Clinical, morphologic, and genetic features of renal leukocyte chemotactic factor 2 amyloidosis

Abstract

Leukocyte chemotactic factor 2 amyloidosis (ALECT2) is a recently described form of amyloidosis that most frequently manifests clinically with progressive renal failure. In a series of 414 cases of amyloidosis, there were 40 cases of ALECT2: the second most common type of renal amyloidosis in this series. This was particularly common in Hispanic patients in the Southwest United States, where more than half of amyloidosis cases were ALECT2. It is possible that this represents a familial amyloidosis as there were two brothers with ALECT2 in our study. Morphologically, there was consistent amyloid deposition in the renal cortex with medullary involvement in only about a third of cases. There were no mutations detected in the LECT2 gene, although all patients tested were homozygous for the G nucleotide in a non-synonymous SNP at position 172. Most patients presented with chronic kidney disease and, on follow-up, showed progression with an average deterioration in renal function of 0.5 ml/min/1.73 m(2) per month. Unfortunately, the etiology of ALECT2 is currently unknown and there is currently no efficacious treatment of the disease.

Leukocyte Cell–Derived Chemotaxin 2–Associated Amyloidosis

“…In sharp contrast to other types of systemic amyloidosis, ALECT2 amyloidosis exhibits a strong ethnic bias, with 88%-92% of reported patients being Hispanics (5,11,12). All reported Hispanic patients who disclosed their origin were of Mexican descent (12,16).…”

“…In a recent series of 474 patients with biopsy-proven renal amyloidosis from the Mayo Clinic, 86% were Ig derived, 7% were AA derived, 3% were ALECT2 derived, and 1% were fibrinogen A derived (6). In another United States series from Nephropath of 414 patients, 83% were Ig derived, 10% were ALECT2 derived, and 5% were AA derived (5). In this series, ALECT2 amyloidosis accounted for 54% of patients with renal amyloidosis (2% of total kidney biopsies received during the study period) from the southwestern United States (New Mexico, Arizona, and far west Texas) (5), which has a high concentration of Hispanics.…”

“…It accounts for 2.7%-10% of patients with renal amyloidosis in the United States (5,6,14). In a recent series of 474 patients with biopsy-proven renal amyloidosis from the Mayo Clinic, 86% were Ig derived, 7% were AA derived, 3% were ALECT2 derived, and 1% were fibrinogen A derived (6).…”

“…Kidney involvement is present in most patients with AL amyloidosis (3) and AA amyloidosis (4) and may also occur in several rare hereditary forms of amyloidosis, such as those derived from fibrinogen A, transthyretin (ATTR), gelsolin (particularly in homozygotes), lysozyme, apo AI (AApo AI), AApo AII, and AApo AIV (5)(6)(7)(8). The overall renal biopsy incidence of amyloidosis ranges from 1.3% to 4% (5)(6)(7)9).…”

“…Three recent large studies (5,11,12) that included a total of 144 patients (112 patients with renal amyloidosis and 32 patients with liver amyloidosis) have established that ALECT2 amyloidosis is now a frequent type of renal and hepatic amyloidosis and highlighted its distinct clinical and pathologic characteristics, including clear ethnic predisposition, typical presentation with chronic renal insufficiency with or without proteinuria, and superior patient survival to AL amyloidosis and AA amyloidosis. This mini-review highlights the current status of ALECT2 amyloidosis, including incidence, organ distribution, clinical presentation, pathogenesis, histologic characteristics, renal and patient survival, poor prognostic indicators, and recurrence in the renal allograft.…”