Amyloidosis as a cause or factor in the progression of cardiorenal damage

The amyloidoses are a group of protein folding disorders in which a protein misfolds from the normal α helical configuration into a β pleated sheet. This results in insolubility and extracellular deposition of fibrillar protein into organs. There are currently 42 proteins that have been identified as amyloidogenic. Approximately 16 have been recognized to affect the kidney, while approximately 11 proteins can deposit in the heart. The amyloidosis that frequently affects both the heart and kidney is amyloid light-chain (AL) amyloidosis. The most common symptoms related to amyloidosis, especially AL, are fatigue, dyspnea, and unintentional weight loss, which occur in more than half of patients. Given the non-specific nature of these symptoms, the diagnosis understandably is not typically high in the differential diagnosis. There are several methods employed to identify subtypes of amyloidosis: the most used is immunohistochemistry (with a panel of known antibodies against, most commonly AA, λ and ҝ light chains, and TTR), while the gold standard is laser microdissection with LC-MS/shotgun proteomics (has high sensitivity/specificity and can identify rare amyloid proteins and different amyloids that may exist concurrently). The therapeutic strategies depend on the diagnosed type of amyloidosis and are briefly discussed in the text.