson et al. (35) 1.09 (1.03 to 1.15) <0.01 1.08 (1.01 to 1.14) <0.05 Age, sex, SF-36 MCS (without mental health subscale), SF-36 PCS, unknown insurance, albumin, creatinine, hemoglobin
 Soucie et al. (41) 1.30 (1.00 to 1.60) <0.05 Age, sex, race, dialysis vintage, dialysis modality, activity level, albumin, education, student status, housing, employment, alcoholism, smoking, substance abuse
 Jassal et al. (31) <0.001
 Couchoud et al. (25) 3.00 (2.00 to 4.40) <0.001 1.50 (1.20 to 1.80) <0.05 Age, sex, DM, CHF, peripheral vascular disease, cerebrovascular disease, dysrhythmia, chronic respiratory disease, active malignancy, severe behavioral disorders, severe disabilities, unplanned dialysis
 Couchoud et al. (26) 2.60 (2.07 to 3.26) <0.001 1.44 (1.12 to 1.85) <0.001 Age, sex, DM, CHF, peripheral vascular disease, ischemic heart disease, cerebral vascular disease, dysrhythmia, chronic respiratory disease, cancer, cirrhosis, mobility, albuminemia, BMI
 Rakowski et al. (40) <0.10 1.91 (1.77 to 1.98) <0.001 Age, sex, race, DM, hematocrit, erythropoietin, creatinine, Medicaid, BMI, albumin, DM as cause of ESRD, inability to transfer, inability to walk, stroke, heart failure, ischemic heart disease, peripheral vascular disease, COPD, hypertension, alcohol use, drugs use
 Genestier et al. (29)
 Genestier et al. (29) <0.001
 Jassal et al. (31) <0.001 0.71 (0.54 to 0.93) a 0.01 Age, phosphate, albumin, comorbidity, KPS, alcohol intake, dyskinesia
 Jassal et al. (31) (>65 yr old) <0.001 0.53 (0.37 to 0.75) a <0.001
 Thamer et al. (42) <0.05 1.47 (1.38 to 1.57) Age, sex, race, catheter use, no or late nephrology care, albumin, creatinine, living in a nursing home, cancer peripheral vascular disease, alcoholism, CHF, hospitalization in 6 mo before dialysis
 Arai et al. (18) b 4.22 (1.87 to 9.57) <0.05
 Couchoud et al. (25) 1.10 (0.90 to 1.30) c ; 2.30 (1.90 to 2.80) d 0.35; <0.001 −1.70 (1.40 to 2.00) <0.05 Age, sex, DM, CHF, peripheral vascular disease, cerebrovascular disease, dysrhythmia, chronic respiratory disease, active malignancy, severe behavioral disorders, severe disabilities, unplanned dialysis
 Couchoud et al. (25) 2.80 (2.40 to 3.30) c ; 9.40 (7.90 to 11.3) d <0.001; <0.001 2.47 (2.10 to 2.91); 6.53 (5.38 to 7.92) <0.05; <0.05 Age, sex, DM, CHF, peripheral vascular disease, ischemic heart disease, cerebral vascular disease, dysrhythmia, chronic respiratory disease, cancer, cirrhosis, severe behavioral disorder, albuminemia, BMI
 Rakowski et al. (40) <0.100 1.47 (1.43 to 1.52) d ; 1.36 (1.30 to 1.43) e <0.001; <0.001 Age, sex, race, DM, hematocrit, erythropoietin, creatinine, Medicaid, BMI, albumin, DM as cause of ESRD, inability to transfer, inability to walk, stroke, heart failure, ischemic heart disease, peripheral vascular disease, COPD, hypertension, alcohol use, drugs use
 Chandna et al. (22) <0.001 1.02 (1.02 to 1.03) f 0.01 Age, comorbidity score, myeloma
 Chilcot et al. (23) <0.01 >0.05
 Doi et al. (28) (≥3 versus 0) <0.16 6.75 (1.51 to 0.10) <0.05 Age, sex, BMI, renal disease, eGFR, urea nitrogen, hemoglobin, albumin, potassium, calcium, phosphorus, CRP, comorbidities, fatigue, edema, pulmonary edema, nausea, dysorexia, diarrhea, constipation, CNS manifestations, peripheral nerve abnormalities, itch, hemorrhagic diathesis, hypertension, diabetic retinopathy, ESA use
 Genestier et al. (29) <0.001 1.14 (0.98 to 1.32) f 0.08 Early referral, CCI, AGGIR group, institution, polypharmacy
 Jassal et al. (31) <0.001 1.85 (1.20 to 2.85) a 0.01 Alcohol intake, dyskinesia, age, phosphate, albumin, comorbidity, Barthel score
 Jassal et al. (31) (>65 yr old) <0.001 2.16 (1.25 to 3.72) a 0.01
 Joly et al. (33) (≤40 versus >40) 2.96 (1.05 to 8.33) <0.05 2.34 (1.00 to 5.50) <0.05 Age, sex, catheter use, late referral, BMI, peripheral vascular disease, heavy comorbidity
 Lopez Revuelta et al. (37) 1.69 (1.44 to 1.97) 0.18 1.13 (0.86 to 1.48) a 0.40 Age, sex, DM, CCI, smoking, systolic and diastolic BPs, hemoglobin, creatinine, albumin, urea reduction ratio, first dialysis modality, center
 Mauri et al. (38) (<70 versus ≥70) 1.88 (1.45 to 2.43); 3.83 (2.84 to 5.16) <0.05 Age, sex, primary renal disease, CVD, COPD, malignant process, chronic liver disease, BMI<20
 McClellan et al. (39) <0.001 1.28 (0.61 to 2.01) f >0.05
 Soucie et al. (41) (<6 versus ≥6) 2.30 (1.40 to 3.60) <0.05 Age, race, sex, time on dialysis, dialysis modality, albumin, education, student status, housing, employment, alcoholism, clinical depression, smoking, substance abuse
 Alfaadhel et al. (17) 1.22 (1.04 to 1.43) f 0.002 Age, sex, race, CCI, diabetic ESRD, GFR, albumin, dialysis modality, location of start dialysis
 Bao et al. (19) 1.79 (1.44 to 2.24) <0.001 1.57 (1.25 to 1.97) <0.001 Age, sex, race, smoking, comorbidities, Medicaid versus other payer, eGFR, albumin, hemoglobin, dialysis modality, erythropoietin use, early nephrology referral
 Johansen et al. (32) 3.42 (2.45 to 4.76) 2.24 (1.60 to 3.15) <0.05 Age, sex, race, BMI, albumin, dialysis modality, comorbidities, employment status, marital status, smoking
Malnutrition g
 Chan et al. (21) <0.001 1.74 (1.11 to 2.72) 0.02 Age, sex, dialysis modality, albumin, BMI, smoking, comorbidities
 Chung et al. (24) 2.34 (1.72 to 3.30) <0.001 2.01 (1.46 to 2.86) <0.001 Age, sex, albumin, residual renal function, dialysate/plasma creatinine concentration ratio at 4 h dwell creatinine
 Churchill et al. (43) 1.33 (1.18 to 1.52) f Age, DM, CVD, country, albumin, Kt/V
 Honda et al. (30) <0.05 1.89 (1.09 to 3.28) 0.02 Age, DM, CVD, CRP
 Kim et al. (34) 1.52 (0.85 to 2.63) 0.16
HR, hazard ratio; OR, odds ratio; 95% CI, 95% confidence interval; CVD, cardiovascular disease; CRP, C-reactive protein; WBC, white blood count; KPS, Karnofsky performance score; DM, diabetes mellitus; —, not mentioned; SF-36 MCS, Short–Form (36) Health Survey Mental Component Score; SF-36 PCS, Short–Form (36) Health Survey Physical Component Score; CHF, chronic heart failure; BMI, body mass index; COPD, chronic obstructive pulmonary disease; ADL, activity of daily living; CNS, central nervous system; ESA, erythropoietin stimulating agent; CCI, Charlson Comorbidity Index; AGGIR, Autonomie Gérontologique Groupes Iso-Ressources.
aRisk per increase in score of 10.
bThe OR was calculated by comparing group 1 (independent mobility at start) and group 2 (independent mobility at start but decline in mobility after start) with group 3 (impaired mobility at start). Multivariate analysis was, therefore, not possible.
cNeed assistance for transfers.
dTotally dependent for transfers.
eUnable to ambulate.
fRisk per point increase.
gReference group is similar to that in Table 2T3.

Table 5. - The relation of geriatric impairment with hospitalization
Geriatric Impairment and Authors Relation with Hospitalization Outcome Adjusted for in Multivariate Analysis (if Applicable)
Univariate Multivariate
HR/RR/OR (95% CI) P Value HR/RR/OR (95% CI) P Value
 Lacson et al. (36) <0.001 1.13 (1.02 to 1.25) 0.02 Hospitalization rate Age, sex, race, DM, albumin, creatinine, hemoglobin, calcium, phosphorus, transferrin saturation, SF-36 PCS, SF-36 MCS (two mental health items of interest removed), dialysis vintage
 Lacson et al. (36) <0.001 1.20 (1.07 to 1.35) 0.002 Duration of hospitalization Age, sex, race, DM, albumin, creatinine, hemoglobin, calcium, phosphorus, transferrin saturation, SF-36 PCS, SF-36 MCS (two mental health items of interest removed), dialysis vintage
 Churchill et al. (43) (≤80 versus >80) 1.63 (—) <0.05 Duration of hospitalization Age, sex, KPS, CVD, DM, albumin, malnutrition, CCr, Kt/V, β2M, country
 Lopez Revuelta et al. (37) 1.25 (1.05 to 1.48) a 0.01 1.12 (0.92 to 1.36) a 0.51 Duration of hospitalization KPS, CCI, logarithmic time, hospital, SF-36 PCS, SF-36 MCS
 Churchill et al. (43) 0.82 (—) b <0.05 Duration of hospitalization Age, sex, KPS, CVD, DM, albumin, CCr, Kt/V, β2M, country
 Bao et al. (19) 1.44 (1.26 to 1.66) <0.001 1.26 (1.09 to 1.45) <0.001 Time to first hospitalization Age, sex, race, smoking, comorbidities, Medicaid versus other payer, eGFR, albumin, hemoglobin, dialysis modality, erythropoietin use, early nephrology referral
 Johansen et al. (32) 1.90 (1.67 to 2.17) <0.05 1.56 (1.36 to 1.79) <0.05 Time to first hospitalization or death Age, sex, race, BMI, albumin, dialysis modality, comorbidities, employment status, marital status, smoking
 Johansen et al. (32) 1.98 (1.41 to 1.87) <0.05 Time to first nonvascular–related hospitalization or death Age, sex, race, BMI, albumin, dialysis modality, comorbidities, employment status, marital status, smoking
HR, hazard ratio; RR, relative risk; OR, odds ratio; 95% CI, 95% confidence interval; —, not mentioned; DM, diabetes mellitus; SF-36 PCS, Short–Form (36) Health Survey Physical Component Score; SF-36 MCS, Short–Form (36) Health Survey Mental Component Score; KPS, Karnofsky performance score; CVD, cardiovascular disease; CCr, creatinine clearance; β2M, β2-microglobulin; CCI, Charlson Comorbidity Index.
aRisk per increase in score of 10.
bRisk per point increase.

Relation of Geriatric Impairments and Mortality

Overall, 1-year mortality ranged from 12% (23) to 35% (29); the latter was in a study focusing on elderly patients (mean age =81±4 years old). Frailty was associated with mortality in all three studies assessing this domain, with HRs ranging from 1.22 (95% confidence interval [95% CI], 1.04 to 1.43) per point increase of the frailty scale (17) to 2.24 (95% CI, 1.60 to 3.15) between frail and nonfrail (32) (Tables 4 and 5). Four of five studies assessing malnutrition found it to be associated with mortality (21,24,30,43), with HRs ranging from 1.33 (95% CI, 1.18 to 1.52) (43) per point increase of the Subjective Global Assessment (SGA) to 2.01 (95% CI, 1.46 to 2.86) between two SGA categories (21). Functional dependency on the basis of ADLs, performance status, or mobility was related to mortality in the majority of studies assessing these domains, despite a broad variety of assessment tools and cutoff values used. A positive association between depressive symptoms and mortality was found in three of seven studies only (23,35,41). However, when focusing on the database studies, which included the vast majority of patients, depressive symptoms were associated with mortality in two studies (OR, 1.30; 95% CI, 1.00 to 1.60 [41] and OR, 1.08; 95% CI, 1.01 to 1.14 [35]), and in one study, depression was associated with noncardiovascular mortality (HR, 1.94; 95% CI, 1.10 to 3.42 [20]).

In elderly patients, impaired mobility was associated with 1-year mortality in an univariate analysis of a single publication (OR, 4.22; 95% CI, 1.87 to 9.57) (18), and total dependence for transfers was independently associated with 3- and 6-month mortality (OR, 6.53; 95% CI, 5.38 to 7.92 and OR, 1.7; 95% CI, 1.4 to 2.0, respectively) (25,26). Dependence in ADLs was associated with mortality in two of three studies (OR, 1.41; 95% CI, 1.08 to 1.85) (31,42). Impaired cognitive function, defined as severe behavioral disorder, was associated with mortality as well (25,26), but two smaller studies did not find this relation (29,31). Depressive symptoms were not associated with mortality is this population (29,31). One study systematically assessed malnutrition in the elderly and found no relation with mortality (34). No studies focused on frailty in the elderly population specifically.

Relation of Geriatric Impairments and Hospitalization

Hospitalization days after dialysis initiation were assessed in three studies (Table 3) showing that malnutrition (43), depression (36), and performance status (37,43) were associated with more days in hospital. However, the association between performance status and hospitalization duration was lost after adjustment for potential confounders in one of the two studies (P=0.50) (37). Depressive symptoms were related to hospitalization rate (HR, 1.13; 95% CI, 1.02 to 1.25) (36). One study assessed the association of frailty and time to first hospitalization (19), and another study focused on the combined outcome time to first hospitalization or death or time to first nonvascular hospitalization and death (32). All three outcomes were individually associated with frailty at dialysis initiation.


As shown by this review, the relation between geriatric impairment and poor outcome has not been assessed elaborately within the incident dialysis population. Only malnutrition and frailty have been well assessed using a systematic approach, and evidence on the relation with mortality is clear, although it is lacking in the elderly population specifically. Other geriatric impairments seem to be related to poor outcome, and data resulting from a systematic assessment of these impairments are sparse. None of the studies performed a GA incorporating a systematic assessment across multiple impairments. Only two small studies assessed impairment across multiple domains in a geriatric population. These studies found performance status (31) and ADLs (29) to be associated with survival of elderly patients on dialysis.

In other fields within geriatric medicine, expanding evidence on the predictive value of geriatric impairments has led to the implementation of a systematic assessment for prognostic and diagnostic purposes (8,9). A systematic assessment aids in staging the aging, thereby discriminating between fit and relatively vulnerable patients (44), and it reveals deficits that are not routinely captured in standard history and examination (8). A multidisciplinary discussion on the basis of the results of a GA can lead to adjustments of initial treatment proposals in elderly patients in the oncology department by either increasing or decreasing the treatment intensity (45,46).

A GA has been proposed as a supportive instrument for treatment decision making in ESRD as well (4,26). It provides the best available evidence on the patients’ physiologic reserves and consequently, a better estimation of residual life expectancy (47). Concrete information on impaired domains that could compromise dialysis treatment may facilitate shared decision making with the patient and relatives. In addition, it may reveal treatable conditions that would otherwise be overlooked (4,48), thereby forming a starting point for (preventive) interventions to optimize quality of life, such as physical and ADL impairments and social problems (45,49). Finally, the information derived from a GA may help to estimate adverse outcomes of surgical interventions (50) and other complex interventions (51). This review supports the suggestion that assessment of geriatric impairments may contribute to decision making in dialysis by showing that multiple impaired domains are related to poor outcome. However, this evidence is derived from a heterogeneous cohort of studies, of which the majority did not use a systematic approach. In addition, the predictive value of a GA itself has not been assessed so far, and this should be subject of additional research.

Currently, there is no consensus on which domains a GA should comprise (6,52). In addition to the items discussed in this review, comorbidity burden and social status may be of added value when focusing on risk assessment, because both are associated with mortality. However, for social status, this was assessed in the prevalent population only (53). A GA focusing on rehabilitation may additionally include geriatric syndromes, such as delirium, incontinence, constipation, osteoporosis, and sensory deficits, because these issues may be amenable to interventions that could potentially improve quality of life (52).

For many domains, the superiority of one tool over another has not been proven. An overview of the applied tests in this review and appraisal of their use in ESRD can be found in Supplemental Table 4. Some disease–specific issues might be missed by tests not specifically developed for the dialysis population. For instance, the mental test (54) was not developed to detect cognitive impairment caused by vascular damage and may consequently lack sensitivity to detect mild disturbances in the dialysis population (55). Other tests (e.g., Beck Depression Inventory for depression and Barthel test for ADLs) are successfully adapted from geriatric research, because populations are comparable at this point (8). Multiple strategies exist for the assessment of functional dependency, including performance status, ADLs and instrumental ADLs, and mobility, and a considerable overlap may occur when tests are not well adjusted to each other. Cross-study comparison would benefit from agreement on uniformity of a certain subset of tests and cutoff values.

The GA should target those most likely to benefit, such as potentially frail and elderly patients. Selection of patients who would benefit from a multidisciplinary assessment in the decision-making process concerning dialysis might be facilitated by a frailty screening test (56) or a prediction rule (26). Implementation of such an approach will greatly depend on the capacity and the targets of the dialysis center. More liberal acceptance criteria for dialysis may be partly influenced by financial and capacity considerations in addition to expected patient benefit, and critical assessment of geriatric impairments may be more difficult to implement here.

The interpretation of the results retrieved by this review was limited by several factors. Not all included studies performed an assessment before the start of dialysis therapy. Consequently, confounding might have occurred here, because the influence of dialysis may have led to under- or overestimation of the prevalence of geriatric impairments at the start. However, the trajectory of these impairments shortly after dialysis initiation is not yet known. In addition, the heterogeneity of the various tests being used, the different cutoff points, and the wide variety in the factors adjusted for in multivariate analyses (Tables 4 and 5) all limit the conclusions that may be drawn regarding the relation of most geriatric domains and poor outcome after dialysis initiation, and a meta-analysis of geriatric impairments was not feasible.

Matching nephrology care to the needs of vulnerable patients with ESRD is becoming increasingly relevant with aging of the population. As was shown in other fields of research, a GA may be successful in identifying vulnerable patients at risk of poor outcome and contribute to early interventions improving quality of life. In nephrology, a systematic approach to frail patients is currently lacking. This review shows that geriatric impairment across multiple physical and mental domains at dialysis initiation is related to poor outcome. However, systematic assessment of impairment in relation to outcome is sparse, especially in the elderly. Whether systematic assessment of geriatric impairments could discriminate between fit and vulnerable patients in the context of treatment decisions concerning dialysis initiation should be assessed in more detail before the implementation in clinical practice. In addition, research should focus on standardization of assessment tools specifically for the CKD population, thereby enhancing the comparability of clinical and research results.



Published online ahead of print. Publication date available at

This article contains supplemental material online at


This study was supported by the Cornelis de Visser Stichting.

The study sponsor had no role in study design, collection, analysis, and interpretation of data; writing the report; or the decision to submit the report for publication.


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end-stage renal disease; decision-making; geriatric assessment; elderly; frailty; Activities of Daily Living; Cognition; hospitalization; Humans; Kidney Failure, Chronic; Nutritional Status

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