What Are the Signs of AA Amyloidosis in FMF?
At a Glance
Early kidney damage (AA amyloidosis) from Familial Mediterranean fever is completely silent and causes no physical symptoms. It can only be detected through routine urine tests for protein. Late signs include foamy urine and swelling, but daily colchicine therapy can prevent this damage.
In this answer
4 sections
The most important thing to know about early kidney damage (AA amyloidosis) from Familial Mediterranean fever (FMF) is that it is completely “silent.” In its early stages, AA amyloidosis does not cause any physical symptoms that you can see or feel [1]. Standard blood tests for kidney function, like Creatinine or eGFR on a basic metabolic panel, often remain completely normal during this silent phase [2][3]. Because of this, you cannot rely on how you feel or on standard blood panels to know if your kidneys are healthy [2][3]. The only way to detect early damage is through routine urine tests specifically looking for protein [2].
How AA Amyloidosis Affects the Kidneys
During FMF flares—and sometimes even when you feel perfectly fine—your body produces high levels of inflammation [4][5]. This chronic inflammation triggers the liver to make large amounts of a protein called Serum Amyloid A (SAA) [4][6]. Over time, these SAA proteins can clump together into abnormal deposits called amyloid [4][5].
These amyloid deposits often build up in the kidneys’ filtering system [4]. When the filters are damaged, they begin to leak important proteins from your blood into your urine, a condition known as proteinuria [1].
The Silent Stages: Microalbuminuria and Beyond
In the beginning, only tiny amounts of a protein called albumin leak into the urine, a stage called microalbuminuria (small amounts of albumin in the urine). Even as the protein leak worsens into moderate stages (macroalbuminuria), you will not feel pain, fatigue, or notice any visible changes [1].
- No physical signs: Kidney damage can remain completely silent even as protein leakage increases.
- Detection: These silent stages can only be found through a simple spot urine test—often checking the albumin-to-creatinine ratio—ordered by your doctor [2][3]. This testing is typically done every 6 to 12 months, or as directed by your care team [2][3].
Finding amyloidosis at an early, silent stage is crucial. Strict, consistent adherence to daily colchicine therapy can control the underlying inflammation, protect the kidneys, and prevent the damage from progressing [7][8].
Later Signs of Kidney Damage
If kidney damage progresses without detection and the protein leak becomes massive, you may develop a condition called nephrotic syndrome [9]. Only when significant amounts of protein are lost from your blood will you start to experience physical symptoms [9][10].
If you notice any of these late-stage signs, contact your doctor right away:
- Foamy urine: Urine that looks unusually bubbly or frothy, like the foam on a beer, caused by high amounts of protein [9][10].
- Edema (swelling): Noticeable swelling, especially in your feet, ankles, legs, or around your eyes [9][10]. This happens because the loss of protein in your blood causes fluid to build up in your body’s tissues.
- Extreme fatigue: Feeling unusually tired or exhausted, which can result from systemic organ involvement or failing kidney function [11][12].
Why Routine Testing is Essential
Never wait for foamy urine, swelling, or fatigue to check your kidney health. By the time these physical symptoms appear, the kidneys have already sustained significant damage [9]. To protect yourself:
- Take your medication consistently: Taking colchicine exactly as prescribed every day is the most effective way to prevent FMF attacks and AA amyloidosis [13][14]. While a single accidentally missed dose won’t instantly cause damage, frequent missed doses or stopping the medication entirely greatly increases your risk [15].
- Get regular lab work: Your doctor should check your urine for protein and your blood for inflammation markers (like SAA and CRP) every 6 to 12 months, even when you feel healthy [3][6]. Remember that standard kidney blood tests are not enough to catch this early [2].
If colchicine alone is not enough to keep your inflammation markers down, doctors have other effective options, such as targeted biologic medications (IL-1 inhibitors), to protect your kidneys [16][17].
Common questions in this guide
Does early AA amyloidosis cause any physical symptoms?
How is early kidney damage from FMF detected?
What are the physical signs of late-stage AA amyloidosis?
How can I prevent AA amyloidosis if I have FMF?
How often should I get tested for kidney damage if I have FMF?
Questions for Your Doctor
5 questions
- •How frequently should we schedule my urine protein checks (urinalysis) and Serum Amyloid A (SAA) blood tests?
- •When you check my urine, are you specifically running an albumin-to-creatinine ratio test to catch early protein leaks?
- •What are my baseline SAA and CRP levels during periods when I am not having a flare?
- •If my current dose of colchicine isn't bringing my inflammation markers down to normal, what are our next steps or alternative medication options?
- •If I accidentally miss a dose of colchicine, what is the best way to get back on track?
Questions for You
3 questions
- •Am I taking my colchicine consistently every single day, even when I feel perfectly healthy?
- •When was the last time I had a specific urine test checking for protein, rather than just a standard blood test?
- •Have I noticed any unusual swelling in my legs or ankles, or any changes in how my urine looks recently?
Related questions
References
References (17)
- 1
AA Amyloidosis and Atypical Familial Mediterranean Fever with Exon 2 and 3 Mutations.
Yabuuchi J, Hayami N, Hoshino J, et al.
Case reports in nephrology and dialysis 2017; (7(2)):102-107 doi:10.1159/000478006.
PMID: 28868300 - 2
Familial Mediterranean Fever-Related Amyloidosis in Turkey: A Need for a Familial Mediterranean Fever Registry.
Helvaci O, Yasar E
Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation 2023; (21(Suppl 2)):101-104 doi:10.6002/ect.IAHNCongress.24.
PMID: 37496356 - 3
Familial mediterranean fever and long-term cardiovascular disease burden.
Magen E, Aamar S, Merzon E, et al.
The American journal of medicine 2026; doi:10.1016/j.amjmed.2026.01.006.
PMID: 41520806 - 4
Infections and AA amyloidosis: An overview.
Deshayes S, Aouba A, Grateau G, Georgin-Lavialle S
International journal of clinical practice 2021; (75(6)):e13966 doi:10.1111/ijcp.13966.
PMID: 33368925 - 5
Characteristics and course of patients with AA amyloidosis: single centre experience with 174 patients from Turkey.
Bektas M, Koca N, Oguz E, et al.
Rheumatology (Oxford, England) 2024; (63(2)):319-328 doi:10.1093/rheumatology/kead465.
PMID: 37738242 - 6
Outcomes of Canakinumab Treatment in Recipients of Kidney Transplant With Familial Mediterranean Fever: A Case Series.
Sendogan DO, Saritas H, Kumru G, et al.
Transplantation proceedings 2019; (51(7)):2292-2294 doi:10.1016/j.transproceed.2019.03.049.
PMID: 31400972 - 7
Prognostication of survival and progression to dialysis in AA amyloidosis.
Palladini G, Riva E, Basset M, et al.
Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis 2017; (24(sup1)):136-137 doi:10.1080/13506129.2017.1289917.
PMID: 28434292 - 8
The Preferential Use of Anakinra in Various Settings of FMF: A Review Applied to an Updated Treatment-Related Perspective of the Disease.
Giat E, Ben-Zvi I, Lidar M, Livneh A
International journal of molecular sciences 2022; (23(7)) doi:10.3390/ijms23073956.
PMID: 35409316 - 9
Clinical profile and outcome of AA amyloidosis associated kidney disease in India.
Bansal B, Sarkar A, Barwad A, et al.
Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis 2026; (33(1)):15-24 doi:10.1080/13506129.2025.2573233.
PMID: 41204056 - 10
Secondary amyloidosis as a cause of nephrotic syndrome in Takayasu arteritis.
Swaminathan H, Udaya R, Dayalan R, David VG
BMJ case reports 2025; (18(9)) doi:10.1136/bcr-2024-263648.
PMID: 40903100 - 11
AA amyloidosis with multiorgan involvement secondary to familial Mediterranean fever (FMF): dreadful consequences of delayed diagnosis and management.
Kataria A, Mannan MS, Nadeem A, Anwer F
BMJ case reports 2025; (18(6)) doi:10.1136/bcr-2025-266424.
PMID: 40588309 - 12
Menorrhagia due to uterine amyloidosis in familial Mediterranean fever: case-based review.
Cansu DÜ, Teke HÜ, Arik D, Korkmaz C
Rheumatology international 2021; (41(1)):205-211 doi:10.1007/s00296-020-04721-2.
PMID: 33052444 - 13
Familial Mediterranean Fever: Assessing the Overall Clinical Impact and Formulating Treatment Plans.
Manna R, Rigante D
Mediterranean journal of hematology and infectious diseases 2019; (11(1)):e2019027 doi:10.4084/MJHID.2019.027.
PMID: 31205631 - 14
Familial Mediterranean fever: overview of pathogenesis, clinical features and management.
Migita K, Asano T, Sato S, et al.
Immunological medicine 2018; (41(2)):55-61 doi:10.1080/13497413.2018.1481579.
PMID: 30938266 - 15
A survey of resistance to colchicine treatment for French patients with familial Mediterranean fever.
Corsia A, Georgin-Lavialle S, Hentgen V, et al.
Orphanet journal of rare diseases 2017; (12(1)):54 doi:10.1186/s13023-017-0609-1.
PMID: 28302131 - 16
Efficacy and safety of interleukin-1 inhibitors in familial Mediterranean fever patients complicated with amyloidosis.
Varan Ö, Kucuk H, Babaoglu H, et al.
Modern rheumatology 2019; (29(2)):363-366 doi:10.1080/14397595.2018.1457469.
PMID: 29578360 - 17
Long-term Results of Kidney Transplantation in Patients With Familial Mediterranean Fever and Amyloidosis.
Sarıtaş H, Sendogan DO, Kumru G, et al.
Transplantation proceedings 2019; (51(7)):2289-2291 doi:10.1016/j.transproceed.2019.04.074.
PMID: 31400971
This page explains the signs of AA amyloidosis and kidney damage in FMF for educational purposes. Always consult your rheumatologist or nephrologist regarding routine testing, medication adjustments, and any new symptoms.
Get notified when new evidence is published on Familial Mediterranean fever.
We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.