No sex differences in the incidence, risk factors and clinical impact of acute kidney injury in critically ill patients with sepsis

Peng, Junnan; Tang, Rui; Yu, Qian; Wang, Daoxin; Qi, Dawei

doi:10.3389/fimmu.2022.895018

Cited by 4 publications

(6 citation statements)

References 59 publications

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“…Furthermore, Modra et al (2022) reported in a systematic review and meta-analysis of 545,538 ICU patients that women were less likely to receive invasive mechanical ventilation or renal replacement therapy [ 25 ]. However, Peng et al (2022) found no significant association between sex and the incidence of sepsis-associated acute kidney injury (SA-AKI) in 6463 patients [ 26 ].…”

Section: Discussionmentioning

confidence: 99%

“…As investigated in animal models, sexual immunomodulation, i.e., testosterone depletion or estrogen supplementation, affects the release of pro-inflammatory and anti-inflammatory cytokines, which are linked to multiorgan failure, and may result in beneficial outcomes in sepsis [ 30 , 31 ]. Additionally, ischemia-reperfusion injury is a common cause of AKI, and experimental studies suggest that sex hormones are involved in the regulation of cellular pathways of this injury and may therefore contribute to AKI susceptibility [ 26 , 32 , 33 ]. Furthermore, recently investigated biomarkers of mortality, such as free light chains (FLCs) or serum high mobility group box 1 (HMGB1), may serve as important parameters that reflect inflammation and immune dysfunction in CKD and AKI patients [ 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

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Association of Sex Differences with Mortality and Organ Dysfunction in Patients with Sepsis and Septic Shock

Mewes

Runzheimer

Böhnke³

et al. 2023

JPM

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Background: Despite recent advances in the clinical management and understanding of sepsis and septic shock, these complex clinical syndromes continue to have high mortality rates. The effect of sex on these diseases’ mortality, clinical presentation and morbidity remains controversial. This study aimed to investigate the association of sex with mortality and organ dysfunction in patients with sepsis and septic shock. Methods: Prospectively enrolled patients with clinically defined sepsis and septic shock in three intensive care units at University Medical Center Göttingen, Germany, were investigated. The primary outcomes were 28- and 90-day mortality, while the secondary endpoints included the evaluation of organ dysfunction as measured by clinical scores and laboratory parameters. Results: A total of 737 septic patients were enrolled, including 373 in septic shock, 484 males, and 253 females. No significant differences in 28- and 90-day mortality were observed in the cohort. However, men with sepsis had significantly higher SOFA scores, SOFA respiratory and renal subscores, bilirubin and creatinine values, and lower weight-adapted urine outputs, indicating higher organ dysfunction compared to women. Conclusions: Our findings revealed notable differences in organ dysfunction between male and female patients, with males exhibiting more pronounced dysfunction across multiple clinical indicators. These results highlight the potential influence of sex on sepsis disease severity and suggest the need for tailored approaches in sepsis management according to patient sex.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Association of Sex Differences with Mortality and Organ Dysfunction in Patients with Sepsis and Septic Shock

Mewes

Runzheimer

Böhnke³

et al. 2023

JPM

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“…Nevertheless, the choice of which fluids should be administered, for example, 0.9% saline versus colloids, depends upon various parameters. In early SA-AKI, a more aggressive fluid administration to restore hemodynamic stabilization seems mandatory, whereas in late SA-AKI, the main concern for clinicians is fluid overload [ 5 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ]. Apart from this major difference between the needs in early versus late SA-AKI, a more personalized approach, bearing in mind the performance status of each patient as well as comorbidities, should be pursued.…”

Section: Therapeutics Of Sa-aki: Current Knowledge and Future Perspec...mentioning

confidence: 99%

Sepsis-Associated Acute Kidney Injury: Where Are We Now?

Kounatidis,

Vallianou,

Psallida

et al. 2024

Medicina

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Worldwide, sepsis is a well-recognized cause of death. Acute kidney injury (AKI) may be related to sepsis in up to 70% of AKI cases. Sepsis-associated AKI (SA-AKI) is defined as the presence of AKI according to the Kidney Disease: Improving Global Outcomes criteria in the context of sepsis. SA-AKI is categorized into early, which presents during the first 48 h of sepsis, and late, presenting between 48 h and 7 days of sepsis. SA-AKI is associated with a worse prognosis among patients with sepsis. However, there are different SA-AKI phenotypes as well as different pathophysiological pathways of SA-AKI. The aim of this review is to provide an updated synopsis of the pathogenetic mechanisms underlying the development of SA-AKI as well as to analyze its different phenotypes and prognosis. In addition, potential novel diagnostic and prognostic biomarkers as well as therapeutic approaches are discussed. A plethora of mechanisms are implicated in the pathogenesis of SA-AKI, including inflammation and metabolic reprogramming during sepsis; various types of cell death such as apoptosis, necroptosis, pyroptosis and ferroptosis; autophagy and efferocytosis; and hemodynamic changes (macrovascular and microvascular dysfunction). Apart from urine output and serum creatinine levels, which have been incorporated in the definition of AKI, several serum and urinary diagnostic and prognostic biomarkers have also been developed, comprising, among others, interleukins 6, 8 and 18, osteoprotegerin, galectin-3, presepsin, cystatin C, NGAL, proenkephalin A, CCL-14, TIMP-2 and L-FABP as well as biomarkers stemming from multi-omics technologies and machine learning algorithms. Interestingly, the presence of long non-coding RNAs (lncRNAs) as well as microRNAs (miRNAs), such as PlncRNA-1, miR-22-3p, miR-526b, LncRNA NKILA, miR-140-5p and miR-214, which are implicated in the pathogenesis of SA-AKI, may also serve as potential therapeutic targets. The combination of omics technologies represents an innovative holistic approach toward providing a more integrated view of the molecular and physiological events underlying SA-AKI as well as for deciphering unique and specific phenotypes. Although more evidence is still necessary, it is expected that the incorporation of integrative omics may be useful not only for the early diagnosis and risk prognosis of SA-AKI, but also for the development of potential therapeutic targets that could revolutionize the management of SA-AKI in a personalized manner.

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“…No difference has been reported in the incidence of sepsis-associated acute kidney injury in men and women [ 68 ]. However, a meta-analysis of 21 studies including a total of 545,538 participants revealed that females were less likely to receive renal replacement therapy compared with males (adjusted OR 0.81 [0.73–0.89], I 2 = 57.4%) [ 69 ].…”

Section: Clinical Studiesmentioning

confidence: 99%

Interactions between Gender and Sepsis—Implications for the Future

et al. 2023

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Sex and gender dimorphisms are found in a large variety of diseases, including sepsis and septic shock which are more prevalent in men than in women. Animal models show that the host response to pathogens differs in females and males. This difference is partially explained by sex polarization of the intracellular pathways responding to pathogen–cell receptor interactions. Sex hormones seem to be responsible for this polarization, although other factors, such as chromosomal effects, have yet to be investigated. In brief, females are less susceptible to sepsis and seem to recover more effectively than males. Clinical observations produce more nuanced findings, but men consistently have a higher incidence of sepsis, and some reports also claim higher mortality rates. However, variables other than hormonal differences complicate the interaction between sex and sepsis, including comorbidities as well as social and cultural differences between men and women. Conflicting data have also been reported regarding sepsis-attributable mortality rates among pregnant women, compared with non-pregnant females. We believe that unraveling sex differences in the host response to sepsis and its treatment could be the first step in personalized, phenotype-based management of patients with sepsis and septic shock.

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No sex differences in the incidence, risk factors and clinical impact of acute kidney injury in critically ill patients with sepsis

Cited by 4 publications

References 59 publications

Association of Sex Differences with Mortality and Organ Dysfunction in Patients with Sepsis and Septic Shock

Association of Sex Differences with Mortality and Organ Dysfunction in Patients with Sepsis and Septic Shock

Sepsis-Associated Acute Kidney Injury: Where Are We Now?

Interactions between Gender and Sepsis—Implications for the Future

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