Fatty acid‐binding protein 4 (FABP4) has been confirmed to be involved in the pathogenesis of ischaemia/reperfusion‐ and rhabdomyolysis‐induced acute kidney injury (AKI), and targeting inhibition of FABP4 might be a potential strategy for AKI. Cisplatin as a commonly used cancer chemotherapeutic drug possessed a dose‐limited side effect of nephrotoxicity. However, whether FABP4 inhibition exerted a favourable renoprotection against cisplatin‐induced AKI and the involved mechanisms remained unknown. In the study, cisplatin‐injected mice developed severe AKI symptom as indicated by renal dysfunction and pathological changes, companied by the high expression of FABP4 in tubular epithelial cells. Selective inhibition of FABP4 by BMS309403 at 40 mg/kg/d for 3 days and genetic knockout of FABP4 significantly attenuated the serum creatinine, blood urea nitrogen level and renal tubular damage. Mechanistically, cisplatin injection induced the increased apoptosis and regulated the corresponding protein expression of BCL‐2, BCL‐XL, BAX, cleaved caspase 3 and caspase 12 in the injured kidney tissues. Cisplatin also triggered multiple signal mediators of endoplasmic reticulum (ER) stress including double‐stranded RNA‐activated protein kinase‐like ER kinase, activating transcription factor‐6 and inositol‐requiring enzyme‐1 pathway, as well as CHOP, GRP78 and p‐JNK proteins in the kidneys. Oral administration of BMS309403 significantly reduced the number of renal TUNEL‐positive apoptotic cells. Knockout of FABP4 and BMS309403 notably improved ER stress‐related apoptotic responses. In summary, pharmacological and genetic inhibition of FABP4 modulated apoptosis via the inactivation of ER stress in the tubular epithelial cells of cisplatin‐induced AKI.

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Sepsis is a systemic inflammatory state in response to infection, and concomitant acute kidney injury (AKI) significantly increases morbidity and mortality. Growing evidence suggests that fatty acid-binding protein 4 (FABP4) is critically involved in kidney diseases, while its role in septic AKI remains unknown. Here, FABP4 was mainly upregulated in renal tubular epithelial cells (RTECs) following cecal ligation and puncture (CLP)- or lipopolysaccharide (LPS)-induced septic AKI. FABP4 inhibition by genetic deletion or BMS309403 treatment both attenuated kidney dysfunction and pathological injury in CLP- or LPS-treated mice. Notably, RTEC-specific deletion of FABP4 also showed similar renoprotective effects. Moreover, FABP4 inhibition alleviated inflammation and apoptosis in CLP-injured kidneys and LPS-stimulated mouse tubular epithelial cells. Mechanistically, TLR4 blockage improved sepsis-induced kidney injury, as well as suppressed c-Jun phosphorylation and FABP4 expression, where c-Jun knockdown also inhibited LPS-stimulated FABP4 level. Meanwhile, FABP4 inhibition reduced the elevated phosphorylated c-Jun, while the levels of TLR4 and MyD88 were uninfluenced. Collectively, the increased FABP4 in RTECs is dependent on TLR4/c-Jun signaling activation and contributes to kidney injury, by forming a positive feedback loop with c-Jun to aggravate inflammation and apoptosis in septic AKI. Thus, FABP4 may be a therapeutic target for septic AKI.

Objective: To explore the effects of anxiety and depression on the self-management ability and endogenous creatinine clearance rate of renal transplant patients.Method: Eighty-eight renal transplant recipients who were followed up in the outpatient clinic of the Affiliated Hospital of Zunyi Medical University were selected using convenient sampling. The self-made general data sheet, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and Self-Management Scale for Kidney Transplant Recipients were used. Correlation analysis was used to find factors related to endogenous creatinine clearance, while multiple linear regression was used to identify factors influencing endogenous creatinine clearance. Patients with or without anxiety and depression were divided into groups, and the indexes of the groups were compared using the independent samples t test, rank-sum test, or chi-squared test.Results: Anxiety was present in 12.5% of patients, depression in 25%, and a moderate level of self-management in 34.1%. Only 9.1% of renal transplant recipients had endogenous creatinine clearance within the normal range, and 34.1% had a body mass index not in the normal range (25% were overweight, and 9.1% were underweight). The endogenous creatinine clearance rate was negatively correlated with age and degree of depression, and positively correlated with body mass index, treatment management score, and psychosocial management score. The main influencing factors of endogenous creatinine clearance rate were age, sex, depression, body mass index, and treatment management score. The endogenous creatinine clearance rate and psychosocial management ability were significantly higher in patients without anxiety and depression than in patients with anxiety and depression (all P < 0.05).Conclusions: Anxiety and depression showed significant negative effects on the psychosocial self-management ability and endogenous creatinine clearance rate of renal transplant recipients and thus should be given more attention.