Shear Wave Elastography in The Evaluation Of Renal Parenchymal Stiffness in Patients With Chronic Kidney Disease: A Meta-Analysis Ⅱ

Discussions

At present, the incidence of CKD is very high worldwide. However, regardless of the underlying cause, the progression of CKD includes substantial fibrosis, tubular interstitial atrophy, and glomerular compartment sclerosis. CKD is a common cause of kidney fibrosis, associated with the severity of the disease [25-27]. The histological examination of kidney biopsy specimens is currently the only clinical histological evaluation method for renal fibrosis. Invasiveness is associated with specific risks of surgery and the risk of sampling errors [20]. The detection mainly relies on biomarkers in medical practice. SWE generates shear waves through sensors and measures tissue stiffness non-invasively. Existing human and animal studies have shown a correlation between the SWE estimation of renal YM and the presence of CKD or fibrosis [20, 28, 29].

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Figure 3. Quality assessment of the studies according to QUADAS-2. QUADAS: Quality Assessment of Diagnostic Accuracy Studies.

Figure 4. The Forest plots showing diagnostic performance estimates (sensitivity and specificity) of CKD fibrosis. CKD: chronic kidney disease; CI: confidence interval.

With the development of noninvasive quantitative technology and the rapid development of diagnostic techniques in the field of liver fibrosis, renal elastography technology has become available. As the incidence of CKD increases, the application of elastography may be of critical value in the assessment of tissue stiffness. This study has collected domestic and foreign research on the diagnosis of CKD by SWE technology. When extracting data, we collected according to uniform standards the literature that involves and summarizes the same quantitative parameters. The analysis of the diagnostic value of SWE summarizes in the diagnosis of CKD with fibrosis and provides strong evidence for SWE in the study of CKD with renal stiffness in the future.

Meta-analyses showed that in six studies, SWE imaging techniques assessed the sensitivity and specificity of tissue stiffness in 80.0-89.2% and 65.0-93.3%. The efficacy of SWE imaging technology in assessing tissue stiffness is judged from a single study. It is not easy. The sensitivity and specificity by meta-analysis are 84% (95% CI: 80-87%) and 80% (95% CI: 76-84%). The DOR is 21.50 (95% CI: 14.69 - 31.46) and the SROC curve is 89% (95% CI: 86-92%), indicating that the application of elastography technology has a higher value in the evaluation of chronic kidney fibers. The results of Leong et al [18] show that YM measurements are significantly correlated with estimated glomerular filtration rate (eGFR), serum creatinine and urea, which is consistent with our results. SWE can achieve equivalent S-SEN and S-SPE, which shows that SWE is a truly valuable imaging method for evaluating renal fibrosis. Mehmet Sami et al [30] use SWE to evaluate the fibrosis of CKD in a study, and the results show a highly correlation with the elasticity measurement of fibrosis patients in renal biopsy (P = 0.046). Likelihood ratio (LR) is a comprehensive indicator that reflects the diagnostic value of diagnostic experiments [31, 32]. In our study, PLR-P is 4.29 (95% CI: 3.43 - 5.37) and PLRN is 0.20 (95% CI: 0.16 - 0.25), providing "strong" diagnostic evidence. In this study, it is found that the AUC of chronic renal fibrosis exceeds 89%, indicating that SWE can accurately assess different causes of renal fibrosis and has a high diagnostic performance.

The SWE cannot accurately and quantitatively assess renal fibrosis, which will lead to an increase in P-SEN and a decrease in P-SPE. The results are consistent with the study of Sia et al [33]. A large number of published research results [34-36] show that kidney stiffness of the estimated value seems to increase with increasing in the CKD stage. The strong correlation with histological markers of fibrosis indicates that the observed difference is due to renal parenchymal stiffness. In the meta-analysis, studies with low sample sizes are included and no subgroup analysis is performed. Therefore, extensive analysis and multi-subgroup analysis are needed to assess the diagnostic value of SWE in the diagnosis of CKD fibrosis in future studies.

The meta-analysis with the P-SEN (I2 = 0.00%) and PSPE (I2 = 44.367%) of the forest plot 95% CI shows a moderate degree of heterogeneity. The main reason is maybe due to the different staging and grouping study designs and patient characteristics of CKD. Secondly, it is related to the threshold of each study. There are multiple confounding factors in the study object.

Limitations of this study include: 1) Shear modulus is a new imaging technique for evaluating tissue stiffness, and the stiffness measurement of the kidney is affected by factors such as anisotropy and blood perfusion rate; 2) In some research projects, CKD patients had not clinically undergone renal biopsy, and the stage of CKD was not accurately determined; 3) There are differences between the two investigators in the evaluation of renal stiffness, as well as the ultrasound equipment used in the literature. Different manufacturers and models may cause large differences in the measured values. However, due to the limited sample size of the included literature, it is impossible to conduct the subgroup analysis based on the sources of heterogeneity in this aspect of the data; 4) We also use known imperfect eGFR reference standards to estimate the severity of CKD. There are no kidney biopsy data available to quantify the histological fibrosis

In short, this study shows that SWE has a high performance in evaluating the hardness of CKD, especially when using a higher shear modulus threshold, which can provide a reference for clinical judgment and has a great application prospect. Nonetheless, this result still needs to be approved.

Figure 8. Fagan's nomogram for SWE illustrates post-test probability with a fixed pre-test probability of 20% for CKD. CKD: chronic kidney disease; SWE: shear wave elastography; SEN: sensitivity; SPE: specificity

Larger multi-center studies and longitudinal follow-up are needed to conduct a more comprehensive evaluation to assess the development of CKD more accurately

Conclusions The meta-analysis shows that SWE is accurate in diagnosing renal fibrosis. However, as mentioned above, due to the various causes of renal fibrosis, different renal stiffness may be produced. Therefore, the diagnostic critical threshold needs to be adjusted under the specific case. The institute involves a limited number of research, and it is necessary to further study the relationship between tissue elasticity and the severity of renal fibrosis. 

Acknowledgments Thanks for the help of the Dream Team of the Ultrasound Department of Shenzhen People's Hospital. 

Financial Disclosure None to declare. 

Conflict of Interest The authors disclose no conflict of interest. 

Informed Consent Informed consent was waived in this manuscript

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