Law, Steven John;
(2025)
Natural history, Staging and Prognosis in Systemic Amyloidosis.
Doctoral thesis (M.D(Res)), UCL (University College London).
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Abstract
Background: Systemic amyloidosis is a rare disorder of protein misfolding and aggregation ranging from indolent localised disease to rapidly progressive multi-organ failure. Systemic light-chain (AL) and transthyretin (ATTR) amyloidosis are the commonest amyloid types. Treatment options have improved significantly in recent years with further novel agents under evaluation. / Aims: To characterise the presentation and natural history of patients with ATTR amyloidosis to inform management in an era of novel disease modifying therapies. To evaluate trends in patient and renal survival in renal AL amyloidosis and assess outcomes following kidney transplantation to inform clinical decision making and patient selection for transplantation. Specific chapter aims include: • Identify markers of disease progression in ATTR-cardiomyopathy (ATTR-CM) • Characterise the natural history of early stage ATTR-CM • Describe a rare group of patients with variant ATTR (ATTRv) amyloidosis with atypical cardiac radionucleotide uptake • Report the healthcare utilization prior to diagnosis with ATTR amyloidosis • Describe trends in patient and renal survival in renal AL amyloidosis • Report kidney transplant outcomes in amyloidosis compared with other aetiologies of renal disease / Results and Conclusions: National Amyloidosis Centre (NAC) ATTR Stage is prognostic throughout follow up in ATTR-CM whilst increasing NT-proBNP and NYHA class are independently associated with mortality. Patients with early stage ATTR-CM have comparable survival to the matched UK general population but significantly increased cardiovascular morbidity suggesting potential benefit from disease modifying treatment. Variant ATTR cardiomyopathy associated with the p.Ser97Tyr TTR gene variant demonstrates relatively low cardiac radionucleotide uptake warranting special diagnostic consideration. Healthcare utilization is high and varied prior to diagnosis in ATTR-CM highlighting opportunities for, and potential benefits of, early diagnosis and treatment. Renal and patient survival in renal AL amyloidosis has progressively improved. Patient and allograft survival post kidney transplantation in selected individuals with AA and AL amyloidosis are comparable to patients with diabetic nephropathy.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | M.D(Res) |
| Title: | Natural history, Staging and Prognosis in Systemic Amyloidosis |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2025. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10207455 |
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