Sepsis remains one of the leading causes of morbidity and mortality among critically ill patients worldwide and continues to impose a major burden on emergency departments and intensive care units. It is currently defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection, resulting in systemic inflammation, endothelial injury, circulatory failure, and multiorgan dysfunction (1). Despite advances in antimicrobial therapy, hemodynamic monitoring, and organ support strategies, sepsis continues to have high fatality rates, especially when associated with organ failure.

Among the various organ dysfunctions encountered in sepsis, acute kidney injury (AKI) is one of the most frequent and clinically significant complications. Sepsis-associated acute kidney injury (SA-AKI) develops in nearly 40–50% of patients admitted to intensive care units with sepsis and is strongly associated with prolonged hospitalisation, increased need for renal replacement therapy, and higher mortality (2,3). The pathogenesis of AKI in sepsis is complex and multifactorial. It involves renal hypoperfusion, intrarenal microcirculatory dysfunction, release of inflammatory cytokines, endothelial injury, mitochondrial dysfunction, and tubular cell apoptosis. Unlike ischemic AKI alone, septic AKI may occur even in the presence of preserved renal blood flow due to altered cellular metabolism and immune-mediated injury (4). This makes early diagnosis and prognostication particularly challenging. Patients with sepsis who develop AKI have significantly worse outcomes compared with septic patients without renal involvement, including increased rates of mechanical ventilation, vasopressor support, dialysis requirement, and in-hospital death. Serum creatinine is the most commonly used biochemical marker for assessing renal function and remains the cornerstone for diagnosing and staging AKI according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines (5).

It is inexpensive, universally available, and easily measurable even in resource-limited settings. Rising serum creatinine reflects a decline in glomerular filtration rate and worsening renal dysfunction. Although newer biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL), cystatin-C, kidney injury molecule-1 (KIM-1), and interleukin-18 have shown promise in early AKI detection, their availability and affordability remain limited in many tertiary care hospitals. Therefore, serum creatinine remains the most practical marker for bedside decision-making. Several previous studies have demonstrated that elevated serum creatinine levels in septic patients correlate with adverse outcomes. Bagshaw et al. reported that AKI severity in sepsis was independently associated with mortality and longer ICU stay (6). Hoste et al. observed that increasing creatinine-based AKI stage was linked with a progressive rise in the need for dialysis and death among critically ill patients (7). A multicenter observational study by Uchino et al. also showed that even modest increases in serum creatinine significantly increased the risk of mortality in hospitalised patients (8).

These findings suggest that serum creatinine is not merely a diagnostic parameter but also a prognostic indicator in septic patients. However, important research gaps still exist. Most earlier studies focused broadly on incidence and outcomes of AKI in critically ill populations rather than specifically examining the association between admission serum creatinine levels and clinical outcomes in sepsis patients already diagnosed with AKI. In addition, data from Indian tertiary care centres and geographically unique populations with high background prevalence of chronic kidney disease, tribal populations, dehydration, delayed healthcare access, and infectious disease burden remain sparse. Baseline renal dysfunction may affect the interpretation of serum creatinine, and regional epidemiological factors may influence outcomes differently than in Western cohorts.

Our tertiary care hospital caters to a large rural and tribal population with high rates of infectious diseases and frequent late presentation to the hospital. In such settings, serum creatinine remains one of the few readily available investigations that guide triage and treatment intensity. Determining whether higher serum creatinine levels are associated with increased need for mechanical ventilation, central venous access, emergency hemodialysis, prolonged ICU stay, and mortality would have substantial practical relevance. Hence, the present study was conducted to evaluate the association between serum creatinine levels and outcomes in patients with acute kidney injury and sepsis. The findings of this study may help in early risk stratification, prompt escalation of care, efficient resource allocation, and improved prognostication in patients with sepsis-associated AKI.

Source of Data

This study was conducted in the Department of Emergency Medicine, GEMS and Hospital, Srikakulam. Patients presenting with sepsis and acute kidney injury (AKI) during the study period were included after fulfilling eligibility criteria and providing informed consent.

Study Design

This was a prospective observational study in which patients diagnosed with sepsis and AKI at presentation were enrolled based on predefined criteria. All patients were followed throughout their hospital stay, and outcomes were systematically recorded.

Duration of Study and Sample Size

The study was conducted over 18 months, from April 2023 to September 2024. A total of 114 patients were included in the study. The sample size was calculated using a standard proportion formula with a 95% confidence interval (Z = 1.96), a margin of error of 9%, and an assumed prevalence of 50%, yielding an approximate sample size of 114.

Inclusion Criteria

• Age ≥18 years
• Diagnosed with sepsis based on the SOFA score
• Serum creatinine increased 2–3 times from baseline or GFR reduction of 50–75%
• Urine output <0.5 mL/kg/hour for at least 12 hours
• Presence of comorbidities
• Provided informed consent

Exclusion Criteria

• Pre-existing end-stage renal disease on dialysis
• Patients with retroviral disease
• Terminally ill patients
• Patients refusing dialysis or ventilator support
• Patients leaving against medical advice (LAMA)

Study Tool

• Structured case record proforma
• Included sections for demographics, clinical presentation, laboratory data, interventions, and outcomes
• Standardised documentation ensured uniform data collection

Data Collection

• Demographic details (age, sex)
• Clinical features (symptoms, SOFA score)
• Serum creatinine levels (baseline and serial monitoring)
• Urine output assessment
• Comorbid conditions
• Requirement of interventions:

o              Mechanical ventilation

o              Central venous line

o              Hemodialysis

• Duration parameters:

o              Emergency department stay

o              ICU stay

o              Total hospital stay

• Outcome (survival or mortality)

Investigations

• Complete blood count (Hb, TLC, DLC, ESR, platelets)
• Liver function tests
• Renal function tests (daily monitoring)
• Arterial blood gas (ABG)
• Chest X-ray
• ECG
• Blood and urine culture with sensitivity
• Viral markers

Statistical Analysis

Data were analysed using SPSS version 24. Continuous variables were expressed as mean ± standard deviation, while categorical variables were presented as frequencies and percentages. Comparison between low (<2.3 mg/dL) and high (≥2.3 mg/dL) serum creatinine groups was performed using an independent samples t-test for continuous variables and a chi-square or Fisher’s exact test for categorical variables. A p-value <0.05 was considered statistically significant.

Table 1: Baseline Demographic and Clinical Characteristics of Study Participants According to Serum Creatinine Groups.

Table 1 shows the baseline demographic characteristics of study participants, categorised by serum creatinine levels. The majority of patients in both groups were aged 51–60 years, accounting for 35.42% in Group 1 and 45.45% in Group 2, followed by those aged 61–70 years. The difference in age distribution between the two groups was not statistically significant (p=0.14), indicating comparable age characteristics. Male patients predominated in both groups, comprising 64.58% in Group 1 and 65.15% in Group 2, while females constituted 35.42% and 34.85%, respectively. Sex distribution was also comparable, with no significant difference. These findings suggest that both study groups were demographically similar at baseline.

Table 2: Distribution of Comorbidities and Risk Factors Among Study Participants According to Serum Creatinine Groups

Table 2 depicts the distribution of comorbid conditions and lifestyle-related risk factors among the two study groups. Diabetes mellitus was the most common comorbidity, observed in 54.17% of Group 1 and 46.97% of Group 2 patients. Hypertension was present in 43.75% of Group 1 compared to 28.79% of Group 2. Hyperlipidemia was noted in a smaller proportion of patients in both groups. The coexistence of diabetes mellitus with hypertension was significantly higher in Group 2 (40.91%) than in Group 1 (22.92%), with a statistically significant difference (p=0.001), indicating a greater burden of combined metabolic risk factors in patients with higher serum creatinine levels. Smoking history was present in 37.5% of Group 1 and 60.61% of Group 2, while alcohol use was reported in 22.92% and 43.94%, respectively; however, these differences were not statistically significant. Overall, patients with elevated serum creatinine had a higher prevalence of multiple associated risk factors.

Figure 1 illustrates the clinical presentation of patients at admission in both study groups. Pallor was the most common presenting sign and was observed more frequently in Group 2 (65.15%) compared to Group 1 (33.33%). Icterus was present in 36.36% of Group 2 patients, compared with 18.75% in Group 1. Cyanosis was also more common in Group 2 (25.76%) than in Group 1 (8.33%), suggesting greater systemic compromise among patients with higher serum creatinine levels. Oedema was observed in 45.45% of Group 2 compared to 6.25% of Group 1, indicating increased fluid retention or renal dysfunction in the high-creatinine group. Lymphadenopathy was noted in 16.67% of Group 2 and 2.08% of Group 1 patients. The overall difference in clinical presentation between the two groups was statistically significant (p=0.02). These findings suggest that patients with elevated serum creatinine presented with more severe and multisystem clinical manifestations.

Figure 2 shows the major therapeutic interventions required among patients in the two study groups. Hemodialysis was required in nearly half of patients in both groups, slightly higher in Group 1 (47.91%) than in Group 2 (45.40%), indicating substantial renal support needs in both groups. Inotropic support was required in 39.50% of Group 1 patients and 46.96% of Group 2 patients, reflecting a greater incidence of hemodynamic instability among patients with higher serum creatinine levels. Ventilator support was markedly higher in Group 2 (59.09%) compared to Group 1 (35.41%), suggesting more severe respiratory failure and critical illness in the elevated creatinine group. Overall, patients with higher serum creatinine required more intensive organ support measures, indicating a poorer clinical status and greater severity of sepsis-associated acute kidney injury.

Table 3: Comparison of Hospital Resource Utilization Among Study Participants According to Serum Creatinine Groups

Table 3 compares hospital resource utilization between the two study groups. The mean duration of emergency department stay was significantly longer in Group 2 (86.64 ± 13.67 hours) compared to Group 1 (32.72 ± 6.27 hours). Similarly, the mean ICU stay was markedly prolonged in Group 2 (4.73 ± 1.19 days) when compared with Group 1 (1.67 ± 0.83 days). Total hospital stay was also significantly higher among patients with elevated serum creatinine, with Group 2 staying for 15.34 ± 5.64 days versus 9.45 ± 3.15 days in Group 1. All differences were highly statistically significant (p=0.0001). These findings indicate that higher serum creatinine levels were associated with increased severity of illness, greater need for prolonged critical care, and higher utilization of hospital resources.

Table 4: Comparison of Clinical Outcome Among Study Participants According to Serum Creatinine Groups

Table 4 compares the final clinical outcomes between the two study groups. Survival was observed in the majority of patients in both groups; however, the proportion discharged alive was higher in Group 1 (95.83%) than in Group 2 (87.88%). Mortality was considerably higher among patients with elevated serum creatinine, with 12.12% deaths recorded in Group 2 as compared to 4.17% in Group 1. The difference in outcome between the two groups was statistically significant (p=0.05). These findings indicate that higher serum creatinine levels were associated with poorer prognosis and increased risk of mortality in sepsis patients with acute kidney injury.

This prospective observational study was conducted to evaluate the association between serum creatinine levels and clinical outcomes in sepsis patients with acute kidney injury (AKI). Serum creatinine remains the most practical and widely available marker of renal dysfunction in emergency and critical care settings, particularly in resource-limited institutions. In the present study, patients were categorised into two groups based on serum creatinine levels, and outcomes were compared. The findings clearly demonstrate that elevated serum creatinine was associated with increased disease severity, prolonged hospitalisation, greater requirement for organ support measures, and higher mortality. Age is a recognised determinant of both sepsis severity and renal dysfunction. In the present study, the majority of patients were in the 51–60-year age group, followed by 61–70 years, with no statistically significant difference between the two creatinine groups (p=0.14). This suggests that the age distribution was comparable and unlikely to confound the observed differences in outcomes. Similar age predominance in the fifth and sixth decades has been reported in Indian sepsis cohorts, where advancing age increases susceptibility to infection, endothelial dysfunction, and reduced renal reserve (11,12).

Chronic comorbid illnesses and immunosenescence may further contribute to worse outcomes in older adults. Male predominance was observed in both groups, accounting for nearly two-thirds of study participants. This pattern has been noted in previous studies of sepsis and AKI, likely reflecting greater prevalence of smoking, alcohol use, occupational exposure, and delayed healthcare-seeking behaviour among males in many populations (13). However, sex distribution was similar between groups and therefore did not explain differences in outcomes. Comorbidity burden was high in the present study. Diabetes mellitus was the most common associated illness, followed by hypertension. Importantly, the coexistence of diabetes and hypertension was significantly more common in the higher creatinine group (40.91% vs 22.92%, p=0.001). These findings are clinically relevant because both diabetes and hypertension predispose to chronic microvascular kidney injury, impaired renal autoregulation, and increased vulnerability to septic insults.

Patients with underlying metabolic disease may therefore experience more severe AKI when exposed to sepsis. Previous epidemiological studies have similarly shown that diabetes and hypertension independently increase the risk of septic AKI and adverse outcomes (14,15). Regarding presenting clinical features, pallor, icterus, cyanosis, oedema, and lymphadenopathy were more frequent in the high creatinine group, with overall significance (p=0.02). Pallor may indicate anemia of chronic disease, hemodilution, or occult nutritional deficiency. Icterus may reflect hepatic dysfunction, cholestasis, or multiorgan failure. Cyanosis suggests hypoxemia and severe circulatory compromise, while oedema indicates fluid overload, capillary leak, or renal sodium retention. These findings imply that patients with elevated creatinine presented with more advanced systemic illness and greater organ dysfunction. Similar observations were reported in multicenter ICU studies, showing that worsening renal function often parallels failure of other organ systems in sepsis (6,7).

The requirement for interventions was markedly higher in patients with elevated creatinine. Ventilator support was needed in 59.09% of Group 2 compared with 35.41% of Group 1. Inotropic support was also more common in the high creatinine group. This reflects the close pathophysiological interaction between renal dysfunction, respiratory failure, and circulatory shock. Fluid overload, metabolic acidosis, pulmonary oedema, and uremic complications may necessitate ventilatory support, while septic vasodilatation and myocardial depression increase vasopressor needs. Earlier studies have similarly shown that AKI severity in sepsis is strongly associated with the need for organ support therapies (16,17). Interestingly, the need for hemodialysis was high in both groups, though slightly higher in Group 1. This may reflect clinician-driven early dialysis decisions based on acidosis, electrolyte abnormalities, oliguria, or toxin clearance, rather than on the serum creatinine level alone. Current critical care practice emphasises a composite clinical approach rather than creatinine thresholds alone when initiating renal replacement therapy (18).

One of the most striking findings of the present study was the significant prolongation of hospital resource utilisation in the elevated creatinine group. Emergency department stay was markedly longer in Group 2 (86.64 ± 13.67 hours vs 32.72 ± 6.27 hours, p=0.0001). ICU stay was nearly three times higher (4.73 ± 1.19 days vs 1.67 ± 0.83 days), and total hospital stay was also significantly prolonged (15.34 ± 5.64 days vs 9.45 ± 3.15 days). These findings indicate that elevated creatinine identifies patients requiring more prolonged stabilisation, monitoring, and supportive care. Similar prolonged ICU and hospital stays among septic AKI patients have been reported in both Western and Asian cohorts (19,20). This has major implications for bed occupancy, healthcare expenditure, and workforce burden. Mortality was higher in the elevated creatinine group (12.12%) compared with the lower creatinine group (4.17%), reaching borderline statistical significance (p=0.05).

This supports the role of serum creatinine as a prognostic marker in sepsis-associated AKI. Rising creatinine reflects worsening glomerular filtration, accumulation of toxins, fluid imbalance, and often parallel progression of multiorgan dysfunction. Previous large-scale studies have consistently shown that even modest increases in serum creatinine are associated with increased mortality risk in hospitalized and critically ill patients (8,21). The present study therefore reinforces the prognostic importance of routine renal function testing in septic patients. The strengths of the present study include its prospective design, clinically relevant bedside outcomes, and real-world applicability in a tertiary care centre serving a high-risk population. However, certain limitations must be acknowledged.

This was a single-centre study with a moderate sample size. Baseline chronic kidney disease status may not have been fully characterised in all patients. Novel biomarkers and multivariable risk adjustment were not available. Despite these limitations, the study provides valuable evidence from an Indian clinical setting in which serum creatinine remains a key decision-making tool. Overall, the present findings strongly suggest that elevated serum creatinine in sepsis patients with AKI is associated with more severe illness, greater intervention requirements, prolonged hospitalisation, and higher mortality. Early recognition of rising creatinine should therefore prompt aggressive monitoring, hemodynamic optimisation, infection control, and timely nephrology involvement.

Serum creatinine is a simple, inexpensive, and clinically valuable prognostic marker in sepsis patients with acute kidney injury. Patients with higher creatinine levels had significantly greater comorbidity burden, worse clinical presentation, increased need for ventilatory and inotropic support, longer emergency department, ICU, and hospital stay, and higher mortality. Routine early assessment and serial monitoring of serum creatinine can help in prompt risk stratification and improve management outcomes in sepsis-associated AKI.

Conflict of Interest: Nil

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