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

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Abstract

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.

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A malnutrition-inflammation score is correlated with morbidity and mortality in maintenance hemodialysis patients.

K. Kalantar-Zadeh, J Kopple, G Block … (2001)

Malnutrition inflammation complex syndrome (MICS) occurs commonly in maintenance hemodialysis (MHD) patients and may correlate with increased morbidity and mortality. An optimal, comprehensive, quantitative system that assesses MICS could be a useful measure of clinical status and may be a predictor of outcome in MHD patients. We therefore attempted to develop and validate such an instrument, comparing it with conventional measures of nutrition and inflammation, as well as prospective hospitalization and mortality. Using components of the conventional Subjective Global Assessment (SGA), a semiquantitative scale with three severity levels, the Dialysis Malnutrition Score (DMS), a fully quantitative scoring system consisting of 7 SGA components, with total score ranging between 7 (normal) and 35 (severely malnourished), was recently developed. To improve the DMS, we added three new elements to the 7 DMS components: body mass index, serum albumin level, and total iron-binding capacity to represent serum transferrin level. This new comprehensive Malnutrition-Inflammation Score (MIS) has 10 components, each with four levels of severity, from 0 (normal) to 3 (very severe). The sum of all 10 MIS components ranges from 0 to 30, denoting increasing degree of severity. These scores were compared with anthropometric measurements, near-infrared-measured body fat percentage, laboratory measures that included serum C-reactive protein (CRP), and 12-month prospective hospitalization and mortality rates. Eighty-three outpatients (44 men, 39 women; age, 59 +/- 15 years) on MHD therapy for at least 3 months (43 +/- 33 months) were evaluated at the beginning of this study and followed up for 1 year. The SGA, DMS, and MIS were assessed simultaneously on all patients by a trained physician. Case-mix-adjusted correlation coefficients for the MIS were significant for hospitalization days (r = 0.45; P < 0.001) and frequency of hospitalization (r = 0.46; P < 0.001). Compared with the SGA and DMS, most pertinent correlation coefficients were stronger with the MIS. The MIS, but not the SGA or DMS, correlated significantly with creatinine level, hematocrit, and CRP level. During the 12-month follow-up, 9 patients died and 6 patients left the cohort. The Cox proportional hazard-calculated relative risk for death for each 10-unit increase in the MIS was 10.43 (95% confidence interval, 2.28 to 47.64; P = 0.002). The MIS was superior to its components or different subversions for predicting mortality. The MIS appears to be a comprehensive scoring system with significant associations with prospective hospitalization and mortality, as well as measures of nutrition, inflammation, and anemia in MHD patients. The MIS may be superior to the conventional SGA and the DMS, as well as to individual laboratory values, as a predictor of dialysis outcome and an indicator of MICS.

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Subjective global assessment of nutrition in dialysis patients.

G Enia, C Sicuso, G Alati … (1992)

Malnutrition is a major negative prognostic factor in dialysis patients. Simple and reliable estimations of nutritional status may therefore prove of particular value in the follow-up of these patients. To validate subjective global assessment (SGA) in dialysis patients we compared subjective global assessment with objective measurements (anthropometry, bioelectrical impedance, biochemical measurements) in 59 chronic uraemic patients treated by haemodialysis (n = 36) or CAPD (n = 23). Subjective global assessment was performed by an observer unaware of the results of objective measurements and was related to serum albumin (r = -0.51, P < 0.001) and bioelectric impedance phase angle (r = -0.58, P < 0.001) as well as with MAMC (r = -0.28 P = 0.028), %fat (r = -0.27, P = 0.042) and nPCR (r = -0.29 P = 0.027). Multiple regression analysis showed that the relationship of subjective global assessment (as a dependent variable) with objective measurements (covariates) was stronger (multiple r = 0.77) than the relationship found with univariate analysis. This finding indicates that subjective global assessment gives a well-based and balanced estimation of nutritional status. Our data show that subjective global assessment is a clinically adequate method for assessing nutritional status in dialysis patients. Being an inexpensive method of well-proven reliability, subjective global assessment can be recommended for a more frequent assessment of nutritional status in dialysis patients.

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Dialysis-related amyloidosis: challenges and solutions

R Scarpioni, Martiniano M Ricardi, V Albertazzi … (2016)

Amyloidosis refers to the extracellular tissue deposition of fibrils composed of low-molecular-weight subunits of a variety of proteins. These deposits may result in a wide range of clinical manifestations depending upon their type, location, and the amount of deposition. Dialysis-related amyloidosis is a serious complication of long-term dialysis therapy and is characterized by the deposition of amyloid fibrils, principally composed of β2 microglobulins (β2M), in the osteoarticular structures and viscera. Most of the β2M is eliminated through glomerular filtration and subsequent reabsorption and catabolism by the proximal tubules. As a consequence, the serum levels of β2M are inversely related to the glomerular filtration rate; therefore, in end-stage renal disease patients, β2M levels increase up to 60-fold. Serum levels of β2M are also elevated in several pathological conditions such as chronic inflammation, liver disease, and above all, in renal dysfunction. Retention of amyloidogenic protein has been attributed to several factors including type of dialysis membrane, prolonged uremic state and/or decreased diuresis, advanced glycation end products, elevated levels of cytokines and dialysate. Dialysis treatment per se has been considered to be an inflammatory stimulus, inducing cytokine production (such as interleukin-1, tumor necrosis factor-α, interleukin-6) and complement activation. The released cytokines are thought to stimulate the synthesis and release of β2M by the macrophages and/or augment the expression of human leukocyte antigens (class I), increasing β2M expression. Residual renal function is probably the best determinant of β2M levels. Therefore, it has to be maintained as long as possible. In this article, we will focus our attention on the etiology of dialysis-related amyloidosis, its prevention, therapy, and future solutions.

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Journal

Journal ID (nlm-ta): J Clin Med

Journal ID (iso-abbrev): J Clin Med

Journal ID (publisher-id): jcm

Title: Journal of Clinical Medicine

Publisher: MDPI

ISSN (Electronic): 2077-0383

Publication date (Electronic): 19 September 2019

Publication date Collection: September 2019

Volume: 8

Issue: 9

Electronic Location Identifier: 1494

Affiliations

[1 ]Néphrologie, Centre Hospitalier du Mans, 72037 Le Mans, France; giulia.santagati@ 123456hotmail.it (G.S.); emanuela.cataldo@ 123456gmail.com (E.C.); valecolumbano@ 123456hotmail.it (V.C.); antoine.chatrenet@ 123456gmail.com (A.C.); lgendrot@ 123456ch-lemans.fr (L.G.); lnielsen@ 123456ch-lemans.fr (L.N.)

[2 ]Affidea IRMET, PET CENTER, Torino via Onorato Vigliani 89, 10135 Torino, Italy; daniele.penna@ 123456affidea.it (D.P.); ettore.pelosi@ 123456affidea.it (E.P.); vincenzo.arena@ 123456affidea.it (V.A.)

[3 ]Medecine Nucleaire, Centre Hospitalier du Mans, 72037 Le Mans, France; mammarh@ 123456gmail.com (M.H.); cboursot@ 123456ch-lemans.fr (C.B.)

[4 ]Radiology, Centre Hospitalier du Mans, 72037 Le Mans, France; fcinquantini@ 123456ch-lemans.fr

[5 ]MINT Université d’Angers, 49100 Angers, France; patrick.saulnier@ 123456chu-angers.fr

[6 ]Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, 10100 Torino, Italy

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[* ]Correspondence: gbpiccoli@ 123456yahoo.it

Author information

Daniele Penna https://orcid.org/0000-0003-4610-1838

Ettore Pelosi https://orcid.org/0000-0002-5885-4047

Giorgina Barbara Piccoli https://orcid.org/0000-0002-2632-4009

Article

Publisher ID: jcm-08-01494

DOI: 10.3390/jcm8091494

PMC ID: 6781261

PubMed ID: 31546847

SO-VID: ec197432-cfd4-4cca-99d4-4e511626b5e2

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Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/Licenses/by/4.0/).

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

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Most cited references 71

A malnutrition-inflammation score is correlated with morbidity and mortality in maintenance hemodialysis patients.

Subjective global assessment of nutrition in dialysis patients.

Dialysis-related amyloidosis: challenges and solutions

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