Complex renal cysts
The development of complex renal cysts associated with crizotinib treatment is well documented in the literature. Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor used in the treatment of ALK positive metastatic non-small cell lung cancer (NSCLC). Lin et al. explored the presence of complex renal cysts in patients enrolled in prospective clinical trials for crizotinib treatment. In the 32 patients included in the study, 13 % developed new complex renal cysts and 22 % had significant renal cyst change following initiation of crizotinib treatment. After cessation of crizotinib treatment, the cysts were found to regress significantly [1]. In a similar retrospective study, Schnell et al. reported that of 17 patients found with complex renal cysts associated with crizotinib use, 11 required hospitalization due to the cysts, with seven having cystic invasion into adjacent structures in the form of inflammatory cystic masses. The majority of patients were asymptomatic, but a small number presented with flank pain or fevers [2].
Imaging findings
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].
Interstitial nephritis
Interstitial nephritis refers to inflammation of the renal interstitium. Histologically, this is characterized by interstitial infiltration by lymphocytes, monocytes, and granulomas. Symptoms may include oliguria and less commonly, hematuria. Patients may also have nonspecific symptoms of fever, rash, and loin pain, but in many cases patients are asymptomatic [6]. Interstitial nephritis can be associated with a decline in creatinine clearance, eosinophilia, eosinophiluria, and proteinuria. Multiple chemotherapy regimens have been associated with interstitial nephritis, most notably ipilimumab. In ipilimumab-induced interstitial nephritis, patients are treated with prednisone and quickly return to their baseline kidney function [7].
Imaging findings
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.
Renal papillary necrosis
Renal papillae are present at the apex of the renal pyramid at the site where urine is discharged from the renal tubules. Papillary necrosis occurs secondary to ischemia and can be triggered by a number of factors, the most common ones being analgesic nephropathy, diabetes, sickle cell disease, and infection. Histologically, renal papillary necrosis (RPN) appears as coagulative necrosis, characterized by a pale centre with surrounding inflammatory cells [11]. Symptoms of RPN most commonly include fevers, chills, flank pain, and hematuria. Sloughed papillae can cause ureteral obstruction and hydronephrosis, further worsening renal function. The platinum based agents, cisplatin and nedaplatin, are associated with RPN [12]. Care needs to be taken in interpretation of this pathological outcome as it can be difficult to determine whether the cause is the chemotherapy itself or chronic analgesic use since cancer patients are often on powerful analgesic regimens.
Imaging findings
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].
Renal infarction
Renal infarction presents with persistent pain often resistant to analgesia, nausea and vomiting, proteinuria, hematuria, and elevated lactate dehydrogenase [17]. In the literature, it has been reported with use of methotrexate and combination regimens of cisplatin and gemcitabine [18, 19]. In a case series with 44 patients with long-term follow-up for renal infarction, 61 % of patients regained normal renal function while the remaining patients alive at follow-up had progressed to irreversible kidney dysfunction [20].
Imaging findings
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].
Acute tubular necrosis
ATN refers to acute renal failure caused by an ischemic or toxic insult to the tubular epithelial cells. This results in epithelial cell detachment from the basement membrane causing tubular dysfunction. It presents with a decrease in GFR, urine osmolality, and urine/plasma creatinine ratio. Urine sediment is characterized by renal tubular epithelial cells, epithelial cell casts, and muddy brown granular casts [26]. ATN is associated with cisplatin and ifosfamide treatment [27, 28]. Patients may return to baseline kidney function following ATN; however, some patients develop an irreversible decline in function. Risk factors for permanent injury include age over 65 years, atheroembolic disease, and preexisting chronic kidney disease. ATN that develops in the hospital setting is associated with a high mortality rate [29, 30].
Imaging findings
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].