Epidemiology and Outcome of Acute Kidney Injury in Critical Care Unit: A Prospective Observational Study

Introduction

Acute kidney injury (AKI), characterized by an abrupt reduction in kidney function, is a global burden with short and long-term consequences.¹ AKI affects 30–60% of patients admitted to the critical care unit (CCU) and is associated with increased morbidity and mortality.²

Data on AKI in the CCU population from India are limited. The largest study on AKI in India has been conducted specifically on community-acquired AKI (CA-AKI).³ There are only a few single-center Indian studies on AKI in critically ill patients.^4-7 No data exist from the eastern zone of India regarding the profile and long-term outcomes of AKI in patients admitted to CCU, beyond hospital discharge.

Regional data are essential for understanding unique etiologies, tailoring prevention and management with proper resource allocation. To the best of our knowledge, this is the first study from Eastern India addressing AKI in patients admitted to the CCU.

This study prospectively evaluated the epidemiology, clinical profile, risk factors, and both short- and long-term outcomes of AKI in a tertiary care CCU setting. Additional attempts have been made to assess possible risk factors for AKI outcome.

Materials and Methods

This hospital-based single-center prospective observational study was conducted over 18 months (from February 2023 to July 2024) in the CCU of IPGME&R, SSKM Hospital, Kolkata, one of the largest tertiary care centers in eastern India after approval by the Institutional Ethics Committee (IPGME&R/IEC/2023/815; 25/09/2023). This study has been conducted in a mixed CCU that cares for predominantly medical, but also surgical and other critically ill patients.

The primary aim of this study was to analyze the incidence, clinical profile, and both short-term and long-term outcomes of AKI, including mortality and long-term renal recovery of patients with AKI in a mixed CCU setting. The goal is to better understand the various factors associated with patient and renal outcomes.

Patients > 18 years, admitted to CCU, with new onset renal dysfunction were included by the consecutive sampling method. Patients with pre-existing CKD, structural anomalies (e.g., congenital anomaly of the kidney and urinary tract, polycystic kidney disease), and age <18 years or >75 years were excluded. We followed strict inclusion/ exclusion criteria to avoid sampling/ selection bias to the best of our abilities.

The subjects underwent uniform evaluation. Baseline clinical data included demographics, clinical history, comorbidities, etiology, and severity of AKI, detailed physical examination, monitoring of urine output, and assessment of fluid balance. A Foley catheter connected to a urinometer and recorded hourly was the primary method of monitoring urine output. Fluid balance was calculated from standardized CCU charts as total cumulative fluid intake (Lt) - total collective fluid output (Lt) over a 24-hour cycle. Laboratory parameters included complete blood count (CBC), urea, creatinine, sodium, potassium, arterial blood gas (ABG), C-reactive protein (CRP), procalcitonin, and liver function test (LFT) with serum albumin. Although serum creatinine monitoring was done as per the clinical decision of the Intensivist, the value was recorded at prespecified points in time as per the study protocol. Infective work-up included culture of tissue samples, including blood and urine. Imaging studies included chest X-ray, ECG, USG abdomen, 2-D Echocardiography, and IVC assessment. Detailed recording of treatment interventions includes medication history, IV fluids, vasopressor support, mechanical ventilator support, dialysis requirements, dialysis modality, number of sessions, and others. Data were collected on days 0, 3, 7, at discharge, day 30, and day 180. The study design is shown in Figure 1.

Close

Figure 1:

Study flow design.

Export to PPT

The primary or short-term outcome was defined as discharge rate from the hospital and in-hospital mortality; whereas the secondary or long-term outcome was defined as renal recovery and dialysis dependency at 6 months.

Pertinent definitions related to the study are described in the Supplementary Methods. Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for classifying and managing acute kidney injury (AKI) was followed for relevant definitions in this study.⁸

Results

Of 994 patients admitted to the CCU during the study period, 350 with AKI were included; the incidence was 35%. The age-wise distribution is described in Table 1. The mean age of study participants was 45.1 years, with male predominance [n=210, (60.0%)], and 56% were from an urban area. The mean duration of CCU stay was 15.3 days. Prevalent comorbid diseases included hypertension (HTN) (39.4%), diabetes mellitus (DM) (35.7%), ischemic heart disease (IHD) (11.4%), and hypothyroidism (10.3%).

At baseline, the prevalence of anemia, leucocytosis, and leukopenia, were 80%, 60%, and 20%, respectively. The average baseline creatinine was considered as 2.3 mg/dL, the lowest average creatinine value during the hospital stays. Pneumonia (45.7%) and ascites (34.0%) were the most common findings in Chest X-ray and USG, respectively.

The clinical spectrum of AKI in study subjects has been shown in Table 1. Hospital-acquired, non-oliguric, and sepsis-related (61.71%), followed by post-operative (17.71%) AKI, were the most common. Positive fluid balance on days 0, 3, and 7 were detected in 95.24%, 82.31%, and 92.86% of subjects, respectively. Among culture-positive cases (26.8%), the majority had growth of MDR E. Coli (22.3%), A. Baumannii (17.02%), Pseudomonas (9.57%), and MRSA (7.45%). The spectrum of renal biopsy findings (n=51) have been depicted in Table 1.

Therapy related to critically ill patients, such as intravenous fluid, ventilator support, and kidney replacement therapy (KRT), have been shown in Table 1. In our study, KRT was initiated at the discretion and clinical judgement of the nephrologist and intensivist.

Short-term outcome was discharge rate from the hospital (n=203, 58.0%) and in-hospital mortality (n=147, 42.0%). About 5.1% (n=18) of subjects were dialysis dependent at the time of discharge. Hospital mortality was mostly caused by sepsis (n=85, 24.3%), Acute Respiratory Distress Syndrome (ARDS) (n=49, 14.0%), cardiogenic shock (n=22, 6.3%), and other causes (head injury, acute liver failure, cerebrovascular accident (CVA), acute exacerbation of chronic obstructive pulmonary disease (AECOPD), hypovolemic shock, dengue shock syndrome, meningoencephalitis, metastatic cancer). At 6 months, the outcomes were complete recovery (CR), 34.3% (n=120); partial recovery (PR), 26.9% (n=94); no recovery (NR), 38.9% (n=136); and dialysis dependency, 7.1% (n=25). At 6 months, mortality rose to 46% (n=161).

Age > 60 yrs, and subjects from urban areas had relatively higher in-hospital mortality. As shown in Table 2, the presence of underlying HTN, positive sepsis work-up, moderate to severe AKI, HA-AKI, biopsy-proven TMA, requirement of kidney replacement therapy (KRT), mechanical ventilator and inotrope support are significantly associated with increased in-hospital mortality.

The disease-specific outcome of AKI has been demonstrated in Supplementary Table 1. Post-operative AKI showed a better outcome than AKI due to medical illness.

Of 19 subjects with obstetric AKI, patients requiring intermittent hemodialysis (IHD), slow low-efficiency dialysis (SLED), and Plasma Exchange (PLEX) were 16 (84.21%), 3 (15.78%), and 8 (42.10%), respectively; 16 were discharged (84.21%) and 3 (15.78%) died; 11 patients with obstetric AKI underwent renal biopsy. Compared to biopsy-proven acute tubular necrosis (ATN) (n=4), acute cortical necrosis (ACN) (n=3) and thrombotic microangiopathy (TMA) (n=4) had poor long-term renal outcome and it increased with dialysis dependency at 6 months.

Overall, factors significantly associated with poor long-term renal outcome and dialysis dependency at 6 months included a younger population, associated comorbid diseases (diabetes, HTN, hypothyroid), HA-AKI, severe AKI, RRT requirement, PD, SLED, and ventilator support [Tables 3 and 4].

Association of I.V. fluid with mortality has been shown in Supplementary Table 2. Normal saline was associated with higher mortality than other fluids. Significantly high mortality was observed with noradrenaline (76.2%) and dobutamine (100%), with a p-value of 0.001 for both the vasopressors; with a high rate of NR at 6 months of 53.8% and 28.0% for noradrenaline and dobutamine, respectively. Vasopressin was associated with lower mortality of 28.0% high CR (58%).

Among the dynamic parameters, factors found to be associated with overall poor outcome included high neutrophil, low lymphocyte, high CRP and Procalcitonin value, low serum albumin, and high APACHE II score [Supplementary tables 3, 4 and 5]. High IVC diameter at day 7 is significantly associated with poor short- and long-term outcomes.

Positive fluid balance was associated with high in-hospital mortality [Supplementary files 6 and 7] [Figure 2] and poor long-term renal recovery.

Close

Figure 2:

Day 7 ROC curve fluid balance as outcome predictor.

Export to PPT

This study has detected higher urine protein levels correlating with higher mortality, especially on day 0 [Supplementary table 8].

Outcome of early mortality and dialysis dependence at 6 months in relation to the offending drugs has been depicted in Supplementary Table 9. AKI, AKI associated with drugs like acyclovir, vancomycin, MRA, sulbactam, and SGLT2i are associated with a high percentage of non-recovery of renal function at 6 months. ARBs had a statistically significant protective effect with respect to long-term mortality.

Multivariate logistic regression analysis in Supplementary Tables 10, 11, and 12 explored predictors of renal recovery in terms of CR and PR, hospital mortality, and dialysis dependency at 6 months, respectively. After the multivariate analysis, the presence of sepsis is found to be associated with decreased mortality, which is in contrast to the univariate analysis.

Discussion

This prospective observational study offers a real-world picture of a large spectrum of AKI in a mixed CCU of a developing country. Our findings have highlighted significant factors associated with renal recovery and mortality.

In our study, the incidence of AKI in CCU was 35%, consistent with existing global data.^9,10 In India, there is a variable incidence of AKI in critically ill patients, ranging from 17.3 per person year to the overall incidence of AKI of 20-50%.^11,12 Predominance of AKI in elderly age and male sex in the current study, with a spectrum of underlying comorbid illnesses like HTN, diabetes, and ischemic heart disease, is similar to global and Indian data.^9,13,14 The average CCU stay (15.3 days) exceeds the typical median CCU stay (7-10 days) for patients with AKI, probably due to severe underlying illness.¹⁵

Hospital-acquired AKI (HA-AKI) and moderate to severe AKI were common, frequently linked to the critical condition of patients and severity of underlying disease, similar to other studies.¹³ Sepsis was found to be the most common etiology of AKI in this study. The etiology of AKI varies across different regions of India.^16,17 However, studies from different regions of India have identified sepsis as the predominant etiology of AKI.^4,5 Literature from India has demonstrated a change in the etiologic spectrum of AKI over passage of time, shifting from diarrhea, dehydration, and tropical infection to AKI associated with surgery, sepsis, and nephrotoxic drugs.¹⁸ Prakash et al. compared AKI from the eastern part of India between 1983–1995 and 1996–2008 and documented an increase in sepsis and drug-induced AKI and a decrease in AKI due to obstetrical, surgical, and diarrhea.¹⁹ Regarding microbiological profile, prevalence of MDR E. coli and A. baumani aligns with global trends.⁹ Higher percentage of dialysis requirement (72.0%) in our study compared to global data (4.3%-13.5% of KRT in critically ill patients) is likely due to the high burden of severely ill patients, often with delayed presentation.²⁰

High short-term mortality and a large percentage of long-term no recovery (NR) and dialysis dependency in this study are in concordance with global studies.^9,11 Indian data have documented mortality ranged between 19.6 and 29.2%, in studies that included patients developing AKI due to medical, surgical, and obstetric causes.²¹ Sepsis, ARDS, cardiogenic shock, and metastatic cancer are leading causes of mortality in the current study, like others.^15,22,23

In this study, older populations and male cohorts had high hospital mortality, but better long-term renal outcomes and dialysis dependency. The male population probably had an underlying severe disease, with early detection of renal dysfunction due to larger muscle mass. Influence of age and sex on AKI outcome has been emphasized in the literature, including a study from India by Kher et al.^14,15,24 We observed slightly higher mortality in the rural population, probably due to healthcare access disparities, much like the Indian study by Mahajan et al.²⁵

Our study highlighted the impact of chronic diseases like DM, HTN, and CLD on adverse patient and renal outcomes, like other studies.^26,27 Among comorbid diseases, HTN is found to be significantly associated with higher in-hospital mortality and poor long-term renal outcomes, both in univariate and multivariate analysis. Existing literature documented similar evidence.²⁸

In this study, HAAKI, severe AKI, hypotension, mechanical ventilator support, dialysis requirement, and high APACHE II score, associated with multi-organ failure and severe AKI, were found to be associated with high hospital mortality and poor renal outcome, like other studies.^13,29 Regarding the etiology of AKI, while surgical, snake bite, obstetric, and drug-induced AKI had better outcomes (lower mortality), AKI associated with RTA, people living with HIV/AIDS (PLHA), poisoning, and CVA had higher mortality. The impact of AKI etiology on outcome has been demonstrated in a few studies.³⁰

Despite univariate analysis showing significantly increased mortality associated with sepsis AKI, no such association is documented in multivariate analysis. This is probably explained by adjustments for confounding factors, indicating the severity of the disease. Moreover, early detection and prompt intervention of sepsis AKI might improve outcomes compared to AKI from other causes. This paradoxical finding is sometimes seen in observational studies as confounding factors are controlled, and a more nuanced understanding emerges.³¹

In the current study, biochemical parameters like hyperglycemia, hypoalbuminemia, high inflammatory and infective markers like CRP and procalcitonin, and high urine protein level, probably reflecting persistent renal damage, correlate with poor short-and long-term patient and renal outcomes, like other similar studies.^15,25 Sepsis AKI due to Acinetobacter baumannii, often multidrug-resistant (MDR) and complicating nosocomial infections, exhibited the highest mortality rate, like other studies.^13,15 Adverse patient and renal outcomes associated with TMA, compared to other renal biopsy findings, was supported by other studies.^32,33

Positive fluid balance was found to be significantly associated with higher hospital mortality, worse AKI outcomes, and increased dialysis dependency at 6 months. Studies have shown the impact of fluid balance on AKI outcomes.^33,34 Dilated IVC, being a marker of fluid overload, was associated with increased mortality and dialysis dependency in our study, as noted by Cullaro et al.³⁵

We documented high in-hospital mortality associated with normal saline (NS), dobutamine, and noradrenaline compared to other intravenous fluids and vasopressors. These findings highlight the critical role of choice of intravenous fluids and vasopressors in reducing both short- and long-term mortality in AKI.¹³

Varied effects of drug-associated AKI, like overall poor prognosis of NSAIDs and long-term renal benefit of ACEi, ARBs, and SGLT2i, matched other studies.^4,13,29,30

Our study has some limitations. Generalizability was limited by the single center. Patient heterogeneity and uncontrolled confounding variables may complicate results. Variability in laboratory and clinical data can affect consistency. Selection bias could overrepresent more severe AKI cases.

In conclusion, this study demonstrates that AKI in a mixed CCU has a high incidence. The majority were sepsis-related, severe in nature, and associated with significant mortality and poor long-term renal recovery. Both short- and long-term outcome of AKI in this setting is influenced by various factors like age, sex, underlying chronic illness, etiology, and severity of AKI, biochemical parameters, and fluid balance. Moreover, treatment-related factors like specific types of IV fluids and specific vasopressors, and dialysis requirements also influence short- and long-term AKI outcomes. Sepsis, AKI, and hospital mortality have a complex association when other factors are accounted for.