ABBREVATIONS

AKI - Acute Kidney Injury

ICU - Intensive Care Unit

CKD - Chronic Kidney Disease

sCr - Serum Creatinine

UO - Urine Output

KDIGO - Kidney Disease Improving Global Outcomes

AKD - Acute Kidney Diseases

RIFLE - Risk, Injury, Failure, Loss of function, End-stage renal disease

AKIN - Acute Kidney Injury Network

PICU - Pediatric Intensive Care Unit

GFR - Glomerular Filtration Rate

NO - Nitric Oxide

RAAA - Renin-Angiotensin-Aldosterone Axis

RBF - Renal Blood Flow

RVR - Renal Vascular Resistance

CT - Computed Tomography

NSAID - Non-Steroidal Anti-Inflammatory Drug

TLS - Tumor Lysis Syndrome

SOFA - Sequential Organ Failure Assessment

FINNAKI - Finnish Acute Kidney Injury

WBC - White Blood Cell

RRT - Renal Replacement Therapy

ARF - Acute Renal Failure

MV - Mechanical Ventilation
HRQoL - Health-Related Quality of Life

AKIC - Acute Kidney Injury- Chronic Kidney Disease

ESRD - End-Stage Renal Disease

LOS - Length of Stay

NIV - Non-Invasive Mechanical Ventilation

OR - Odds Ratio

CI - Confidence Interval

APACHE II - Acute Physiology and Chronic Health Evaluation II

SPSS - Statistical Package for Social Sciences

INTRODUCTION

Acute kidney injury (AKI) poses a significant clinical challenge in intensive care units

(ICUs), manifesting with a broad spectrum of clinical presentations and associated with high

morbidity and mortality rates1. AKI is a syndrome with various etiologies, followed by

numerous comorbidities, which makes predicting its outcome very complicated. AKI often

occurs in the older population of patients with pre-existing chronic kidney disease (CKD),

and it is associated with increased risk for dialysis2. Acute kidney injury (AKI) is defined as

a sudden reduction of renal function, increase of serum creatinine (sCr), and/or decrease of

urine output (UO) and is a common complication in intensive care unit (ICU) patients 3. The

clinical guidelines from Kidney Disease Improving Global Outcomes (KDIGO) define AKI

as a subgroup of acute kidney diseases (AKD) and disorders, and classify AKI according to

severity (stages) and cause, which impacts both prognosis and management4. According to

the risk, injury, failure, loss of function, and end-stage renal disease (RIFLE) criteria,11

AKI is defined by serum creatinine levels and urine output5. Although small changes in

serum creatinine or acute reduction in urine output can be used in the diagnosis of AKI, these

changes are often evident after the chance of effective management for renal protection has

already passed6.

Despite advancements in medical care, the incidence of AKI continues to rise, attributed in

part to demographic shifts, increased disease severity, and complex interventions7. Notably,

AKI often occurs in older patients with pre-existing chronic kidney disease (CKD), further

exacerbating the risk of adverse outcomes, including the need for dialysis8. Recognizing the

severity and multifactorial nature of AKI, various risk factors associated with AKI-related

mortality have been identified, including advanced age, vasopressor use, and mechanical

ventilation, sepsis emerges as a predominant contributor, accounting for approximately half

of all AKI cases, particularly in the ICU setting1. Recent evidence suggests that septic AKI

may present with distinct pathophysiological features, highlighting the need for tailored

approaches to management and prognostication2.

Despite the significant burden of septic AKI on patient outcomes, there remains a gap in

understanding the clinical characteristics, profile, and renal function outcomes compared to

non-septic AKI patients. Existing studies often focus on outcomes among dialysis-dependent

patients or overlook those not requiring ICU care9-11. This underscores the importance of

comprehensive research to elucidate the unique challenges and prognostic factors associated

with septic AKI.

The clinical implications of septic AKI extend beyond immediate mortality, encompassing

prolonged hospital stays, increased treatment costs, worsened prognosis, and heightened risk

of CKD development12. With the "0 by 25" initiative aiming to eradicate untreated AKI-

related deaths by 2025, there is a pressing need to enhance the understanding of septic AKI to

inform targeted interventions and improve patient outcomes13.

This study seeks to address these knowledge gaps by comprehensively evaluating the risk

factors and outcomes of AKI in septic and non-septic patients admitted to ICUs. By

examining clinical characteristics, prognostic indicators, and renal function outcomes, to

enhance the understanding of septic AKI's unique challenges and inform evidence-based

strategies to mitigate its impact on patient morbidity and mortality. Ultimately, this research

endeavor holds the potential to inform evidence-based interventions aimed at improving the

management and outcomes of AKI in ICU populations.

AIMS AND OBJECTIVES

AIM:

● To determine risk factors and compare outcomes in patients presenting with AKI

in septic versus non-septic patients admitted to medical intensive care units.

OBJECTIVES:

● To determine demographics including age, gender, primary diagnosis, and co-

morbidities of adult patients with AKI in medical intensive care units.

● To classify adult medical ICU patients based on the AKIN criteria (Acute Kidney

Injury Network criteria).

● To estimate the proportion and occurrence of various risk factors in these patients

leading to AKI.

● To evaluate the clinical outcomes and morbidity associated with AKI.

REVIEW OF LITERATURE

Acute kidney injury (AKI) is a common complication amongst critically ill patients and has

an important modifying effect on mortality, kidney recovery, and resource utilization 14-16.

Sepsis is the most common predisposing factor for the development of AKI15. Septic AKI

patients generally have a poorer prognosis when compared to AKI of non-septic origin9,10,17.

Experimental data have suggested there may be important pathophysiologic differences

between septic and conventional ischemic/toxic-induced AKI18-20. Considering these

differences, discriminating septic and non-septic AKI may have clinical relevance and

prognostic importance.

DEFINITION OF ACUTE KIDNEY INJURY (AKI)

Acute kidney injury is any insult to the kidney, resulting in sudden loss of function leading to

disruption of fluid and electrolyte homeostasis. The visible and measurable symptoms of AKI

include oliguria or anuria and accumulation of products normally excreted by the kidneys

such as Cr, urea, and potassium, which as the situation progresses leads to acidosis21

The first consensus criteria for AKI (RIFLE, Risk, Injury, Failure, Loss, End-stage) were

proposed in 2004, and supplemented with some changes by the Acute Kidney Injury Network

resulting in the AKIN criteria a few years later5,13. Serum Cr concentration and urine output

are the basis of all the current criteria.

TABLE 1: ACUTE KIDNEY INJURY NETWORK CRITERIA

DEFINITION OF SEPSIS

Sepsis is a systemic, deleterious host response to infection leading to severe sepsis (acute

organ dysfunction secondary to documented or suspected infection) and septic shock (severe

sepsis plus hypotension not reversed with fluid resuscitation)17,22,23. Severe sepsis and septic

shock are major healthcare problems, affecting millions of individuals around worldwide

each year, killing one in four (and often more), and increasing in incidence24,25.

Sepsis, severe sepsis, and septic shock were defined using the American College of Chest

Physicians/Society of Critical Care Medicine consensus conference definitions26.

⦁ Sepsis was defined by two or more of the following conditions as a result of infection:

[I]. Temperature greater than 38°C,

 [ii] Heart rate greater than 90 beats/min,

[iii].Respiratory rate greater than 20 breaths/min or PaCO2 less than32 mmHg, and

(iv) WBC count greater than 12,000 cells/μL or less than 4,000 cells/μL.

⦁ Severe sepsis was defined as sepsis associated with organ dysfunction, hypoperfusion

abnormalities, or sepsis-induced hypotension. Hypoperfusion abnormalities included lactic

acidosis, oliguria, and acute alteration of mental status.

⦁ In addition, septic shock was defined as sepsis with hypotension despite adequate fluid

resuscitation. Hypotension was defined as a systolic blood pressure of 90 mmHg or less, or a

reduction of greater than 40 mmHg from baseline in the absence of other causes of low blood

pressure.

RISK FACTORS FOR AKI:

In the ICU, AKI is usually multifactorial with several different insults affecting the kidneys

in an additive way. The combined risk for each patient comprises both acute exposures and

insults causing AKI, and chronic conditions and patient related factors that define how

susceptible each patient is to develop AKI. The type and intensity of the acute exposure is

also of relevance. Estimating the absolute risk for AKI is challenging and attempts have been

made to develop risk-prediction scores, but are mostly limited to patients after cardiac

surgery or contrast medium administration27-32. ICU patients are exposed to numerous

potential factors causing AKI, and any critical illness per se is a risk factor for AKI.

Age32-35 and the female gender28,36 are associated with higher risk of developing AKI. Of

chronic comorbidities chronic kidney disease (CKD) is one of the factors most clearly

associated with increased AKI risk, with even a mild elevation in creatinine37,38. Diabetes27,28
and cardiac dysfunction27 also increase the susceptibility for AKI. In cardiac surgery patients,

pulmonary disease28 and liver disease39,40 are risk factors for AKI. Increasing data suggest

that genetic factors41-43 predispose some patients for AKI. CKD, sepsis, liver failure, heart

failure, and malignancy as comorbidities increase the risk for drug induced kidney injury.

Patients with malignant conditions might have a higher risk of AKI in the ICU44. Cancer can

cause AKI either by direct invasion to the kidneys, via septic infections or by the patient

being subjected to nephrotoxic chemotherapeutic agents. Tumour lysis syndrome (TLS) is a

metabolic complication of cancer or cancer treatment that often leads to AKI45.

Sepsis is the most common underlying cause for AKI with up to 50% of AKI cases being

related to sepsis46-48. Conditions that lead to severe hypovolaemia or sustained hypotension

predispose patients to AKI49.

The use of hydroxyl ethyl starch (HES) in ICU patients might be disadvantageous concerning

kidney function. Three meta-analyses have concluded that the use of HES in critically ill

patients can increase the risk for AKI50,51. HES compared to crystalloids increases the risk of

severe AKI and initiation of RRT52. In AKI patients with severe sepsis HES was associated

with increased need for RRT53.

Albumin has been found to increase survival and decrease the incidence of AKI in chirrhotic

patients54. In ICU patients, however, no benefit from the use of albumin has been

shown55.The evidence to date of gelatin in relation to AKI is inconclusive56. The use of

gelatin in ICU patients is not recommended because of lacking apparent benefit and the affect

gelatin has on clotting57.

Excessive fluid overload has been acknowledged as a risk factor for AKI and adverse

outcome58. How fluid accumulation leads to AKI is not totally understood. Known 30
pathways from fluid overload to AKI are abdominal hypertension or abdominal compartment

syndrome59,60, and elevated venous pressure and venous congestion in the kidneys61. Major

surgery and especially cardiac surgery with CPB are risk factors for AKI due to potential

changes in haemodynamics, intravascular volume, delivery of oxygen, and the systemic

inflammation reaction (systemic inflammatory response syndrome, SIRS) caused by the

surgery and CPB62.

Several drugs used in the ICU are known to be nephrotoxic. Up to one quarter of severe AKI

cases are somehow related to drug toxicity63.

Potentially nephrotoxic drugs in the intensive care unit include

ACE inhibitor, angiotensin converting enzyme inhibitor

ARB, Angiotensin receptor blocker

Acyclovir

Aminoglycosides

Amphotericin

Contrast media

Calcineurin inhibitors (cyclosporine, tacrolimus)

Diuretics

Immunoglobulins

Metformin
Methotrexate

NSAID (Non steroidal Anti - inflammatory drugs)

Peptidoglycans (Vancomycin)

It has been estimated that contrast media are responsible for over 10% of the new AKI cases

in hospitalized patients. In ICU patients the risk for contrast media-induced AKI is due to

coexisting AKI risk factors64. AKI is a known complication of rhabdomyolysis in which

excessive release of myoglobin from muscle cells due to e.g. trauma or medications damage

the kidneys65.

ETIOLOGY OF AKI
PATHOPHYSIOLOGY OF AKI:

The pathophysiology of AKI is in many parts still unknown. Currently AKI is regarded as a

complex, multi-etiological syndrome with several different pathophysiological mechanisms.

FIGURE 2: MAJOR CAUSES OF INTRINSIC RENAL FAILURE

SEPSIS ASSOCIATED AKI

AKI complicates more than 50% cases of severe sepsis and greatly increases death. Sepsis is

also a very important cause of AKI in developing world. Decreases in GFR with sepsis can
occur even in absence of overt hypotension although most cases of severe AKI typically

occur in setting of hemodynamic compromise requiring vasopressor. While there is clearly

tubular injury associated with AKI in sepsis as manifest by presence of tubular debris and

casts in urine, post mortem examination of kidneys from individuals with severe sepsis

suggest that other factors perhaps related to inflammation and interstitial edema must be

considered .The hemodynamic effects of sepsis arising from generalized arterial vasodilation

mediated in part by cytokines that upregulate the expression of inducible NO synthase in

vessels can lead to reduction in GFR. Sepsis may lead to endothelial damage resulting in

micro vascular thrombosis, activation of reactive oxygen sepsis and leucocyte adhesion and

migration all may injure tubular cells.

In sepsis the excessive systemic inflammatory reaction most likely plays a key role in the

development of kidney injury and multiple organ failure66. The release of various

inflammatory mediators, from pathogens and from immune cells, induces direct toxicity to

tubular cells and triggers a complex cascade of inflammation67.

PATHOPHYSIOLOGY OF SEPTIC AKI

At the cellular level, immunomodulators such as tumour necrosis factor α, Interleukin 6, and

leukotrienes are suggested to cause apoptosis or even necrosis in tubular cells. In addition, the

inflammatory stimulus induces the release of nitric oxide (NO) in response to endothelial

damage causing disturbances in intrarenal hemodynamics and shunting in the periglomerular

system68. It has been suggested that excess dilatation of the efferent arteriole compared to the

afferent arteriole would lead to “local hypotension” in the glomeruli and loss of GFR. In

response, the renin-angiotensin-aldosterone (RAAA) system is activated leading to increased

renal vascular resistance, further decreasing RBF69,70.

Oxidant stress, mitochondrial dysfunction, and microcirculatory abnormalities have also been

proposed as contributors to septic kidney injury, but the role of these mechanisms remains

unclear71.

ISCHEMIA ASSOCIATED AKI

Kidneys receive 20% of cardiac output and account for 10% of resting oxygen consumption,

despite constituting only 0.5% of human mass. The outer medulla is particularly vulnerable

because of architecture of blood vessels. Enhanced leukocyte-endothelial interactions in

small vessels lead to inflammation and reduced local blood flow to the metabolically very

active s3 segment of proximal tubule which depends on oxidative metabolism. Clinically

AKI occurs when ischemia occurs in setting of limited renal reserve or coexisting insults such

as sepsis, vasoactive or nephrotoxic drugs, rhabdomyolysis and burns or pancreatitis.

PATHOPHYSIOLOGY OF ISCHEMIC ACUTE RENAL FAILURE

PROGRESSION OF ISCHEMIC AKI

NEPHROTOXIC AKI

Kidney susceptible to nephrotoxicity due to extremely high blood flow and concentration of

circulating substances this results in high concentration of toxins to tubular ,interstitial,

endothelial cells. Hypoalbumenemia increases risk due to increased free drug concentration.

CONTRAST AGENTS

Iodinated contrast agents used for cardiovascular and CT imaging are leading cause of AKI.

It is characterized by rise in creatinine beginning 24-48 hrs following exposure peaking in 3-5

days and resolving in 1 week. More severe dialysis requiring AKI is uncommon except in the

setting of significant pre existing chronic kidney disease, often in association with congestive

cardiac failure or ischemia associated AKI. Hypoxia, cytotoxic damage and transient tubule

obstruction are proposed pathogenic mechanism.

DIFFERENCE BETWEEN SEPTIC AND NON-SEPTIC AKI

The pathogenesis of sepsis-induced AKI is much more complex than isolated hypoperfusion

due to decreased cardiac output and hypotension. In non resuscitated septic patients with a

low cardiac output, a decrease in renal blood flow (RBF) could contribute to the development

of AKI. In resuscitated septic patients with a hyperdynamic circulatory state, RBF is

unchanged or increased. However, in resuscitated septic patients, sepsis-induced AKI can

occur in the setting of renal hyperemia in the absence of renal hypoperfusion or renal

ischemia. Alterations in the microcirculation in the renal cortex or renal medulla can occur

despite normal or increased global RBF. Increased renal vascular resistance (RVR) may

represent a key hemodynamic factor that is involved in sepsis-associated AKI. Sepsis-

induced renal microvascular alterations (vasoconstriction, capillary leak syndrome with tissue

edema, leukocytes and platelet adhesion with endothelial dysfunction and/or

microthrombosis) and/or an increase in intra-abdominal pressure could contribute to an

increase in RVR. Further studies are needed to explore the time course of renal microvascular

alterations during sepsis as well as the initiation and development of AKI. Doppler

ultrasonography combined with the calculation of the resistive indices may indicate the extent

of the vascular resistance changes and may help predict persistent AKI and determine the

optimal systemic hemodynamics required for renal perfusion.

Septic AKI is different from non-septic AKI due to apoptotic processes underlying septic

AKI. Shock complicating sepsis may cause more AKI but also will render treatment of this

condition in a hemodynamically unstable patient more difficult. Ample proof exists to sustain

a more prominent role of apoptosis rather than pure necrosis in the pathophysiology of sepsis

and nonseptic71. Despite substantial advances in elucidating the etiology of tubular apoptotic

lesions72. Studies that look for a possible key role of apoptosis in the mechanism of organ

dysfunction in humans have conflicting results14,73. Apoptosis has been put forward as a

major player in septic AKI74. However histopathological studies are scare. Kidney biopsies

from 19 consecutive patients who died from septic shock were compared with post-mortem

biopsies taken from 8 trauma patients and 9 patients with non-septic AKI73. Acute tubular

apoptosis was demonstrated in septic AKI patients whereas almost no apoptosis seen in non-

septic patients.

STUDIES ON ACUTE KIDNEY INJURY

Krishnamurthy S et al conducted study on Incidence and etiology of acute kidney injury in

southern India. This prospective observational study was conducted in the paediatric wards

and the paediatric intensive care unit (PICU) of a tertiary hospital in southern India. The

incidence of AKI was 5.2 % in the paediatric wards and 25.1 % in the PICU. AKI occurred in

association with infections (55.4 %), acute glomerulonephritis (16.9 %), cardiac disease (4.8
%), envenomations (4.2 %) and haemolytic uremic syndrome (3.6 %). Pneumonia constituted

26.1 % of the infections. Tropical febrile illnesses (dengue, scrub typhus, enteric fever,

cholera, tuberculosis, malaria and leptospirosis) constituted 15.6 % of children with AKI.

Dialysis was required in 14.5 % of patients; mortality was 17.5 %. A significant proportion of

children (17.5 % of survivors) had partial renal recovery at discharge. Presence of

dysnatremia and meningo encephalitis are poor predictors of outcome in AKI75.

James Case et al. conducted study on Epidemiology of Acute Kidney Injury in the Intensive

Care Unit. The incidence of AKI in ICU patients ranges from 20% to 50% with lower

incidence seen in elective surgical patients, liver transplant patients and higher incidence in

19 sepsis patients. The incidence of contrast-induced AKI is less (11.5%–19% of all

admissions) than seen in the ICU population at large. AKI represents a significant risk factor

for mortality and can be associated with mortality greater than 50%.Future studies may

benefit by better identifying modifiable risk factors to prevent the development of AKI76.

K.P. Ng et al. Studied Short and long-term outcome of patients with severe acute kidney

injury requiring renal replacement therapy. This Single centre retrospective analysis of 481

consecutive patients over a period of 39 months. Follow-up: 12 months. Primary and

secondary outcomes: overall mortality and RRT dependency at 30 days, 90 days and 1 year.

Survival at 30 days, 90 days and 1 year was 54.4, 47.2 and 37.6%, respectively. RRT

independency at 30 days, 90 days and 1 year was 35.2, 27.2 and 25.8%, respectively. Of

those RRT independent at 90 days, 55% had ongoing chronic kidney disease77.

Clec'h C et al. studied to assess the association between acute kidney injury (AKI) and

mortality in critically ill patients using an original competing risks approach following data

were recorded: baseline characteristics, daily serum creatinine level, daily Sequential Organ

Failure Assessment (SOFA) score, vital status at time of hospital discharge and length of
hospital stay. Patients were classified according to the maximum RIFLE class reached during

their ICU stay. Of the 8,639 study patients, 32.9% had AKI, of whom 19.1% received renal

replacement therapy. Patients with AKI had higher crude mortality rates and longer lengths of

hospital stay than patients without AKI. By using a competing risks approach, we confirmed

this study that AKI affecting critically ill patients is associated with increased in-hospital

mortality.

• Sara Nisula et al. Study on Incidence, risk factors and 90-day mortality of patients with

acute kidney injury in Finnish intensive care units: the FINNAKI study. It was prospective,

observational, multi-centre study comprised adult emergency admissions and elective patients

whose stay exceeded 24 h during a 5-month period in 17 Finnish ICUs. They included 2,901

patients. The incidence of AKI was 39.3 % (37.5–41.1 %). The incidence was 17.2 % (15.8–

18.6 %) for stage 1, 8.0 % (7.0–9.0 %) for stage 2 and 14.1 % (12.8–15.4 %) for stage 3 AKI.

Of the 2,901 patients 296 [10.2 % (9.1–11.3 %)] received renal replacement therapy. The

population-based incidence of ICU-treated AKI was 746 (717–774) per million population

per year (reference population: 3,671,143, i.e. 85 % of the Finnish adult population). In

logistic regression, pre-ICU hypovolaemia, diuretics, colloids and chronic kidney disease

were independent risk factors for AKI. Hospital mortality for AKI patients was 25.6 % (23.0–

28.2 %) and the 90-day mortality for AKI patients was 33.7 % (30.9–36.5 %). All AKIN

stages were independently associated with 90-day mortality71.

Bagshaw SM et al. study on a multi-centre evaluation of the RIFLE criteria for early acute

kidney injury in critically ill patients. It is a Retrospective interrogation of prospectively

collected data from the Australian New Zealand Intensive Care Society Adult Patient

Database. We evaluated 120 123 patients admitted for >/=24 h from 1 January 2000 to 31

December 2005 from 57 ICUs across Australia. In a large heterogeneous cohort of critically
ill patients, the RIFLE criteria classified >36% with AKI on the day of admission. For

successive increases in severity of RIFLE category, there were increases in hospital

mortality72.

Uchino S et al. worked on Acute renal failure in critically ill patients: a multinational,

multicenter study. It is to determine the period prevalence of ARF in intensive care unit

(ICU) patients in multiple countries; to characterize Occurrence of ARF, factors contributing

to etiology, illness severity, treatment, need for renal support after hospital discharge, and

hospital mortality. Of 29 269 critically ill patients admitted during the study period, 1738 had

ARF during their ICU stay, including 1260 who were treated with RRT. The most common

contributing factor to ARF was septic shock. Overall hospital mortality was 60.3%. Dialysis

dependence at hospital discharge was 13.8% (95% CI, 11.2%-16.3%) for survivors.

Independent risk factors for hospital mortality included use of vasopressors, mechanical

ventilation, septic shock, cardiogenic shock and hepatorenal syndrome14.

Sean M. Bagshaw et al. Studied on Septic Acute Kidney Injury in Critically Ill Patients:

Clinical Characteristics and Outcomes. Sepsis is the most common cause of acute kidney

injury (AKI) in critical illness, but there is limited information on septic AKI. A prospective,

observational study of critically ill patients with septic and nonseptic AKI was performed

from September 2000 to December 2001 at 54 hospitals in 23 countries. A total of 1753

patients were enrolled. Sepsis was considered the cause in 833 (47.5%); the predominant

sources of sepsis were chest and abdominal (54.3%). Septic AKI was associated with greater

aberrations in hemodynamics and laboratory parameters, greater severity of illness, and

higher need for mechanical ventilation and vasoactive therapy. Oliguria was more common in

septic AKI (67 versus 57%; P < 0.001). Septic AKI had a higher in-hospital case-fatality rate

compared with nonseptic AKI (70.2versus 51.8%; P < 0.001). Median (IQR) duration of
hospital stay for survivors (37 [19 to 59]versus 21 [12 to 42] d; P < 0.0001) was longer for

septic AKI. There was a trend to lower serum creatinine (106 [73 to 158] versus 121 [88 to

184] μmol/L; P = 0.01) and RRT 22 dependence (9 versus 14%; P = 0.052) at hospital

discharge for septic AKI .Need for support when compared with nonseptic AKI, further

showed that septic AKI exerts an important and independent increase in the risk for hospital

death. In survivors, septic AKI is associated with prolonged ICU and hospital stays, sicker

and had a higher burden of illness and greater abnormalities in acute physiology, increased

risk for death and longer duration of hospitalization but also a trend toward greater recovery

of kidney function73.

Helmut Schiffl1 et al. Worked on Long-term outcomes of survivors of ICU acute kidney

injury requiring renal replacement therapy: a 10-year prospective cohort study. It is

associated with high in-hospital morbidity and mortality in critically ill patients. The aim of

this study was to characterize AKI–chronic kidney disease (CKD) nexus in critically ill

patients with AKI (RIFLE class F) and performed a single-centre prospective observational

study of 425 consecutive critically ill patients with AKI requiring RRT. None of these

patients had preexisting kidney disease. Primary outcomes were vital status and renal

function at hospital discharge and at 5 and 10 years of follow-up. The overall in-hospital

mortality of the study cohort was 47%, the mortality rates at 1, 5 and 10 years were 65, 75

and 80%, respectively. At hospital discharge, recovery of renal function was complete in 56%

of survivors. None of these patients developed CKD during follow-up. Ninety percent of the

100 survivors with partial recovery of renal function had ongoing CKD during long-term

follow-up. CKD progressed to end-stage renal disease (ESRD) in 12 patients (3% of the

cohort or 5% of survivors). The patients with post-AKICKD had a higher prevalence of

hypertension, a higher rate of fatal cardiac diseases and a higher allcause death rate. Long-
term survival of critically ill patients with AKI requiring RRT is poor and determined by the

development of de novo CKD74.

Oeyen S et al. Study on Long-term outcome after acute kidney injury in critically-ill patients.

Assessment of short-term outcome in critically-ill patients who develop acute kidney injury

(AKI) may underestimate the true burden of disease. It is important to focus on longterm

survival, renal recovery and quality of life beyond hospital discharge. Although the majority

of critically-ill patients with AKI die during hospital stay, there is only a minor increase in

mortality after hospital discharge among AKI patients treated in the intensive care unit (ICU).

Estimates of mortality rates at 1 year following hospital discharge range from 57% to 78%

with an absolute difference between hospital mortality and 1-year mortality ranging from 4%

to 18%. Renal recovery is another important measure of outcome since chronic renal

replacement therapy (RRT) does not only significantly affect health-related quality of life

(HRQoL), it is also costly. Potential factors associated with reduced recovery of renal

function are female sex, high comorbidity, older age, a parenchymal aetiology of AKI, late

initiation of RRT, and use of intermittent haemodialysis (IHD)79.

Mandelbaum T et al. studied Outcome of critically ill patients with acute kidney injury using

the Acute Kidney Injury Network (AKIN) criteria. It is a Retrospective cohort study

conducted in seven intensive care units at a large, academic, tertiary medical center. Acute

kidney injury affects 5% to 7% of all hospitalized patients with a much higher incidence in

the critically ill. Adult patients without evidence of end-stage renal disease with more than

two creatinine measurements and at least a 6-hr urine output recording who were admitted to

the intensive care unit between 2001 and 2007. From 19,677 adult patient records, 14,524

patients met the inclusion criteria. Fifty-seven percent developed acute kidney injury during

their intensive care unit stay. In hospital mortality rates were: 13.9%, 16.4%, 33.8% for acute
kidney injury 1, 2, and 3, respectively, compared with only 6.2% in patients without acute 24

kidney injury (p < .0001). After adjusting for multiple covariates, acute kidney injury was

associated with increased hospital mortality. Using multivariate logistic regression, they

found that in patients who developed acute kidney injury, urine output alone was a better

mortality predictor than creatinine alone or the combination of both. Concluding the study

More than 50% of their critically ill patients developed some stage of acute kidney injury

resulting in a stage wise increased mortality risk80.

Mahamud Egal et al. Studied on Invasive mechanical ventilation is associated with a

threefold increase in odds of acute kidney injury in critically ill patients. AKI is depending on

the definition used a common complication in the intensive care unit (ICU) with a high

mortality, while it may also adversely affect long-term survival. It affects up to 29% of

patients who are mechanically ventilated. Drury et al. were the first to describe the effects of

positive airway pressure on renal function in healthy individuals. Since then, studies have

demonstrated that mechanical ventilation (MV) affects the kidney. However, a causal or

epidemiological relation between MV and AKI has only been suggested in narrative reviews.

Kuiper et al proposed that MV may lead to the development of AKI through haemodynamic

factors or ventilator-induced lung injury by triggering a pulmonary inflammatory reaction

and subsequent systemic release of inflammatory mediators. Some studies specifically

examined the release of these mediators during MV. The precise relation between MV and

subsequent AKI remains unclear, however In this systematic review, primary objective was

to answer the following questions: does invasive MV contribute to the development of AKI

in critically ill adult patients, and could differences in ventilator settings like tidal volume

(Vt) and positive end-expiratory pressure (PEEP) have an effect on the development of AKI?

A secondary 25 objective was to answer the question whether there is a difference between

invasive MV and non-invasive MV (NIV) in the risk for AKI. They excluded studies clearly
reporting that invasive MV was initiated after the onset of AKI and studies in which renal

function was evaluated during a mean time interval shorter than 48 hours, invasive MV is

associated with a threefold increase in odds of AKI in critically ill patients. In general, Vt or

PEEP settings do not seem to modify the risk81.

Ratanarat R et al. Studied on The clinical outcome of acute kidney injury in critically ill Thai

patients stratified with RIFLE classification. It was retrospective cohort study, a large single

tertiary care academic center in Thailand on 121 patients admitted during November 2005-

November 2006. They classified patients according to the maximum RIFLE class (class R,

class I or class F) reached during their hospital stay. Patients with maximum RIFLE class R,

class I and class F had hospital mortality rates of 35.7%, 35.7% and 65.9%, respectively,

compared with 20% for patients without acute kidney injury. Mortality was not significantly

different among those with the "Risk" and "Injury" class of RIFLE AKI compared with those

without AKI, but mortality increased significantly with the "Failure" class. There was the

highest rate of renal replacement therapy in the failure group (52.3%) compared with no AKI

group (5.7%), and injury group (7.1%) (p < 0.001)82.

Wen Y et al. Worked on Prevalence, risk factors, clinical course, and outcome of acute

kidney injury in Chinese intensive care units. The objectives of this study were to

characterize AKI defined by RIFLE criteria, assess the association with hospital mortality,

and evaluate the impact of AKI in the context of other risk factors. This prospective

multicenter observational study enrolled 3,063 consecutive patients from 1 July 2009 to 31

August 2009 in 22 ICUs across mainland China. There were 1255 patients in the final

analysis. AKI was 26 diagnosed and classified according to RIFLE criteria. There were 396

patients (31.6%) who had AKI, with RIFLE maximum class R, I, and F in 126 (10.0%), 91

(7.3%), and 179 (14.3%) patients, respectively. In comparison with non AKI patients,
patients in the risk class on ICU admission were more likely to progress to the injury class,

while patients in the risk class and injury class had a significantly higher probability of

deteriorating into failure class. The adjusted hazard ratios for 90-day mortality were 1.884 for

the risk group, 3.401 for the injury group, and 5.306 for the failure group. Concluding the

study as the prevalence of AKI was high among critically ill patients in Chinese ICUs. In

comparison with non-AKI patients, patients with RIFLE class R or class I on ICU admission

were more susceptibility to progression to class I or class F83.

Lars Englberger et al. Study on Clinical accuracy of RIFLE and Acute Kidney Injury

Network (AKIN) criteria for acute kidney injury in patients undergoing cardiac surgery,

investigated 4,836 consecutive patients undergoing cardiac surgery with cardiopulmonary

bypass from 2005 to 2007 at Mayo Clinic, USA. AKI was defined by RIFLE and AKIN

criteria. Significantly more patients were diagnosed as AKI by AKIN (26.3%) than by RIFLE

(18.9%) criteria (P < 0.0001). Mortality was increased with an odds ratio of 4.5 for one class

increase by RIFLE and an OR of 5.3 for one stage increase by AKIN. The multivariate model

showed lower predictive ability of RIFLE for mortality. Patients classified as AKI in one but

not in the other definition set were predominantly staged in the lowest AKI severity class

(9.6% of patients in AKIN stage 1, 2.3% of patients in RIFLE class R). Concluding the study

by modification of RIFLE by staging of all patients with acute renal replacement therapy

(RRT) in the failure class F may improve predictive value. AKIN applied in patients

undergoing cardiac surgery without correction of serum creatinine for fluid balance 27 may

lead to over-diagnosis of AKI (poor positive predictive value). Balancing limitations of both

definition sets of AKI, we suggest application of the RIFLE criteria in patients undergoing

cardiac surgery84.
Plataki M et al. Studied on Predictors of acute kidney injury in septic shock patients. Acute

kidney injury (AKI) is a frequent complication in critically ill patients and sepsis is the most

common contributing factor. They aimed to determine the risk factors associated with AKI

development in patients with septic shock. It was Observational cohort study consisted of

consecutive adults with septic shock admitted to a medical intensive care unit (ICU) of a

tertiary care academic hospital from July 2005 to September 2007. Study conducted in

390patients met inclusion criteria, of which 237 (61%) developed AKI. AKI development

was independently associated with delay to initiation of adequate antibiotics, intra-abdominal

sepsis, blood product transfusion, use of angiotensin-converting enzyme

inhibitor/angiotensin-receptor blocker, and body mass index (kg/m²). Higher baseline GFR

and successful early goal directed resuscitation were associated with a decreased risk of AKI.

Hospital mortality was significantly greater in patients who developed AKI (49 versus

34%)85.

Marilia Galvao Cruz et al This study evaluated an open cohort of 117 critically ill patients

with acute kidney injury who were consecutively admitted to an intensive care unit,

excluding patients with a history of advanced-stage chronic kidney disease, kidney

transplantation, hospitalization or death in a period shorter than 24 hours. The presence of

sepsis and in-hospital death were the exposure and primary variables in this study,

respectively. A confounding analysis was performed using logistic regression. No significant

differences were found between the mean ages of the groups with septic and non-septic acute

kidney injury. In the septic and non-septic acute kidney injury groups, a 28 predominance of

females and Afro-descendants was observed. Compared with the non-septic patients, the

patients with sepsis had a higher mean Acute Physiology and Chronic Health Evaluation II

score and a higher mean water balance (p=0.001). Arterial hypertension (p=0.01) and heart

failure (p18.5 were associated with death in the multivariate analysis86.

Ali T et al We tested the hypothesis that the incidence is higher by including all patients with

AKI (in a geographical population base of 523,390) regardless of whether they required renal

replacement therapy irrespective of the hospital setting in which they were treated. We also

tested the hypothesis that the Risk, Injury, Failure, Loss, and End-Stage Kidney (RIFLE)

classification predicts outcomes. Clinical outcomes were obtained from each patient's case

records. The incidences of AKI and ACRF were 1811 and 336 per million population,

respectively. Median age was 76 yr for AKI and 80.5 yr for ACRF. Sepsis was a precipitating

factor in 47% of patients. The RIFLE classification was useful for predicting full recovery of

renal function (P < 0.001), renal replacement therapy requirement (P < 0.001), length of

hospital stay [excluding those who died during admission (P < 0.001)], and in-hospital

mortality (P = 0.035). RIFLE did not predict mortality at 90 d or 6 months. Thus the

incidence of AKI is much higher than previously thought, with implications for service

planning and providing information to colleagues about methods to prevent deterioration of

renal function. The RIFLE classification is useful for identifying patients at greatest risk of

adverse short-term outcomes87.

Sang Heon Suh et al Among 992 patients with sepsis and septic shock, 573 patients

developed AKI. According to the RIFLE criteria, 277 patients (48.3%) were subdivided into

stage 1 AKI, 182 (31.8%) into stage 2 AKI, and 114 (18.9%) into stage 3 AKI. The renal

replacement therapy was required in a total of 40 patients with AKI. Most patients (n=32)

were stage 3 AKI, and the rest (n=8) were stage 2 AKI. The mean age of patients with septic

AKI was significantly higher than that of patients without AKI (p< 0.0001) and similar to

patients with sepsis preceding AKI (48 vs. 44%; p = 0.41). Compared with sepsis-free

patients, those with sepsis developing after AKI were also more likely to be dialyzed (70 vs.

50%; p < 0.001) and had longer LOS (37 vs. 27 days; p < 0.001). Oliguria, higher fluid
accumulation and severity of illness scores, non-surgical procedures after AKI, and provision

of dialysis were predictors of sepsis after AKI6.

Malte Heeg et al A total of 1.017 patients were included into the study. Six-hundred and eight

were male, 409 were female, the mean age of all patients was 65 ±16 years with 65 ±14 years

in men and 66 ±18 years in women. All patients were treated at the intensive care unit of the

department of nephrology and rheumatology of the university hospital Göttingen (Germany)

between 2009 and 2011. Sepsis was diagnosed in 330 patients (32% - 208 male [63%], 122

female [37%]), 687 patients (68%) did not fulfil the respective criteria. Twohundred and

twelve patients (21% - 138 male [65%], 74 female [35%]) suffered from a malignant disease

at the time of admission to the ICU (non-solid tumour: 88, solid tumor: 124). Thirty-three

patients with a non-solid tumour underwent bone marrow-/stem cell transplantation in their

history. Four-hundred and thirty-five patients (43% - 278 male [64%], 157 female [36%])

either presented with AKI at the time of ICU admission or developed AKI during the

treatment course at the ICU. Liver cirrhosis was diagnosed in 83 patients (8% - 57 male

[69%], 25 female [31%])88.

Wasim Ahmed et al One hundred and ninety-nine patients' data were analysed. There were 84

patients in the historic control group and 115 patients in the intervention group. Mean age of

the patients of the whole group was 68.2 ± 19.8 years in the control and 65.6 ± 18.8 years (P

= 0.35) in the intervention group. There were 53.5% males in the historic control group

versus 50% in the intervention group. There was no significant difference in the distribution

of severe sepsis and septic shock and (April 16, 2014) of the two groups of patients at

baseline. The intervention group had more diabetic patients (P = 0.014) as compared with

controls, whereas the other comorbidities were equally distributed. In terms of outcomes for

patients who developed AKI in the two groups, there was no statistical difference in the mean
serum creatinine at discharge from. There was no difference in the number of patients who

were dialysis dependent at the time of discharge or death. There was no statistical difference

in the 28-day mortality in the two groups (P = 0.67)89

Aida Hamzic-Mehmedbasic et al A total of 100 patients with diagnosis of AKI were included

in the study. Considering etiology, patients were divided into two groups: patients with AKI

of non-septic etiology (66 patients) and patients with AKI of septic etiology (34 patients).

Characteristics of septic and non-septic AKI patients are summarized in. There was no

evidence of statistically significant difference in mean values of age and gender between

these two groups of patients, while hospital stay was significantly longer in septic AKI

patients (p=0.03). Pre-existing chronic kidney disease had 10.6% of non-septic AKI patients

and 2.3 greater proportion of septic AKI patients (23.5%). Comorbid conditions were present

in 70.6% and 60.6% of septic and non-septic patients, respectively. In the group of septic

AKI patients, only 32 8.8% patients underwent RRT, while 24.4% of non-septic AKI patients

were treated with RRT. The mean hospital stay prior to the RRT commencement was

significantly longer in septic AKI patients when compared to non-septic AKI patients (10.6

days vs. 2 days, p=0.03). Septic AKI patients also had significantly greater proportion of

hospital mortality in comparison to non-septic AKI patients. Factors statistically significant in

predicting nonrecovering of renal function in all AKI patients were sepsis and hypertension.

Failure was an independent predictor of non-recovered renal function in the group of septic

AKI patients. In the group of non-septic AKI patients, only hypertension was independent

predictor of renal function non-recovery2.

Zang ZD Yanj et al Of the enrolled 703 AKI patients, 56.2% were caused by sepsis, which

indicated that sepsis is main cause. For septic AKI stratified by KDIGO classification, 146

(37.0%) patients belonged to AKI I, 154 (39.0%) to AKI II, and 95 (24.1%) to AKI III.
Compared with the patients with non-septic AKI, septic AKI patients had greater APACHE II

and SOFA score. Although there was no significant difference in baseline serum creatinine

between the two groups, patients with sepsis had higher serum creatinine [(143.5 ± 21.6)

µmol/L vs (96.2 ± 15.5)µmol/L; P < 0.05], a higher proportion fulfilled KDIGO categories

for both AKI II and III (63.0% vs 33.1%; P < 0.05), a higher renal replacement therapy

(RRT) rate (22.3% vs 6.2%; P < 0.05) and a lower proportion of complete renal recovery

(74.4% vs 82.8%) (all P values < 0.05). The 90-day mortality of septic AKI patients was

higher than that of nonseptic AKI patients90.

MATERIALS AND METHODS

The present study was proposed to be conducted in the Department of General Medicine
ICU, MNR Medical College and Hospital, Sangareddy, Telangana, India.

STUDY DESIGN: Prospective Observational Study.

STUDY PERIOD: 18 months

STUDY DURATION: December 2022 to June 2024

STUDY SETTING: Department of General Medicine ICU, MNR Medical College and
Hospital, Sangareddy, Telangana, India

STUDY POPULATION: Patients admitted in ICU of General Medicine ward with AKI,
MNR Medical College and Hospital, Sangareddy, Telangana, India

ELIGIBILITY CRITERIA:

INCLUSION CRITERIA:

1. All patients admitted to Medical ICU aged 18-90 years developed AKI as diagnosed
by AKIN criteria
2. Patients with AKI on Chronic Kidney Disease
3. Patients with AKI with and without sepsis

EXCLUSION CRITERIA:

1. Patients admitted in non medical ICU

2. Kidney transplant patients
3. Patients with ESRD on maintenance hemodialysis (CKD-Stage 5)
4. Patients not willing to particpate

SAMPLE SIZE: 246 patients

SAMPLE SIZE CALCULATION:

According to Chandiraseharan VK et,al. prevalence of AKI among ICU admitted patients

was 19%91
Formulae for calculating sample size:

n = (Z1-α/2 + Z1-β)2pq / d2
Where,
Z1-α/2 = value from the standard normal distribution holding 1-α/2 below it = 1.64 for 90% CI

Z1-β = value from the standard normal distribution holding 1-β below it = 0.84 for a power of
80%

d = Assumed precision is 7%

p=prevalence (19%)

q=100-p=81%

Substituting all the values in the above formula, sample size of 246 was obtained. i.e 123 in
each group

SAMPLING TECHNIQUE: Simple Random Sampling

ETHICAL CLEARANCE: Ethical clearance was obtained from institutional review board
of MNR Medical College and Hospital, Sangareddy, Telangana, India.

INFORMED CONSENT: Before start of the study the purpose of the study was explained
to the study participants and written informed consent was obtained.

MEASURED VARIABLES/PARAMETERS STUDIED:

Demographics: Age and sex of the study participants were recorded.

Clinical examination: serum creatinine, serum urea were evaluated from previous records.

Etiology of AKI was recorded whether septic or non-septic AKI (Septic AKI patients were
later confirmed by American college of Chest Physicians/Society of Critical Care Medicine
Consensus conference definition

History of co-morbidities

Risk factors: Pre renal/Renal/Post renal/ Combined were evaluated

Criteria for subdivision of patients: Based on serum creatinine patients were further
classified into AKIN 1AKIN 2/AKIN 3
Outcomes: Length of hospital stay, Serum creatinine levels at the time of discharge, dialysis
history, mortality were evaluated

METHOD OF DATA COLLECTION

Patients admitted to the medical ICU at MNR Medical College, who presented with acute

kidney injury (AKI) during their ICU stay, were included in the study after meeting the

inclusion criteria and excluding those based on the exclusion criteria. Informed consent was

obtained from each patient after providing a detailed explanation of the study's purpose.

A comprehensive collection of data was performed, encompassing detailed histories of

presenting complaints, physical examinations, and laboratory findings extracted from the

patients' case sheets. This data included serum creatinine and urea levels, as well as baseline

creatinine, if available from previous records.

Patients were categorized into two groups based on the etiology of AKI: septic AKI and non-

septic AKI, in accordance with the American College of Chest Physicians/Society of Critical

Care Medicine consensus conference definitions. Assessment of risk factors leading to AKI,

such as pre-renal, renal, post-renal, or combined causes, was conducted. Past medical

histories, including conditions such as diabetes mellitus, hypertension, coronary artery

disease, and chronic kidney disease, were also documented.

These two groups were further subdivided into three categories based on serum creatinine

levels and urine output, classified as AKIN 1, AKIN 2, and AKIN 3. Patients were followed

until the end of their ICU stay without any intervention from the observer's side. Parameters

such as serum creatinine levels at ICU discharge, length of hospital stay, and the need for

dialysis were recorded.

Outcome measures, including mortality rates, length of ICU stay, normalization or partial

recovery of serum creatinine levels, and the requirement for dialysis, were compared between

the two groups. No experimental or invasive procedures were conducted on patients for the

purpose of the study, and their clinical course was observed during their hospital stay.

STATISTICAL ANALYSIS

Statistical analysis was performed using IBM SPSS version 16. Descriptive statistics included

mean and standard deviation for continuous variables and frequency with percentages for

categorical variables. Inferential statistics were conducted following the Kolmogorov–

Smirnov test, which confirmed normal distribution of the data. Chi-square test was used to

examine associations among categorical variables, while independent t-tests were employed

for continuous variables, with significance set at p ≤ 0.05.

RESULTS

TABLE 1: AGE DISTRIBUTION OF STUDY PARTICIPANTS

AGE FREQUENCY PERCENTAGE

18-30 34 13.9
31-50 64 26
51-80 143 58.1
>80 5 2
MEAN ±SD 63.25±12.9

GRAPH 1: AGE DISTRIBUTION OF STUDY PARTICIPANTS

58.10%
60.00%

50.00%

40.00%
26%
30.00%

20.00% 13.90%

10.00% 2%

0.00%
18-30 31-50 51-80 >80

18-30 31-50 51-80 >80

Table 1 and Graph 1 presents the age distribution of study participants, with a total sample

size of 246 individuals. The majority of participants, constituting 58.1% (n=143), fell within

the 51-80 age range, followed by those aged 31-50, comprising 26% (n=64) of the cohort.

Participants aged 18-30 accounted for 13.9% (n=34) of the sample, while individuals over the

age of 80 represented the smallest proportion at 2% (n=5).

TABLE 2: GENDER DISTRIBUTION OF STUDY PARTICIPANTS

GENDER FREQUENCY PERCENTAGE

MALE 143 58.1
FEMALE 103 41.9

GRAPH 2: GENDER DISTRIBUTION OF STUDY PARTICIPANTS

FEMALE
41.9%

MALE
58.1%

Table 2 and Graph 2 displays the gender distribution among the study participants, totaling

246 individuals. Of the participants, 58.1% (n=143) were male, while 41.9% (n=103) were

female.
TABLE 3: DISTRIBUTION OF PARTICIPANTS BASED ON DIAGNOSIS

DIAGNOSIS FREQUENCY PERCENTAGE

SEPTIC 123 50
NON SEPTIC 123 50

GRAPH 3: DISTRIBUTION OF PARTICIPANTS BASED ON DIAGNOSIS

50% 50%

50%
45%
40%
35%
30%
25%
20%
15%
10%
5%
0%
SEPTIC NON SEPTIC

In Table 3 and Graph 3, the distribution of participants based on diagnosis is presented,

indicating an equal distribution between septic and non-septic cases, each comprising 50% of

the sample. Specifically, 123 participants were identified as septic cases, while an equal

number were categorized as non-septic. This balanced distribution ensures a comprehensive

representation of both conditions within the study cohort, facilitating a robust analysis of

outcomes and comparisons between the two diagnostic categories.

 TABLE 4: ETIOLOGIES CONTRIBUTING TO ACUTE KIDNEY INJURY (AKI)

ETIOLOGY FREQUENCY PERCENTAGE

PRE-RENAL CAUSES

Lower urinary tract obstruction 23 9.3

Acute decompensated heart failure (ADHF) 12 4.9

Sepsis 123 50

RENAL CAUSES

Enterocolitis 18 7.3

Hemorrhagic fever with renal syndrome (HFRS) 14 5.7

Nephrotoxic drug-related acute tubular necrosis (ATN) 14 5.7

Drug-induced acute interstitial nephritis (AIN) 10 4.1

Small-vessel vasculitis 7 2.8

POST-RENAL CAUSES

Infectious 19 7.7

Acute cholecysto pancreatitis 6 2.5

GRAPH 4: ETIOLOGIES CONTRIBUTING TO ACUTE KIDNEY INJURY (AKI)

Small-vessel vasculitis 2.80%

Drug-induced acute interstitial nephritis (AIN) 4.10%

Nephrotoxic drug-related acute tubular necrosis (ATN) 5.70%

Hemorrhagic fever with renal syndrome (HFRS) 5.70%

Enterocolitis 7.30%

Sepsis 50%

Acute decompensated heart failure (ADHF) 4.90%

Lower urinary tract obstruction 9.30%

0.00% 10.00% 20.00% 30.00% 40.00% 50.00%

In Table 4 and Graph 4, the distribution of etiologies contributing to acute kidney injury

(AKI) is presented, categorized into pre-renal, renal, and post-renal causes. Among pre-renal

causes, sepsis emerged as the predominant factor, accounting for 50% of AKI cases, followed

by lower urinary tract obstruction (9.3%) and acute decompensated heart failure (4.9%).

Within renal causes, enterocolitis, hemorrhagic fever with renal syndrome (HFRS), and

nephrotoxic drug-related acute tubular necrosis (ATN) each contributed approximately 7.3%,

5.7%, and 5.7% respectively, with drug-induced acute interstitial nephritis (AIN) and small-

vessel vasculitis representing 4.1% and 2.8% of cases, respectively. Post-renal causes

encompassed infectious etiologies and acute cholecysto pancreatitis, accounting for 7.7% and

2.5% of AKI cases, respectively.

 TABLE 5: HISTORY OF CO-MORBIDITIES

CO-MORBIDITIES FREQUENCY PERCENTAGE

Diabetes 132 53.7

Hypertension 196 79.7

CAD 30 12.2

CKD 91 37

GRAPH 5: HISTORY OF CO-MORBIDITIES

79.70%
80.00%
70.00%
53.70%
60.00%
50.00%
37%
40.00%
30.00%
20.00% 12.20%

10.00%
0.00%
Diabetes Hypertension CAD CKD

Diabetes Hypertension CAD CKD

Table 5 and Graph 5 provides a comprehensive overview of the co-morbidities prevalent

within the studied population. Among the observed co-morbidities, hypertension exhibited

the highest frequency, with 196 cases, representing 79.7% of the total population. Diabetes

followed closely, with 132 cases accounting for 53.7% of the population. Coronary artery

disease (CAD) was identified in 30 cases, comprising 12.2% of the total, while chronic

kidney disease (CKD) was observed in 91 cases, representing 37% of the population.
TABLE 6: AKIN STAGES BASED ON SERUM CREATININE

AKIN STAGE FREQUENCY PERCENTAGE

STAGE 1 60 24.4

STAGE 2 123 50

STAGE 3 63 25.6

GRAPH 6: AKIN STAGES BASED ON SERUM CREATININE

60.00%

50%
50.00%

40.00%

30.00% 25.60%
24.40%

20.00%

10.00%

0.00%
STAGE 1 STAGE 2 STAGE 3

STAGE 1 STAGE 2 STAGE 3

Table 6 and Graph 6 presents the distribution of AKIN stages based on serum creatinine

levels among the study population. Among the participants, 60 (24.4%) were categorized as

Stage 1, 123 (50%) as Stage 2, and 63 (25.6%) as Stage 3.

 TABLE 7: OUTCOMES OF STUDY PARTICIPANTS

OUTCOMES FREQUENCY PERCENTAGE

Mortality 47 19.1

Partial recovery of creatinine 100 40.7

Normal creatinine 25 10.2

Dialysis requirement 103 41.9

GRAPH 7: OUTCOMES OF STUDY PARTICIPANTS

40.70% 41.90%
45.00%
40.00%
35.00%
30.00%
25.00% 19.10%
20.00%
15.00% 10.20%
10.00%
5.00%
0.00%
Mortality Partial recovery Normal Dialysis
of creatinine creatinine requirement

Mortality Partial recovery of creatinine Normal creatinine Dialysis requirement

Table 7 and Graph 7 illustrates the outcomes observed among study participants. Mortality

occurred in 47 individuals (19.1%), while 100 participants (40.7%) experienced partial

recovery of creatinine levels. A total of 25 subjects (10.2%) achieved normal creatinine

levels. Notably, dialysis requirement was observed in 103 individuals (41.9%).

TABLE 8: LENGTH OF HOSPITAL STAY AMONG STUDY PARTICIPANTS

LENGTH OF HOSPITAL MEAN STANDARD DEVIATION

STAY

DAYS 12.1 2.8

Table 8 summarizes the length of hospital stay among study participants. The mean duration

of hospitalization was 12.1 ±2.8 days.

TABLE 9: DEMOGRAPHIC DISTRIBUTION AMONG SEPTIC AND NON-SEPTIC

AKI PATIENTS

VARIABLE SEPTIC NON-SEPTIC P-

MEAN/N SD/% MEAN/N SD/% VALUE
AGE 65.5 13.9 63.8 12.2 0.412*
GENDER MALE 73 59.3 70 56.9 0.652
FEMALE 50 40.7 53 43.1
*Independent t test

Chi-square

P≤0.05 is statistically significant

Table 9 displays the demographic distribution among septic and non-septic acute kidney

injury (AKI) patients. The mean age of septic AKI patients was 65.5 years (SD = 13.9), while

non-septic AKI patients had a mean age of 63.8 years (SD = 12.2). The difference in age

between the two groups was not statistically significant (p = 0.412). Regarding gender

distribution, among septic AKI patients, 73 (59.3%) were male, and 50 (40.7%) were female.

In comparison, among non-septic AKI patients, 70 (56.9%) were male, and 53 (43.1%) were

female. Gender distribution did not show a significant difference between the two groups (p =

0.652).
 TABLE 10: HISTORY OF CO-MORBIDITIES AMONG SEPTIC AND NON-SEPTIC

AKI PATIENTS

CO- SEPTIC NON-SEPTIC P-VALUE

MORBIDITIES N % N %

Diabetes 80 60.6 52 39.4 0.000

Hypertension 119 60.7 57 39.3 0.000

CAD 22 73.3 8 26.7 0.000

CKD 58 63.7 33 36.3 0.000

Chi-square

P≤0.05 is statistically significant

GRAPH 8: HISTORY OF CO-MORBIDITIES AMONG SEPTIC AND NON-SEPTIC

AKI PATIENTS

100%
90% 26.70%
39.40% 39.30% 36.30%
80%
70%
60%
50%
40% 73.30%
60.60% 60.70% 63.70%
30%
20%
10%
0%
Diabetes Hypertension CAD CKD

SEPTIC NON-SEPTIC

Table 10 and Graph 8 presents the comparative history of co-morbidities among septic and

non-septic acute kidney injury (AKI) patients. A statistically significant difference was

observed in the prevalence of diabetes, hypertension, coronary artery disease (CAD), and
chronic kidney disease (CKD) between the two groups (p < 0.05). Among septic AKI

patients, diabetes was notably higher (60.6%) compared to non-septic AKI patients (39.4%).

Similarly, hypertension was more prevalent among septic AKI patients (60.7%) compared to

non-septic AKI patients (39.3%). CAD was substantially more prevalent among septic AKI

patients (73.3%) compared to non-septic AKI patients (26.7%). Additionally, CKD was more

prevalent among septic AKI patients (63.7%) compared to non-septic AKI patients (36.3%).

These findings underscore the importance of considering co-morbidities in the management

and prognosis of AKI patients, especially in the context of sepsis.

TABLE 11: AKIN STAGES BASED ON SERUM CREATININE AMONG SEPTIC

AND NON-SEPTIC AKI PATIENTS

AKIN STAGE SEPTIC NON-SEPTIC P-VALUE

N % N %

STAGE 1 18 30 42 70 0.032

STAGE 2 62 50.4 61 49.6

STAGE 3 43 65 20 35

Chi-square

P≤0.05 is statistically significant

GRAPH 9: AKIN STAGES BASED ON SERUM CREATININE AMONG SEPTIC

AND NON-SEPTIC AKI PATIENTS

100%
90% 35%
80% 49.60%
70% 70%
60%
50%
40% 65%
30% 50.40%
20% 30%
10%
0%
STAGE 1 STAGE 2 STAGE 3

SEPTIC NON-SEPTIC

In Table 11 and Graph 9, the distribution of AKIN stages based on serum creatinine levels

among septic and non-septic acute kidney injury (AKI) patients is depicted. A statistically

significant difference was observed in the distribution of patients across AKIN stages

between the two groups (p = 0.032). Among septic AKI patients, the majority were classified
as Stage 3 (65%), followed by Stage 2 (50.4%), while Stage 1 accounted for a smaller

proportion (30%). Conversely, among non-septic AKI patients, Stage 1 was predominant

(70%), followed by Stage 2 (49.6%), with Stage 3 representing a smaller proportion (35%).
 TABLE 12: OUTCOMES AMONG SEPTIC AND NON-SEPTIC AKI PATIENTS

VARIABLES SEPTIC NON-SEPTIC P-VALUE

MEAN/N SD/% MEAN/N SD/%
Length of hospital 14.8 1.9 8.7 1.2 0.412*
stay (Days)
Mortality 47 100 0 0 0.000

Partial recovery of 65 65 35 35 0.000

creatinine

Normal creatinine 8 32 17 68 0.031

Dialysis requirement 83 80.6 20 19.4 0.001

*Independent t test

Chi-square

P≤0.05 is statistically significant

Table 12 illustrates the outcomes among septic and non-septic acute kidney injury (AKI)

patients. A significant disparity was observed in mortality rates between the two groups (p =

0.000), with all septic AKI patients experiencing mortality compared to none in the non-

septic group. Additionally, there were notable differences in other outcome variables. Septic

AKI patients had a longer mean length of hospital stay (14.8 days) compared to non-septic

AKI patients (8.7 days), though this difference was not statistically significant (p = 0.412).

The requirement for dialysis was significantly higher among septic AKI patients (80.6%)

compared to non-septic AKI patients (19.4%) (p = 0.001). Furthermore, a higher proportion

of septic AKI patients experienced partial recovery of creatinine levels (65%) compared to

non-septic AKI patients (35%) (p = 0.000), whereas a higher proportion of non-septic AKI

patients achieved normal creatinine levels (68%) compared to septic AKI patients (32%) (p =

0.031).
DISCUSSION

AKI poses a significant global challenge, straining resources and exhibiting variable

prevalence between high- and low-income countries. Its link to mortality, morbidity, and

complications like CKD is well-established, particularly in critically ill patients and those

admitted to the ICU92. Sepsis stands out as a primary cause of AKI in these settings, though

the condition itself has multifactorial origins. Early detection and intervention are crucial to

mitigate its impact, as even milder forms of AKI can lead to long-term consequences like

CKD and increased mortality. Understanding the risk factors and outcomes of AKI in both

septic and non-septic patients in the ICU is vital for tailoring interventions and improving

patient outcomes in these critical care settings. This study shed light on the nuanced

differences in AKI development and management within these patient populations,

potentially informing more targeted approaches to prevention and treatment.

In the present study, 58.1% of the participants fell within the age range of 51-80 years, with a

mean age of 63.25±12.9 years. This contrasts with findings from other studies, where mean

ages ranged from 54.3±20.8 to 64.3±14.2 years, as reported by Oweis AO et al., Park WY et

al., and Cho E et al., respectively1,92,93,. Acute Kidney Injury (AKI) is more common among

individuals in their 60s due to several interconnected factors. Age-related physiological

changes, including decreased renal mass and renal blood flow, render older adults more

susceptible to kidney injury. The prevalence of comorbidities such as hypertension, diabetes,

and cardiovascular disease exacerbates this vulnerability, as these conditions can impair

kidney function. Polypharmacy, common among older adults for managing chronic illnesses,

increases the risk of nephrotoxicity from medications. Moreover, diminished physiological

reserve in older age reduces the body's ability to withstand stressors like infection or

hypoperfusion, which can trigger AKI. Additionally, the higher incidence of critical illnesses
requiring hospitalization, such as sepsis or cardiac surgery, further contributes to AKI

prevalence in this age group.

In the current research, around 58.1% of the individuals involved were male, mirroring

similar proportions found in prior studies: 59% in Magboul SM et al., 58% in Oweis AO et

al., 62.6% in Park WY et al., 60.6% in Hamzic-Mehmedbasic A et al., and 63.6% in Ying

WE et al1,2,92,94,95. Acute kidney injury (AKI) is more prevalent in males compared to

females, likely due to a combination of hormonal differences, with testosterone potentially

increasing risk while estrogen may offer protection, along with a higher prevalence of

underlying conditions such as hypertension, diabetes, and cardiovascular disease in males.

Behavioral and lifestyle factors such as smoking and excessive alcohol consumption,

occupational exposures, genetic predispositions, and differences in healthcare utilization may

also contribute to this gender disparity.

In the present study, there were no notable variations observed in the age and gender

demographics among individuals with septic and non-septic acute kidney injury (AKI)

groups. This lack of distinction suggests that factors such as age and gender are unlikely to

significantly influence the differentiation between septic and non-septic AKI cases within the

scope of this research inline with Cruz MG et al., Hamzic-Mehmedbasic A et al2,7.

In the current study sepsis emerged as the predominant factor, accounting for 50% of AKI

cases, followed by lower urinary tract obstruction (9.3%) and acute decompensated heart

failure (4.9%) among pre-renal causes. Within renal causes, enterocolitis, hemorrhagic fever

with renal syndrome (HFRS), and nephrotoxic drug-related acute tubular necrosis (ATN)

each contributed approximately 7.3%, 5.7%, and 5.7% respectively, with drug-induced acute

interstitial nephritis (AIN) and small-vessel vasculitis representing 4.1% and 2.8% of cases,

respectively. Post-renal causes encompassed infectious etiologies and acute cholecysto

pancreatitis, accounting for 7.7% and 2.5% of AKI cases, respectively. In a study by

Hamzic-Mehmedbasic A et al., most common causes of non-septic AKI: lower obstruction of

the urinary tract (18.18%), Hantavirus hemorrhagic fever with renal syndrome (HFRS)

(13.64%), hypovolemia due to acute enterocolitis (13.64%) and nephrotoxic drug-related

acute tubular necrosis (ATN) (10.61%)2.

In the study conducted by Hamzic-Mehmedbasic et al., sepsis was identified as the causative

factor for acute kidney injury (AKI) development in 34% of patients, whereas in the current

study, this figure was 50%2. Similarly, Bagshaw and Daher, along with their teams, reported

sepsis as a contributing factor in AKI for approximately 41.5% and 47.5% of patients,

respectively9,97. Comparatively, our study revealed a higher prevalence of hemorrhagic fever

with renal syndrome (HFRS), which could be attributed to the endemic nature of HFRS in the

Balkans, characterized by periodic outbreaks and sporadic cases documented annually since

the disease's recognition. Additionally, our study found a lower prevalence of nephrotoxic

drug-related acute tubular necrosis (ATN) compared to the BEST Kidney and PICARD

studies, but similar to the findings reported by Daher et al. and colleagues14,63,97.

In the current investigation, a notable variance in the prevalence of co-morbidities was

observed between individuals experiencing septic and non-septic acute kidney injury (AKI)

with the highest prevalence in Septic AKI patients which may be attributed to the systemic

inflammatory response associated with sepsis. This finding contrasts with the conclusions

drawn by Hamzic-Mehmedbasic et al2.

The diagnosis of AKI was based on the rise in serum creatinine in this study, 60 cases (24.4%)

were classified as Stage 1 AKIN, 123 cases (50%) as Stage 2, and 63 cases (25.6%) as Stage

3. This distribution significantly differed between septic and non-septic AKI, with the highest
proportion of Stage 3 cases observed in septic AKI and the highest proportion of Stage 1

cases seen in non-septic AKI.

In the current investigation, the outcomes observed among study participants underscore the

severity and varied clinical courses associated with acute kidney injury (AKI). Mortality

occurred in 47 individuals, representing a rate of 19.1%, while 100 participants experienced

partial recovery of creatinine levels. Notably, 25 subjects achieved normal creatinine levels,

indicating successful renal function restoration, yet 103 individuals required dialysis,

indicative of severe renal impairment. These findings emphasize the critical need for

effective management strategies in AKI cases, as well as the challenges in achieving

favorable outcomes.

Comparing current results with previous studies reveals notable differences. For instance,

Oweis AO reported a substantially higher mortality rate of 54.5%, contrasting with the 19.1%

mortality rate observed in this study92. Similarly, Hamzic-Mehmedbasic et al.'s findings align

with our results, indicating a significantly higher mortality rate among septic AKI patients

compared to non-septic2 AKI patients, thus emphasizing the impact of sepsis on AKI

outcomes. Pinheiro KH et al. highlighted longer ICU stays and increased mortality rates in

cases where kidney injury was compounded by sepsis, further corroborating the intricate

relationship between these conditions. Moreover, Tahir S et al. demonstrated increased

mortality rates and prolonged hospital stays in septic AKI patients compared to non-septic98

AKI patients, echoing the findings of this study and emphasizing the clinical significance of

sepsis in AKI outcomes.

STRENGTHS

● The study employed a prospective observational design, allowing for the collection of

detailed data on demographics, clinical characteristics, risk factors, and outcomes

among AKI patients in ICU settings.

● By including both septic and non-septic AKI patients, the study provides a

comprehensive understanding of AKI etiology, clinical course, and outcomes, thus

contributing to the existing literature on this topic.

● The study's clear inclusion and exclusion criteria help ensure that the sample

population is well-defined, enhancing the validity and reliability of the study findings.

LIMITATIONS

● The study was conducted at a single medical center, which may limit the

generalizability of the findings to other settings and populations.

● The study utilized simple random sampling, which may introduce selection bias, as

patients who consented to participate may differ systematically from those who

declined.

● The reliance on retrospective data extraction from medical records may introduce

errors or missing data, potentially impacting the accuracy and completeness of the

study findings.

RECOMMENDATIONS

● Future research should consider multicenter studies to enhance the generalizability

and robustness of findings across diverse patient populations and healthcare settings.

● Longitudinal studies tracking AKI patients over time could provide insights into the

trajectory of renal function recovery, complications, and long-term outcomes, thus

informing optimal management strategies.

 ● Investigating the efficacy of specific interventions or treatment protocols in improving

outcomes among AKI patients, particularly in the context of sepsis, could provide

valuable insights for clinical practice.

● Utilizing standardized data collection tools and protocols, along with prospective data

collection methods, could improve the accuracy and completeness of data, minimizing

errors and missing information.

● Further exploration of specific risk factors, such as medication exposure,

comorbidities, and ICU interventions, could help identify modifiable factors for

targeted interventions aimed at preventing AKI and improving outcomes.

SUMMARY

Demographic Characteristics and Distribution

The study analyzed data from 246 participants, predominantly aged between 51-80 (58.1%),

with males comprising 58.1% of the cohort. Equal representation was observed between

septic and non-septic cases (50% each), ensuring a balanced sample.

Etiologies of Acute Kidney Injury (AKI)

Pre-renal causes, notably sepsis, were predominant, followed by various renal and post-renal

factors. Sepsis accounted for 50% of AKI cases, while lower urinary tract obstruction and

acute decompensated heart failure followed.

Prevalent Co-morbidities
Hypertension was the most common co-morbidity (79.7%), followed by diabetes (53.7%).

Coronary artery disease (CAD) and chronic kidney disease (CKD) were also noted, with

varying frequencies.

Severity and Outcomes of AKI

AKIN stages revealed varying degrees of kidney injury, with Stage 2 being the most

prevalent. Mortality occurred in 19.1% of cases, with a significant proportion requiring

dialysis. Partial recovery was observed in 40.7% of cases, with 10.2% achieving normal

creatinine levels.

Comparison between Septic and Non-septic AKI

Both groups showed similar age and gender distributions. However, significant differences

were observed in co-morbidity prevalence. Septic AKI patients had higher rates of diabetes,

hypertension, CAD, and CKD. Septic AKI patients also showed a higher mortality rate,

longer hospital stays, and increased dialysis requirements compared to non-septic AKI

patients.

CONCLUSION

In conclusion, this study contributes valuable insights into the complex landscape of acute

kidney injury (AKI) within intensive care unit (ICU) settings, with a particular focus on the

distinctions between septic and non-septic AKI cases. Through a comprehensive evaluation

of demographics, clinical characteristics, risk factors, and outcomes among AKI patients, this

research sheds light on the multifactorial nature of AKI and its significant implications for

patient morbidity and mortality. The findings highlight several important observations.

Firstly, sepsis emerges as a predominant contributor to AKI, with half of the cases in this

study attributed to septic etiologies. This underscores the critical role of sepsis recognition
and management in AKI prevention and treatment strategies. Additionally, the study

elucidates the distinct clinical profiles and outcomes associated with septic AKI, including

higher mortality rates, prolonged hospital stays, and increased dialysis requirements

compared to non-septic AKI cases. The study also underscores the substantial burden of

comorbidities among AKI patients, particularly hypertension, diabetes, coronary artery

disease, and chronic kidney disease. These comorbidities not only increase the risk of AKI

development but also exacerbate its severity and complicate management strategies.

Despite these insights, the study is not without limitations, including its single-center design,

relatively small sample size, and potential for selection bias. Future research endeavors

should aim to address these limitations by conducting multicenter studies with larger sample

sizes and implementing standardized data collection methods to enhance the robustness and

generalizability of findings. Moving forward, interventions aimed at improving AKI

outcomes should prioritize early recognition and management of sepsis, personalized

treatment approaches tailored to individual patient profiles and risk factors, and ongoing

monitoring of renal function to mitigate complications and optimize patient care. By

addressing these challenges and leveraging emerging evidence, clinicians and researchers can

work collaboratively to enhance the management and outcomes of AKI in ICU populations,

ultimately improving patient morbidity and mortality rates.

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