Gastrointestinal tumors remain a global health problem. Acute kidney injury (AKI) is a common complication during the treatment of gastrointestinal tumors. AKI can cause a decrease in the remission rate and an increase in mortality. In this review, we analyzed the causes and risk factors for AKI in gastrointestinal tumor patients. The possible mechanisms of AKI were divided into three groups: pretreatment, intrafraction and post-treatment causes. Treatment and prevention measures were proposed according to various factors to provide guidance to clinicians and oncologists that can reduce the incidence of AKI and improve the quality of life and survival rate of gastrointestinal tumor patients.

Background/Objectives: Hemodialysis-induced myocardial stunning (HIMS) is a frequent complication in patients undergoing maintenance hemodialysis, characterized by transient left ventricular dysfunction due to ischemic episodes. Mitochondrial dysfunction and fluctuations in key ions such as potassium (K⁺) and calcium (Ca²⁺) are implicated in the pathogenesis of HIMS. This study aims to investigate the role of mitochondrial dysfunction and the protective potential of mitochondrial ATP-sensitive potassium channels (mitoK_ATP) in mitigating HIMS. Methods: A 5/6 nephrectomy rat model was established to mimic chronic kidney disease and the subsequent HIMS. The effects of mitoK_ATP channel modulators were evaluated by administering diazoxide (DZX), a mitoK_ATP opener, and 5-hydroxydecanoate (5-HD), a mitoK_ATP blocker, before hemodialysis. Mitochondrial function was assessed by measuring membrane potential, ATP synthase activity, and intramitochondrial Ca²⁺ levels. Myocardial function was evaluated using speckle tracking echocardiography. Results: Rats undergoing hemodialysis exhibited significant reductions in left ventricular strain and synchrony. DZX administration significantly improved mitochondrial function and reduced myocardial strain compared to controls. Conversely, 5-HD worsened mitochondrial swelling and disrupted myocardial function. Higher K⁺ and Ca²⁺ concentrations in the dialysate were associated with improved mitochondrial energy metabolism and myocardial strain. Conclusions: Mitochondrial dysfunction and ion imbalances during hemodialysis are key contributors to HIMS. The activation of mitoK_ATP channels provides mitochondrial protection and may serve as a potential therapeutic strategy to mitigate HIMS.

Acute kidney injury (AKI) is recognized as a critical clinical problem, and pharmacological therapeutic options for AKI remain limited. Our previous study confirmed that Rac GTPase-activating protein 1 (RacGAP1) effectively promoted the repair of tubular epithelial cells in vitro. Further investigation is needed to determine whether boosting the expression of RacGAP1 in vivo helps protect against AKI. Herein, lipid-coated calcium phosphate (LCP) nanoparticles loaded with RacGAP1 plasmids (pRacGAP1-LCP) were generated and subsequently characterized based on their size, zeta potential, and morphological features. Animal models of AKI induced by ischemia/reperfusion (I/R) injury (IRI) were established in C57BL/6 mice, and pRacGAP1-LCP was injected into the tail vein to explore the role of RacGAP1 on renal IRI in vivo. The therapeutic efficacy of pRacGAP1-LCP against IRI was assessed through western blotting, real-time PCR, and histological analyses. The effects of RacGAP1 on mitochondrial homeostasis were further examined in mouse renal tubular epithelial cells (mRTECs). Serial administrations of pRacGAP1-LCP led to a significant increase in RacGAP1 expression in murine kidneys. This therapeutic intervention effectively attenuated AKI, as evidenced by down-regulation of AKI biomarkers, amelioration of renal histopathological damage, and suppression of both apoptosis and inflammatory responses. Characteristic mitochondrial abnormalities, diminished ATP production, and excessive lipid droplet accumulation were observed in tubular cells of IRI mice. Notably, pRacGAP1-LCP treatment reversed these pathological alterations and up-regulated the expression of PGC-1α and CPT-1α, indicating that RacGAP1 exerted its reno-protective effects through enhanced mitochondrial biogenesis and fatty acid oxidation (FAO). To further investigate the role of RacGAP1 in mitochondrial homeostasis, we employed an ATP depletion-repletion (ATP D-R) model in mRTECs. Crucially, RacGAP1 effectively restored ATP production, mtDNA copy number, and oxygen consumption rate (OCR) in mRTECs after ATP D-R treatment. RacGAP1 overexpression also suppressed mitochondrial depolarization, fragmentation, and reactive oxygen species (ROS) generation. Conversely, RacGAP1 knockdown exacerbated mitochondrial defects in mRTECs exposed to ATP D-R. In summary, this study uncovers that RacGAP1 overexpression protects against renal injury and mitochondrial dysfunction, highlighting its therapeutic promise for AKI. The LCP nanoparticle exhibits potential as a precise and efficient delivery platform and presents a viable option for AKI therapy.