Introduction: The incidence of chronic kidney disease (CKD) is growing rapidly, along with the increasing geriatric population. CKD patients have higher incidence of fractures, stroke, and hospitalizations requiring rehabilitation. This is accompanied with the need for suitable rehabilitation programs to decrease disability and improve functionality to help elderly CKD patients maintain independence in activities of daily living. Considering that survivors of acute kidney injury (AKI) tend to experience decreased quality of life with increased frailty, rehabilitation in the elderly with kidney injury becomes even more complex. The aim of this study was to examine the impact of AKI on the outcomes of rehabilitation among elderly patients with CKD. Methods: For this retrospective, observational study, the electronic medical records of all patients who were hospitalized in the rehabilitation department were reviewed. We assessed functional status at the beginning and end of rehabilitation, renal outcome, and all-cause mortality among elderly patients with CKD who experienced an AKI and compared them to those who did not have an AKI. Results: The study cohort included 183 elderly patients with non-dialysis-dependent CKD. Patients with AKI (23% of study cohort) had a higher prevalence of heart failure and lower baseline estimated glomerular filtration rate, as compared with patients who did not have AKI. They were admitted to rehabilitation at a poorer functional capacity and were also discharged with lower functional independence measure scores. Overall odds ratio for all-cause death among patients with AKI versus without AKI was 3.2 (95% CI: 1.6–6.5; p = 0.001). Conclusion: AKI and CKD are interrelated syndromes. AKI was prevalent among elderly CKD patients and was associated with worse rehabilitation outcomes and higher mortality compared to similar patients without AKI.

The prevalence of chronic kidney disease (CKD) worldwide is estimated to be 8–16%, reaching about 45% in people over the age of 70 years in the USA [1]. As the worldwide population ages, so does the impact of CKD. Whereas disability-adjusted life years largely decreased for most diseases among people in the age groups 50–74 and 75+ years, it has increased for CKD [2].

CKD represents a substantial portion of the global health burden. In the 2010 Global Burden of Disease study (GBD), CKD was ranked 27th on the list of causes of global deaths for 1990 [1]. CKD rose to 18th in rank for all-cause mortality in the 2019 GBD and was found to be one of the 10 most important drivers of increasing disease burden [2‒4].

Acute kidney injury (AKI) is another common disorder of kidney disease, with an estimated prevalence of about 15% of adult patients admitted to the hospital and an incidence 10 times higher in the geriatric population [5]. This can be explained by the higher number of comorbidities, extensive polypharmacy, and decreased renal reserve that characterizes the geriatric population. Rosner and colleagues found that the average age of patients with AKI in a large European cohort was 76 years, which increased to 80.5 years for patients with acute on chronic kidney disease (AoCKD). The AoCKD group tended to have a much higher risk of poor outcomes [6].

AKI, CKD, and acute kidney disease and disorders were defined by “Kidney Disease: Improving Global Outcomes” (KDIGO), as occurring when serum creatinine increases by ≥0.3 mg/dL within 48 h, baseline creatinine increases ≥1.5 times within 7 days, or when urine volume decreases below 0.5 mL/kg/h for 6 h [7]. Both AKI and CKD are defined according to a time period, whereas CKD is defined by kidney damage for more than 3 months [7].

In one of the largest prospective cohort studies of AKI performed by the “Beginning and Ending Supportive Therapy for the Kidney” (BEST) study, in-hospital mortality rates reached 60%. It was also reported that advanced age was independently associated with increased hospital mortality risk among AKI patients [8]. In another large European population cohort, AKI was found to be an independent predictor of 90-day unplanned readmission or death [9].

Although there have been many studies on the effect of AKI in different circumstances, and on renal rehabilitation after acute injury, to our knowledge, the effect of AKI on rehabilitation outcomes among CKD elderly inpatients has not been assessed. In a recent workshop of the National Institute of Diabetes and Digestive and Kidney Disease, a multidisciplinary group of clinicians and scientists communicated the need for interventions directed at promoting physical and psychological rehabilitation for AKI patients after hospitalization, especially among those with moderate to severe AKI and AoCKD [10].

As the geriatric population, especially in developed countries, is rapidly growing, so is the incidence of AKI and CKD. This is accompanied with a need for suitable rehabilitation programs to decrease disability and improve functionality to maintain independence in activities of daily living. Considering that survivors of AKI tend to experience decreased quality of life (QOL) and increasing frailty, rehabilitation in the elderly with AoCKD becomes even more complex, playing an indispensable part in the goal of achieving functional independence in this segment of the population [10, 11]. Numerous studies have shown the impact of rehabilitation programs in improving QOL and survival in CKD patients [12‒19], with current guidelines recommending moderate exercise therapy [20, 21]. However, there is a paucity of literature regarding the effect of AKI on the rehabilitation of CKD patients. The aim of this study was to examine the impact of AKI on the outcomes of rehabilitation among elderly patients with CKD.

Study Design

For this retrospective, observational study, the electronic medical records of all patients who were hospitalized in the rehabilitation department at a tertiary medical center in Israel from January 1, 2008, to December 31, 2018 were reviewed. Meir Medical Center (MMC) is a university-affiliated hospital with a rehabilitation department providing in-hospital rehabilitation for 300–400 patients annually. Rehabilitation was categorized as neurologic poststroke, orthopedic, or for deconditioning. Patients with end-stage kidney disease who required renal replacement therapy were excluded from the analysis (Fig. 1).

Fig. 1.

Study flow diagram.

Fig. 1.

Study flow diagram.

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Study Population

The study cohort included all patients older than 65 years of age who were admitted to the rehabilitation department at MMC during the study period, with available serum creatinine and estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2 values at baseline. Baseline eGFR was estimated for each patient individually using the CKD epidemiology collaboration (CKD-EPI) equation. CKD-EPI is a validated tool that is widely accepted for estimating GFR. CKD stages were defined according to KDIGO 2012 criteria regarding baseline eGFR: stage 2, mildly decreased eGFR 60–89 mL/min; stage 3A, mildly to moderately decreased eGFR 45–59 mL/min/1.73 m2; stage 3B, moderately to severely decreased eGFR 30–44 mL/min/1.73 m2; stage 4, severely decreased eGFR 15–29 mL/min/1.73 m2; and stage 5, kidney failure with eGFR below 15 mL/min/1.73 m2 [5].

Patients were grouped as AKI or non-AKI based on at least 3 measurements of their serum creatinine at 3 different points during the rehabilitation period (1 month before admission to rehabilitation until rehabilitation discharge). Patients were categorized as having AKI if their baseline serum creatinine increased by ≥0.3 mg/dL within 48 h, or baseline creatinine increased ≥1.5 times within 7 days [7].

Demographic and Clinical Data

Demographic data abstracted from electronic medical records included age, sex, comorbidities (such as diabetes mellitus and other chronic diseases), and baseline laboratory data.

Study Measures

The functional independence measure (FIM) is a well-known, validated scale for functional assessment that measures a person’s mobility, self-care, communication, social, and cognitive skills. There are 18 items, each with a score ranging from 1 to 7, for a total possible score of 18–126 points [22].

FIM scores were obtained by trained observers (physical and occupational therapists) and were calculated for each patient at admission and discharge from rehabilitation. Delta FIM was determined for each patient by calculating the difference between FIM scores at admission and discharge. We also recorded the length of stay for each patient, and then assessed FIM efficiency (FIM gain/length of stay) of patients [23, 24].

The efficacy of rehabilitation was assessed by the FIM score at discharge, FIM gain or loss, and FIM efficiency, and by assessing functional status at discharge from rehabilitation. Patients were categorized as independent if they were able to be discharged home without 24-h caregiver supervision. In hospital, 30-day and 1-year mortality rates were recorded.

The Mini-Mental State Examination (MMSE) is used extensively to help clinicians evaluate cognitive impairment. In our study, patients were tested by a trained occupational therapist at admission to rehabilitation. Based on the 30-point scale, scores below 24 may suggest mild cognitive impairment, but age, education, and cultural background significantly affect the score [25].

Statement of Ethics

The study was approved by the MMC Institutional Ethics Committee, approval number MMC 0263-18, and was performed in keeping with the principles of the Declaration of Helsinki.

Statistical Analysis

Data were expressed as mean ± standard deviation for continuous variables and as numbers and percentages for nonmetric parameters. Metric data were checked for normality using the Shapiro-Wilk test. As some of the variables were not normally distributed, t test or Mann-Whitney nonparametric test was used to compare the two. χ2 or Fisher’s exact test was used to compare categorical parameters. The Cox proportional hazard model was used to estimate hazard ratios for mortality in AKI versus non-AKI patients.

A multivariate logistic regression model including all relevant variables from the univariate analysis was applied to estimate odds ratios for all-cause mortality. p values <0.05 were considered statistically significant.

The study cohort included 183 patients with non-dialysis-dependent CKD, at an average age of 81.7 ± 7 years at admission to rehabilitation and mean eGFR of 55.3 ± 17.9 mL/min (range: 10.1–88.1 mL/min). Baseline eGFR according to CKD stage was calculated for each patient individually, and the study flow diagram including the number of patients at each CKD stage is shown in Figure 1. AKI was present in 43 patients (23.5%). Their demographics and comorbidities as compared to those who did not have AKI are shown in Table 1. The prevalence of heart failure was higher among patients who developed AKI and their baseline estimated GFR was lower than that of patients who did not have AKI. Most AKI cases were inpatients admitted for orthopedic rehabilitation (19/43, 44.2%), versus 8 cases for neurologic rehabilitation (18.6%), and the remaining 16 were admitted for deconditioning (p = 0.359).

Table 1.

Baseline demographics and comorbidities of study cohort (N = 183)

AKI (N = 43)Non-AKI (N = 140)p value
Age, years 82.8±6.8 81.34±7 0.219 
Baseline serum creatinine, mg/dL 1.3±0.5 1.1±0.5 0.018 
eGFR baseline, mL/min/m2 48.7±17.8 57.3±17.6 0.006 
Male sex, n (%) 23 (53.5) 58 (41.4) 0.164 
Ischemic heart disease, n (%) 17 (39.5) 42 (30) 0.242 
Heart failure, n (%) 19 (44.2) 20 (14.3) <0.01 
Hypertension, n (%) 38 (88.4) 116 (82.9) 0.386 
Diabetes mellitus, n (%) 22 (51.2) 52 (37.1) 0.101 
Previous stroke, n (%) 18 (41.9) 53 (37.9) 0.637 
Atrial fibrillation, n (%) 19 (44.2) 42 (30) 0.084 
Peripheral vascular disease, n (%) 2 (4.7) 6 (4.3) 0.918 
Chronic lung disease, n (%) 9 (20.9) 20 (14.3) 0.297 
AKI (N = 43)Non-AKI (N = 140)p value
Age, years 82.8±6.8 81.34±7 0.219 
Baseline serum creatinine, mg/dL 1.3±0.5 1.1±0.5 0.018 
eGFR baseline, mL/min/m2 48.7±17.8 57.3±17.6 0.006 
Male sex, n (%) 23 (53.5) 58 (41.4) 0.164 
Ischemic heart disease, n (%) 17 (39.5) 42 (30) 0.242 
Heart failure, n (%) 19 (44.2) 20 (14.3) <0.01 
Hypertension, n (%) 38 (88.4) 116 (82.9) 0.386 
Diabetes mellitus, n (%) 22 (51.2) 52 (37.1) 0.101 
Previous stroke, n (%) 18 (41.9) 53 (37.9) 0.637 
Atrial fibrillation, n (%) 19 (44.2) 42 (30) 0.084 
Peripheral vascular disease, n (%) 2 (4.7) 6 (4.3) 0.918 
Chronic lung disease, n (%) 9 (20.9) 20 (14.3) 0.297 

Comparison of 43 patients with CKD who had AKI versus 140 patients who did not have AKI peri-rehabilitation.

Values are presented as absolute numbers (percentage) or as mean ± SD.

AKI, acute kidney injury; SD, standard deviation.

Patients with AKI had worse functional capacity at admission to rehabilitation (mean FIM score 55) as compared to 65 inpatients without AKI (p = 0.004, Fig. 2). Patients with AKI were also discharged with lower FIM scores (p = 0.001) and had a shorter duration of rehabilitation (21.2 ± 14.4 vs. 32.6 ± 19.7 days, p = 0.001). The net efficacy of the rehabilitation was assessed by FIM efficiency, which was also significantly lower among patients who had AKI (−0.6 ± 6.4 vs. 0.54 ± 0.84, p = 0.039). Some of these patients had lower FIM at discharge than at admission; therefore, the mean FIM efficiency of this group was negative. Patients who experienced AKI had lower MMSE at admission to rehabilitation compared to patients without AKI (19.8 ± 6.4 vs. 23.1 ± 5.9, respectively; p = 0.002).

Fig. 2.

FIM scores at admission and discharge according to AKI. FIM, functional independence measure; AKI, acute kidney injury. 43/183 patients (23.5%) had AKI and were admitted for rehabilitation at a mean FIM score of 55.3 ± 17.9, discharged with 68.1 ± 20.9 (delta FIM 10.8 ± 20.4), versus mean FIM score of 64.6 ± 17.9 at admission, 80.1 ± 19.2 at discharge, and delta FIM of 14.4 ± 14.3 for patients without AKI (p = 0.004, 0.001, 0.170, respectively).

Fig. 2.

FIM scores at admission and discharge according to AKI. FIM, functional independence measure; AKI, acute kidney injury. 43/183 patients (23.5%) had AKI and were admitted for rehabilitation at a mean FIM score of 55.3 ± 17.9, discharged with 68.1 ± 20.9 (delta FIM 10.8 ± 20.4), versus mean FIM score of 64.6 ± 17.9 at admission, 80.1 ± 19.2 at discharge, and delta FIM of 14.4 ± 14.3 for patients without AKI (p = 0.004, 0.001, 0.170, respectively).

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Discharge Destination

Data concerning discharge destination were available for 179 patients. Of these, 64 (36%) were discharged from in-hospital rehabilitation to home, as independent. The proportion of patients discharged home as independent was significantly lower among AKI patients (9/40 [22.5%] compared to those without AKI 55/139 [39.6%]; p = 0.047; OR = 0.44, 95% CI: 0.196–1.0). More patients in the AKI group required nursing home care after rehabilitation (16.3% vs. 7.9%, p = 0.003). A multivariate analysis model showed that AKI and not baseline eGFR was the predictor of independent status at discharge, as shown in Table 2.

Table 2.

Multivariate analysis model for predictors of independence status at discharge from in-hospital rehabilitation

VariableOR (95% confidence interval)p value
AKI 2.5 (1.0–6.1) 0.05 
Age, years 0.9 (0.86–0.95) 0.001 
eGFR at baseline 1 (0.98–1.02) 0.85 
Heart failure 1.4 (0.6–3.3) 0.44 
VariableOR (95% confidence interval)p value
AKI 2.5 (1.0–6.1) 0.05 
Age, years 0.9 (0.86–0.95) 0.001 
eGFR at baseline 1 (0.98–1.02) 0.85 
Heart failure 1.4 (0.6–3.3) 0.44 

Renal Outcomes

Fourteen patients had CKD stages 4–5, half had AoCKD, and 2 reached end-stage kidney disease and required renal replacement therapy (hemodialysis). Among 14 patients at CKD stage 4–5, 9 died during follow-up (64.2%).

All-Cause Mortality

During 861 ± 400 days of follow-up, 60/183 (32.8%) patients died. Overall OR for all-cause death among AKI versus non-AKI patients was 3.2 (95% CI: 1.6–6.5; p = 0.001).

Patients with AKI had OR of 3.771 for in-hospital mortality as compared to patients who did not have AKI (95% CI: 1.3–10.8; p = 0.009). The OR for 30-day mortality was also higher in this group, at 9.1 (95% CI: 1.7–48.6; p = 0.002).

Among patients with AKI, 13/43 (30.2%) died versus 15/140 (10.7%) non-AKI patients. OR for 1-year mortality was 3.6 (95% CI: 1.6–8.4; p = 0.002). Heart failure and AKI were the most important predictors of all-cause mortality (Table 3).

Table 3.

Multivariate analysis model for predictors of all-cause mortality

VariableOR (95% confidence interval)p value
AKI 2.3 (1.1–5.1) 0.035 
Sex (female) 0.6 (0.3–1.3) 0.209 
Ischemic heart disease 0.5 (0.2–1.1) 0.07 
Diabetes mellitus 1.1 (0.5–2.1) 0.89 
Heart failure 4.5 (1.9–10.3) <0.001 
Peripheral vascular disease 3.5 (0.7–17.4) 0.121 
VariableOR (95% confidence interval)p value
AKI 2.3 (1.1–5.1) 0.035 
Sex (female) 0.6 (0.3–1.3) 0.209 
Ischemic heart disease 0.5 (0.2–1.1) 0.07 
Diabetes mellitus 1.1 (0.5–2.1) 0.89 
Heart failure 4.5 (1.9–10.3) <0.001 
Peripheral vascular disease 3.5 (0.7–17.4) 0.121 

AKI, acute kidney injury.

This study assessed the clinical outcomes of AKI among 183 elderly patients with non-dialysis-dependent CKD, hospitalized for rehabilitation. We found that rehabilitation was less effective among patients with AKI, as expressed by lower FIM scores at discharge, lower FIM efficiency, and lower functional status, as well as by increased mortality.

AKI and CKD are interrelated syndromes with common outcomes and associated morbidity and mortality [10]. Previous studies have suggested an association between kidney impairment and the risk of functional decline. Individuals with CKD have a 40–70% increased risk for functional limitations than do those without CKD [26]. The mechanism underlying this association involves the high burden of comorbidities among CKD patients, as well as factors such as malnutrition-inflammation syndrome and depression [26]. The effect of AKI in different scenarios and circumstances has been studied widely. Chao et al. [27] found a close relation between the incidence of AKI at admission to hospitalization and functional status in the elderly. However, to our knowledge, the effect of AKI on rehabilitation outcomes and functional status at discharge has not been assessed.

The current study included 183 CKD patients, mostly at CKD stage 3, of whom 23% experienced AKI during the rehabilitation period, at considerably higher rate than reported previously among hospitalized patients [28, 29]. This is likely due to our definition of AKI which can lead to overdiagnosed cases of AKI. Another explanation could be the more vulnerable population included in our study: older patients with preexisting kidney disease and multiple comorbidities.

Decreased renal function at baseline and heart failure, which are well-known predictors of in-hospital AKI, were significantly associated with AKI prevalence. However, other common predictors of AKI, such as diabetes and older age were not [30].

In a study of elderly patients admitted to the hospital, Folstein et al. [25] found that poor functional status, reflected by low Barthel Index score, was independently associated with the presence of AKI at admission. Similarly, our study showed that patients who had AKI were admitted to rehabilitation at a lower functional capacity, reflected as a mean FIM score of 55, as compared to 65 in non-AKI patients.

Patients with AKI were also discharged with lower FIM scores, as described in previous studies on the impact of AKI on performance outcomes and patient frailty [28]. Patients with AKI also had a significantly shorter duration of rehabilitation, which may be explained by the cessation of rehabilitation due to more severe medical conditions, re-hospitalizations, and worse short-term mortality rates, as described in this population [29]. Thus, FIM efficiency, which reflects the efficacy of rehabilitation, was lower among patients with AKI.

The present study demonstrated that elderly patients with AoCKD have poorer rehabilitation outcomes. Some of these patients had a lower FIM score at discharge than on admission, indicating a poor rehabilitation process. One explanation for the poor rehabilitation outcome is that AoCKD patients had lower MMSE scores on admission and were consequently unable to cooperate with the rehabilitation regimen and successfully complete their rehabilitation.

Liangos et al. [28] demonstrated that AKI in hospitalized patients was associated with discharge to short- or long-term care facilities. Similarly, in this study, patients with AoCKD were less likely to be discharged home as independent and more required discharge to a nursing home (16% vs. 7–9%, p = 0.003). These findings reflect the poorer functional status and lower FIM scores at discharge and suggest that AKI independently and adversely affects the recovery of physical function. A multivariate analysis model showed that AoCKD was a significant, negative predictor of functional dependency at discharge and more predictive than the baseline eGFR. Although AKI was more prevalent as the eGFR decreased, the multivariate model confirmed the importance of AKI event itself among the elderly CKD patients included in this cohort.

Mortality was found to be significantly higher in the AoCKD group than among non-AKI CKD patients. The OR for overall mortality was 3.2 (p = 0.001); higher in-hospital, 30-day, and 1-year mortality rates were found throughout the follow-up period. This is consistent with other studies showing that an episode of AKI carries significant short- and long-term mortality risks [28], in addition to the preexisting CKD, which has a significant impact on long-term outcomes [29]. In our cohort, heart failure and AKI were the most important predictors of mortality.

Heart failure was prevalent in our study (21.3%) and was associated with AKI (p < 0.01) and predicted mortality independently (OR 4.5, p < 0.01). The effect of heart failure on morbidity and mortality is well known, as it affects signaling pathways in various cells of the cardiovascular system, increases inflammation, increases mitochondrial dysfunction and insulin resistance, and activates the renin-angiotensin-aldosterone system and others. Strategies such as renin-angiotensin-aldosterone, SGLT2 blockade to reduce inflammation, and improve metabolism have been developed [31‒34].

This study reinforces the already-known implications of AKI on health outcomes and mortality and specifically addresses rehabilitation outcomes in the vulnerable CKD population. AoCKD may constitute a unique clinical syndrome with different outcomes and a substantial cost burden. Thus, it can affect healthcare professionals’ decisions regarding rehabilitation for patients. An international strategy providing physical and psychological rehabilitation following AKI is needed. The introduction of novel digital technology could potentially improve the rehabilitation process and should be applied to this frail population. With the increasing aging of the population and the expected increase in the prevalence of CKD and AKI, coupled with limited healthcare system resources and rehabilitation beds, further investigation and a competitive approach in the field of geriatric nephrology are much needed [35]. Therefore, from a public health perspective, kidney research should be prioritized.

Since rehabilitation, including physical activity and improved nutritional status is beneficial for CKD patients, a comprehensive, individualized interventional program may improve functional independence and activities of daily living among this population. Goal-oriented interventions including prevention programs should be provided for patients with CKD, whether they are dialysis-dependent or non-dialysis-dependent. Improving functional and nutritional status may lead to better QOL and reduce complications, as well as morbidity and mortality [36‒39].

This study had several limitations. It was retrospective and used a single-center database, which might have led to selection and misclassification biases. The cohort included only 183 cases, which may widen the 95% confidence interval and limit the ability to draw robust conclusions. The study sample was heterogeneous with a variety of comorbidities, limiting the ability to make direct associations between CKD and rehabilitation. There is also the possibility of bias in preselecting patients without significantly advanced kidney disease for rehabilitation.

AKI and CKD are interrelated syndromes. This study found poorer rehabilitation outcomes and higher mortality rates among patients with AoCKD admitted to an inpatient rehabilitation program.

The authors thank Faye Schreiber, MS, for editing the manuscript.

The study was approved by the Local Institutional Ethics Committee and was in keeping with the principles of the Declaration of Helsinki. In accordance with Israeli Ministry of Health regulations, the Ethics Committee did not require written informed consent because data were collected anonymously from the electronic medical records without active patient participation. This study protocol was reviewed and approved by the Meir Medical Center Institutional Ethics Committee, approval number MMC 0263-18.

The authors have no conflict of interest to declare.

No funding was received for this work.

Conception and design of research: K.C.-H., N.N., and S.B.; data collection: N.N., E.S., D.E., I.R., and M.G.; analyzed the data, interpreted the results, and prepared the figures: K.C.-H., N.N., R.H.A., E.S., and S.B.; drafted manuscript: N.N., K.C.-H., E.S., and S.B.; edited and revised manuscript: K.C.-H. and N.N.; and all authors approved the final version of manuscript.

Additional Information

Naomi Nacasch and Erez Sarel contributed equally to this work.

Data are not publicly available due to legal and ethical grounds. Further inquiries can be directed to the corresponding author.

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