Visual Abstract
Keywords: chronic renal disease, renal pathology
Case Description
A 47-year-old Hispanic man, originally from Mexico and now working as a roofer, was referred for evaluation of stage 3 CKD. His medical history included hypertension, hyperlipidemia, osteoarthritis, heart failure with preserved ejection fraction (67%), coronary artery bypass grafting (December 2023), and right carotid endarterectomy (2024; Figure 1).
Figure 1.
Pathologic features of ALECT2 amyloidosis. (A) Hematoxylin and eosin stain showing amorphous amyloid deposits involving the interstitium and vasculature. (B) Congo red staining showing apple-green birefringence under polarized light involving glomerular structures as well as the interstitium and vessel walls. (C) Immunohistochemistry demonstrating strong LECT2 positivity within glomerular and interstitial amyloid deposits. ALECT2, leukocyte chemotactic factor 2 amyloidosis; LECT2, leukocyte chemotactic factor 2.
He reported fatigue, joint pain, and a 12 lb unintentional weight loss over 3 months. His physical examination was unremarkable without edema. Serum creatinine was 1.85 mg/dl and BUN 27 mg/dl; eGFR declined from 43 to 34 ml/min per 1.73 m2. Urinalysis showed a bland sediment without hematuria or casts. Twenty-four-hour urine protein was 352 mg. Antinuclear antibody was weakly positive, anti-double-stranded DNA was 10 IU/ml, complements were normal, and ANCA was negative. Serum and urine protein electrophoresis showed no monoclonal protein. Renal ultrasound revealed mildly echogenic kidneys without obstruction.
Given progressive CKD with bland urine sediment and no clear diabetic, hypertensive, or autoimmune explanation, a kidney biopsy was pursued.
Kidney biopsy demonstrated Congo Red–positive amyloid deposition with apple-green birefringence under polarized light involving the interstitium, vasculature, and glomeruli. Immunohistochemical staining was positive for leukocyte chemotactic factor 2 (LECT2) within amyloid deposits, confirming the diagnosis of LECT2 amyloidosis (ALECT2).
Discussion
LECT2 amyloidosis is an increasingly recognized cause of CKD, most commonly affecting individuals of Hispanic, particularly Mexican, ancestry.1,2 It is frequently misclassified as hypertensive or diabetic nephropathy because patients typically present with slowly progressive renal dysfunction, bland urine sediment, and subnephrotic proteinuria.2
LECT2 amyloid deposits predominantly involve the renal interstitium and vasculature, but glomerular involvement has also been described and may be variably present, as demonstrated in this case.2 This distribution helps explain the generally modest degree of proteinuria observed in most patients. Unlike immunoglobulin light-chain or AA amyloidosis, LECT2 amyloidosis is not associated with plasma cell dyscrasias, chronic inflammatory conditions, or widespread systemic involvement.
Diagnosis requires Congo red staining with confirmatory immunohistochemistry for LECT2; mass spectrometry may be used when available.3 There is no disease-specific therapy, and management is supportive, with emphasis on BP control, avoidance of nephrotoxins, and close monitoring of kidney function. Accurate identification is clinically important, as it avoids unnecessary hematologic evaluation and allows for appropriate prognostic counseling.
Teaching Points
ALECT2 amyloidosis is an increasingly recognized cause of CKD, particularly among individuals of Hispanic ancestry.
Renal involvement in ALECT2 amyloidosis most commonly affects the interstitium and vasculature, but glomerular involvement may also be present.
Patients typically present with slowly progressive kidney dysfunction, bland urine sediment, and subnephrotic proteinuria.
Diagnosis requires Congo red–positive amyloid with confirmatory immunohistochemistry for LECT2 or mass spectrometry when available.3,4
Management is supportive, and accurate diagnosis avoids unnecessary evaluation for plasma cell dyscrasias or chronic inflammatory conditions.
Disclosures
Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/KN9/B640.
Author Contributions
Conceptualization: Ankita Ojha, Banshi Mohan Rathi.
Investigation: Sara Faiz, Ankita Ojha.
Methodology: Ankita Ojha.
Resources: Ankita Ojha.
Software: Ankita Ojha.
Supervision: Banshi Mohan Rathi.
Validation: Ankita Ojha, Banshi Mohan Rathi.
Visualization: Ankita Ojha.
Writing – original draft: Ankita Ojha.
Writing – review & editing: Ankita Ojha, Banshi Mohan Rathi.
Funding
None.
References
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