Amyloidosis-Induced Chronic Kidney Disease

Amyloidosis is a rare but serious disorder in which abnormal proteins called amyloid fibrils build up in organs and tissues. These misfolded proteins form insoluble deposits that gradually interfere with normal organ function. While amyloidosis can affect multiple systems, including the heart, liver, nerves, and gastrointestinal tract, the kidneys are the organs that are most at risk of serious and irreversable damage[1].

There are several types of amyloidosis. The two most relevant for kidney disease are AL amyloidosis (light-chain amyloidosis, linked to plasma cell disorders such as multiple myeloma) and AA amyloidosis (secondary amyloidosis, which develops in chronic inflammatory conditions like rheumatoid arthritis, familial Mediterranean fever, or chronic infections). In both cases, the kidneys often become a primary target.

Amyloid deposits accumulate in the glomeruli, the tiny filtering units of the kidney. This leads to progressive damage: the glomerular basement membrane thickens, podocytes are injured, and the filtration barrier becomes leaky[2]. Patients typically develop significant proteinuria (often in the nephrotic range), hypoalbuminemia, edema, and a gradual decline in glomerular filtration rate (GFR). Over time, interstitial fibrosis and tubular atrophy follow, culminating in chronic kidney disease (CKD) and, in many cases, end-stage renal disease requiring dialysis or transplantation.

Unlike some toxin-induced forms of kidney injury, amyloidosis-related CKD often progresses insidiously. Early symptoms may be subtle and can include fatigue, foamy urine, or swelling in the legs. Many patients are diagnosed only after substantial kidney damage has occurred. In AL amyloidosis, systemic signs such as macroglossia, periorbital purpura, or cardiomyopathy may provide diagnostic clues. In AA amyloidosis, the underlying inflammatory disease usually dominates the clinical picture until renal involvement becomes evident.

Recent studies highlight the growing recognition of amyloidosis as an important cause of CKD, particularly in older adults. Advances in imaging (such as technetium-labeled bone tracers) and the use of mass spectrometry on kidney biopsies have improved diagnostic accuracy. Treatment depends on the type: chemotherapy or targeted therapies for AL amyloidosis aim to suppress the production of light chains, while aggressive management of the underlying inflammation is key in AA amyloidosis. However, once advanced fibrosis is established, renal recovery may be limited even if the amyloid production is halted.

Early recognition through urine and blood tests (including serum free light chains and serum amyloid A protein) combined with timely biopsy remains essential[3]. As the understanding of protein-folding disorders improves, new therapies, including fibril disruptors and anti-amyloid antibodies, offer hope for better outcomes in patients with renal amyloidosis.

We propose to call this Chronic Kidney Disease of non-Traditional causes (CKDnT): Amyloidosis-Induced Chronic Kidney Disease.

[1] Nader et al: Amyloidosis and the Kidney: An Update in Seminars in Nephrology – 2022
[2] Dember: Amyloidosis-associated kidney disease in Journal of the American Society of Nephrology – 2006
[3] Mirioglu et al: AA Amyloidosis: A Contemporary View in Current Rheumatology Reports - 2024