Acute pyelonephritis is an inflammatory condition significantly affecting the renal parenchyma, predominantly caused by various pathogens, especially bacteria. When this condition is accompanied by upper urinary tract obstruction, it is known as Acute Obstructive Pyelonephritis (AOP), which may result from urinary stones, ureteral strictures, or external pressures on the urinary tract1. Notably, pyelonephritis is classified as the fifth most common kidney disease, with AOP impacting a significant 84% of individuals suffering from all types of pyelonephritis1. The progression to urosepsis and bacteriotoxic shock in AOP cases is a dangerously high possibility, presenting a mortality risk of 70-90%2. These statistics underscore the need for immediate attention and action, positioning AOP as a predominant concern in urological emergencies.

The Complete Blood Count (CBC) stands as a foundational diagnostic tool in clinical practices. This accessible, economical test provides crucial insights into the blood's fundamental elements—red cells, white cells, and platelets—thereby reflecting the body’s reaction to infection, inflammation, and an array of conditions including cancer. Emerging research has spotlighted a number of pertinent hematological markers such as the Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and the Systemic Immune-Inflammation Index (SII). These indices are gaining recognition for their role in gauging the immune system's response to both infectious and non-infectious factors3, 4, 5. Elevated levels of NLR, PLR, or SII are increasingly associated with less favorable health outcomes, enhancing their utility as diagnostic and prognostic indicators for a wide spectrum of diseases, encompassing cardiovascular disorders, respiratory conditions, rheumatic diseases, and various cancers—gastric, lung, colorectal, and ovarian malignancies, among others, even stretching to urologic ailments3, 4, 5.

This paper aims to assess the prognostic importance of these hematological indices, derived from admission-phase CBC, in forecasting the development of septic shock in AOP patients. Through this lens, we seek to advance our understanding and approach towards effectively managing this critical urological emergency.

Among the 60 patients diagnosed with AOP (Acute obstructive pyelonephritis), 36.7% (22 patients) developed septic shock, a severe complication of AOP. These patients had a median age of 60.13 years, ranging from 21 to 103 years, with a gender distribution of 13 men to 47 women.

In comparing the characteristics of patients with and without septic shock (as shown in Table 1), those in the septic shock group were found to have a higher prevalence of diabetes mellitus (59.1% versus 31.6%, p = 0.037), a lower platelet count (181.27 ± 95.08 vs 302.68 ± 150.78, p < 0.001), a lower lymphocyte count (1.06 ± 0.62 vs 1.48 ± 0.83, p = 0.043), and a higher Neutrophil-to-lymphocyte ratio (NLR) (21.01 ± 12.18 vs 14.20 ± 12.89, p = 0.049). Meanwhile, factors such as age, gender, White Blood Cell (WBC) count, Neutrophil (N) count, Platelet-to-lymphocyte ratio (PLR), and Systemic Immune-Inflammation Index (SII) showed no significant differences between the two groups.

Thresholds for certain laboratory values were defined as thrombocytopenia (platelet count less than 150 x 10⁹/L) and lymphopenia (total lymphocyte count less than 1 x 10⁹/L). An NLR cut-off value was established at 8.7, with the Area Under the Curve (AUC) calculated to be 0.70, demonstrating a sensitivity of 95.5% and specificity of 39.5% (p = 0.012).

Further analysis through Multivariate Logistic Regression (Table 2) revealed that a history of diabetes mellitus, an elevated NLR equal to or greater than 8.7, and thrombocytopenia were independently associated with an increased risk of developing septic shock in the context of AOP. Specifically, patients with diabetes mellitus were around 4.8 times more likely to develop septic shock (OR = 4.773, 95% CI = 1.248-18.253, p = 0.022), those with an NLR ≥ 8.7 were about 12.5 times more likely (OR = 12.529, 95% CI = 1.272-123.426, p = 0.03), and patients with thrombocytopenia were roughly 4.4 times more likely to develop septic shock (OR = 4.375, 95% CI = 1.008-18.987, p = 0.049. Nevertheless, patients with lymphopenia were significantly less likely to progress septic shock due to AOP (OR = 2.132, 95% CI = 0.541-8.397, p = 0.279). These findings emphasize the importance of these factors in assessing the risk and managing patients with AOP to prevent the onset of septic shock.

The urinary tract infection is the second or third most common cause of septic shock. It accounted for 6.2% to 38% of patients diagnosed with severe sepsis or septic shock6. Obstructive pyelonephritis is a complicated urinary tract infection requiring medical-surgical emergency intervention due to the possibility of serious consequences like bacteremia or uroseptic shock. Risk factors evaluated to predict the worsening development into septic shock in acute obstructive pyelonephritis (AOP) include diabetes mellitus (DM), procalcitonin, C-reactive protein, age, neutrophil count, serum creatinine level, serum albumin level, and platelet count2, 6, 8, 9.

Additionally, we discovered in this study that septic shock was more common in patients with DM than in those without, with p = 0.037. DM has always been associated with an increased risk of urinary tract infection, mostly due to glycosuria, which is exacerbated by obstruction. Furthermore, DM significantly induces peripheral neuropathy and an immunosuppressive condition, which may attenuate the host defense against urinary pathogens as well as the efficacy of the urinary apparatus’s sensory and voiding functions1.

Upon evaluating hematological indices obtained from the peripheral blood count upon admission, we found a lower lymphocyte count, lower platelet count, and a greater NLR in the septic shock group, compared with the non-septic group. In multivariate logistic regression analysis, only higher NLR and thrombocytopenia were independent factors for uroseptic shock. Numerous investigations demonstrate a substantial correlation between severe sepsis and the reduction in platelets1. Thrombocytopenia is an important criterion of the SOFA score, a useful tool to determine the severity of organ dysfunction in critically ill patients7. Decreased platelet generation, hemodilution, platelet consumption, elevated platelet sequestration in microvessles, and immune-mediated platelet destruction contribute to the declined peripheral platelet count in sepsis. In the severe forms of sepsis, disseminated intravascular coagulation (DIC) is diagnosed by the widespread activation of coagulation inducing thrombotic occlusion in small and mid-sized vessels. The platelets consumption via thrombin-mediated activation in concurrent DIC, triggered by cell-specific membrane components of microorganisms, results in the subsequent depletion of platelets. Furthermore, the activated platelets can encourage the recruitment of neutrophils to the site of injury and promote the formation of neutrophil extracellular traps (NETs) to capture and eliminate pathogens9, 10.Regarding the neutrophil-to-lymphocyte ratio (NLR), Zahorec (2001) first proposed the formula of the ratio between neutrophil and lymphocyte counts, which represents the two arms of the immune system: the innate immune response (neutrophil) and the adaptive immune response (lymphocyte)11. Since then, the Zahorec index, also known as NLR, has been the subject of much research in infectious diseases. It has been proposed as a biomarker for invasive systemic inflammatory responses in oncological diseases and other conditions5. For sepsis and a variety of infection types with different etiologies, NLR is a fairly sensitive but non-specific indication12. According to Zahorec, an adult’s physiological NLR value should normally fall between 1 and 2, with values more than 3 or less than 0.7 suggesting abnormal conditions5. This may be regarded as a novel biomarker within the panel of inflammatory responses like C-reactive protein (CRP), procalcitonin, interleukin-6, lactate, and platelet counts13, 14, 15. Ljungstrom et al. assessed the efficacy of several indicators in a total of 1572 adult patients for identifying bacterial sepsis. The outcomes demonstrated that NLR performed similarly to CRP and PCT. With a threshold of 3 (the upper limit of normal), NLR has a greater sensitivity for sepsis (95%) when compared to other tests. Sepsis is thus ruled out by a normal NLR (< 3). On the other hand, an NLR considerably more than 10 would support a sepsis diagnosis13. De Jager et al. found that lymphocytopenia and NLR outperformed CRP and the total count of white blood cells (WBC) for the diagnosis of bacteremia15. In our study, we found the cutoff for admission NLR was 8.7 with AUC = 0.70 (Sensitivity = 95.5% and Specificity = 39.5, p = 0.012) in diagnosing septic shock due to AOP. In a univariate analysis, there were also more patients with lymphocytopenia in the septic shock group than in the non-septic shock group, while no significant difference in the total white blood cell count and neutrophil count was found. Furthermore, the fluctuation of NLR may be utilized to forecast the severity of septic shock as well as the mortality risk12. A dynamic increase in NLR was associated with late death after five days14. Monitoring of NLR levels is necessary to assess the severity of sepsis, inflammatory response, and mortality risk. Sari et al. reported that non-responders or non-survivors had a very high NLR ≥ 15 on the third day of intensive care unit (ICU) stay, with a mortality odds ratio of 6.9616. Thus far, the three fundamental indicators are considered as the gold standard laboratory tests for monitoring sepsis and septic shock, including C-reactive protein, procalcitonin, and NLR12. Although NLR emerged as a routine, informative, and cost-effective biomarker, it has high sensitivity and low specificity because it can be influenced by various factors like age, race, medicine, diabetes, obesity, mental health, cancer, anemia, and stress5.

In this paper, we acknowledge some limitations, such as the small sample size, assessment only at the time of admission, and not considering the mortality risk of the patients as well as medical intervention.

In conclusion, this study highlights the significance of the neutrophil-to-lymphocyte ratio (NLR) ≥ 8.7, thrombocytopenia, and diabetes mellitus as important predictors for the onset of septic shock in individuals with acute obstructive pyelonephritis (AOP). Our findings reinforce the utility of routine hematological parameters, easily obtainable from complete blood counts at admission, in identifying patients at heightened risk for this serious complication. Given the potential for septic shock to rapidly deteriorate patient outcomes, early recognition of these risk factors permits timely intervention and close monitoring, thereby possibly improving the management and prognosis of AOP. This study underscores the value of integrating simple hematological indices with clinical evaluation to stratify risk and optimize care for patients facing this urological emergency.

AOP - Acute Obstructive Pyelonephritis, AUC - Area Under the Curve, CBC - Complete Blood Count, C.I - Confidence Interval, CRP - C-reactive Protein, CT - Computed Tomography, DM - Diabetes Mellitus, ICU - Intensive Care Unit, L - Lymphocyte count, N - Neutrophil count, NLR - Neutrophil-to-Lymphocyte Ratio, OR - Odds Ratio, P - Platelet count, PLR - Platelet-to-Lymphocyte Ratio, qSOFA - quick Sequential [Sepsis-related] Organ Failure AssessmentSII - Systemic Immune-Inflammation Index, SOFA - Sequential [Sepsis-related] Organ Failure Assessment, WBC - White Blood Cell count

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Study concept and design: Minh Hoang Truong, Trung Quang Ngo, Phong Thanh Tran; Data acquisition: Trung Quang Ngo, Quang Thanh Nguyen, Phat Thanh To

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Data and materials used and/or analyzed during the current study are available from the corresponding author on reasonable request.

This study’s procedures involving human subjects were carried out with the approval by the ethical standards of the People’s Hospital 115 ethics committee (1562/BVND115-NCKH). This was a retrospective cohort study, therefore, the informed consent to participate was waived by the Instituition Review Board of People’s Hospital 115.

Not applicable.

The authors declare that they have no competing interests.