Acute kidney injury in nonagenarians: clinical characteristics and mortality

Abstract Introduction: Nonagenarians constitute a rising percentage of inpatients, with acute kidney injury (AKI) being frequent in this population. Thus, it is important to analyze the clinical characteristics of this demographic and their impact on mortality. Methods: Retrospective study of nonagenarian patients with AKI at a tertiary hospital between 2013 and 2022. Only the latest hospital admission was considered, and patients with incomplete data were excluded. A logistic regression analysis was conducted to define risk factors for mortality. A p-value < 0.05 was considered statistically significant. Results: A total of 150 patients were included, with a median age of 93.0 years (91.2–95.0), and males accounting for 42.7% of the sample. Sepsis was the most common cause of AKI (53.3%), followed by dehydration/hypovolemia (17.7%), and heart failure (17.7%). ICU admission occurred in 39.3% of patients, mechanical ventilation in 14.7%, vasopressors use in 22.7% and renal replacement therapy (RRT) in 6.7%. Death occurred in 56.7% of patients. Dehydration/hypovolemia as an etiology of AKI was associated with a lower risk of mortality (OR 0.18; 95% CI 0.04–0.77, p = 0.020). KDIGO stage 3 (OR 3.15; 95% CI 1.17–8.47, p = 0.023), ICU admission (OR 12.27; 95% CI 3.03–49.74, p < 0.001), and oliguria (OR 5.77; 95% CI 1.98–16.85, p = 0.001) were associated with mortality. Conclusion: AKI nonagenarians had a high mortality rate, with AKI KDIGO stage 3, oliguria, and ICU admission being associated with death.

Introduction: Nonagenarians constitute a rising percentage of inpatients, with acute kidney injury (AKI) being frequent in this population.Thus, it is important to analyze the clinical characteristics of this demographic and their impact on mortality.Methods: Retrospective study of nonagenarian patients with AKI at a tertiary hospital between 2013 and 2022.Only the latest hospital admission was considered, and patients with incomplete data were excluded.A logistic regression analysis was conducted to define risk factors for mortality.A p-value < 0.05 was considered statistically significant.Results: A total of 150 patients were included, with a median age of 93.0 years (91.2-95.0),and males accounting for 42.7% of the sample.Sepsis was the most common cause of AKI (53.3%), followed by dehydration/hypovolemia (17.7%), and heart failure (17.7%).ICU admission occurred in 39.3% of patients, mechanical ventilation in 14.7%, vasopressors use in 22.7% and renal replacement therapy (RRT) in 6.7%.Death occurred in 56.7% of patients.Dehydration/hypovolemia as an etiology of AKI was associated with a lower risk of mortality (OR 0.18; 95% CI 0.04-0.77,p = 0.020).KDIGO stage 3 (OR 3.15; 95% CI 1.17-8.47,p = 0.023), ICU admission (OR 12.27; 95% CI 3.03-49.74,p < 0.001), and oliguria (OR 5.77; 95% CI 1.98-16.85,p = 0.001) were associated with mortality.Conclusion: AKI nonagenarians had a high mortality rate, with AKI KDIGO stage 3, oliguria, and ICU admission being associated with death.

IntRoductIon
In recent decades, the increase in life expectancy and aging of the population have raised the number of elderly people admitted to hospitals 1 .Among the elderly, the population aged over 80 is the fastestgrowing demographic 2 .Nevertheless, there are still few studies on patients aged over 90 years, and the available data are inconclusive regarding the profile of comorbidities and prognosis in this population 3 .
With aging, different physiological and functional changes occur in the kidneys, such as a reduction in glomerular filtration rate, loss of cortical volume and nephrosclerosis 4 .Advanced age and polypharmacy may be considered risk factors for kidney diseases, and in hospitalized patients, Acute Kidney Injury (AKI) is a prominent condition in the elderly, altering the individual's prognosis [3][4][5] .
Among the elderly, nonagenarians seem to have unique characteristics, comorbidities and clinical outcomes 2,3,5,6 .The incidence of AKI is high in patients in this age group hospitalized for any underlying pathology 3 .However, published studies on AKI in nonagenarians are still insufficient.A recent study conducted in Brazil, including 436 nonagenarians admitted to hospital, identified an AKI incidence of 45%.The mortality rate was 66.8% in patients with AKI, and only 23.8% among those who did not develop AKI (p < 0.001) 6 .The clinical profile of nonagenarian patients who develop AKI is poorly understood, and more data on the subject is needed in order to broaden the scientific basis available to medical professionals.
The aim of this study is to analyze the clinical characteristics and risk factors associated with mortality in a population of nonagenarian patients with AKI admitted to a tertiary hospital.

Study deSign and Patient Selection
Retrospective study of patients who developed AKI between January 2013 and December 2022 at a tertiary hospital (Instituto de Nefrologia Ribamar Vaz -Santa Casa de Misericórdia de Maceió, Maceió, Alagoas, Brazil).All patients assessed by the nephrology team following a consultation referral who presented with AKI during this period were included in a database, totaling 1528 patients.Only patients aged 90 years or older were initially included, with a total of 159 patients.Kidney transplant recipients and individuals with incomplete clinical data were excluded.Only the latest hospital admission was considered.Thus, 150 patients were included for final analysis.All clinical information was collected through electronic medical records.The study was approved by the local research ethics committee (CAAE 67867222.5.0000.5641).

definitionS
AKI was defined using the Kidney Disease Improving Global Outcomes (KDIGO) diagnostic criteria and classification 7 .AKI is defined as an increase ≥0.3 mg/dL in baseline serum creatinine within 48 h, a 1.5 to 1.9-fold increase in baseline serum creatinine (if known or assumed to be that of the last seven days) or a reduction in urine output <0.5 mL/Kg for at least 6 h (KDIGO 1).KDIGO stage 2 is defined as an increase in serum creatinine of 2 to 3 times the baseline value or a reduction in urine output <0.5 mL/Kg for ≥12 h.KDIGO stage 3 is considered if there is an increase in creatinine greater than or equal to 3 times the baseline value, or an increase ≥4 mg/dL, or initiation of RRT, or urine output <0.3 mL/Kg for ≥24 h, or anuria for ≥12 hours.The etiology was defined by the nephrologist who evaluated and registered the patient in the database.If multifactorial AKI was suspected, the nephrologist would determine the main cause and register it.The diagnosis of chronic kidney disease was also defined based on clinical and laboratory data from medical records and evolution during hospitalization.Previous glomerular filtration rate lower than 60 mL/min/1.73m 2 or albuminuria greater than 30 mg/g was used to define CKD, and patients were classified as having AKI superimposed on CKD.KDIGO guidelines were used to classify the stage of CKD.The renal replacement therapy (RRT) method was indicated by the nephrologist who evaluated and recommended treatment, either intermittent hemodialysis, prolonged hemodialysis or continuous therapy (hemodiafiltration).Oliguria was defined as diuresis <400 mL in 24 h.The Charlson Comorbidity Index assesses an individual's 10-year survival based on their age and the presence of 17 comorbidities 8 .

StatiStical analySiS
Statistical analysis was performed using IBM SPSS ® version 20.0.Data were presented as mean ± standard deviation, median (1st and 3rd quartile), and percentage rates.Comparison between variables normally distributed was performed using the Student's t-test, and variables with non-normal distribution were compared using the Mann-Whitney U test.The chisquare test was used to analyze categorical variables.To analyze whether certain variables could affect death in this population, univariate and multivariate analyses were performed using logistic regression.All variables with p < 0.10 in the univariate analysis were included in the multivariate analysis model.Logistic regression data were presented as odds ratios (OR) and 95% confidence intervals (95% CI).A p-value was considered significant when <0.05.
It is important to highlight that although only 10 patients underwent RRT treatment, another 45 patients were discussed for the possibility of initiating therapy.However, RRT was contraindicated because it was considered a futile treatment in 40 patients (88.9%) and due to patient or family refusal in 5 patients (11.1%).Mortality in this group occurred in 43 patients (95.3%).

dIscussIon
Advancing age leads to several clinical and epidemiological differences between young and elderly patients.Even among the elderly, age groups should be considered in the patient's clinical management, since studies have shown differences in clinical profile and outcomes when comparing different age groups among patients aged 60 or older [9][10][11]    In the studied group, there was a high prevalence of CKD patients (40%).Published studies suggest that these patients have a higher incidence of AKI 12 .The primary AKI etiology was sepsis, similar to the over-60s population in other studies 13,14 , followed by dehydration/hypovolemia and heart failure.
In-hospital mortality in nonagenarians with AKI according to published articles ranges from 23% to 70%, depending on mean age, patient severity, comorbidity profile and criteria for defining AKI 3,4,6 .In our study, we observed a mortality rate of 56.7%, similar to other published data, which may be justified by the prevalence of comorbidities and severity of the study group.Although 90% of patients who underwent RRT died, treatment was not a predictor of mortality, possibly due to the small number of patients undergoing the procedure (10 patients).Higher scores on the Charlson Comorbidity Index were not related to mortality in our cohort, and despite the divergence from other data observed in a similar population 15 , the utility of this tool for predicting mortality in advanced age is questionable 16 .
In the surviving group, there was a high prevalence of CKD, KDIGO 1 and dehydration/hypovolemia.Data suggest that CKD patients who develop AKI have a lower risk of death 17 , and are not associated with worse outcomes 3 .In our study, although CKD was more prevalent in the survivor group (50.8%, p = 0.019), it was not identified as a lower risk factor for mortality in the multivariate analysis.Prolonged hospitalizations were not associated with higher mortality in our cohort.This result differs from that published in another Brazilian study that evaluated AKI in nonagenarians 6 .
Only KDIGO 3, ICU admission and oliguria remained as independent risk factors for mortality in multivariate analysis.An independent association with mortality has been demonstrated for all KDIGO stages, with a greater risk at higher stages 6 , as well as a reported relationship between nonagenarians with more severe AKI stages and mortality 3 .In our cohort, only KDIGO 3 had this association, with a threefold higher chance of mortality for the individual.Admission of elderly people with AKI to the ICU was  considered a risk factor for mortality in previously published data 6,18 .Our study demonstrated a twelvefold increased risk for these cases.Some studies on the elderly have described an association of oliguria with an increased risk of death 18,19 .However, this factor has not been evaluated in studies on nonagenarians.
In our analysis, this factor led to an almost sixfold increased risk for mortality.Dehydration/ hypovolemia as a cause of AKI was associated with a lower risk of death.
Published studies report that the need for RRT in elderly people with AKI ranges from 3.5% to 39.5%.This variation may be related to the number of patients with advanced AKI stages in each study [20][21][22][23] .In our study, 55 (36.7%) patients had clinical and/or laboratory indications for RRT initiation prescribed by the medical team.However, in 45 (30%) patients RRT was contraindicated due to treatment futility or family refusal, and only 10 (6.7%) underwent treatment.
A publication that evaluated the outcome of 703 AKI patients, with a mean age of 63.5 ± 14.8 years, and requiring dialysis, reported a mortality rate of 42% 24 .Our study showed a 90% mortality rate in those who underwent RRT, similar to another study that evaluated patients over 90 years of age 6 .RRT was not an independent risk factor for mortality possibly because only 10 patients underwent treatment; thus, we cannot extrapolate the impact of treatment on mortality.The use of RRT in elderly patients, especially those over 90, is a medical practice dilemma, as studies are still searching for precise indication criteria for a survival outcome in those undergoing such an invasive procedure [25][26][27] .
This study has some limitations.It was a singlecenter study, limiting data extrapolation to other centers; it had a retrospective design, restricting the collection of data available in electronic medical records and leading to the exclusion of patients with incomplete data; and also because we only selected the last admission of patients, which may indicate greater severity in this last hospitalization.

conclusIon
The presence of hospitalized nonagenarians is a reality nowadays, and AKI has a high incidence in this group, in addition to being associated with a high mortality rate.In this retrospective analysis, AKI KDIGO stage 3, oliguria, and ICU admission were risk factors associated with death.AKI due to dehydration/hypovolemia was associated with a lower risk of death.Further studies are needed in nonagenarians with AKI to better understand clinical needs and define optimal treatment.

tAble 1
74; p < 0.001), and oliguria (OR 5.77, 95% CI 1.98-16.85;p = 0.001) remained associated with mortality.RRT was not associated with the risk of death in either the univariate or multivariate analysis (Table

tAble 2
Stratified mortality according to clinical and demograPhic variableS

tAble 3 mortality
PredictorS by univariate and multivariate logiStic regreSSion