Abstract
Background:
Falls occur in 28% of hemodialysis patients and increase the risk of physical impairment, morbidity, and mortality. Therefore, it is likely that KT candidates with recurrent falls are less likely to access KT and more likely to experience adverse post-KT outcomes.
Methods:
We used a two-center cohort study of KT candidates (n=3666) and recipients (n=770) (1/2009–1/2018). Among candidates, we estimated time to listing, waitlist mortality, and transplant rate by recurrent falls (≥2 falls) prior to evaluation using adjusted regression. Among KT recipients, we estimated risk of mortality, graft loss, and length of stay (LOS) by recurrent falls prior to KT using adjusted regression.
Results:
Candidates with recurrent falls (6.5%) had a lower chance of listing (aHR=0.68,95%CI:0.56–0.83) but not transplant rate; waitlist mortality was 31-fold (95%CI:11.33–85.93) higher in the first year and gradually decreased over time. Recipients with recurrent falls (5.1%) were at increased risk of mortality (aHR=51.43,95%CI:16.00–165.43) and graft loss (aHR=33.57,95%CI:11.24–100.21) in the first year, which declined over time, and a longer LOS (aRR=1.13,95%CI:1.02–1.25). In summary, 6.5% of KT candidates and 5.1% of recipients experienced recurrent falls which were associated with adverse pre- and post-KT outcomes.
Conclusions:
While recurrent falls were relatively rare in KT candidates and recipients, they were associated with adverse outcomes. Transplant centers should consider employing fall prevention strategies for high-risk candidates as part of comprehensive prehabilitation.
INTRODUCTION
Similar to community-dwelling older adults,1–3 falls are common among adult patients of all ages with end stage kidney disease (ESKD) and occur in approximately 28% of adult4 and 47% of older (aged ≥65) adults undergoing hemodialysis.5 Serious, injurious falls are less common, occurring in 4% of adult and 10% of older patients in their first year after dialysis initiation.6 However, among candidates being evaluated for kidney transplantation (KT), which includes both patients on dialysis and preemptive KT candidates, it is unclear how common falls are and whether falls prior to evaluation are associated with access to KT.
Moreover, falls are recognized to increase the risk of adverse outcomes including physical impairment, morbidity, and mortality in patients undergoing hemodialysis.4,7–9 Falls may be important sentinel events that identify high-risk KT candidates and recipients who may develop frailty, poor health-related quality of life (HRQOL), and physical impairment. Given the short-term deterioration associated with falls,1–3 it is likely that a history of falls is associated with an increased risk of waitlist mortality among KT candidates and adverse post-KT outcomes among KT recipients. However, like other high-risk events in patients with ESKD,10 the risk of mortality is acutely elevated after a fall. In other words, the mortality risk associated with a fall likely varies over time such that there is an increased risk of mortality in the short-term and this risk likely attenuates over time.
A previous fall is the strongest risk factor and more than doubles the risk of a subsequent fall in patients with ESKD of all ages.5 Therefore, it is important to understand whether a single fall or recurrent falls are associated with adverse outcomes among KT candidates and recipients. Knowing whether and how often a patient has fallen prior to evaluation or transplantation could help clinicians improve risk stratification and identify vulnerable patients11 who could benefit from targeted multidimensional falls prevention strategies as part of prehabilitation.12,13
To address the gap in knowledge of surrounding falls among KT candidates and recipient, we leveraged a two-center prospective cohort study of candidates being evaluated for KT (n=3666) and KT recipients (n=770). The goals of this study were to: 1) estimate the percentage of KT candidates and recipients with a history of falls and recurrent falls; 2) test whether a history of falls and recurrent falls are associated with decreased access to KT among KT candidates; and 3) quantifying the time-varying risk of post-KT adverse outcomes associated with a history of falls and recurrent fall prior to KT.
METHODS
Study design
This was a two-center, longitudinal study (1/2009–1/2018) of 3666 adult KT candidates (Table 1A) followed prospectively from time of evaluation for KT and 770 KT recipients (Table 1B) followed prospectively from time of admission for KT.14,15 Participants were recruited at the Johns Hopkins Hospital (3403 candidates; 703 recipients) and the University of Michigan University Hospital (263 candidates; 67 recipients). History of falls in the past 6-months was self-reported at evaluation by the KT candidates and at admission for KT by the recipients, as described below, and followed over time for the respective outcomes of interest including chance of listing, waitlist mortality, and KT for candidates, and post-KT mortality, graft-loss, and length of stay (LOS) for recipients. Recipient, donor, and transplant factors at time of evaluation/admission were self-reported or abstracted from medical records (age, sex, race, body mass index [BMI], dialysis type, time on dialysis, causes of ESKD, mobility disability (or self-reported walking impairment), and donor type, Charlson comorbidity index [CCI] adapted for ESKD16,17). Additional aging metrics were directly measured at time of evaluation and admission for KT and included: 1) frailty18 (≥3 of the 5 frailty physical frailty phenotype as has been previously published14,19–21)), 2) lower extremity impairment measured by the short physical performance battery (SPPB)22 (score ≤10 as has been previously published23,24), and 3) health related quality of life (HRQOL) based on the question “In general, would you say your health is” … “Excellent,” “Very Good,” “Good,” “Fair,” or “Poor.”
Table 1A: Characteristics in Kidney Transplant (KT) Candidates by Falls in the 6 Months Prior to KT Evaluation (n=3666).
Percentages are presented unless otherwise indicated.
| No Falls | Single Fall | Recurrent Falls | ||
|---|---|---|---|---|
| Falls = 0 | Falls = 1 | Falls ≥ 2 | P value | |
| n=3068 | n=359 | n=239 | ||
| Age, mean (SD) | 54.0 (13.6) | 56.6 (13.1) | 56.1 (12.5) | <0.001 |
| Female, % | 40.1 | 46.1 | 45.4 | 0.04 |
| Black, % | 45.9 | 48.6 | 41.6 | 0.25 |
| Frailty, % | ||||
| Non frail | 50.5 | 42.8 | 31.5 | <0.001 |
| Intermediate Frail | 30.7 | 30.1 | 30.2 | |
| Frail | 18.8 | 27.1 | 38.3 | |
| Lower extremity impairment, % | 33.1 | 51.6 | 65.4 | <0.001 |
| Poor HRQOL, % | 41.4 | 48.9 | 61.9 | <0.001 |
| BMI kg/m2, mean (SD) | 28.8 (6.4) | 29.6 (6.9) | 29.0 (6.1) | 0.08 |
| Comorbidities, % | ||||
| Myocardial Infarction | 8.9 | 11.7 | 11.4 | 0.16 |
| Peripheral Vascular | 6.1 | 5.5 | 12.4 | 0.002 |
| Cerebral Vascular | 5.4 | 6.5 | 11.4 | 0.002 |
| Dementia | 0.4 | 0.0 | 1.5 | 0.03 |
| Chronic Lung Disease | 5.7 | 3.9 | 8.5 | 0.10 |
| Rheumatologic | 6.4 | 8.2 | 6.9 | 0.51 |
| Peptic Ulcer | 3.3 | 3.6 | 5.0 | 0.42 |
| Diabetes | 40.0 | 53.3 | 55.0 | <0.001 |
| Diabetes with Complication | 21.0 | 30.1 | 34.0 | <0.001 |
| Moderate/Severe Liver | 3.2 | 4.3 | 5.9 | 0.10 |
| Metastatic Cancer | 1.2 | 0.3 | 1.5 | 0.36 |
| Leukemia | 0.3 | 0.0 | 1.0 | 0.15 |
| Lymphoma | 1.0 | 1.3 | 0.0 | 0.31 |
| Congestive Heart | 16.4 | 19.4 | 22.7 | 0.30 |
| HIV | 3.0 | 2.6 | 4.5 | 0.46 |
| CCI score, % | ||||
| 0 | 49.7 | 40.2 | 35.7 | <0.001 |
| 1 | 6.5 | 3.1 | 5.9 | |
| 2 | 13.4 | 16.0 | 13.5 | |
| 3 | 15.9 | 20.5 | 18.9 | |
| 4+ | 14.4 | 20.2 | 26.1 | |
| Dialysis type, % | ||||
| HD | 55.9 | 59.6 | 64.3 | 0.09 |
| PD | 11.7 | 10.1 | 11.0 | |
| Not on dialysis | 32.4 | 30.3 | 24.7 | |
| Months on dialysis, median (IQR) | 3.3 (22.0) | 4.4 (17.8) | 3.9 (25.5) | 0.01 |
Table 1B: Characteristics in Kidney Transplant (KT) Recipients by Falls in the 6 Months Prior to Admission for KT (n=770).
Percentages are presented unless otherwise indicated.
| No Falls | Single Fall | Recurrent Falls | ||
|---|---|---|---|---|
| Falls = 0 | Falls = 1 | Falls ≥ 2 | P value | |
| n=673 | n=57 | n=39 | ||
| Age, mean (SD) | 53.5 (14.1) | 62.2 (11.3) | 56.0 (12.8) | <0.001 |
| Female, % | 39.1 | 26.3 | 33.3 | 0.14 |
| Black, % | 41.5 | 40.4 | 43.6 | 0.96 |
| Frailty, % | ||||
| Non frail | 55.5 | 43.9 | 35.9 | 0.02 |
| Intermediate Frail | 30.5 | 31.6 | 35.9 | |
| Frail | 14.0 | 24.6 | 28.2 | |
| Lower extremity impairment, % | 34.9 | 60.0 | 51.9 | 0.001 |
| Poor HRQOL, % | 20.4 | 21.4 | 18.0 | 0.92 |
| BMI kg/m2, mean (SD) | 27.9 (5.8) | 29.8 (6.7) | 29.0 (5.1) | 0.04 |
| Comorbidities, % | ||||
| Myocardial Infarction | 4.6 | 8.8 | 2.6 | 0.30 |
| Peripheral Vascular | 4.8 | 8.8 | 10.3 | 0.16 |
| Cerebral Vascular | 1.8 | 0.0 | 0.0 | 0.42 |
| Dementia | - | - | - | - |
| Chronic Lung Disease | 8.2 | 5.3 | 2.6 | 0.34 |
| Rheumatologic | 20.3 | 22.8 | 15.4 | 0.67 |
| Peptic Ulcer | 3.6 | 1.8 | 2.6 | 0.74 |
| Diabetes | 31.1 | 43.9 | 51.3 | 0.007 |
| Diabetes with Complication | 17.8 | 29.8 | 35.9 | 0.003 |
| Moderate/Severe Liver | 1.5 | 1.8 | 2.6 | 0.87 |
| Metastatic Cancer | - | - | - | - |
| Leukemia | - | - | - | - |
| Lymphoma | - | - | - | - |
| Congestive Heart | 5.7 | 12.5 | 10.8 | 0.08 |
| HIV | 2.4 | 3.5 | 0.0 | 0.53 |
| CCI score, % | ||||
| 0 | 43.1 | 36.8 | 38.5 | 0.002 |
| 1 | 15.9 | 12.3 | 7.7 | |
| 2 | 15.3 | 8.8 | 7.7 | |
| 3 | 15.5 | 14.0 | 25.6 | |
| 4+ | 10.3 | 28.1 | 20.5 | |
| Cause of ESKD, % | ||||
| Glomerular Diseases | 23.2 | 12.3 | 7.7 | |
| Diabetes | 19.0 | 29.8 | 38.5 | |
| Hypertension | 32.7 | 36.8 | 33.3 | 0.01 |
| Cystic Diseases | 12.0 | 8.8 | 10.3 | |
| Other | 13.1 | 12.3 | 10.3 | |
| Dialysis Type, % | ||||
| HD | 68.5 | 76.9 | 20.5 | 0.64 |
| PD | 20.1 | 11.5 | 23.1 | |
| Not on dialysis | 11.4 | 11.5 | 56.4 | |
| Years on dialysis, median (IQR) | 1.71 (3.9) | 1.4 (3.3) | 2.6 (3.8) | 0.24 |
The Institutional Review Boards of Johns Hopkins Hospital and the University of Michigan approved this study, and all participants provided written informed consent. The clinical and research activities being reported are consistent with the Declaration of Helsinki and Declaration of Istanbul.
Falls
At the time of KT evaluation or admission for KT, participants were asked to report a history of falls. Specifically, they were uniformly asked to provide the number of falls they experienced in the past 6 months as part of study questionnaire. History of falls was defined as having reported any falls in the past 6 months and we categorized the reported number of falls as: no falls, a single fall (1 fall in the past 6 months), and recurrent falls (≥2 falls in the past 6 months).
Falls and Aging Metrics
We estimated prevalence ratios (PR) for 3 aging metrics (frailty, lower extremity impairment, and poor HRQOL) among KT candidates and recipients by history of falls (3-categories) using modified Poisson regression. The model was adjusted for age, sex, race, time on dialysis, BMI, and cause of ESKD.
Access to KT by Falls Prior to Evaluation
Among KT candidates, adjusted Cox proportional hazards models were used to estimate the chance of KT listing by history of falls (3-categories). Time to listing among KT candidates was defined as the time from evaluation for KT to active placement on the waitlist; participants were censored for mortality or administrative censoring at 1/31/2018. Proportional hazard assumptions were confirmed by visual inspection of the complementary log-log plots and Schoenfeld residuals.
Rate of transplantation by history of falls (3-categories) among KT candidates was assessed using Poisson regression to generate incidence rate ratios (IRR), adjusting for age, sex, race, BMI, time on dialysis, and cause of ESKD. Person-time was calculated from the date of active placement on the KT waitlist to the date of KT. All models were adjusting for age, sex, race, BMI, time on dialysis, and cause of ESKD.
Waitlist Mortality by Falls Prior to Evaluation
Additionally, among KT candidates the risk of waitlist mortality by history of falls among KT candidates was estimated using Cox proportional hazards models to estimate hazard ratios (HR), adjusting for age, sex, race, BMI, time on dialysis, and cause of ESKD; participants were censored for KT or administratively censored at 1/31/2018. We quantified the association between falls and waitlist mortality by year since listing through the estimation of time-varying hazard ratios (annually) in which an interaction term with history of falls and time (years) since date of listing was included in the Cox model.
Post-KT Adverse Outcomes
Among KT recipients, the risk of mortality and risk of all-cause graft loss by history of falls were estimated using Cox proportional hazards models to generate hazard ratios (HR), adjusting for age, sex, race, BMI, time on dialysis, and cause of ESKD. An interaction term with history of falls and time (years) since KT was also included to estimate the yearly risk associated with a history of falls. Proportional hazard assumptions were confirmed by visual inspection of the complementary log-log plots and Schoenfeld residuals. A similar approach was used to test the association between a history of falls and all-cause graft loss. We also quantified the association between history of falls and LOS among KT recipients using a multilevel Poisson regression model, considering the differences among hospitals and adjusting for age, sex, race, donor type, time on dialysis, BMI, and cause of ESKD. Patients with a LOS more than 30 days (n=16) were excluded from this analysis to avoid bias related to methodological and generalizability concerns raised in prior studies.24,25 We used a similar approach to test whether recurrent falls prior to KT were associated with mortality, all cause graft failure, and LOS among KT recipients.
Sensitivity analyses
We conducted a sensitivity analysis additionally adjusting for CCI and another sensitivity analysis adjusting for the specific comorbidities that were found to be associated with falls including peripheral vascular disease, cerebrovascular disease, dementia, and diabetes to determine if the impact of falls on outcomes among KT candidates and recipients remained robust to the presence of comorbidities.
Statistical analyses
All statistical analyses were performed using Stata version 15 (StataCorp, College Station, TX). Two-sided p-values < 0.05 were considered statistically significant.
RESULTS
Study Population of KT Candidates
Of the 3,666 KT candidates followed for a median of 2.1 years (interquartile range [IQR]=1.1, 3.6), the mean age was 54 (standard deviation [SD]=14), 38.1% were female, 45.9% were black. In the 6 months prior to KT evaluation, 16.3% of the KT candidates had a history of falls prior to KT evaluation; 6.5% had recurrent falls (≥2 falls in the 6 months prior to evaluation). KT candidates with a history of falls prior to evaluation were more likely to report mobility disability at this time (no falls: 11.7%; a single fall=22.4%; recurrent falls=35.0%).
Correlates of Falls at Time of Evaluation
KT candidates with falls in the 6 months prior to evaluation were older (no falls: mean age=54; single fall: mean age=57; recurrent falls: mean age=56) and had a higher burden of comorbidity (CCI score of ≥4: no falls=14.4%; single fall=20.2%; recurrent falls=26.1%) (Table 1A). Additionally, these candidates were more likely to be frail (no falls=18.8%; single fall=27.1%; recurrent falls=38.3%), have lower extremity impairment (no falls=33.1%; single fall=51.6%; recurrent falls=65.4%), and poor HRQOL (no falls=41.4%; single fall=48.9; recurrent falls=61.9%). After adjustment, frailty (aPR=1.36, 95%CI: 1.12–1.64), SPPB impairment (aPR=1.40, 95%CI: 1.24–1.58), and poor HRQOL (aPR=1.18, 95%CI: 1.05–1.32) were all more common among KT candidates who had a history a single fall (Table 2). The risks of these adverse aging metrics were greater for KT candidates who experienced recurrent falls prior to evaluation (frailty: aPR=1.90, 95%CI: 1.58–2.29; SPPB: aPR=1.75, 95%CI: .56–1.96; poor HRQOL: aPR=1.48, 95%CI: 1.32–1.64) (Table 2).
Table 2: Falls and Aging Metrics Among Kidney Transplant (KT) Candidates (n=3666) and Recipients (n=770).
At the time of evaluation and at the time of KT, falls in the past 6 months were reported and aging metrics were collected.
| Aging Metric | No Falls | Single Fall | Recurrent Falls |
|---|---|---|---|
| Falls = 0 | Falls = 1 | Falls ≥ 2 | |
| PR (95% CI) | PR (95% CI) | ||
| KT candidates | |||
| Frailty | Ref | 1.36 (1.12, 1.64) | 1.90 (1.58, 2.29) |
| Lower extremity impairment | Ref | 1.40 (1.24, 1.58) | 1.75 (1.56, 1.96) |
| Poor HRQOL | Ref | 1.18 (1.05, 1.32) | 1.48 (1.32, 1.64) |
| KT recipients | |||
| Frailty | Ref | 1.67 (1.02, 2.74) | 2.04 (1.20, 3.45) |
| Lower extremity impairment | Ref | 1.35 (1.02, 1.78) | 1.36 (0.95, 1.94) |
| Poor HRQOL | Ref | 1.08 (0.64, 1.83) | 0.85 (0.44, 1.62) |
For transplant candidates, models are adjusted for age, sex, race, time on dialysis, BMI, and Cause of ESKD; for transplant recipients, models are adjusted for age, sex, race, time on dialysis, BMI, Cause of ESKD and donor type
PR: Prevalence Ratio
HRQOL: Health-related quality of life
Falls and Adverse Outcomes Among KT Candidates
KT candidates with recurrent falls in the 6 months prior to evaluation had a lower chance of listing (aHR=0.68, 95%CI: 0.56–0.83) but a single fall was not associated with a chance of listing (Table 3). Those with 1 fall and those with recurrent falls had a greater risk of mortality within both at the time of listing and in the first year after listing. This risk gradually decreased over time (Figure 1). Finally, those with 1 fall had a lower KT rate (aIRR=0.68, 95%CI: 0.52–0.90).
Table 3. Access to Kidney Transplantation (KT) and Adverse Post-KT Outcomes Among Candidates (n=3666) and Recipients (n=770) by Falls.
Hazard Ratios and 95% Confidence Intervals are presented from Cox Regressions unless otherwise indicated. Associations that are statistically significant at p<0.05 are bolded.
| No Falls | Single Fall | Recurrent Falls | |
|---|---|---|---|
| Falls = 0 | Fall = 1 | Fall ≥ 2 | |
| HR (95% CI) | HR (95% CI) | ||
| KT candidates | |||
| Chance of Listing | REF | 0.90 (0.77, 1.04) | 0.68 (0.56, 0.83) |
| Risk of Waitlist Mortality | |||
| Listing to 1st year after listing | REF | 6.74 (3.11, 14.60) | 31.20 (11.33, 85.93) |
| 1–2 years postevaluation | REF | 3.25 (1.80, 5.87) | 15.03 (6.68, 33.80) |
| 2–3 years postevaluation | REF | 1.56 (0.96, 2.55) | 7.24 (3.78, 13.87) |
| 3–4 years postevaluation | REF | 0.75 (0.45, 1.26) | 3.49 (1.97, 6.16) |
| >4 years postevaluation | REF | 0.36 (0.19, 0.69) | 1.68 (0.92, 3.06) |
| Transplantation Rate (IRR) | REF | 0.68 (0.52, 0.90) | 0.94 (0.68, 1.30) |
| KT recipients | |||
| Risk of Mortality | |||
| Time of KT to 1st year after KT | REF | 9.17 (3.35, 25.09) | 51.43 (16.00, 165.43) |
| 1–2 years post-KT | REF | 5.83 (2.47, 13.75) | 32.67 (11.91, 89.57) |
| 2–3 years post-KT | REF | 3.70 (1.78, 7.72) | 20.75 (8.73, 49.28) |
| 3–4 years post- KT | REF | 2.35 (1.23, 4.50) | 13.18 (6.24, 27.82) |
| >4 years post- KT | REF | 1.49 (0.80, 2.77) | 8.37 (4.29, 16.33) |
| Risk of all-cause graft loss | |||
| Time of KT to 1st year after KT | REF | 7.34 (2.90, 18.57) | 33.57 (11.25, 100.21) |
| 1–2 years post-KT | REF | 4.66 (2.11, 10.30) | 21.34 (8.33, 54.69) |
| 2–3 years post-KT | REF | 2.96 (1.49, 5.88) | 13.57 (6.06, 30.39) |
| 3–4 years post- KT | REF | 1.88 (1.01, 3.51) | 8.63 (4.28, 13.37) |
| >4 years post- KT | REF | 1.20 (0.65, 2.21) | 5.48 (2.90, 10.36) |
| Longer length of stay | REF | 1.07 (0.98, 1.17) | 1.13 (1.03, 1.25) |
For KT candidates, models were adjusted for age, sex, race, time on dialysis, body mass index (BMI), and cause of ESKD. For KT recipients, models were adjusted for age, sex, race, time on dialysis, BMI, cause of ESKD, and donor types.
Figure 1. Risk of Waitlist Mortality by Falls.
The time-varying risk of waitlist mortality among listed kidney transplant (KT) candidates (n=2130) and 95% Confidence Intervals (CI) by falls within the 6 months prior to KT evaluation.
Falls at Time of KT
Of the 770 KT recipients followed for a median of 3.0 years (IQR=1.0, 4.0), the average age was 54.3 (SD=14.0), 37.9% were female, and 41.4% were black. In the 6 months prior to KT, 12.5% experienced at had a history of falls prior to KT; 5.1% had recurrent falls (≥2 falls in the 6 months prior to admission for KT). KT candidates with a history of falls prior to evaluation were more likely to report mobility disability at this time (no falls: 5.5%; a single fall=16.1%; recurrent falls=18.9%). Furthermore, KT recipients with a history of falls at evaluation were more likely to report a fall at the time of KT (29.5% vs. 12.0%; p=0.004).
Correlates of Falls at Time of KT
KT recipients with falls in the 6 months prior to evaluation were older (no falls mean age=54; single fall mean age=62; recurrent falls mean age=56) and had a higher burden of comorbidity (CCI score of ≥4: no falls=10.3%; single fall=28.1%; recurrent falls=20.5%) (Table 1B). Additionally, these recipients were more likely to be frail (no falls=14.0%; single fall=24.6%; recurrent falls=28.2%) and have lower extremity impairment (no falls=34.9%; single fall=60.0%; recurrent falls=51.9%), but not poor HRQOL. After adjustment, frailty (aPR=1.67, 95%CI: 1.02–2.74) and lower extremity impairment (aPR=1.35, 95%CI: 1.02–1.78) were more common among KT recipients who had a history of a single fall (Table 2). The prevalence of frailty was greater for KT recipients who experienced recurrent falls prior to KT (aPR=2.04, 95%CI: 1.20–3.45); however, recurrent falls were not associated with the other adverse aging metrics among KT recipients.
Falls and Adverse Outcomes Post-KT
A single fall in the 6 months prior to KT was associated with a greater risk of mortality at the time of KT within the first year post-KT (aHR=9.17, 95%CI: 3.35–25.09) (Table 3), and this risk gradually decreased each year (Figure 2). The risk of all-cause graft loss was also highest at the time of KT (aHR=7.34, 95%CI: 2.90–18.57). Similarly, the mortality and all-cause graft risks associated with recurrent falls were highest at the time of KT and declined thereafter. KT recipients with recurrent falls were at increased risk of a longer LOS (aHR=1.13, 95%CI: 1.02–1.25) (Table 3).
Figure 2. Risk of Post- Kidney Transplant (KT) Mortality by Falls.
The time-varying risk of post-KT mortality among KT recipients (n=770) and 95% Confidence Intervals (CI) by falls within the 6 months prior to KT.
Sensitivity analyses
After additionally adjusting for CCI and after additionally adjusting for specific comorbidities associated with falls, particularly peripheral vascular disease, cerebrovascular disease, dementia, and diabetes, we found that inferences did not change. Specifically, we found that candidates with recurrent falls had a lower chance of listing but not transplant rate, and that waitlist mortality was 31-fold higher in the first year and gradually decreased over time. For recipients with recurrent falls, there was an increased risk of mortality and graft loss in the first year, which declined over time. Consistent with main findings, we additionally found that recipients with recurrent falls were at increased risk of having a longer LOS.
DISCUSSION
In this prospective cohort study of 3666 KT candidates, we found that 16.3% had a history of falls prior to KT evaluation, with 6.5% experiencing recurrent falls; among 770 KT recipients 12.5% had a history of falls prior to KT, with 5.1% having experienced recurrent falls. Furthermore, KT candidates with a history of falls and recurrent falls were associated with lower extremity impairment and frailty. Recurrent falls were associated with a 32% decreased chance of listing and a 1.13-fold longer LOS after KT. Finally, the association between a history of falls and recurrent falls with waitlist mortality changed over time; the same was true for post-KT mortality and graft loss. The majority of the mortality risk attributable to these falls occurred immediately after listing among KT candidates and immediately after KT for KT recipients. For example, a history of falls was associated with a 6.74-fold increased risk of waitlist mortality in the first year after listing which dropped to a 3.25-fold risk in the second year after listing and no association in the third year.
The observed prevalence of falls prior to evaluation and KT was lower than what was observed among a cohort adults who were undergoing hemodialysis (28%)4 and older adults undergoing hemodialysis (47%).5 However, our findings on the burden of falls are specific to KT candidates and KT candidates which are a distinct group of patients with ESKD including some patients who are preemptive KT candidates and recipients. Additionally, our findings are consistent with a study of KT recipients; serious, injurious falls occurred in 4% of KT recipients in their first year after dialysis initiation.6
Frailty is associated with higher risk of falls in ESKD patients undergoing hemodialysis, which could be 1 path linking falls to adverse outcomes in both ESKD and KT.4 In this study we were able to confirm the association between previous falls and frailty among KT candidates and recipients as well as extend these findings to show that recurrent falls are also associated with frailty status. We also extended the previous findings that injurious falls prior to HD initiation were associated with a 61% decreased chance of listing and 29% decreased likelihood of transplantation.6 Therefore, our results are consistent and suggest that even a self-report of a history of falls prior to evaluation is associated with a decreased chance of listing. Compared to KT candidates, the risk of mortality was much greater in KT recipients, likely due to acute insult of surgical stressor compared to the chronic stressors introduced by dialysis. In this study, falls were strongly associated with the risk of mortality over the first year post-KT and this risk dissipated over time as expected, given that falls was measured only once as a fixed exposure at the clinically relevant time points of evaluation or admission for KT. We would expect the risk to decrease with time given that outcomes are less likely to be causally related to falls as more time passes. We chose to measure falls at the time when transplant providers interact with patients and make important clinical decisions for listing and preoperative management or postoperative discharge. Future studies may consider examining whether this risk of mortality would change based on differing patterns of reported falls over the length of follow-up.
The main strength of our study was the large sample of KT candidates and recipients. Additionally, this study directly measured important intermediaries of falls and long-term outcomes, namely gerontologic factors including frailty, lower extremity impairment, and health-related quality of life. Finally, this study relied on the patient report of falls which allowed us to capture minor, noninjurious falls, which may allow for better risk stratification and the opportunity to intervene and prevent recurrent, injurious falls. The main limitation of this study is that falls were self-reported and were unable to be validated. However, previous studies have used this measure of falls4 and it has high-agreement with more frequent measures including a falls calendar.26 Additionally, we were unable to confirm whether KT candidates and recipients were frail prior to experiencing a fall or whether falls led these patients to be frail. Finally, we cannot conclude that the outcomes studied were causally related to the falls; results must be interpreted cautiously.
In conclusion, 16.3% of KT candidates and 12.5% of recipients experience a fall in the 6 months prior to evaluation and KT. Falls, and particularly recurrent falls are associated with an increased prevalence of frailty and subsequent adverse outcomes. Falls are associated with waitlist mortality and post-KT mortality but these risks diminish over time. Clinicians have been found to have difficulty identifying vulnerable patients with ESKD,11 which stresses the need to identify factors, like a history of falls, that can improve risk stratification. History of falls is easily self-reported at evaluation and admission for KT, and a predictive measure that can be utilized to improve risk stratification in transplantation. Our results help to identify patients who could potentially benefit from targeted multidimensional falls prevention strategies and transplant centers should consider employing falls screening and prevention strategies to improve patient outcomes.
Funding
Funding for this study was provided in part by the National Institute of Diabetes and Digestive and Kidney Disease (NIDDK) and the National Institute on Aging (NIA); grant numbers F32AG053025 (PI: Christine Haugen), K23DK115908 (PI: Garonzik-Wang), K24DK101828 (PI: Dorry Segev), R01AG055781 (PI: Mara McAdams-DeMarco), and R01DK114074 (PI: Mara McAdams-DeMarco). Data are available for collaboration upon request and review from the PI (MMD).
ABBREVIATIONS PAGE
- BMI
body mass index
- CCI
Charlson comorbidity index
- ESKD
end stage kidney disease
- HR
hazard ratios
- HRQOL
health-related quality of life
- IRR
incidence rate ratios
- IQR
interquartile range
- KT
kidney transplantation
- LOS
length of stay
- PR
prevalence ratios
- SD
standard deviation
Footnotes
Disclosure
None
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