Diagnostic Utility of Serum Soluble Urokinase-Type Plasminogen Activator Receptor in Acute Kidney Injury with Sepsis

Mir Rashedul Hasan^*,1, Md. Sohel Rana², Jebun Nahar³, Muslima Swapnil⁴, Amit Sarker⁵, Abdullah Hill Baki⁶

¹Resident Physician, Department of Nephrology, National Institute of Kidney Diseases and Urology (NIKDU), Sher E Bangla Nagar, Dhaka, Bangladesh

²Registrar, Department of Nephrology, Khulna Medical College & Hospital, Khulna, Bangladesh

³Assistant professor, Department of Child and Adolescent Psychiatry, National Institute of Mental Health, Dhaka, Bangladesh

⁴Dialysis Medical Officer, Department of Nephrology, Faridpur Medical College Hospital, Faridput, Bangladesh

⁵Medical officer, Department of Nephrology, District Hospital, Pirojpur, Bangladesh

⁶Associate Physician, Department of Nephrology, Shaheed Suhrawardy Medical College Hospital, Dhaka, Bangladesh

*Corresponding Author: Mir Rashedul Hasan, Resident Physician, Department of Nephrology, National Institute of Kidney Diseases and Urology (NIKDU), Sher E Bangla Nagar, Dhaka, Bangladesh.

Received: 21 July 2026; Accepted: 24 July 2026; Published: 07 August 2026

Introduction

The global prevalence of acute kidney injury (AKI) is rising. Acute kidney damage affects 2–5% of hospitalized individuals and has a significant impact on morbidity and health-care utilization. Critically ill patients bear the greatest burden of acute renal damage ^[1]. The condition is primarily caused by inflammation and oxidative stress, which include many immune cell subtypes ^[2]. Sepsis is potentially fatal infection-related disease that causes organ dysfunction ^[3]. Sepsis-associated AKI (S-AKI) is the most common type of AKI with a reported incidence of up to 59% ^[4]. S-AKI has been linked to poor clinical outcomes, including a higher risk of in-hospital death and longer hospital stays than other types of AKI ^[5]. Many clinical and basic studies have conducted in-depth discus­sions on S-AKI; however, effective measures to prevent and treat S-AKI remain elusive. Therefore, identifying biomarkers for S-AKI as early as possible is important to guide clinical treatment and improve patient outcomes. Soluble urokinase plasminogen activator receptor (suPAR), a circulating version of a glycosyl-phosphatidylinositol-anchored three-domain membrane protein, has been linked to kidney injury, according to pre-existing literature ^[6]. Endothelial cells, podocytes, and, with increased expression, immunologically active cells like monocytes and lymphocytes, all express this receptor typically at very low levels on a number of different cells. The suPAR is a promising biomarker that has been shown in recent studies to be useful for the diagnosis, assessment, and prognosis of a variety of diseases. This membrane protein has a molecular weight of about 55-60 kDa and a value of 2000 pg/ml has been found in healthy people ^[7]. In a recently published study, it was discussed that the suPAR might be directly involved in the pathogenesis of AKI in humans by sensitizing kidney proximal tubules to damage by modulating cellular energy production and increasing oxidative stress ^[8]. Subsequently, suPAR has emerged as a possible biomarker for sepsis ^[9]. In addition, suPAR is largely expressed by neutrophils, monocytes, macrophages, and activated T-cells under normal physiological settings, and its serum content is rather steady throughout the day ^[10]. While membrane-bound uPAR appears to facilitate bacterial phagocytosis, suPAR exhibits chemotactic characteristics and promotes neutrophil and monocyte recruitment ^[11]. Apart from infections, blood suPAR concentrations may be elevated in inflammatory disorders such as arthritis, cancer, and some glomerular disease ^[10].

In addition, several researchers have demonstrated increased systemic suPAR concentrations in critically ill patients with AKI compared to healthy controls. Currently, the assessment of kidney function in AKI patients is based on clinical judgment and conventional criteria: measuring the parameters indirectly indicative of glomerular filtration disturbances, such as serum creatinine, urea concentration, and urine output. Moreover, changes in serum creatinine concentration following kidney injury are delayed and not always representative of true kidney damage, therefore, ineffective in predicting outcome in AKI patients ^[12]. In recent years, the use of the suPAR and other markers of organ damage such as neutrophilic gelatinase-associated lipocalin (NGAL), cystatin C, kidney injury molecule 1 (KIM-1), tissue inhibitors of metalloproteinase-2 (TIMP-2), and insulin-like growth factor -7 binding protein (IGFBP-7) offer hope for the development of an algorithm in risk stratification, prevention and treatment of AKI ^[13]. This study was conducted to observe the diagnostic value of serum suPAR level in septic AKI, and relationship between serum suPAR level and other markers of infection (ESR, CRP, Procalcitonin) in AKI with sepsis. The findings of this investigation will aid early diagnosis and treatment of patients with septic AKI and thus help to reduce morbidity and mortality of patients with septic AKI.

Methods

Study design and participants

This cross-sectional analytical study was conducted in the Department of Nephrology, Dhaka Medical College Hospital, Bangladesh, between September 2022 and February 2024. Ethical approval was obtained from the Ethical Review Committee of Dhaka Medical College before study commencement.

A total of 66 participants were enrolled using purposive convenience sampling, comprising 33 consecutive adult patients with sepsis-associated acute kidney injury (AKI) (Group A) and 33 apparently healthy volunteers without evidence of acute or chronic inflammatory or renal disease (Group B). Written informed consent was obtained from all participants prior to enrollment.

Adult patients (≥18 years) with sepsis-associated acute kidney injury (AKI) were included in Group A. Sepsis was identified using the quick Sequential Organ Failure Assessment (qSOFA) criteria, and AKI was diagnosed and staged according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Patients with chronic kidney disease, glomerulonephritis, inflammatory arthritis, malignancy, burn injury, pregnancy, or lactation were excluded.

Data collection and laboratory measurements

Demographic information, clinical characteristics, and laboratory findings were collected using a standardized case record form. Laboratory investigations included complete blood count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum procalcitonin, serum creatinine, and other routine investigations as clinically indicated.

Venous blood samples were collected at baseline before initiation of treatment. Serum soluble urokinase plasminogen activator receptor (suPAR) concentrations were measured using a commercially available enzyme-linked immunosorbent assay (ELISA) kit (Catalog No. MBS2526189) according to the manufacturer's instructions at the Department of Transfusion Medicine, National Institute of Burn and Plastic Surgery, Dhaka.

Statistical analysis

Data were analyzed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation (SD) or median (interquartile range), as appropriate, while categorical variables were presented as frequencies and percentages. Comparisons between groups were performed using the independent t-test for continuous variables and the chi-square test for categorical variables. Pearson's correlation analysis was used to assess the association between serum suPAR levels and laboratory parameters. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of serum suPAR and determine the optimal cut-off value. Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy were calculated. A two-sided p value <0.05 was considered statistically significant.

Results

Table 1: Baseline characteristics of the study participants (n = 66)

Values are presented as mean ± SD or n (%). Continuous variables were compared using the independent t-test and categorical variables using the χ² test. A p-value <0.05 was considered statistically significant.

The mean age was comparable between the two groups (45.67 ± 15.56 vs. 38.27 ± 16.51 years; p=0.085). Similarly, there was no significant difference in sex distribution, with males accounting for 48.5% of the AKI with sepsis group and 60.6% of the control group (p=0.323). Table 1 describes the baseline characteristics of the participants.

Table 2: Comparison of laboratory parameters between the study groups (n = 66)

Values are expressed as mean ± SD. Independent t-test was used. A p-value <0.05 was considered statistically significant.

Patients with sepsis-associated AKI exhibited significantly higher inflammatory and renal function markers than healthy controls. Mean WBC count, ESR, CRP, serum procalcitonin, serum creatinine, and serum suPAR levels were all significantly elevated in the AKI with sepsis group (all p<0.05). Table 2 compares the different laboratory parameters between the study groups.

Figure 1: Receiver operating characteristic (ROC) curve of serum suPAR for diagnosing sepsis-associated AKI.

ROC curve analysis demonstrated excellent diagnostic performance of serum suPAR for identifying sepsis-associated AKI, with an area under the curve (AUC) of 0.917 (95% CI: 0.855–0.979; p<0.001).

Table 3: Diagnostic performance of serum suPAR for the diagnosis of sepsis-associated AKI

AUC, area under the receiver operating characteristic curve; CI, confidence interval; PPV, positive predictive value; NPV, negative predictive value

Using a serum suPAR cut-off value of ≥4.15 ng/mL, the biomarker demonstrated a sensitivity of 78.8% and specificity of 81.8% for diagnosing sepsis-associated AKI. The corresponding PPV, NPV, and overall diagnostic accuracy were found to be 81.3%, 79.4%, and 80.3% respectively. Table 3 highlights the diagnostic performance of serum suPAR for the diagnosis of sepsis-associated AKI.

Table 4: Correlation between serum suPAR and laboratory parameters

Pearson correlation was used. A p-value <0.05 was considered statistically significant.

Serum suPAR levels demonstrated significant positive correlations with all evaluated laboratory parameters (p<0.05). Moderate positive correlations were observed with WBC count (r=0.473), ESR (r=0.602), CRP (r=0.538), and serum creatinine (r=0.596), while a weak positive correlation was found with serum procalcitonin (r=0.333). The strongest correlations were observed with ESR and serum creatinine. Table 4 explains the correlation between serum suPAR and laboratory parameters.

Discussion

Sepsis-associated AKI remains a major contributor to morbidity and mortality among critically ill patients, highlighting the need for reliable biomarkers for early diagnosis. In the present study, patients with sepsis-associated AKI had significantly higher serum suPAR levels than healthy controls. As suPAR is released following activation of immune and inflammatory pathways, elevated circulating levels likely reflect the heightened inflammatory response associated with sepsis and renal injury. Previous studies by Desmedt et al., Chew-Harris et al., and Peerapornratana et al. have similarly reported low circulating suPAR concentrations in healthy individuals and significantly elevated levels in patients with sepsis and AKI, supporting its role as a marker of systemic inflammation and kidney injury ^{[10, 14, 15]}. Moreover, Zhang et al. also demonstrated persistently higher suPAR concentrations in patients with sepsis-associated AKI compared with septic patients without AKI, similar to our findings ^[16].

In addition, a key finding of this study was the excellent diagnostic performance of serum suPAR for identifying sepsis-associated AKI. Receiver operating characteristic analysis yielded an AUC of 0.917, with a cut-off value of ≥4.15 ng/mL providing good sensitivity (78.8%) and specificity (81.8%). Although studies specifically evaluating suPAR in sepsis-associated AKI remain limited, our findings compare favorably with those reported by Zhang et al. who identified an optimal cut-off value of 4.72 ng/mL with a lower AUC of 0.671 ^[16]. Similarly, studies conducted in other clinical settings have consistently demonstrated the utility of suPAR in predicting AKI, including patients undergoing percutaneous coronary intervention, emergency department admissions, and cardiac surgery by Qin et al., Walls et al., and Mossanen et al. respectively ^[17-19]. Furthermore, recent meta-analyses by Jankowski et al. and Huang et al. have confirmed that elevated suPAR levels are associated with AKI development and possess moderate-to-good diagnostic performance across diverse patient populations ^{[20, 21]}. The higher diagnostic accuracy observed in the present study may be explained by variations in patient population, disease severity, and study design.

Importantly, serum suPAR levels also demonstrated significant positive correlations with serum creatinine and inflammatory biomarkers, including WBC count, ESR, CRP, and procalcitonin. The strongest correlations were observed with ESR and serum creatinine, which suggest that increasing suPAR levels parallel both inflammatory activity and the severity of renal dysfunction. Our findings are similar with those of Iversen et al., who reported a positive association between suPAR and CRP as well as an accelerated decline in renal function among individuals with elevated suPAR concentrations ^[22].

Collectively, these findings support the potential role of serum suPAR as an adjunctive biomarker for the diagnosis of sepsis-associated AKI. Its significant association with established inflammatory markers and renal function indices, together with its excellent diagnostic performance, suggests that suPAR may complement conventional laboratory parameters for the early identification of patients at risk of AKI in the setting of sepsis. Nevertheless, the relatively small sample size and single-center design require cautious interpretation, and larger multicenter prospective studies are recommended to validate these findings and establish the clinical utility of serum suPAR in routine practice.

Conclusion

Patients with AKI and sepsis exhibited notably higher suPAR levels compared to non-AKI individuals, indicating its potential as a diagnostic marker with high accuracy for predicting AKI in sepsis. Measurements of suPAR routinely may therefore aid in the early detection of kidney disease in septic patients, irrespective of its exact molecular mechanisms. Additionally, considering the significant association between suPAR and declining renal function, incorporation of suPAR into predictive models for kidney disease is recommended.

Conflict of interest

The authors disclose no conflict of interest.

Sponsorship and/or funding

Not applicable.

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