The Bosniak classification has been the most widely adopted method to characterize cystic kidney lesions with good reliability regarding their nature [12]. The classification was first introduced for CECT, which is still considered the gold standard, with probability percentages of malignancy and benignity close to surgical ones [13,14]. The introduction of modern CT technologies did not significantly affect the performance of CECT for this task [15]. The Bosniak classification has been successfully applied also with CEUS, with a similar or better performance, compared to CECT [8,16]. Regardless of the technique used, the Bosniak classification system is intrinsically subjective, a problem well acknowledged since its introduction, which led to subsequent amendments of the scoring system [17]. A considerable effort to standardize the Bosniak scoring system and to improve interobserver agreement has been recently addressed by Silverman et al. for CECT and CEMRI, and by Cantisani et al. for CEUS [18,19]. Numerous aspects should be taken into account when complex renal cysts are scored in the US [18]. A multi-parametric approach is required. Scoring is not based on the size or shape of the cyst but only on the intra-cystic content, i.e., the presence or absence of septa, the number and the thickness of the septa, the wall thickness (more or less than 3 mm), and the presence of irregularities and of nodules.

As complexity increases, the probability of being a malignant cyst grows. In the new EFSUMB classification, cystic tumors are included in category IV, or rather, probable malignant cystic tumors, according to histology. Cystic tumors comprise a diverse group of kidney lesions and can have variable biological profiles. Clearly, the US only identifies the presence of liquid and solid components, and CEUS identifies possible vascularization, referring the definition to histology (Figure 2).

CEUS is recommended by the EFSUMB guidelines and by the American College of Radiology (ACR) to characterize incidental renal masses [3,4] Lesions with equivocal enhancement at CECT will be characterized as solid tumors or renal cysts with CEUS. Cysts are graded according to the Bosniak criteria [20] (Figure 3).

With the exception of angio-myolipomas with a visible amount of fat, differentiation of the different solid renal masses is problematic even at CECT and CEMRI. CEUS is limited for this task [21] and its use is not recommended by the EFSUMB guidelines for this purpose [3,4]. Several features, however, can help guess tumor histology at multiparametric US. Clear Cell Renal Cell Carcinoma (ccRCC) is usually hyper-vascular, with heterogeneous enhancement due to necrotic areas. However, differentiation from oncocytoma and lipid-poor angio-myolipomas remains problematic. Papillary Renal Cell Carcinoma (pRCC) is often hypo-vascular [22,23].

Anatomical variations can simulate a renal mass [24]. Among pseudo-tumors in particular, hypertrophy of the Bertin columns, persistence of fetal lobatures, and presence of humps can be confused with focal lesions requiring a CECT or CEMR study for characterization. CEUS is a valid alternative for a correct differential diagnosis [25,26,27]. In fact, pseudo-tumors will present the same enhancement characteristics as the renal parenchyma, without alterations of the vascular structures (Figure 4). In lesions iso-enhancing in all vascular phases, a situation that occurs in up to 5% of cases, differentiation from pseudo-masses is also possible combining grey-scale US and CEUS, since true lesions often present with different echogenicity, and pseudo-lesions usually display a medullary component which is later enhanced compared to cortex [26].

In accordance with the EAU guidelines [28], evaluation of ablative treatments of small kidney lesions requires a close monitoring of the ablated area, both to check for any complications and to assess the success of the procedure. CEUS has progressively taken a role in the follow-up, especially early after the procedure [29,30,31]. The treatment is considered successful if the lesion becomes completely avascular. This usually occurs early after radiofrequency and microwave ablation (Figure 5) [29,32], while it may take up to one month after cryoablation (Figure 6), requiring a tailored follow-up [30,31]. Therefore, an adequate knowledge of the type of ablative treatment allows a correct interpretation of the images, thus reducing the risk of misdiagnosis.

Pyelonephritis is a clinical diagnosis. Ultrasound is required to rule out obstructive causes. Other imaging such as CEUS or CECT are indicated in complicated pyelonephritis, or if clinical improvement is lacking at 72 h after medical treatment with antibiotics [33] (Figure 7). Ultrasound is not specific, and can be completely negative. Conversely, CEUS can visualize hypo-perfused areas of parenchyma up to true avascular, rounded areas, with possible peripheral rim, consistent with abscesses. Inflammatory areas are more visible in the parenchymal late phase [34]. In complicated pyelonephritis, CEUS can be used as a monitoring tool for therapeutic response.

Renal vascular disease can involve vascular structures at all levels; in the clinical suspicion of renal infarction B-mode and Color Doppler US (CDUS) is always required, although they have limitations. In fact, this only provides in real time the average speeds coded with the color on the area of interest. The vascular representation of the more distal arterial branches is not always adequate, especially in elderly and in nephropathic patients.

Renal infarction (often in triangular form) or only cortical ischemia (absence of cortical interlobular vessels) (Figure 8) [9,35] are recognizable on the other hand with CEUS, which is able to enhance the lack of vascularization, and therefore repair the damage. The sensitivity of CEUS is quite similar to that of angiography and CT [9].

CEUS is increasingly being used for evaluation of organ perfusion and lesion characterization, as advocated by the EFSUMB guidelines. Specifically, the guidelines recommend CEUS for differentiating cortical necrosis from renal infarction. Real-time dynamic CEUS depicts microcirculation throughout the kidney and should therefore identify the reverse rim sign to diagnose acute cortical necrosis. The excellent spatial resolution of CEUS allows clear differentiation between renal infarction and cortical necrosis, which appears as non-enhancing cortical areas, and preserved hilar vascularity [35] between hypo-perfused and non-perfused areas is clear following ultrasound contrast agent administration.

CT remains the gold standard for the study of kidney trauma due to its panoramic view and its greater sensitivity compared to ultrasound. Thanks to its exclusively vascular nature, CEUS increases the sensitivity of US for the detection of traumatic lesions [36] allowing the study of all the vascular phases (arterial, venous and parenchymal) in real time, but above all it is useful in the follow-up in cases of conservative therapy (Figure 9) [37].

In addition, active bleeding can be recognized with some extravasated contrast medium bubbles and pseudoaneurysms can be detected. It should be remembered that the excretory system cannot be studied with CEUS and therefore when damage to the excretory tract is suspected, CT is mandatory.