Sayed, Rabya Hussain; (2018) Advances in the Diagnosis and Treatment of Amyloidosis and Related Disorders. Doctoral thesis (M.D(Res)), UCL (University College London).

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Abstract

BACKGROUND: Amyloidosis is a disorder arising from the variable physiological effects of dysregulated, extracellular protein deposition. There are >30 different subtypes, all possessing the same histological characteristics and the two major organs affected are the kidneys and the heart. AIMS AND HYPOTHESIS: To evaluate current UK histological practices leading to a misdiagnosis of amyloidosis; To establish proteomics as a new diagnostic technique for identifying amyloid, in the UK; To investigate the usefulness of a relatively new biomarker i.e. Retinol Binding Protein (RBP), across amyloid subtypes and correlate values with biopsy findings, which has not previously been done; To identify the cause of death in patients with Stage III/ IV cardiac amyloidosis using, for the first time, Implantable Loop Recorders; To present the first comprehensive review of Light Chain Deposition Disease highlighting the relationship between haematological response and overall prognosis. RESULTS: In 65% of cases where renal amyloidosis was misdiagnosed as minimal change disease, Congo red staining was not undertaken and in 35% of cases neither Congo red staining, with cross-polarised light visualisation, nor electron microscopy was undertaken. Proteomics has now been established as a specific and sensitive technique by which to diagnose amyloid and the subtype, demonstrated by distinguishing Fibrinogen Aα-Chain (AFib) renal biopsies from other subtypes. Urinary RBP/Creatinine (RCR) correlated with the: degree of tubular atrophy, number of light chains, eGFR, presence of glycosuria and degree of tubular phosphate reabsorption. RCR values were especially high in AFib and AA amyloidosis. Pulseless Electrical Activity was identified as the terminal rhythm in patients with Stage III/IV cardiac amyloidosis and this was preceded by a high degree AV block. Deep clonal responses to chemotherapy are associated with improved renal and overall outcomes in LCDD and should be pursued even in advanced chronic kidney disease.

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