European Journal of Cardiovascular Medicine

Acute Kidney Injury (AKI) is a clinical syndrome characterized by a rapid reduction in renal function, leading to a decrease in glomerular filtration rate (GFR), accumulation of waste products, and disruption of fluid and electrolyte balances [1]. In the intensive care unit (ICU) setting, where patients are often critically ill with multiple organ dysfunctions, the incidence of AKI is alarmingly high, reported in up to 67% of ICU admissions [2]. The implications of AKI are profound, not only because of its association with increased morbidity and mortality but also due to its potential to transition into chronic kidney disease (CKD) or end-stage renal disease (ESRD) [3].

The pathophysiology of AKI is complex, involving pre-renal, intrinsic renal, and post-renal mechanisms. Pre-renal AKI, the most common type in ICU settings, is often precipitated by hypovolemia, hypotension, or conditions leading to reduced renal perfusion like sepsis or heart failure [4]. Intrinsic renal AKI can result from direct damage to the renal parenchyma due to ischemia or nephrotoxic agents, whereas post-renal AKI arises from obstructions in the urinary tract. Among these, septic AKI stands out as a significant concern, with sepsis being a leading cause of AKI in ICU, contributing to a significant proportion of cases due to its effects on renal hemodynamics and inflammation [5].

The risk factors for developing AKI in ICU patients are multifaceted. Age is a potent risk factor, with older adults being more susceptible due to age-related declines in renal

reserve [6]. Co-morbid conditions such as diabetes mellitus, hypertension, and pre-existing CKD amplify this

risk, with CKD patients having nearly a fourfold increased risk of AKI [7]. The nature of ICU treatments, including the administration of nephrotoxic drugs (like aminoglycosides, radiocontrast agents), the need for vasopressors due to hemodynamic instability, and surgical interventions, particularly those involving cardiopulmonary bypass, all contribute to the risk of AKI [8].

Management of AKI in ICU settings is centered on identifying and reversing the underlying cause promptly. Fluid resuscitation is crucial for pre-renal AKI, aiming to optimize renal perfusion. However, careful management is required to avoid fluid overload, which can exacerbate renal injury. Pharmacological interventions include the judicious use of diuretics for managing fluid balance, although they do not alter the course of AKI but can aid in symptom management [9]. For cases where conservative management fails or in scenarios of severe metabolic disturbances or fluid overload, renal replacement therapy (RRT) becomes indispensable. Continuous Renal Replacement Therapy (CRRT) is often preferred in ICU for its ability to provide stable hemodynamics, especially in patients with multi-organ failure [10].

The outcomes of AKI in ICU patients are variable and depend on several factors including the severity of AKI, the patient's baseline renal function, and the presence of other organ dysfunctions. Even after recovery from an acute episode, patients are at an elevated risk for developing CKD, which underscores the long-term implications of AKI. This transition from acute to chronic renal disease has been well-documented, highlighting the need for long-term follow-up and management strategies post-ICU [3]. Furthermore, AKI significantly impacts healthcare resources, with increased ICU and hospital stay durations, and higher costs associated with treatment and follow-up care.

Recent research has focused on early detection and prevention strategies for AKI. Biomarkers like neutrophil gelatinase-associated lipocalin (NGAL), cystatin C, and kidney injury molecule-1 (KIM-1) have been investigated for their ability to predict AKI before significant rises in serum creatinine, potentially allowing for earlier intervention [5]. Moreover, preventive strategies involve optimizing hemodynamic stability, minimizing nephrotoxic exposure, and considering the timing and type of surgical procedures in patients at risk.

AKI in ICU settings remains a critical clinical challenge with significant implications for patient outcomes. Understanding its risk factors, mechanisms, and effective management strategies is crucial. Continued research into novel biomarkers, therapeutic modalities, and preventive measures holds promise for reducing the burden of AKI and improving survival rates and quality of life for ICU survivors. The complexity of AKI in critical care necessitates a multi-disciplinary approach, integrating insights from nephrology, critical care medicine, and pharmacology to tailor interventions to individual patient profiles.

AIMS

The aim of this study was to investigate the risk factors, treatment modalities, and outcomes of acute kidney injury (AKI) in patients admitted to the intensive care unit (ICU). The objectives included determining the different causes and risk factors associated with AKI in ICU settings, evaluating the severity of the disease, and assessing the effectiveness of management strategies employed for AKI. Additionally, the study sought to understand the correlation between the presence of comorbidities and the outcomes of AKI, focusing on recovery rates, the necessity for renal replacement therapy (RRT), and mortality.

Study Design

This investigation was conducted as a prospective cohort study over a duration of 16 months in the ICU of a tertiary care hospital. The study design was chosen to allow for the detailed observation of patient outcomes over time and to analyze the impact of various interventions on AKI.

Participants

Patients were included if they were 18 years of age or older and met the Kidney Disease: Improving Global Outcomes (KDIGO) criteria for AKI upon admission or during their ICU stay. The AKI diagnosis was based on an increase in serum creatinine by 0.3 mg/dL or more within 48 hours, or an increase to 1.5 times baseline within the prior seven days, or urine volume less than 0.5 mL/kg/h for at least 6 hours.

Exclusion criteria were stringent to ensure the study's focus remained on acute rather than chronic conditions. Patients were excluded if they had a diagnosis of end-stage renal disease (ESRD) prior to ICU admission, if they were already on dialysis, or if there was incomplete data regarding their renal function or treatment course. This exclusion was pivotal to avoid confounding the results with pre-existing chronic renal failures or incomplete medical histories.

Sample Size

The sample size was determined using an expected incidence rate of AKI in ICU from previous literature, aiming for a power of 80% to detect a significant difference in outcomes with an alpha level of 0.05. Based on these parameters, a sample of 100 patients was deemed sufficient to achieve the study's objectives, allowing for meaningful statistical analysis without inflating the study beyond practical and ethical limits.

Data Collection

Data collection was comprehensive, involving demographic information, clinical parameters at admission (including vital signs, medical history, and baseline renal function), and ongoing assessments during the ICU stay. This included daily monitoring of serum creatinine, urea, electrolytes, and urine output. Details on therapeutic interventions, such as fluid management, medications administered (including diuretics and nephrotoxic agents), and the use of RRT, were meticulously recorded.

The study also gathered data on patient outcomes, which included recovery status (improvement or persistent renal dysfunction), complications like hyperkalemia or volume overload, need for RRT, length of ICU stay, and mortality. All data were entered into a secure database, ensuring patient confidentiality and data integrity.

Statistical Analysis

Statistical analysis was performed using descriptive statistics for baseline characteristics, with means and standard deviations calculated for continuous variables, and frequencies and percentages for categorical data. To evaluate associations between categorical variables, such as the presence of comorbidities and outcomes like the need for RRT, Chi-square tests were employed. A p-value less than 0.05 was considered statistically significant. The study also calculated odds ratios where applicable to assess the strength of associations between risk factors and outcomes.

Ethical Considerations

The study received approval from the institutional ethics committee, and informed consent was obtained from all participants or their legal representatives. All procedures adhered to the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2000.

Through this detailed methodology, the study aimed to provide a clear picture of AKI in an ICU setting, highlighting the interplay of risk factors, treatment approaches, and patient outcomes.

The study involved 100 participants admitted to the ICU with AKI, classified according to KDIGO criteria. The age distribution of the study participants showed a mean age of 48 ± 15.7 years, with ages ranging from 22 to 77 years. The breakdown of age groups was as follows: 15% were aged 20-29, 18% were 30-39, 23% were 40-49, 25% were 50-59, 10% were 60-69, and 9% were 70-79 years old.

In terms of gender distribution, males were predominant with 74% (n=74) of the participants, compared to 26% (n=26) females. This gender disparity was consistent across the analysis of various aspects of AKI in the ICU.

The contributing factors to AKI in the study population included hypovolemia in 45% (n=45) of cases, predominantly due to acute gastroenteritis. Other significant factors were drug-induced AKI in 17% (n=17), septic shock in 15% (n=15), cardiogenic shock in 13% (n=13), hepatorenal syndrome in 8% (n=8), and miscellaneous causes in 2% (n=2) of the cases.

The etiological classification of AKI showed that pre-renal causes were the most common, affecting 82% (n=82) of the patients, followed by renal causes in 16% (n=16), and post-renal causes in only 2% (n=2). This distribution underscores the significant role of systemic conditions leading to reduced renal perfusion in ICU settings.

Regarding associated comorbidities, 30% (n=30) of the participants had no pre-existing conditions. Among those with comorbidities, Type 2 Diabetes Mellitus was observed in 18% (n=18), hypertension in 12% (n=12), ischemic heart disease in 12% (n=12), chronic liver disease in 10% (n=10), and chronic obstructive pulmonary disease in 9% (n=9).

In the treatment modality, 65% (n=65) of the patients managed without Renal Replacement Therapy (RRT), while 35% (n=35) required RRT. This decision was influenced by various factors, including the severity of AKI and the presence of comorbidities.

The outcomes of AKI in the ICU revealed that 92% (n=92) of the patients improved, while there was an 8% (n=8) mortality rate. Further analysis of biochemical markers indicated a decreasing trend in serum creatinine and urea levels from admission to discharge or death. On day one of ICU admission, the mean serum creatinine was 4.82 mg/dL (standard deviation not specified, range not specified), which reduced to 3.86 mg/dL by the day of discharge or death. Similarly, mean serum urea levels decreased from 144.84 mg/dL (SD 103.68, range 30-401 mg/dL) on day one to 72.15 mg/dL (SD 58.78, range 10-275 mg/dL) at discharge or death.

When comparing biochemical markers across different types of AKI, pre-renal AKI showed mean creatinine levels of 4.56 ± 2.91 mg/dL on day one, dropping to 3.80 ± 1.57 mg/dL at discharge or death. Renal AKI had higher initial creatinine at 5.91 ± 3.17 mg/dL, reducing to 4.08 ± 3.17 mg/dL. Post-renal AKI had the highest initial creatinine at 6.00 ± 4.95 mg/dL, which decreased to 4.40 ± 5.09 mg/dL. Urea levels followed a similar pattern, with pre-renal AKI showing a decrease from 135.10 ± 100.5 mg/dL to 63.90 ± 53.06 mg/dL, renal from 186.40 ± 108.50 mg/dL to 106.10 ± 69.40 mg/dL, and post-renal from 187.00 ± 1.66 mg/dL to 117.50 ± 102.50 mg/dL.

Statistical analysis of age and RRT requirement indicated that patients who required RRT were significantly older, with a mean age of 59.71 ± 8.85 years, compared to 42.31 ± 15.23 years for those not requiring RRT (p < 0.0001). Gender distribution in relation to RRT showed that 26 males and 9 females received RRT, with a significant p-value of 0.00056 for males and <0.0001 for females.

The relationship between comorbidities and RRT usage was also statistically significant. Patients with diabetes mellitus, hypertension, ischemic heart disease, and COPD were more commonly found among those requiring RRT with p-values of 0.01795, <0.0001, <0.0001, and <0.0001 respectively, while chronic liver disease was more prevalent among those not requiring RRT (p < 0.0001).

Table 1: Demographics and AKI Characteristics

Table 2: Comorbidities and Treatment Modalities

Table 3: Biochemical Markers Trends

Table 4: Comparison by AKI Type

Table 5: Patient Outcomes and Treatment Association

The study provides a comprehensive examination of acute kidney injury (AKI) in ICU settings, revealing several key insights into risk factors, treatment modalities, and outcomes. The predominance of male participants (74%) in this study aligns with some existing literature which suggests that males might be at a higher risk for AKI in critical care settings [11]. However, the gender distribution in our study contrasts with others where no significant gender disparity was observed, highlighting the need for further investigation into gender-specific risk factors [12].

The mean age of 48 ± 15.7 years and the significant association between age and the need for RRT (p < 0.0001) corroborates findings from Hobson et al., where older age was a strong predictor for requiring RRT, with odds ratios escalating with age [13]. Our study's finding of a 59.71 ± 8.85 year mean age for patients requiring RRT is consistent with these observations, underscoring age as a critical factor in AKI severity and management.

Hypovolemia, identified as the leading contributor to AKI in 45% of cases, is in line with the findings from a large cohort study where hypovolemia was responsible for a significant portion of AKI cases in ICUs [14]. This emphasizes the importance of fluid management in preventing and treating AKI. Drug-induced AKI, affecting 17% of our cohort, mirrors the concerns raised by multiple studies regarding the nephrotoxic potential of pharmacological interventions in critically ill patients [15].

The predominance of pre-renal AKI (82%) in our study is consistent with the literature, where pre-renal causes are

Often reported as the most common in ICU settings due to factors like sepsis, cardiac dysfunction, or volume depletion [16]. However, our observed percentages for renal (16%) and post-renal (2%) AKI differ from some studies where renal causes might be more prevalent, possibly due to variations in patient populations or ICU practices [17].

The association between comorbidities and the need for RRT, with significant p-values for conditions like diabetes mellitus (p=0.01795) and hypertension (p<0.0001), aligns with epidemiological data suggesting that these conditions are major risk factors for both the development and progression of AKI [18]. Notably, our finding of a higher prevalence of chronic liver disease (CLD) among those not requiring RRT (p<0.0001) diverges from some studies where CLD is associated with worse renal outcomes, possibly reflecting differences in the severity or management of liver disease in our cohort [19].

The biochemical markers trends observed in our study, with a significant reduction in both serum creatinine and urea from admission to discharge, suggest effective management or recovery processes. This decrease is more pronounced in pre-renal AKI compared to renal or post-renal types, which might reflect the potentially reversible nature of pre-renal injuries when addressed promptly [20].

The high improvement rate (92%) and relatively low mortality (8%) in our study are encouraging, particularly when compared to studies reporting higher mortality rates in ICU settings with AKI, which can exceed 50% in certain populations [21]. This discrepancy might be attributed to differences in patient severity, ICU resource availability, or the timing and type of interventions employed.

However, while our study shows a favorable outcome in terms of recovery from AKI, the transition from AKI to chronic kidney disease (CKD) remains a significant concern. Studies have shown that even after apparent recovery, patients with AKI are at an increased risk of long-term renal impairment [22]. Therefore, the long-term follow-up of these patients is crucial to understand the full spectrum of AKI's impact.

This study adds to the body of evidence on AKI in ICU patients, highlighting the importance of early identification and management of risk factors, particularly through fluid management and caution with nephrotoxic agents. The findings also underscore the need for tailored approaches to AKI based on patient demographics and comorbidities, which might influence the likelihood of requiring RRT and the prognosis of the renal injury.

This study has underscored the critical role of demographics and specific risk factors in the development and management of AKI in ICU settings. The predominance of male patients (74%) and the association of older age with the need for RRT (mean age of 59.71 years for RRT patients vs. 42.31 years for non-RRT, p < 0.0001) suggest that these factors should be considered in risk stratification and treatment strategies. Hypovolemia being the most common contributing factor at 45% highlights the importance of meticulous fluid management in ICU care.

The management of AKI with a significant portion of patients not requiring RRT (65%) indicates that conservative management can be effective for many, yet the 35% who did require RRT reflect the severity of AKI in some patients. The high improvement rate (92%) and relatively low mortality (8%) are encouraging, although long-term follow-up is necessary to assess the transition to chronic kidney disease, considering the literature points to a 20-30% risk of progression to CKD following AKI episodes [22].

The findings advocate for the development of protocols focusing on early detection, prevention, and precise management tailored to patient-specific risk profiles. Further research should explore the long-term implications of AKI, particularly how different AKI etiologies and treatment modalities affect renal recovery and patient outcomes.

In conclusion, while the immediate outcomes in this cohort were favorable, the study emphasizes the need for a holistic approach in managing AKI in ICU patients, considering not only the acute phase but also the potential for long-term renal consequences.

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