Discussion

Sepsis is a serious infection-related condition. It can quickly lead to organ dysfunction if not detected early [14]. In the present study, NLR and serum creatinine showed good value for early detection of sepsis-related organ dysfunction. These tests are simple, low-cost, and easily available in routine hospital laboratories. To our knowledge, this is one of the few studies from Pakistan to evaluate the combined predictive value of NLR and serum creatinine for sepsis-related organ dysfunction. The findings provide locally relevant evidence supporting the use of these inexpensive and routinely available biomarkers for early risk stratification in resource-limited healthcare settings.

Patients with organ dysfunction were older and had more diabetes, hypertension, and chronic kidney disease. This is logical because these patients already have a weak body reserve. In sepsis, infection causes inflammation, poor blood flow, and cellular injury. Older patients and those with chronic diseases are less able to tolerate this stress [15]. Therefore, they are more likely to develop organ dysfunction.

In our study, neutrophil count was higher in patients with organ dysfunction. Neutrophils are the first immune cells that respond to infection. During sepsis, their number increases due to bacterial infection and systemic inflammation. However, excessive neutrophil activity can also damage tissues by releasing enzymes and inflammatory mediators. In addition to neutrophilia, persistent lymphopenia is an important feature of sepsis-induced immune dysregulation. Apoptosis of lymphocytes contributes to immune suppression, reducing the host’s ability to eliminate pathogens and increasing susceptibility to secondary infections. Several studies have associated lymphopenia with prolonged intensive care unit stay, persistent organ dysfunction, and increased mortality, highlighting that the prognostic value of NLR reflects changes in both neutrophil activation and lymphocyte depletion [16]. This may explain the higher neutrophil count in patients with organ dysfunction.

Lymphocyte count was lower in the organ dysfunction group. This finding is also biologically acceptable. Severe sepsis can cause lymphocyte apoptosis and immune suppression. Low lymphocyte count shows poor immune regulation. When neutrophils increase and lymphocytes decrease, the NLR becomes high [17]. Therefore, NLR reflects both inflammation and immune weakness in one simple marker.

The mean NLR was significantly higher in patients with organ dysfunction. ROC analysis also showed good predictive ability of NLR. This finding agrees with previous studies and meta-analyses, which reported that higher NLR is linked with greater sepsis severity, higher SOFA score, and poor outcome [18]. NLR is useful because it is calculated from a routine CBC. It does not need any special kit or expensive test.

Serum creatinine was also significantly higher in patients with organ dysfunction. This is important because the kidney is commonly affected in sepsis. Sepsis can reduce renal perfusion and cause inflammatory injury to kidney tissue [10]. Raised creatinine may show early acute kidney injury or reduced renal clearance [9]. In our study, serum creatinine remained an independent predictor after adjustment for confounders. This supports its role as a practical marker of sepsis-related organ dysfunction.

White blood cell count was also higher in the organ dysfunction group. However, total WBC count alone may be less specific than NLR [7,19]. WBC count can increase due to infection, stress, dehydration, or medications. NLR gives better information because it includes both neutrophil rise and lymphocyte fall [20]. This may be the reason why NLR showed better predictive performance than serum creatinine in our ROC analysis.

Older age, diabetes mellitus, and chronic kidney disease remained independently associated with organ dysfunction after multivariable adjustment. However, these findings should be interpreted cautiously because they are well-established risk factors for adverse outcomes in sepsis, and the cross-sectional design does not permit causal inference. Residual confounding from unmeasured clinical factors may also have influenced these associations [9,21,22]. Nevertheless, NLR and serum creatinine remained significant independent predictors after adjustment, suggesting that both biomarkers provide additional predictive value beyond traditional clinical risk factors. These findings support their potential role in the early risk assessment of septic patients at hospital admission.

Patients presenting with an NLR greater than 8.3 and serum creatinine greater than 1.48 mg/dL may represent a higher-risk subgroup requiring closer clinical observation and more frequent reassessment for the development of organ dysfunction. These readily available biomarkers may complement, but should not replace, established clinical assessment tools. Their use may support early risk stratification and timely escalation of monitoring and supportive care according to the patient’s overall clinical condition. Because both tests are inexpensive and routinely available, they may be particularly useful in resource-limited healthcare settings where access to advanced biomarkers is restricted.

This study has some limitations. First, its single-center, cross-sectional design limits causal inference and may reduce the generalizability of the findings. Second, NLR and serum creatinine were measured only at hospital admission; therefore, temporal changes in these biomarkers and their relationship with disease progression could not be evaluated. Third, disease severity was not adjusted for using standardized severity scores such as SOFA in the multivariable regression model, which may have introduced residual confounding. Finally, external validation in larger multicenter cohorts with serial biomarker measurements is required before these findings can be generalized to broader populations.