Positron Emission Tomography Can Support the Diagnosis of Dialysis-Related Amyloidosis

Background: The improvements in dialysis have not eliminated long-term problems, including dialysis-related amyloidosis (DRA), caused by Beta-2 microglobulin deposition. Several types of scintigraphy have been tested to detect DRA, none entered the clinical practice. Aim of the study was to assess the potential of PET-FDG scan in the diagnosis of DRA. Methods: Forty-six dialysis patients with at least one PET scan (72 scans) were selected out 162 patients treated in 2016–2018. Subjective global assessment (SGA), malnutrition inflammation score (A), Charlson Comorbidity Index (CCI), were assessed at time of scan; 218 age-matched cases with normal kidney function were selected as controls. PET scans were read in duplicate. Carpal tunnel syndrome was considered a proxy for DRA. A composite “amyloid score” score considered each dialysis year = 1 point; carpal tunnel-DRA = 5 points per site. Logistic regression, ROC curves and a prediction model were built. Results: The prevalence of positive PET was 43.5% in dialysis, 5% in controls (p < 0.0001). PET was positive in 14/15 (93.3%) scans in patients with carpal tunnel. PET sensitivity for detecting DRA was 95% (specificity 64%). Carpal tunnel was related to dialysis vintage and MIS. A positive PET scan was significantly associated with dialysis vintage, MIS and amyloid score. A prediction model to explain PET positivity combined clinical score and MIS, allowing for an AUC of 0.906 (CI: 0.813–0.962; p < 0.001). Conclusions: PET-FDG may identify DRA, and may be useful in detecting cases in which inflammation favours B2M deposition. This finding, needing large-scale confirmation, could open new perspectives in the study of DRA

Doxycycline treatment in dialysis related amyloidosis: discrepancy between antalgic effect and inflammation, studied with FDG-positron emission tomography: a case report

Abstract Background No effective treatment is currently available and dialysis related amyloidosis continues to be invalidating in long-term dialysis patients. A recent case series reported reduction of osteoarticular pain on doxycycline treatment, extending the indications of this drug, used in other uncommon forms of amyloidosis, to dialysis patients. Explanations of the antalgic effect were the anti-inflammatory properties and anti-coiling effects of tetracycline. Case presentation Our report regards a 54-year-old woman, who was never transplanted and has been on hemodialysis and hemodiafiltration for overall 37 years, due to renal hypoplasia. In spite of high efficiency hemodiafiltration, she complained of increasing, invalidating osteoarticular pain; history and imaging suggested beta-2 microglobulin amyloid. Positron emission tomography (PET scan) identified metabolically active lesions in the involved settings. Low-dose doxycycline (100 mg/day) was started, leading to a considerable decrease in pain (over 6 months, from 7 to 8 to 4–5 on a 0–10 scale). At 6 months, a PET scan showed unmodified or increased uptake in the involved settings. Conclusions In summary, the previously described antalgic effect of doxycycline in dialysis related amyloidosis is confirmed in our case, the first studied using PET scan. The pattern at PET can suggests that the antalgic effect is independent from inflammation and points to other factors, such as interaction with fibril geometry or with bone structure

Example of left lower lobe pulmonary target lesion (same patient as Figure 4).

<p>Example of left lower lobe pulmonary target lesion (same patient as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0087629#pone-0087629-g004" target="_blank">Figure 4</a>).</p

New subcarinal adenopathy on PET3 (same patient as Figure 2).

<p>New subcarinal adenopathy on PET3 (same patient as <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0087629#pone-0087629-g002" target="_blank">Figure 2</a>).</p

Kaplan-Meier estimates of PFS and OS.

<p>No statistically significant difference (P = 0.007) in PFS was observed between metabolic non-progressive (mNP) patients (median PFS, 292 days ; range, 190–727) and metabolic (mP) progressive patients (median PFS, 64 days ; range: 37–216). Improved PFS in non-progressive patients was associated with prolonged OS (mNP; n = 4; median OS: 1031 days ; 296 to 1249 days versus mP; n = 8 ; 337, 5 days ; 71 to 734 days) (HR, 0.34; 95% CI, 0.06 to 0.84; P = 0.03).</p

Example of a patient with discordant PET2 and conventional imaging.

<p>Patient with right upper lobe NSCLC associated with subcarinal lymphadenopathy and ipsilateral lung metastasis (patient #9). Sum of the SUVmax of the most hypermetabolic lesions (2 lung lesions, 1 mediastinal lymph node) were 25.2, 29.3 (+16.3%) and 23.8 (−5.4%) for PET1, PET2 (% versus PET1) and PET3 (% versus PET1), respectively. Based on a SUVmax cut-off value of −21.6, the patient was classified as mP on PET2, in contrast with RECIST evaluation on CT scan (performed 71 days after starting erlotinib). This patient was subsequently reclassified as mNP on PET3 in accordance with RECIST evaluation with a 5.4% decrease of SUVmax (cut-off: 18.5%).</p