Autosomal dominant polycystic kidney disease (ADPKD)
ADPKD is the most common hereditary kidney disease that leads to end-stage renal disease [1]. Over the course of years, patients with ADPKD develop multiple cysts in their kidneys. Hepatic cysts are the most common extrarenal manifestation of ADPKD, which can be found in 80% of patients at the age of 30. While ADPKD is often asymptomatic in childhood, progressive expansion of the cysts leads to end-stage renal disease between age 58 and age 80 on average, depending on the causative genetic mutation (PKD1 or PDK2, respectively) [2].
The clinical symptoms of ADPKD are often directly related to the expansion of renal cysts. Patients usually present with complaints of pain, hematuria, but gastrointestinal symptoms such as obstipation and weight loss can also occur [3]. Elevated blood pressure due to increased activity of the renin–angiotensin system is also common [4].
ADPKD is usually diagnosed according to the criteria of Ravine [5], which are based on ultrasonographic imaging and take into account the family history and age of the patient. Patients with a positive family history between the ages of 15 and 29 with more than two renal cysts in total, between 30 and 59 with two cysts in each kidney, or above 60 with more than 4 cysts in each kidney are diagnosed as having ADPKD. Without a positive family history, ADPKD can be diagnosed if more than ten cysts are present in each kidney, regardless of age.
Besides hypertension, end-stage renal disease and pyelonephritis, cyst infection is a common complication of ADPKD [6, 7]. Patients with a cyst infection usually present with symptoms such as flank pain and fever, mostly accompanied by an increased level of C-reactive protein (CRP) and leukocytosis. Because flank pain and fever are also common in cyst hemorrhage, pyelonephritis, and nephrolithiasis, further diagnostic methods are necessary to settle the correct diagnosis [8].
Although cyst infection has a prevalence of up to one in two patients with ADPKD, diagnosis remains challenging [9]. The diagnostic reference is analysis of the cyst fluid, but cyst punctures can cause bleeding, rupture, and contamination of adjacent cysts and are therefore rarely performed [10].
The purpose of this pictorial essay was to illustrate and discuss the potential value of FDG-PET/CT compared to conventional imaging methods (ultrasonography, CT, and MRI) in diagnosing cyst infection in ADPKD.
Conventional imaging
Ultrasonography is often the initial step in locating the source of lower abdominal pain that is common in patients with cyst infections. It is relatively cheap compared to other cross-sectional imaging methods, does not use any potentially harmful ionizing radiation, and also allows exclusion of hydronephrosis.
However, ultrasonography and other conventional radiologic modalities such as CT and standard magnetic resonance imaging (MRI) are often of limited use in diagnosing infection [11,12,13]. A diagnosis of infection with these modalities is mostly based on wall thickening and heterogeneous content of the cysts. However, since the presence and expansion of numerous cysts in polycystic disease often severely affects the normal anatomy of the affected organ, wall thickening can reflect residual functional parenchyma, and harmless intracystic cellular debris can also cause a heterogeneous cyst appearance. As a consequence, it is hard to distinguish between infected and non-infected cysts [13].
Besides these limitations, iodinated CT contrast agents and gadolinium-based MRI contrast agents can be contraindicated in patients with impaired renal function (due to ADPKD) because of the potential risks of nephrotoxicity and nephrogenic systemic fibrosis, respectively [13]. Of interest, diffusion-weighted MRI is a relatively new MRI technique that is sensitive to the random (Brownian) motion of water molecules, and can provide a high lesion-to-background contrast. Although it is particularly used in oncology, it may also be used to diagnose (cyst) infections. A recent study showed a sensitivity and specificity around 80% for diagnosing cyst infection with combined MRI findings, which included high intracystic signal intensity on diffusion-weighted imaging MRI and wall thickening. However, only patients with severe cyst infection were included, and the specificity dropped to 66% when patients had organomegaly, which is common in ADPKD [14]. Therefore, there is a need for alternative imaging methods for the evaluation of these patients.
FDG-PET/CT
18F-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) is considered a potentially useful imaging technique for detecting cyst infection. Activated inflammatory and infectious cells (such as macrophages, lymphocytes and neutrophils) require a high amount of glucose and therefore also accumulate FDG [15]. The FDG accumulation can be visualized by PET with a high contrast-to-background ratio, and the concomitantly acquired low-dose CT can be used to anatomically pinpoint the sites of FDG accumulation and therefore sites of potential infection.
Various recent studies have investigated the diagnostic value of FDG-PET/CT in diagnosing cyst infections. For example, Sallée et al. [16] described 8 patients in whom a cyst infection was diagnosed based on FDG-PET/CT. Five patients had a definite cyst infection based on cyst aspiration, and three patients a probable cyst infection based on the presence of all of the following five factors: fever, abdominal pain, increased CRP, the absence of cyst bleeding and the absence of any other possible cause of fever. In all 8 patients, FDG-PET/CT results were positive for infection (Figs. 1, 2, 3, 4 and 5).
Bobot et al. [10] described 32 cases of clinically suspected cyst infections in 24 patients where FDG-PET/CT achieved a sensitivity of 77% and a specificity of 100% for diagnosing cyst infection. Three FDG-PET/CT positive cases were regarded as definitive cyst infection based on cyst aspiration, the other 11 FDG-PET/CT positive cases were considered as ‘likely cyst infections’ based on the five criteria of Sallée et al. [16]. Long treatment with antibiotics before the FDG-PET/CT scan was suggested as the most likely explanation for false-negative cases.
Balbo et al. [17] described 32 cases of clinically suspected cyst infections in 27 patients where FDG-PET/CT was reported to have a sensitivity of 95% and a specificity of 100%. Among these, there were 24 episodes of cyst infection in 18 patients. Six cases were definite cyst infections based on cyst aspiration, the other 18 cases were ‘probably cyst infections’, also based on the criteria of Sallée et al. [16].
Finally, we recently analyzed 37 cases in 32 patients where FDG-PET/CT achieved a sensitivity of 86% and a specificity of 81%, with 18 true-positive and 11 true-negative cases (data not published yet). All cases were assessed based on the criteria of Sallée et al. [16], because no cyst punctures were performed.