Proteomic Analysis for the Diagnosis of Fibrinogen Aα-chain Amyloidosis.

Introduction: Hereditary fibrinogen Aα-chain (AFib) amyloidosis is a relatively uncommon renal disease associated with a small number of pathogenic fibrinogen Aα (FibA) variants; wild-type FibA normally does not result in amyloid deposition. Proteomics is now routinely used to identify the amyloid type in clinical samples, and we report here our algorithm for identification of FibA in amyloid.

Methods: Proteomics data from 1001 Congo red-positive patient samples were examined using the Mascot search engine to interrogate the Swiss-Prot database and generate protein identity scores.

Natural history and outcomes in localised immunoglobulin light-chain amyloidosis: a long-term observational study.

Background: Localised immunoglobulin light-chain amyloidosis, involving one type of tissue, is rare. Little systematic data exists regarding clinical presentations, course or outcomes, or risk of progression to systemic amyloidosis. We aimed to report clinical features and outcomes of a large series of patients with localised light-chain amyloidosis.

Natural history and outcome of light chain deposition disease.

Light chain deposition disease (LCDD) is characterized by the deposition of monotypic immunoglobulin light chains in the kidney, resulting in renal dysfunction. Fifty-three patients with biopsy-proven LCDD were prospectively followed at the UK National Amyloidosis Center. Median age at diagnosis was 56 years, and patients were followed for a median of 6.

Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis.

Background: The prognosis and treatment of the 2 main types of cardiac amyloidosis, immunoglobulin light chain (AL) and transthyretin (ATTR) amyloidosis, are substantially influenced by cardiac involvement. Cardiovascular magnetic resonance with late gadolinium enhancement (LGE) is a reference standard for the diagnosis of cardiac amyloidosis, but its potential for stratifying risk is unknown.

Methods And Results: Two hundred fifty prospectively recruited subjects, 122 patients with ATTR amyloid, 9 asymptomatic mutation carriers, and 119 patients with AL amyloidosis, underwent LGE cardiovascular magnetic resonance.

A study of implanted cardiac rhythm recorders in advanced cardiac AL amyloidosis.

Aims: AL amyloidosis may respond to chemotherapy but two-thirds of patients with severe cardiac involvement die within a year of diagnosis, purportedly from tachyarrhythmias or electromechanical dissociation. We sought to characterize the nature of cardiac arrhythmias in severe cardiac AL amyloidosis using implanted cardiac rhythm recorders.

Methods And Results: Implantable loop recorders (ILRs) were inserted within 24 h of baseline evaluation at the UK National Amyloidosis Centre, into 20 consecutive patients with newly diagnosed severe cardiac AL amyloidosis and symptoms of syncope or pre-syncope.

Emerging treatments for amyloidosis.

Amyloidosis results from protein misfolding, and ongoing amyloid deposition can ultimately lead to organ failure and death. Historically, this is a group of diseases with limited treatment options and frequently poor prognosis. However, there are now 'targeted' therapeutics emerging in the form of stabilizers of the precursor protein, inhibitors of fibrillogenesis, fibril disruptors, and blockers of protein translation, transcription, and immunotherapy.

Misdiagnosing renal amyloidosis as minimal change disease.

Background: Minimal change disease (MCD) accounts for 10-15% of all adult nephrotic syndrome cases and requires normal renal histology by light microscopy and negative immunohistology. Foot process effacement on electron microscopy (EM) is typical. Renal amyloid deposits demonstrate pathognomonic green birefringence when viewed under cross-polarized light after staining tissue with Congo red (CR) and may reveal fibrils on EM.

Recognizing isolated IgG4-related nephropathy.

IgG4-related tubulointerstitial nephritis is an uncommon cause of renal impairment. It has been associated with dysfunction in a number of other organs giving rise to the term IgG4-related systemic disease; organ involvement can occur metachronously, hence, making it more difficult to identify patients. The exact cause of this condition remains unknown.

Extracellular volume expansion in peritoneal dialysis patients.

Introduction: Cardiovascular mortality remains high among peritoneal dialysis (PD) patients. Several small studies have suggested that PD patients are volume expanded, and as such this could be a cardiovascular risk factor. We therefore wished to investigate factors which could lead to extracellular water (ECW) expansion.

Is extracellular volume expansion of peritoneal dialysis patients associated with greater urine output?

Background And Objectives: Residual renal function (RRF) is important for peritoneal dialysis (PD) technique failure and patient survival. Reduction in extracellular water (ECW) has been reported to reduce urine output. We audited volume status and RRF to determine whether ECW was linked to urinary output.