Introduction

Kidney injury is a common complication of decompensated cirrhosis, occurring in 30%–50% of hospitalized patients and seriously affecting patients’ prognoses1,2. Previous studies have shown that acute kidney injury in patients with cirrhosis is likely to lead to development of chronic kidney disease and progressive loss of kidney function3-5. Early diagnosis and treatment can delay the progression of kidney injury and improve prognoses. The pathophysiological mechanisms underlying kidney injury in patients with chronic liver disease are intricate. Previous studies have indicated that alterations in renal hemodynamics leading to changes in oxygenation status and inflammatory states are the primary causative factors contributing to kidney injury11-13. Arterial spin labeling (ASL) is a noninvasive and reliable technique for assessing organ blood perfusion without requiring contrast agent injection14-17. The blood oxygenation level-dependent (BOLD) response is highly sensitive to tissue hypoxia and allows effectively evaluating tissue oxygenation status18,19. Increasing studies have used these techniques to noninvasively detect changes in renal perfusion and renal hypoxia in acute kidney injury, renal allografts, chronic kidney disease, and metabolic syndrome19-25. However, these techniques remain limited in their assessment of renal damage in liver cirrhosis, and relevant research is lacking; thus, the value of these techniques remains uncertain. This study was conducted to investigate whether ASL and BOLD magnetic resonance imaging (MRI) can detect alterations in renal hemodynamics and blood oxygenation in chronic liver disease, thereby providing early indicators for kidney injury and offering a reliable basis for early clinical detection and intervention.

Methods

Liver cirrhosis was induced via subcutaneous carbon tetrachloride (CCl4) injection twice weekly for 12 weeks. Thirty-six rats underwent renal MRI followed by pathological analysis at baseline and 2, 4, 6, 8, and 12 weeks (n=6 rats/group/time point). Seven rats underwent MRI examinations at all time points. All MRI examinations were performed on a 3T MRI system (MAGNETOM Prisma, Siemens Healthineers, Erlangen, Germany) equipped with a dedicated eight-channel animal coil (Chenguang, Shanghai, China). Renal ASL was performed using a research three-dimensional turbo gradient spin echo pulsed ASL sequence with the following parameters: repetition time/echo time (TR/TE): 6000/49.86 ms, field of view (FOV): 153 × 153 mm2, slice thickness: 3.00 mm, slice number: 8, matrix: 64 × 64, voxel size reconstructed to 1.2 × 1.2 × 3 mm3, 7 inversion times: 300/500/700/900/1100/1300/1500 ms, bolus length: 700 ms, and acquisition time: 7 min. BOLD MRI was acquired using a multiple echo gradient echo sequence with the following parameters: TR: 255 ms, 6 echoes equally spaced (3.22–16.22 msec), FOV: 85 × 85 mm2, slice thickness: 3.00 mm, matrix: 192 × 154, and acquisition time: 4 minutes. Quantitative renal blood flow (RBF) and T2* maps were generated inline after data acquisition. Mean renal perfusion and T2* were manually calculated by selecting the regions of interest (ROIs) on the corresponding parametric maps. Radiological, biochemical, and pathological indicators were analyzed (Figure 1), and p<0.05 was considered statistically significant.

Results

RBF in the renal cortex and T2* in all anatomical compartments differed significantly among all time points (all p<0.05; Figure 2). From 6–12 weeks after modeling, RBF and T2* in the renal cortex and T2* in the renal outer stripe of the outer medulla were significantly lower than those at baseline. Both RBF and T2* were significantly correlated with renal injury pathological scores, α-smooth muscle actin, hypoxia-inducible factor (HIF)1-α, and peritubular capillary density (|r|=0.406–0.853; Figure 3). RBF demonstrated superior diagnostic capability in identifying severe kidney injury in chronic liver disease compared with the diagnostic capabilities of T2*, serum creatinine, and neutrophil gelatinase-associated lipocalin (area under the curve: 0.964; Figure 4).

Discussion

Our results showed that compared with serum creatinine, ASL and BOLD MRI enable earlier detecting and monitoring of chronic liver disease-associated renal injury. RBF, T2*, renal hematoxylin and eosin score, renal microvessel density, and HIF-1α were all significantly correlated, indicating that ASL and BOLD MRI can effectively reflect the reductions in renal blood perfusion and oxygenation leading to renal injury in chronic liver disease. RBF showed the best diagnostic performance of all tested indicators for diagnosing severe and non-severe renal injuries.

Conclusion

Both ASL and BOLD MRI are effective imaging tools for monitoring kidney injury during liver cirrhosis progression. Cortical RBF is a key indicator for early and advanced kidney injury.

Acknowledgements

The authors thank Siemens Healthcare for providing the prototypic renal ASL and BOLD sequence and technical support.

References

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