Clinical profile and outcome of acute kidney injury in a tertiary care center of eastern Nepal [version 1; peer review: awaiting peer review]

Acute kidney injury (AKI) is a global problem and it is encountered both in community and in-hospital patients. AKI has caused very significant damage to the health sector with high morbidity and mortality rates as well as a financial burden to the family. AKI contributes to a 3% incidence of end-stage renal disease (ESRD). Sepsis and hypovolemia-associated ischemia is the most common cause of AKI. AKI has various risk factors, modes of presentation and outcomes. Also, the prevalence varies across the different populations. There is a paucity of data about the clinical profile of AKI in the eastern part of Nepal. This study aims to assess the age, comorbid conditions, the severity of AKI, mode of treatment, and outcome of patients with AKI admitted to the Nobel Medical College and Teaching Hospital, Biratnagar, Nepal. AD.


Introduction
The abrupt and usually reversible decline in glomerular filtration rate (GFR) over days to weeks is defined as acute kidney injury (AKI). 1 This term also highlights that injury to the kidney that does not result in "failure" is also of great clinical significance. The definition has evolved from the Risk, Injury, Failure, Loss, End-stage (RIFLE) criteria in 2004 to the AKI Network (AKIN) classification in 2007. 2,3 In 2012, both were merged resulting in the Kidney Disease Improving Global Outcomes (KDIGO) classification. 4 Accordingly, AKI is diagnosed if serum creatinine increases by ≥0.3 mg/dl within 48 hours or rises ≥1.5 times from the baseline within 7 days, and urine volume <0.5 mL/kg/hr for 6 hours. AKI stages are defined by the maximum serum creatinine or urine output change.
The epidemiology and outcome of AKI differ significantly across the industrialized and underdeveloped worlds. 5 Developing countries account for more than 85% of the worldwide burden of AKI. 6 In Nepal higher burden of community acquired AKI is seen in younger age group. 7 Even a modest type of AKI is linked to higher long-term mortality in ICU survivors, as well as an elevated risk of chronic and end-stage kidney disease and significant cardiovascular events. 8,9 Specific organ system failures occur at varying rates among AKI patients admitted to the ICU, with varying degrees of correlation between individual organ system failures and ICU mortality. qSOFA is very useful tool to access the extent of organ dysfunction seen in critically ill patient with AKI. 10,11 Sequential (Sepsis-related) Organ Failure Assessment score (SOFA) is modified to form qSOFA score. Components of qSOFA comprises of respiratory rate>22 bpm, SBP<100 mmHg, altered Glasgow coma scale (GCS) and one point is allocated to each component. To indicate organ dysfunction, qSFOA score must be ≥2.
qSOFA ≥2 was highly specific for identifying organ dysfunction and mortality (96.1% and 91.3% respectively), but sensitivity was poor (29.7% and 49.1% respectively). 12 Low-and middle income like Nepal lack adequate information, healthcare resources, and patient adherence to the treatment protocol. Additionally, data on AKI is not sufficiently available in the literature. Therefore, this study aimed to assess the clinical profile and short-term outcomes of acute kidney injury in single-center hospitalized patients.

Ethics and consent
Ethical clearance (ref. no. 171/2018) was granted from the ethics and research committee of Nobel Medical College Teaching Hospital, Biratnagar, Nepal on 22 nd June 2018. Written informed consent was obtained from participants and from parents for the participants who were <18 years for the publication of their clinical details.
Procedure This is a cross-sectional analytical study conducted at Nobel Medical College Teaching Hospital, Biratnagar, Nepal from July 2018 to June 2019 AD. The study population was all patients admitted at Nobel Medical College with a diagnosis of AKI. Non-probability convenient sampling method was used. The research team approached all the admitted patients with the diagnosis of AKI. Patients meeting the inclusion and exclusion criteria were recruited.
Inclusion criteria include age >15 years, and all patients admitted in the ICU and ward with a diagnosis of AKI meeting criteria as per KDIGO guidelines 2012.
Exclusion criteria include preexisting chronic kidney disease (CKD) with baseline CKD EPI (chronic kidney disease epidemiology collaboration) eGFR (estimated glomerular filtration rate) <60 ml/min/1.73 m 2 before the onset of illness or dialysis-dependent, suspected or biopsy-proven glomerulonephritis as a cause of AKI and suspected or diagnosed case of heart failure with functional class 3 or 4. eGFR was calculated at time of study to determine if participants were suitable to take part.
Variables assessed in this study were age, gender, duration of hospital stay, comorbidities, cause of AKI, mode of management, and qSOFA score.
As per the hospital data, around 160 patients were annually admitted with the diagnosis of AKI. So, with 20 allowable error, minimum of 140 cases were selected over the study duration.
Continuous variables were expressed as meansAEstandard deviation (SD). Categorical variables were expressed as proportions and compared with the chi-squared test at 95% confident interval where level of significance considered at p≤0.05. Statistical Package for Social Sciences (SPSS) 25 th version was used for analysis.
AKI is defined as any of the following: • An absolute increase in serum creatinine of 0.3 mg/dl or more (26.4 micro-mol/L or more) within 48 hours, or • Increase in serum creatinine to 1.5 times or more from baseline, which is known or presumed to have occurred within the prior 7 days, or • Urine output of less than 0.5 ml/kg per hour for more than 6 hours.

Results
The study was carried out on 192 patients who were admitted with the diagnosis of AKI. 30 The demographic and clinical profiles of the patients are shown in Table 1.  Table 2. In the present study, 143 (74.5%) patients were 60 years or older, and the remaining 49 (25.5%) patients were below 60 years. This signifies that the younger population is also affected in a big proportion. In the study done by Chhetri PK et al. 17 in Nepal Medical College Teaching Hospital, Kathmandu, 64% of patients belonged to the age group 21-60 years which is different than our study and this might be due to the small study sample of 45 in the study by Chhetri PK et al.
In our study, the mean duration of the patient's hospital stay was 8.91AE4.38. Almost 88% of patients had a hospital stay of ≤2 weeks. In a study by Khakurel et al. 14 in Bir Hospital Kathmandu, the mean hospital stay was 13.6 days. In a study done by Patel et al. 18 Northern Railway Central Hospital, New Delhi, India, most patients (approximately 81%) required hospitalization for around or <2 weeks. This variation in in-hospital stay may be due to inclusion criteria, sample size, socioeconomic status, and nutritional status of patients.  20 In a study done by Ghimire et al. 21 among co-morbid conditions, 9.4% of subjects had DM, followed by 3% with COPD. Therefore, the findings of our study are consistent with the finding from the above studies.
In the present study, 71.9% of patients had sepsis as the major cause of AKI followed by hypovolemia in 15.6% and obstructive uropathy in 8.9%.
In a study by Ghimire et al. 21  The result of the maximum stage of AKI during the hospital stay as shown in Table 4 is consistent with the study by Wang et al. 25 whereas it differs from the study by Fuhrman et al. 26  In the present study, 69.8% of patients had complete recovery, 27.1% had partial recovery, and 3.1% had in-hospital mortality. Our findings are consistent with the study by Maskey et al. 19 where 52% showed complete recovery, 37% had partial and 3% had in-hospital mortality.
The score of qSOFA was significantly (x 2 =24, df=6, p=0.01) associated with the outcome of the patient. This association shows that with an increase in the score of qSOFA there is an increase in the number of patients who underwent dialysis. So, an increase in qSOFA score at the time of admission increases the requirement for dialysis. A qSOFA score of ≥2 points indicates organ dysfunction. qSOFA ≥2 was highly specific for identifying organ dysfunction and mortality (96.1% and 91.3% respectively). 28 In our study, there is a significant association at a 5% significance level between mode of treatment and outcome (x 2 =13.97, df=2, p=0.01). This signifies that fewer patients died in conservative treatment compared to hemodialysis. Also, more patients survived with conservative treatment. Our findings are in agreement with two large randomized controlled trials which have also failed to show any significant benefit on mortality even in those with more intensive dialysis. 2,29 However, our findings need to be interpreted with caution as more deaths in the hemodialysis group may simply reflect that they were sicker (i.e. they had a higher AKI stage at the time of admission, had higher qSOFA score, and were more ventilated) than the patients on conservative treatment.

Conclusion
Sepsis is the most common cause of AKI in our study. Most of the patients present late i.e. stage III of AKI. Patients who presented with stage III AKI, had a qSOFA score of 2, and who were ventilated had higher mortality. AKI patients can be treated without doing RRT if the patient's conditions are detected early with judicial investigations. However late stages in AKI have a poorer prognosis even with RRT. Careful monitoring of urine output, serum creatinine, and blood urea should be done in all patients admitted to the hospital especially in critical care to predict AKI. Timely diagnosis will surely improve the outcome and survival chances of patients drastically. This project contains the following extended data: