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Purpose: To gauge the utility of multiparametric MRI in characterizing pathologic changes after iodinated contrast-induced acute kidney injury (CI-AKI) in rats., Methods: We randomly grouped 24 rats injected with 8 g iodine/kg of body weight (n = 6 each) and 6 rats injected with saline as controls. All rats underwent T1, T2 mapping and diffusion kurtosis imaging (DKI) after contrast injection at 0 (control), 1, 3, 7, 13 days. T1, T2, and mean kurtosis (MK) values were performed in renal outer/inner stripes of outer medulla (OSOM and ISOM) and cortex (CO), and their diagnosis performance for CI-AKI also been evaluated. Serum creatinine (SCr), insulin-like growth factor-binding protein 7 (IGFBP7), tissue inhibitor metalloproteinase 2 (TIMP-2), aquaporin-1 (AQP1), α-smooth muscle actin (α-SMA), and histologic indices were examined., Results: Compared with controls, urinary concentrations of both TIMP-2 and IGFBP7 were obviously elevated from Day 1 to Day 13 (all p < 0.05). T2 values were significantly higher than control group for Days 1 and 3, and T1 and MK increased were more remarkable at all time points (Days 1-13) in CI-AKI (all p < 0.05) than control group. Changes in T1 and MK strongly correlated with renal injury scores of all anatomical compartments and with expression levels of AQP1 and moderately correlated with α-SMA. Changes in T2 values correlating moderately with renal scores of CO, ISOM and OSOM and AQP1. The MK obtained the highest area under the receiver operating characteristic (ROC) curve of 0.846 with a sensitivity of 70.8 % and specificity of 88.9 %., Conclusions: Combined use of multiparametric MRI could be a valid noninvasive method for comprehensive monitoring of CI-AKI. Among these parameters, MK may achieve the best diagnostic performance for CI-AKI., Competing Interests: Declaration of competing interest The authors report there are no competing interests to declare., (Copyright © 2024. Published by Elsevier Inc.)

Acute kidney injury (AKI) is a frequent complication of critical illness and carries a significant risk of short- and long-term mortality. The prediction of the progression of AKI to long-term injury has been difficult for renal disease treatment. Radiologists are keen for the early detection of transition from AKI to long-term kidney injury, which would help in the preventive measures. The lack of established methods for early detection of long-term kidney injury underscores the pressing needs of advanced imaging technology that reveals microscopic tissue alterations during the progression of AKI. Fueled by recent advances in data acquisition and post-processing methods of magnetic resonance imaging (MRI), multiparametric MRI is showing great potential as a diagnostic tool for many kidney diseases. Multiparametric MRI studies offer a precious opportunity for real-time noninvasive monitoring of pathological development and progression of AKI to long-term injury. It provides insight into renal vasculature and function (arterial spin labeling, intravoxel incoherent motion), tissue oxygenation (blood oxygen level-dependent), tissue injury and fibrosis (diffusion tensor imaging, diffusion kurtosis imaging, T1 and T2 mapping, quantitative susceptibility mapping). The multiparametric MRI approach is highly promising but the longitudinal investigation on the transition of AKI to irreversible long-term impairment is largely ignored. Further optimization and implementation of renal MR methods in clinical practice will enhance our comprehension of not only AKI but chronic kidney diseases. Novel imaging biomarkers for microscopic renal tissue alterations could be discovered and benefit the preventative interventions. This review explores recent MRI applications on acute and long-term kidney injury while addressing lingering challenges, with emphasis on the potential value of the development of multiparametric MRI for renal imaging on clinical systems. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2., (© 2023 International Society for Magnetic Resonance in Medicine.)

Objective: We investigated whether diffusion kurtosis imaging (DKI) and arterial spin labeling (ASL) facilitated the assessment of serial alterations in persistent post-contrast acute kidney injury (PC-AKI)., Materials and Methods: We randomly divided 24 rats into four PC-AKI groups (days 1, 3, 7, and 13, n = 6/group), with an additional six control animals. We conducted functional magnetic resonance imaging (MRI), diffusion kurtosis imaging (DKI), and arterial spin-labeling (ASL) analyses. Mean kurtosis (MK), axial kurtosis (Ka), mean diffusivity (MD), fractional anisotropy (FA), radial kurtosis (Kr), and renal blood flow (RBF) maps were normalized to baseline (prior to contrast injection) to calculate adjusted △RBF, △MK, △Ka, △MD, △FA, and △Kr values. We also investigated urinary neutrophil gelatinase associated lipocalin (NGAL), serum cystatin C (CysC), aquaporin-2 (AQP2), hypoxia-inducible factor-1 (HIF-1α), and histological indices., Results: In the inner stripe of the outer medulla, when compared with controls, decreased △FA and △MD levels were observed on days 1, 3, and 7, and a distinct elevation in △MK and △Kr on days 1-13, and a persistent decrease in △RBF on days 1-13, and a prominent increase in △Ka on days 7 and 13 in PC-AKI animals (all p < 0.05). △Ka and △MK were positively correlated with AQP-2 (r = 0.8086, p < 0.0001 and r = 0.7314, p < 0.0001, respectively), and △RBF was highly correlated with HIF-1α (r = -0.7592, p < 0.0001). Moreover, both CysC and NGAL were significantly elevated in PC-AKI animals when compared with controls from days 1-13 (all p < 0.05). Renal histological data indicated severe tubular and glomerular injury at days 1-13 in all PC-AKI groups., Conclusion: ASL and DKI may be noninvasively and longitudinally used to detect PC-AKI and predict further outcomes., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To examine the potential of intravoxel incoherent motion (IVIM) and blood oxygen level-dependent (BOLD) magnetic resonance imaging for detecting renal changes after iodinated contrast-induced acute kidney injury (CI-AKI) development in a diabetic rabbit model., Materials and Methods: Sixty-two rabbits were randomized into 2 groups: diabetic rabbits with the contrast agent (DCA) and healthy rabbits with the contrast agent (NCA). In each group, 6 rabbits underwent IVIM and BOLD imaging at 1 hour, 1 day, 2 days, 3 days, and 4 days after an iohexol injection while 5 rabbits were selected to undergo blood and histological examinations at these specific time points. Iohexol was administrated at a dose of 2.5 g I/kg of body weight. Further, the apparent transverse relaxation rate (R2*), average pure molecular diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) were calculated., Results: The D and f values of the renal cortex (CO) and outer medulla (OM) were significantly decreased compared to baseline values in the 2 groups 1 day after the iohexol injection ( p < 0.05). A marked reduction in the D* values for both the CO and OM was also observed after 1 hour in each group ( p < 0.05). In the OM, a persistent elevation of the R2* was detected for 4 days in the DCA group ( p < 0.05). Histopathological changes were prominent, and the pathological features of CI-AKI aggravated in the DCA group until day 4. The D, f, and R2* values significantly correlated with the histological damage scores, hypoxia-inducible transcription factor-1α expression scores, and serum creatinine levels., Conclusion: A combination of IVIM and BOLD imaging may serve as a noninvasive method for detecting and monitoring CI-AKI in the early stages in the diabetic kidney., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2019 The Korean Society of Radiology.)

Background: To evaluate the application of blood oxygenation level-dependent (BOLD)imaging and intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) on assessing early contrast-induced acute kidney injury (CIAKI)., Materials: Sixty rabbits were randomly chosen to undergo iohexol (1.0, 2.5, and 5.0 [gI/kg], respectively; n = 15 for each group) or saline injection (n = 15). In each group, 6 rabbits underwent MRI at 24 h before injection and after injection of iohexol or saline (1 h and 1, 2, 3, and 4 days); meanwhile, out of the remaining 9 rabbits, 3 were chosen for MRI acquisition, and then they were killed at specific time points (1 h, 1 day, and 3 days, respectively)., Results: The strong attenuation of pure molecular diffusion (D), apparent diffusion coefficient (ADC), and perfusion fraction (f) was observed at 1 day, while pseudodiffusion coefficient (D*) showed a significant decrease at 1 h after iohexol injection. A distinct elevation of apparent transverse relaxation rate (R2*) reached the maximum levels on day 1, which was consistent with the expression of hypoxia-inducible factor-1α and vascular endothelial growth factor. ADC, D, and R2* correlated well with histopathological parameters and biochemical parameters., Conclusion: BOLD combined with IVIM is effective to monitor renal pathophysiology associated with CIAKI., (© 2019 The Author(s) Published by S. Karger AG, Basel.)

Acute kidney injury (AKI) is one of the most common complications in patients with severe sepsis. The development of septic AKI increases patients' mobility and even mortality. Toll-like receptor 2 (TLR2), as a membrane surface receptor for bacterial, fungal, viral and certain endogenous substances, has been described to contribute to the development of septic AKI; however, the renal cell types associating TLR2 overactivation in septic AKI has not been described. In the current study, we investigated the TLR2 activation patterns in the kidney of lipopolysaccharide-induced septic AKI mice. Our results demonstrated that mRNA level of TLR2 significantly increased in the kidney of lipopolysaccharide-treated mice. Immunohistochemistry revealed the overactivation of TLR2 in the glomeruli. Double immunofluorescence analysis shows the precise distribution of TLR2 by showing the colocalization of TLR2 in glomeruli with synaptopodin, a podocyte marker, and Tie2, an endothelial marker. In addition, proapoptotic molecules Bax and Caspase-3 were increased in the glomeruli of lipopolysaccharide-treated mice. Together, the current study indicates that TLR2 is overactivated in the glomerular endothelial cells and podocytes in septic AKI mice, while the abundance of Bax and Caspase-3 were increased in the glomeruli of these mice, it may supply a clue that TLR2 induced these cell apoptosis in AKI. This finding provides an alternative mechanism to understand AKI development and potential targets for treatment.

Reducing inflammation is a promising approach for the prevention and treatment of septic acute kidney injury (AKI), since AKI is characterized by excessive inflammation in the kidney. Previous studies have demonstrated that toll-like receptor 2 (TLR2) is overstimulated, which promotes inflammation by activating the NF-κB signaling pathway, in a lipopolysaccharide (LPS)-induced model of AKI mice. For the present study, it was hypothesized that TLR2 inhibition could reduce inflammation and consequently prevent septic AKI. Therefore, the potential renal protective effects of ortho-vanillin (OV), an inhibitor of TLR2, were investigated in the present study in vitro and in vivo. In vitro treatment with OV on LPS-stimulated mouse podocyte cell line MPC5 did not affect TLR2 expression but interrupted the interaction between TLR2 and its downstream adaptor MyD88, resulting in the reduction of inflammatory cytokines IL-6 and TNF-α expression. In vivo OV treatment in an LPS-challenged mouse model effectively alleviated LPS-induced kidney injury as indicated by histology analysis and the significantly reduced blood urea nitrogen and serum creatinine levels. Additionally, inflammatory cytokines TNF-α, IL-6 and IL-1β expression were also significantly reduced in mice with OV treatment. Signaling pathway analysis further demonstrated that OV treatment did not affect the expression of TLR2 and p65 but suppressed p65 phosphorylation. Taken together, data from the present study demonstrated that OV was effective in protecting renal function against LPS-induced AKI through the inhibition of TLR2/NF-κB signaling and subsequent inflammatory cytokine production. These findings indicated that OV or targeting TLR2 signaling in general, represents a novel therapeutic approach for use in the prevention and treatment of AKI. [ABSTRACT FROM AUTHOR]