## 4 Discussion  
Throughout our research, we discovered 37 renal elastography studies, out of which only 11 were suitable for our pooled analysis. The relationship between the level of kidney SWS and renal disease was quite distinct in different studies using VTQ. We found that in some studies, kidney SWS was increased in patients with CKD (5 studies) [19; 22; 25; 34; 36], while in others it was decreased (12 studies) [18; 23; 27; 28; 29; 31; 35; 37; 38], and four studies showed no relationship between kidney SWS and renal disease [20; 32; 33; 47]. Overall, we found that patients with CKD have a lower kidney SWS than healthy controls with a standardized mean difference of \(-0.216\). In addition, the results of research utilizing different elastography devices were also inconclusive. Out of the four studies that employed the Elast-PQ method, two reported a high KSWS in relationship with CKD while the other two reported low kidney SWS in relation to CKD. Only three studies were performed using the 2D-SWE method but all of them reported high kidney SWS in correlation with CKD. Figure 4: Forest plot for the pooled AUC. Figure 3: Forest plot for the correlation coefficient (between eGFR and kidney SWS). Regarding the relationship between CKD stages and kidney SWS, this has been approached in some studies; however, no statistically significant correlations have been found, despite the tendency of kidney SWS to decrease as the CKD stage rises. It could be concluded that elastography (at least VTQ) is not suitable for differentiating between CKD stages [29]. The connection between kidney SWS and eGFR is debatable as well. Out of our 37 studies, only 13 correlated them with statistical significance. Different studies proposed renal stiffness cut-off values to predict advanced stages of CKD. A total of 19 studies performed AUC and obtained a cut-off value for predicting CKD for differentiating between diabetic and nondiabetic patients, or comparison between different stages of CKD. Across the VTQ studies, the pooled area under the ROC curve for kidney SWS to predict chronic kidney disease was 0.831, \(p\) < 0.0001; however, as already mentioned, CKD has been diagnosed using different criteria across the mentioned studies. An unexplained aspect relates to the fact that kidney SWS in CKD is high in some investigations but also reduced in the majority of them even though they were using the same method (VTQ) for measuring the same type of patients (with CKD and healthy participants). The question remains why CKD seems to be associated to lower kidney SWS because fibrosis should lead to an increase in tissue stiffness. There are some studies that compare elastography with renal histology (eight studies). However, when it came to kidney SWS in CKD, there was no significant difference between the mild and moderate fibrosis groups. Two studies reported mean KSWV in severely impaired kidneys (biopsy proven) being considerably lower than in slightly impaired, moderately impaired, and healthy kidneys [2, 21]. According to one experimental study, the stiffness of the kidney increases as the amount of fibrosis increases [38]. The inconsistent relationship between histological changes and renal stiffness could be due to the fact that histological changes in renal diseases are heterogenous, consisting of changes in the different compartments of the renal tissue (glomerular, vascular, or tubulointerstitial) that are not uniformly involved in different renal diseases. Because intranrenal blood flow decreases as fibrosis progresses, alterations in renal perfusion may influence renal stiffness and explain some inconsistencies in results. As a consequence, a decrease in renal blood flow may be the cause of stiffness reduction as CKD progresses and it may have a greater impact on stiffness than renal fibrosis [23].