ALECT2 Information For Healthcare Professionals

Recognizing and diagnosing ALECT2

This video provides information for healthcare professionals about recognizing and diagnosing ALECT2, including, presentation, common ethnicities, and histological findings. Watch to learn more about this recently identified form of amyloidosis.

Leukocyte Chemotactic Factor 2 Amyloidosis, or ALECT2 is a newly
described form of systemic amyloidosis, clinically implicated as a cause
of slowly progressive chronic kidney disease (CKD). While ALECT2 manifests
clinically as a kidney disease, the leukocyte chemotactic factor 2 (LECT2)
protein which forms the amyloid fibers is primarily of hepatic origin, and also
deposits in the liver.

Current research suggests that LECT2 amyloidosis (ALECT2) is the 2nd or 3rd most
common cause of renal amyloidosis, depending on the population under study,
after immunoglobulin light chain amyloidosis (AL) and/or amyloid A amyloidosis (AA).
In the kidney, ALECT2 is characterized by predominantly interstitial amyloid deposition,
with relative sparing of the glomeruli (figure 1), in contrast to the glomerular disease
that usually characterizes AL or SAA nephropathy.1,2

If you would like to request information about the REFLECTION study and diagnosis of ALECT2 amyloidosis, click below to contact the study team.

Figure 2 shows examples of diagnostic histology
(Click to enlarge)

Figure 1: ALECT2 Renal Histology

Leukocyte chemotactic factor 2 amyloidosis. (a and b) Uptake of Congo red by glomerular and interstitial amyloid deposits (a) with green birefringence upon (b) polarization (original magnification x 200). (c) Extensive amorphous deposits of LECT2 amyloid in the glomeruli and interstitial compartments (hematoxylin and eosin; original magnification x 200). (d) Reactivity of glomerular and interstitial amyloid deposits with an anti-LECT2 antibody (immunoperoxidase technique, x200).

Image reproduced from:
1) Larsen CP, et al. Leaukocyte chemotactic factor 2 amyloidosis (ALECT2) is a common form of renal amyloidosis among Egyptions. Modern Pathology. 2016; 29: 416-420.

Historically, ALECT2 has been diagnosed in middle-aged and older adults. However the typical symptomatology (see below) does
not generally prompt a routine renal biopsy, most likely resulting in delayed diagnosis and/or under-diagnosis.

ALECT2 Symptomatology and Risk Factors

LECT2 amyloidosis is a fairly recently identified condition, with the first case diagnosed in 2008. Much information is still being gathered on the specific causes and risk factors associated with ALECT2, but here is what is held to be true at present:

  • Average age of diagnosis: ~65 years, ranging from 30 to 88 years.3-5
  • Although rare in the general population, ALECT2 seems to be more common in people of certain ethnicities, including hispanic (particularly of Mexican descent), Egyptian, Punjabi, Sudanese, Native Americans (especially in the Southwest USA), and Canadian First Nations.2,4-8
  • At this time, there does not appear to be a familial pattern of disease despite the almost uniform presence of homozygosity for the single nucleotide poly-morphism (SNP), rs31517, in cases where the LECT2 gene was sequenced.6,9,10 However, the presence of rs31517 is not helpful diagnostically, as the vast majority of homozygous individuals in the general population will never develop ALECT2.
  • Disease progression appears to be associated with:
    • Gradual decline of GFR (glomerular filtration rate) with a mean rate of 6 mL/min/1.73 m2/year observed in one USA study.6
    • Variable degrees of proteinuria (including mild or no proteinuria) clinically observed in ALECT2 (versus almost uniform heavy proteinuria in AL or SAA)
    • Gross hematuria and/or microscopic hematuria is seen in a minority of cases.
  • Comorbid conditions have been observed in prior studies, including hypertension, diabetes, and hepatitis B/C
    • In the UK ALECT2 NAC study, Hepatitis B/C occurred concurrently in 5/24 (21%) individuals, and diabetes in 4/24 (17%) individuals.10
    • In US studies, there was a high frequency of diabetes and hypertension, ranging from 26.4% to 38% and 50% to 66% respectively.5,6
    • Circulating LECT2 protein has been shown to be positively correlated with the severity of both obesity and insulin resistance.11

ALECT2 Diagnosis and Treatment

Renal amyloidosis is very rare and can only be diagnosed by a renal biopsy with Congo red staining. Each of the three most common renal amyloidoses (AL, AA and ALECT2) have unique causes, necessitating differentiated treatment. For this reason, determining the type of amyloid present is key to accurate diagnosis (figure 2).

At present, the only effective treatment for ALECT2 is a kidney transplant. Current management of the condition is intended simply to preserve kidney function by maintaining an optimal fluid balance through diet, fluid intake, and use of diuretics.

Researchers in the REFLECTION natural history study are working to improve understanding of prevalence, pathogenesis and risk factors for the condition, with the goal of identifying potential biomarkers, supporting the future development of therapeutics and informing the design of LECT2 amyloidosis clinical trials.

Figure 2: Differential diagnosis of ALECT2 disease

Figure 2: Differential diagnosis of ALECT2 disease
(Click to enlarge)

Who Should Be Considered For The REFLECTION Study?

Given the challenges in accurately diagnosing ALECT2, it is possible that individuals may have LECT2-caused amyloidosis and be undiagnosed. Some individuals may be eligible for diagnostic testing as part of the REFLECTION study, at no cost. For this reason it is important to consider a range of individuals for potential referral, including those with:

  • Biopsy-confirmed diagnosis of LECT2 amyloidosis, with or without end-stage renal disease (ESRD)
  • Uncharacterized renal amyloidosis
  • Chronic kidney disease of an unknown cause with known risk factors for ALECT2 amyloidosis as described above

For more information, please see our “About the REFLECTION Study” page, and the study information at

Physician Follow-up Form

Please enter your contact information. A local study team member will contact you to discuss the REFLECTION study-including eligibility and potential study referrals-in more depth.

Alnylam takes your privacy very seriously and will never disclose or share your data without your consent other than for the purposes specified in the Privacy Notice unless required to do so by law. We will use your personal information only for the purposes of informing you about our clinical research studies, or to ask for general information that may enhance our research program.

By providing and submitting your information to Alnylam, you are agreeing with the terms and conditions in our Privacy Notice. Submission does not oblige you or the patient referenced above to participate in our studies, and Alnylam cannot guarantee that you/they will be able to take part in the study.

You can arrange for your information to be deleted from our database at any time by contacting KPI Agency at Please make a note of this email address.

Toll-free within the U.S: 866-330-0326
International: +1 617-575-7400


  1. Said[LC1] , S.M., et al, Renal amyloidosis: origin and clinicopathologic correlations of 474 recent cases. Clin J Am Soc Nephrol, 2013. 8(9): p. 1515-23.
  2. Larsen, C.P., et al., Prevalence and organ distribution of leukocyte chemotactic factor 2 amyloidosis (ALECT2) among decedents in New Mexico. Amyloid, 2016. 23(2): p. 119-23.
  3. Mereuta, O.M., et al., Leukocyte cell-derived chemotaxin 2 (LECT2)-associated amyloidosis is a frequent cause of hepatic amyloidosis in the United States. Blood, 2014. 123(10): p. 1479-82.
  4. Nasr, S.H., A. Dogan, C.P. Larsen, Leukocyte cell-derived chemotaxin 2-associated amyloidosis: a recently recognized disease with distinct clinicopathologic characteristics. Clin J Am Soc Nephrol, 2015. 10(11): p. 2084-93.
  5. Said, S.M., et al., Characterization and outcomes of renal leukocyte chemotactic factor 2-associated amyloidosis. Kidney Int, 2014. 86(2): p. 370-7.
  6. Larsen, C.P., et al., Clinical, morphologic, and genetic features of renal leukocyte chemotactic factor 2 amyloidosis. Kidney Int, 2014. 86(2): p. 378-82.
  7. Larsen, C.P., et al., Leukocyte chemotactic factor 2 amyloidosis (ALECT2) is a common form of renal amyloidosis among Egyptians. Mod Pathol, 2016. 29(4): p. 416-20.
  8. Hutton, H.L., et al., Renal leukocyte chemotactic factor 2 (LECT2) amyloidosis in First Nations people in Northern British Columbia, Canada: a report of 4 cases. Am J Kidney Dis, 2014. 64(5): p. 790-2.
  9. Murphy, CL et al. Leukocyte chemotactic factor 2 (LECT2)-associated renal amyloidosis: a case series Am J Kidney Dis 2010; 56(6):1100-7
  10. Rezk T e tal., Diagnosis, pathogenesis and outcome in leucocyte chemotactic factor 2 (ALECT2) amyloidosis.
    Nephrol Dial Transplant. 2018 Feb 1;33(2): p.241-247
  11. Lan F et al. LECT2 functions as a hepatokine that links obesity to skeletal muscle insulin resistance. Diabetes 2014 63 (5): p.1649-64