Chemotherapy-related complications in the kidneys and collecting system: an imaging perspective

Urography cannot be used to definitively diagnose complex cysts as they present as indiscernible masses when this technique is used [3]. Sonographically, cysts associated with crizotinib have been described as ovoid, anechoic with internal echoes, near-water density, with smooth clearly demarcated walls and acoustic enhancement behind the cysts, and without septa or calcifications [4]. On ultrasound (US), diagnosis of cysts may be complicated by a number of factors. Vascular malformations or aneurysms could be mistaken for cystic disease if real-time studies do not demonstrate pulsations or large feeding vessels are not delineated. In addition, peripelvic cysts often contain artificially created echoes due to their proximity to structures of the collecting system and need to be confirmed on computed tomography (CT) [3].

On CT, complex renal cysts can be distinguished from benign cysts using criterion laid out by Bosniak. The presence of extensive calcification, septa with irregular walls thicker than 1 mm or associated with solid elements at their attachments, hyperdense fluid with irregularity of contour or hazy margination, internal haemorrhage or debris, and thickening or irregularity of the wall or any evidence of solid tissue within the wall distinguish complex from benign cysts (Fig. 1a–c) [3]. Cysts associated with crizotinib use have been reported as Bosniak classification types II-IV [1, 4]. Bosniak II cysts are well marginated and characterized by a few thin septa less than 1 mm and thin calcifications. Bosniak III cysts are characterized by thick or multiple septations, mural nodule, and are hyperdense on CT. Bosniak IV cysts are characterized as solid masses with large cystic or necrotic components, irregular margins, and solid vascular elements [2]. Complex cysts may mimic metastatic disease and it is thus important to have knowledge of this entity (Fig. 1d–e). On examination of cysts with CT, it is important to obtain pre- and post-contrast imaging so that calcifications and recent haemorrhage can be identified and so high-density non-enhancing renal cysts are not mistaken for solid metastatic lesions. If enhancement is present, renal abscesses and metastases are included in the differential. It is imperative for diagnosis on CT that the fluid in the cyst is near water density with a suggested upper threshold of 20 HU. If the density exceeds 20 HU, other pathologies such as tumours need to be considered [3]. CT and magnetic resonance imaging (MRI) findings of complex renal cysts are equivalent with the two techniques resulting in similar ratings based on the Bosniak system [5].

On urography, acute interstitial nephritis often reveals enlarged kidneys as well as an early, dense, persistent nephrogram, which is similar to the findings of ATN. An important distinguishing characteristic is that ATN results in normal sized or only slightly enlarged kidneys [8]. On US imaging, acute interstitial nephritis may not be apparent or may present with enlargement of the kidneys as well [9]. CT findings include renal oedema and enlargement. The presence of streaky parenchymal low-attenuation areas, which may mimic more common entities like pyelonephritis and multifocal infarcts among others, may also be seen (Figs. 2a, b, and 3) [10]. Radiographic findings are not diagnostic of interstitial nephritis and findings need to be confirmed with biopsy. However, imaging is useful in excluding obstruction that would require decompression.

Urographic findings are diagnostic with irregular contour of the renal papillae and widening of the fornixes (Fig. 4a). After sloughing of the papilla, contrast penetrates the renal parenchyma and ring shaped shadows appear to demonstrate the detached papilla, the so-called ball on a tee sign [13]. Sonographically, renal papillary necrosis appears as multiple cystic spaces in the medullary region arranged around the renal sinus echoes [14]. Necrosed papilla appear as nonshadowing soft tissue masses within the ureter which cannot be differentiated from other pathologies such as blood clots [14]. Hydronephrosis which has similar findings can be differentiated from renal papillary necrosis by the presence of a central dilation of the pelvis [15]. On CT, renal papillary necrosis is characterized by excavation of the calyces, regression of the papillae, detached papilla in the ureter, and blunting of the calyces (Fig. 4b) [16].

Urography findings for renal infarction vary according to the severity. Small infarcts often present with normal urograms. With more severe lesions, there can be an absence of contrast material in the ischemic renal parenchyma with local failure of calyceal filling of the affected tissue during the pyelographic phase. Renal infarction may also result in vasospasm which presents as complete nonvisualization of the kidney [21]. On US, acute renal infarcts may be non-specific in appearance, with heterogeneity of the parenchyma. Chronic infarcts may be wedge shaped and hypoechoic with cortical scarring [22]. On CT, renal infarcts appear as low attenuation, wedge shaped areas in the cortex (Fig. 5a, b). Sometimes the “rim sign” is present, which is a higher-attenuation subcapsular rim surrounding lower-attenuation infarcted renal parenchyma representing subcapsular perfusion through collateral flow [23, 24]. However, as the “rim sign” is a universal and highly specific indicator of renovascular compromise, it can also be present in acute tubular necrosis and renal vein thrombosis. Hydronephrosis similarly is characterized by a “rim sign”; however, this rim sign can be distinguished from that of vascular compromise by its variable thickness, medial concavity, and location surrounding the dilated calices in communication with the central pelvis [25].

On urography, acute tubular necrosis appears as renal enlargement with prolonged opacification of the renal parenchyma and an increase in density of the pyramids [31]. On sonography, ATN presents as increased cortical echogenicity [32]. Inadequacy of perfusion can also be detected as abnormal Doppler velocity waveforms [33]. On CT imaging, ATN presents with contrast retention in the parenchyma (Fig. 6a, b). The “rim sign” can also be used to characterize ATN and is a valuable factor distinguishing infarction from pyelonephritis [25].

Radiologic findings of chemotherapy-induced cystitis are nonspecific and cannot be distinguished from other causes of cystitis. On intravenous urography and cystography, the bladder may be small with thickened walls. Rarely, calcifications can be present within the wall [36]. On CT imaging, acute chemotherapy-induced cystitis may present with diffuse or focal irregular bladder wall thickening, decreased bladder volume and perivesical fat, and oedema. Increased contrast enhancement of the bladder wall is not usually present [36]. On MRI, there is high T2 signal intensity within the bladder wall, which is suggestive of inflammation [37]. Increased signal intensity of the mucosa may also be seen on T1-weighted images and is likely attributable to mucosal haemorrhage [36].

Excretory urograms can be normal in hemorrhagic cystitis [38]. US is a useful technique in evaluation of hemorrhagic cystitis as power Doppler allows estimations of the hypervascularity, and thus the severity of the condition [44]. Hemorrhagic cystitis appears as bladder wall thickening on CT (Fig. 7a, b) [45]. However, as the imaging characteristics are not specific, they need to be correlated clinically with hematuria, which is the most common presenting symptom.