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

Abstract

BackgroundNo 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 presentationOur 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.ConclusionsIn 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.

Treating Protein Misfolding Diseases: Therapeutic Successes Against Systemic Amyloidoses

“…An alternative strategy to promote amyloid clearance is based on the amyloid fibril disrupting activity of 4ʹ-iodo-4ʹ-deoxydoxorubicin and of the structurally related molecule doxycycline ( Merlini et al., 1995 ; Cardoso et al., 2010 ). Several clinical observations support a potential benefit of doxycycline treatment against ATTR, AL and Aβ 2 Mwt amyloidosis ( Obici et al., 2012 ; Montagna et al., 2013 ; Piccoli et al., 2017 ; Wechalekar and Whelan, 2017 ; Karlstedt et al., 2019 ) and several ongoing clinical trials are currently investigating the potential therapeutic effect of doxycycline against different forms of systemic amyloidosis.…”

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

“…The most widely used technique is post-dilutional on-line haemodiafiltration (HDF), with acetate-free, citrate-based dialysate (calcium concentration 1.5–1.75 mmol/L; sodium 138–140 mEq/L; bicarbonate 32–38 mmol/L; temperature 36 °C–37 °C; potassium 2 mmol/L, corrected with potassium infusion in case of need). At the beginning of the study, prescriptions were mainly standardized to include the following: high-permeability membranes with a surface at least as wide as the patient’s body surface, reinfusion of at least 24 litres per session [57]. Conventional haemodialysis was performed with the same dialysate, employing low-, medium- and high-permeability dialysers.…”

Targeting Amyloid Aggregation: An Overview of Strategies and Mechanisms

“…DOX was used in an exploratory off-label study on three patients affected by a severe form of dialysis-related amyloidosis (DRA) and although the amyloid mass was not apparently reduced, the patients experienced a very significant reduction of the ostheoarticular pain, as well as a remarkable improvement of the active and passive movements [ 43 ]. Although the mechanism in vivo is not clarified, the benefits of this treatment were recently confirmed by Piccoli et al, who recommend the DOX treatment as antalgic therapy for this kind of patients [ 44 ]. Although clinical trials for the validation of the treatment of this amyloidosis are not currently ongoing, DOX has received the designation of orphan drug by the European Medicines Agency for the treatment of DRA and hopefully a trial will be designed soon because there is no treatment for this very debilitating disease.…”