Background

Twelve percent of the total population consist of elderly individuals, and it is expected to rise to 21 % by the year 2040. This tendency causes a gradual rise in the number of rehabilitation beds, emergency and acute care beds, as seen mainly in the developed nations [1]. In this sense, the specific renal problems along with their management should be well defined in elderly people.

The increased incidence of acute kidney injury (AKI) in the elderly people is favored by certain predisposing factors such as histological and functional alterations in the aged kidneys, different pharmacokinetics of drugs, polypharmacy and associated comorbid diseases like diabetes mellitus (DM), hypertension (HT) and heart failure [2].

Acute kidney injury, even mild or moderate, can result in increased morbidity and mortality [3]. Elderly adults are more susceptible to AKI, but it is more important to understand whether AKI is associated with more or less severe consequences in elderly population. Although various studies have expanded our knowledge about clinical features and outcomes of acute kidney injury develo** in the hospital (AKI-DI) in the elderly subjects [4], data about acute kidney injury develo** outside the hospital (AKI-DO) in the elderly (age ≥ 65 years old) and very elderly patients (age ≥ 75 years old) are extremely limited. Although the incidence of AKI-DO was 3.5 times more than AKI-DI [5] and increased mortality was reported [6], the studies carried out are still not enough.

The aim of this study is to investigate the incidence, clinical presentations, risk factors, associated factors, mortality, hospital cost and outcomes of AKI-DO in elderly and very elderly patients.

Patients and methods

A prospective, observational case–control study was designed, and patients aged 65 years and older who admitted to our center between May 01, 2012, and May 01, 2013, were included in the study. Data collection and analysis of the study were approved by the Human Research Ethics Committee (2012/104, 22.04.2012). Written informed consent was obtained from patients for their participation in the study.

Subjects of the study

Patients were eligible for enrollment if they were aged ≥ 65 years and were diagnosed AKI-DO that needed hospitalization. As average life expectancy is 74 years in our country (http://www.tuik.gov.tr/PreHaberBultenleri.do?id=8428), patients were divided into two groups as “elderly” (group 1, 65–75 years) and “very elderly” (group 2, >75 years). Patients aged 65 years old and older who were hospitalized with normal serum creatinine level were included in the control group (group 3). The criteria for diagnosis of AKI were increase in serum creatinine level by 0.3 mg/dl within 48 h or increase in serum creatinine level to 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days or urine volume less than 0.5 ml/kg/h for 6 h [7]. Patients were followed up for 6 months after discharge from the hospital. Return of serum creatinine level back to normal range (serum creatinine: 0.6–1.1 mg/dl) was accepted as complete recovery.

Data collection

Vital signs, plasma glucose, urea, serum creatinine, sodium, potassium, magnesium, chloride, calcium, phosphate, serum albumin, thyroid-stimulating hormone (TSH), liver enzymes, C-reactive protein (CRP) levels, analysis of arterial blood gases, urinalysis and albumin/creatinine ratio in spot urine sample were measured at admission for all subjects.

Serum urea, creatinine, sodium, fasting blood glucose, albumin were assessed by “Olympus AU 640, Japan.” Serum potassium, magnesium, chloride, calcium, phosphorus were measured by “Roche Cobas İntegra 800 Chemistry Analyzer, Switzerland.”

Urinalysis was evaluated by “Urisys 2400/UF100, Japan.” Albumin/creatinine ratio in spot urine was assessed by “Roche Cobas İntegra 800 Chemistry Analyzer, Switzerland.”

Estimated glomerular filtration rate (eGFR) was calculated for each participant by “Chronic Kidney Disease Epidemiology Collaboration” (CKD-EPI) formula which can be shown as CKD-EPI = eGFR = 141 × min(Scr/κ,1)α × max(Scr/κ,1)−1.209 × 0.993Age × 1.018 [if female] × 1.159 [if black] [8].

Exclusion criterias

Patients younger than 65 years of age, patients with chronic kidney disease (CKD) (eGFR < 60 ml/min, persistent proteinuria [>1 g/day], persistent glomerular hematuria or persistently high serum creatinine level), patients with renal anatomic abnormalities including polycystic kidney disease, atrophic kidney(s) (vertical length <9 cm), bilateral renal artery stenosis, renal artery stenosis of solitary kidney, transplanted kidney and patients with AKI-DI were all excluded from the study.

Etiologic factors

Use of nephrotoxic agents like intravenous contrast agents, nonsteroidal anti-inflammatory drugs (NSAIDs), angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), aminoglycoside, spironolactone, loop diuretics was recorded. Factors which may cause prerenal AKI like diarrhea, vomiting, decrease in oral intake, gastrointestinal bleeding were noted. Respiratory, urinary and gastrointestinal system infections were recorded. Comorbid diseases like DM, HT, cirrhosis, chronic obstructive pulmonary disease, Alzheimer’s disease, neoplastic diseases, congestive heart failure, stroke, and eventually total number of comorbidities were recorded. The reasons for admission to the hospital were analyzed. Postrenal causes such as benign prostatic hypertrophy and prostatic adenocarcinoma, pelvic malignancies which may result in urethral obstruction, retroperitoneal fibrosis were investigated. Renal biopsy was performed for the patients whose etiology of prolonged AKI could not be determined.

Clinical outcomes of AKI-DO

Clinical outcomes of AKI-DO like complete recovery, progression to CKD and in-hospital mortality and 6-month mortality rates were recorded. Clinical outcomes and mortality reasons of each group were compared with each other. Need for hemodialysis (HD), intensive care unit (ICU) and mechanic ventilator (MV), and length of hospital stay, hospital cost, mortality rates of groups were compared with each other. Rehospitalization rate of each group was calculated.

Related factors of AKI-DO

Associations of AKI-DO and age, sex, serum potassium level, presence of infection, need for HD, need for ICU, duration of hospitalization, clinical outcomes (mortality, progression to CKD, recovery), hospital cost, number of comorbidities, use of NSAID, ACEI, ARB, radiocontrast agents were investigated.

Risk factors for AKI-DO

Age, sex, number of comorbidities, presence of infection, HT, DM, heart failure, use of NSAID, ACEI, ARB and radiocontrast agents were investigated whether they were risk factors for AKI-DO. In addition to this, risk of AKI-DO due to specific drug combinations was investigated. Risk of AKI-DO in the presence of specific comorbid disease was investigated. Mortality risk analysis was performed for patients with AKI-DO by using serum creatinine values.

Invoices regarding laboratory tests, imaging procedures, surgical interventions, histopathologic investigations, medications, feeding, consultations, medical equipment, and all supportive care performed during the hospital stay were evaluated in order to determine total hospital cost.

Statistical analysis

MedCalc packet program was used for statistical analysis. Shapiro–Wilk test was used to identify whether variables were normal distribution. Mean ± standard deviation was used for descriptive statistics for non-normal distribution variables. The mean comparisons of binary groups were done with Student’s t test. Spearman correlation was used to test correlation between two continuous variables. Chi-square statistics were used to compare two categorical variables. Logistic regression and odds ratios were used for risk analysis.

Results

The study included 3229 patients, aged ≥ 65 years. Group 1 consisted of 136 participants [male/female (M/F): 78/58], whereas group 2 consisted of 100 participants (M/F: 58/42), and group 3 (control group) included 190 subjects (M/F: 112/78).

Incidence of AKI-DO

The incidence of AKI-DO in group 1 and group 2 was 5.8 % (136/2324) and 11 % (100/905), respectively (p < 0.001), whereas the overall incidence of AKI-DO was 7.3 % (236/3229) in elderly patients. Incidence of AKI-DO was 4.2 % for males and 3 % for females (p < 0.05). Clinical and laboratory parameters of the groups are shown in Table 1.

Table 1 Clinical and laboratory parameters of elderly and very elderly on admission
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Etiology of AKI-DO

Clinical features of the groups at admission are listed in Table 2. Frequency of prerenal, renal and postrenal causes for AKI-DO was 63, 27 and 10 % in group 1 and 63, 29 and 8 % in group 2, respectively. Prerenal factors were the most common cause of AKI-DO in both groups (p < 0.05). Inadequate oral intake was the most common prerenal factor in both groups. Use of NSAID, ACEI, ARB, radiocontrast agents, loop diuretics, spironolactone and other nephrotoxic agents was 14.7 and 14, 37.5 and 35, 11.8 and 10, 11.8 and 15, 2 and 3, 4.4 and 3, 5.2 and 5.4 % for groups 1 and 2, respectively. Administration of nephrotoxic drugs was similar for two groups (p > 0.05).

Table 2 Clinic features of groups
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The most common reasons for admission to the hospital were as follows: infection/fever 40 versus 43 %, dyspnea 22 versus 11 %, oliguria 12 versus 17 %, vomiting/diarrhea 12 versus 13 %, others 14 versus 16 %, for group 1 and 2, respectively. Fever/focal infection was the most common reason for admission in both groups. No significant difference was obtained between the admission reasons of two groups (p > 0.05), other than dyspnea (p < 0.05).

Males were exposed to radiocontrast agents more common than women (18.6 vs. 9.2 %, p < 0.05), and use of NSAID (17.3 vs. 11.4 %, p < 0.05), ACEI (41 vs. 29 %, p < 0.05), ARB (13.1 vs. 8 %, p < 0.05) was also more common in males. Other etiologic factors were similar in both groups.

Comorbidities

In this study, majority of the patients with AKI-DO had ≥2 comorbid diseases. Among AKI-DO patients, 81.3 % had ≥2 comorbid diseases, whereas 18.7 % had <2 comorbid diseases (p < 0.001). When groups were analyzed separately 73.5 versus 92 % of subjects had ≥2 comorbid diseases and 26.5 versus 8 % had <2 comorbid diseases for groups 1 and 2, respectively (p < 0.05 for all). Only 25.8 % of control group had ≥2 comorbid diseases, whereas 74.2 % had <2 comorbid diseases (p < 0.05). In control group, the number of the subjects with ≥2 comorbid diseases was significantly lower in comparison with groups 1 and 2 (p < 0.001). A total of 85.2 % of males and 72 % of females had ≥2 comorbid diseases (p < 0.05).

Clinical outcomes of AKI-DO

The length of hospital stay, need for MV support, number of comorbidities were found to be higher in very elderly patients than in elderly subjects (p < 0.05) (Table 2).

Need for ICU was 33.8 % for all patients with AKI-DO. Need for ICU in control group was significantly lower than in groups 1 and 2 (p < 0.05) (Table 2). Need for HD was 32.6 % for all patients with AKI-DO, whereas it was significantly lower in control group than in groups 1 and 2 (p < 0.05) (Table 2).

Rehospitalization rate of AKI-DO within 6 months after discharge was 15.6 % for all patients with AKI-DO. Rehospitalization was needed for 15 % of group 1 patients and 17 % of group 2 patients (p > 0.05), whereas 8.4 % of patients in control group needed rehospitalization within this period. Need for rehospitalization during 6 months after discharge in groups 1 and 2 were higher than in control group (p < 0.001).

Chronic kidney disease was developed in 53.3 % of the patients with AKI-DO during 6 months after discharge. Chronic kidney disease was developed 43.4 % of group 1 and 67 % of group 2 (p < 0.001), whereas CKD developed in 5.3 % of control group. Development of CKD was lower in control group than in groups 1 and 2 (p < 0.001) (Table 2).

Mortality rates of the patients with AKI-DO for the 6 months following their discharge were 26.6 %. Mortality rate of group 1 was 23.5 %, whereas it was 31 % for group 2 (p < 0.05) and 4.2 % for control group. Mortality rate of control group was significantly lower than that of groups 1 and 2 (p < 0.001) (Table 2).

Complete recovery was achieved in 20.1 % of AKI-DO patients within 6 months following discharge. When groups were analyzed, complete recovery rate of group 1 was 33.1 %, whereas it was 2 % for group 2 (p < 0.001) and 90.5 % for control group (Table 2).

Hospital expenditure was 1715 ± 871 USD (United States dollar) for all patients in groups 1 and 2. The mean hospital costs for elderly and very elderly groups were found to be 1383.3 ± 529.6 USD and 2167 ± 1213 USD, respectively (p < 0.05). Hospital cost for control group was 120.7 ± 90.3 USD. Hospital cost for control group was significantly lower than for groups 1 and 2 (p < 0.001) (Table 2).

Causes of mortality

The main causes of death were sepsis (61 vs. 63 %), cardiovascular problems (23 vs. 22 %), and miscellaneous (16 vs. 15 %) in elderly and very elderly subjects, respectively (p > 0.05).

Related factor of AKI-DO

There was no association between serum creatinine and age (r = 0.043; p = 0.379). There was positive correlation between serum creatinine and serum potassium level, duration of hospital stay, number of comorbid diseases, presence of infection, need for hemodialysis, need for ICU, mortality, NSAID, ACEI, ARB, spironolactone, loop diuretics and contrast agents (r = 0.368, r = 0.281, r = 0.688, r = 0.783, r = 0.807, r = 0.731, r = 0.406, r = 0.578, r = 0.675, r = 0.876, r = 0.767, r = 0.403, r = 0.566, respectively, p < 0.001 for all).

Risk factors for AKI-DO

Risk factors for AKI-DO for elderly patients were as follows: NSAID (OR: 6.839, 95 % CI = 4.392–10.648), ACEI (OR: 7.846, 95 % CI = 5.161–11.928), ARB (OR: 6.466, 95 % CI = 4.813–8.917), contrast agents (OR: 8.850, 95 % CI = 5.857–13.372), HT (OR: 4.244, 95 % CI = 2.729–6.600), DM (OR: 2.303, 95 % CI = 1.411–3.761), heart failure (OR: 3.647, 95 % CI = 2.276–5.844), presence of infection (OR: 3.149, 95 % CI = 1.696–5.845) (p < 0.001 for all).

Age and sex were not independent risk factors for AKI-DO (p > 0.05). Risk factors for AKI-DO are shown in Table 3. Risk of AKI-DO due to specific substance combinations is shown in Table 4. Use of ACEI, ARB, NSAID, loop diuretics, spironolactone, radiocontrast agents increases risk of AKI-DO more in the presence of comorbid diseases like heart failure, HT, DM. Risk of AKI-DO in a diabetic patient for the use of ACEI, ARB, spironolactone, NSAID, radiocontrast agents or loop diuretics was as follows: OR: 20.25 (95 % CI = 8.89–82.11), OR: 26.83 (95 % CI = 4.92–146.15), OR: 21.54 (95 % CI = 2.46–5.84), OR: 14.50 (95 % CI = 5.16–30.35), OR: 12.50 (95 % CI = 4.88–31.99), OR: 3.34 (95 % CI = 5.63–9.93), respectively. Risk of AKI-DO in a patient with heart failure for the use of ACEI, ARB, spironolactone, NSAID, radiocontrast agents or loop diuretics was as follows: OR: 3.40 (95 % CI = 1.62–7.10), OR: 4 (95 % CI = 0.68–23.51), OR: 2.40 (95 % CI = 1.42–6.10), OR: 3.60 (95 % CI = 0.45–28.56), OR: 1.80 (95 % CI = 1.62–5.10), OR: 3.40 (95 % CI = 1.62–7.10), respectively. Risk of AKI-DO in a patient with hypertension for the use of ACEI, ARB, spironolactone, NSAID, radiocontrast agents or loop diuretics was as follows: OR: 24.15 (95 % CI = 6.59–44.50), OR: 2 (95 % CI = 1.07–3.71), OR: 3.19 (95 % CI = 1.250–2.750), OR: 3.59 (95 % CI = 1.75–4.14), OR: 3.69 (95 % CI = 2.75–5.14), OR: 2.69 (95 % CI = 1.75–4.14), respectively. All of the results are shown in Table 5.

Table 3 Risk factors for AKI-DO
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Table 4 Risk factors of specific substance combinations use for AKI-DO
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Table 5 Risk for AKI-DO due to specific use of substances in the presence of specific diseases
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Mortality risk at the end of 20th day after discharge was 0.519 times high. Mortality risk for patients with AKI-DO was increased at the end of 6th month after discharge (HR 1.721, 95 % CI: 1.451–2.043, p < 0.001). Baseline cumulative hazard function is shown in Table 6.

Table 6 Baseline cumulative hazard function
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Discussion

Despite significant advances in healthcare technology over the past few years, the incidence of AKI-DO in elderly (65–75 year) and very elderly (>75 year) appears to be on increase. Although there are studies about AKI-DO in general population, data for elderly population are still insufficient. Retrospective studies which were held for AKI-DO in elderly might lead to inadequate or misleading data for short- and long-term clinical results of AKI-DO. Our study differs as it has a prospective design.

Incidence of AKI was 13.6/1000 patients/year for subjects aged 66–69 and 46.9/1000 patients/year for subjects aged older then 85 years [9]. Not enough studies have been carried out to find out incidence of AKI-DO. Furthermore, no study about clinical characteristics, hospital cost and outcome of AKI-DO has been published in our country.

We found the incidence of AKI-DO higher than the previously reported ones [10–12]. This may be related to the different risk factors among different populations.

Few studies in the published literature thoroughly attribute to the cause of AKI. Most common cause of AKI in elderly is acute tubular necrosis (53 %) [13]. However, Kaufman et al. reported that prerenal reasons were the most common etiologic factors of AKI-DO in African-Americans. Gastrointestinal diseases and inadequate oral intake were the most common prerenal factors [10]. In our study, prerenal AKI was the most common type of AKI in both groups. The most striking causes for prerenal AKI were decreased oral intake, vomiting and diarrhea.

Heart failure, CKD, renovascular disease, osteoarthritis and surgical operations are more frequent in elderly people. Therefore, possibility of exposure to iodinated radiocontrast agents, renin–angiotensin system blockers or NSAID is higher [14]. These agents may negatively affect renal hemodynamics and cause a risk for the development of AKI [15,

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Authors and Affiliations

  1. Division of Nephrology, Department of Internal Medicine, School of Medicine, Mersin University, 33079, Mersin, Turkey

    K. Turgutalp, S. Bardak, S. Demir & A. A. Kiykim

  2. Division of Nephrology, Department of Internal Medicine, School of Medicine, Istanbul Bahcesehir University, Istanbul, Turkey

    M. Horoz

  3. Silifke School of Applied Technology and Management, Department of Business Information Management and Biostatistic, Mersin University, Silifke, Mersin, Turkey

    İ. Helvacı

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Turgutalp, K., Bardak, S., Horoz, M. et al. Clinical outcomes of acute kidney injury develo** outside the hospital in elderly. Int Urol Nephrol 49, 113–121 (2017). https://doi.org/10.1007/s11255-016-1431-8

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