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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 [ABSTRACT FROM AUTHOR]

Aims: To evaluate the utility of fasudil in a rat model of contrast-associated acute kidney injury (CA-AKI) and explore its underlying mechanism through multiparametric renal magnetic resonance imaging (mpMRI). Methods: Experimental rats (n = 72) were grouped as follows: controls (n = 24), CA-AKI (n = 24), or CA-AKI + Fasudil (n = 24). All animals underwent two mpMRI studies (arterial spin labeling, T1 and T2 mapping) at baseline and post iopromide/fasudil injection (Days 1, 3, 7, and 13 respectively). Relative change in renal blood flow (ΔRBF), T1 (ΔT1) and T2 (ΔT2) values were assessed at specified time points. Serum levels of cystatin C (CysC) and interleukin-1β (IL-1β), and urinary neutrophil gelatinase-associated lipocalin (NGAL) concentrations were tested as laboratory biomarkers, in addition to examining renal histology and expression levels of various proteins (Rho-kinase [ROCK], α-smooth muscle actin [α-SMA]), hypoxia-inducible factor-1α (HIF-1α), and transforming growth factor-β1 (TGF-β1) that regulate renal fibrosis and hypoxia. Results: Compared with the control group, serum levels of CysC and IL-1β, and urinary NGAL concentrations were clearly increased from Day 1 to Day 13 in the CA-AKI group (all p < 0.05). There were significant reductions in ΔT2 values on Days 1 and 3, and ΔT1 reductions were significantly more pronounced at all time points (Days 1–13) in the CA-AKI + Fasudil group (vs. CA-AKI) (all p < 0.05). Fasudil treatment lowered expression levels of ROCK-1, and p-MYPT1/MYPT1 proteins induced by iopromide, decreasing TGF-β1 expression and suppressing both extracellular matrix accumulation and α-SMA expression relative to untreated status (all p < 0.05). Fasudil also enhanced PHD2 transcription and inhibition of HIF-1α expression after CA-AKI. Conclusions: In the context of CA-AKI, fasudil appears to reduce renal hypoxia, fibrosis, and dysfunction by activating (Rho/ROCK) or inhibiting (TGF-β1, HIF-1α) certain signaling pathways and reducing α-SMA expression. Multiparametric MRI may be a viable noninvasive tool for monitoring CA-AKI pathophysiology during fasudil therapy. [ABSTRACT FROM AUTHOR]

To gauge the utility of multiparametric MRI in characterizing pathologic changes after iodinated contrast-induced acute kidney injury (CI-AKI) in rats. 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. 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 %. 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. • Combined use of multiparametric MRI could give one opportunity to comprehensively monitor CI-AKI. • Alterations of renal MK, T1, and T2 values after CI-AKI were useful to detect renal impairment. • T1, T2 and MK values at early time points after CI-AKI induction displayed significant correlations with renal microstructure alterations. [ABSTRACT FROM AUTHOR]

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). 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. 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. ASL and DKI may be noninvasively and longitudinally used to detect PC-AKI and predict further outcomes. • Combining ASL and DKI could give one the opportunity to study PC-AKI and predict further outcomes. • Alterations of renal Mk, Ka, and RBF values after PC-AKI were useful to detect persistent renal impairment. • CysC and NGAL seems to be reliable markers for improving the identification of PC-AKI to PRD transition. [ABSTRACT FROM AUTHOR]

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]

Purpose. To determine the optimal time interval of repeated intravenous injections of iodixanol in rat model and to identify the injury location and causes of renal damage in vivo. Materials and Methods. Rats were randomly divided into Control group, Group 1 with one iodixanol injection, and Group 2 with two iodixanol injections. Group 2 was subdivided into 3 cohorts according to the interval between the first and second iodixanol injections as 1, 3, and 5 days, respectively. Blood oxygen level-dependent (BOLD) imaging and diffusion weighted imaging (DWI) were performed at 1 hour, 1 day, 3 days, 5 days, and 10 days after the application of solutions. Results. Compared with Group 1 (7.2%), Group 2 produced a remarkable R2⁎ increment at the inner stripe of the renal outer medulla by 15.37% (P=0.012), 14.83% (P=0.046), and 13.53% (P>0.05), respectively, at 1 hour after repeated injection of iodixanol. The severity of BOLD MRI to detect renal hypoxia was consistent with the expression of HIF-1α and R2⁎ was well correlated with HIF-1α expression (r=0.704). The acute tubular injury was associated with urinary NGAL and increased significantly at 1 day. Conclusions. Repetitive injection of iodixanol within a short time window can induce acute kidney injury, the impact of which on renal damage in rats disappears gradually 3–5 days after the injections. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]