TY - JOUR
T1 - The characteristics of patients with kidney light chain deposition disease concurrent with light chain amyloidosis
AU - Said, Samar M.
AU - Best Rocha, Alejandro
AU - Valeri, Anthony M.
AU - Paueksakon, Paisit
AU - Dasari, Surendra
AU - Theis, Jason D.
AU - Vrana, Julie A.
AU - Obadina, Modupe O.
AU - Saghafi, Darius
AU - Alexander, Mariam Priya
AU - Sethi, Sanjeev
AU - Larsen, Christopher P.
AU - Joly, Florent
AU - Dispenzieri, Angela
AU - Bridoux, Frank
AU - Sirac, Christophe
AU - Leung, Nelson
AU - Fogo, Agnes B.
AU - McPhail, Ellen D.
AU - Nasr, Samih H.
N1 - Funding Information:
AD reports grants from Alnylam Pharmaceuticals, Pfizer, Takeda Pharmaceutical Co., and Bristol Myers Squibb (BMS), and scientific advisory board participation for Janssen Pharmaceuticals, outside the current work. CS reports grants from Attralus Inc., outside the submitted work. FB reports personal fees from Baxter International, AstraZeneca, and Janssen Pharmaceuticals, outside the current work. NL reports grants from Alnylam Pharmaceuticals, outside the current work. All the other authors declared no competing interests.
Publisher Copyright:
© 2021 International Society of Nephrology
PY - 2022/1
Y1 - 2022/1
N2 - The type of monoclonal light chain nephropathy is thought to be largely a function of the structural and physiochemical properties of light chains; hence most affected patients have only one light chain kidney disease type. Here, we report the first series of kidney light chain deposition disease (LCDD) concomitant with light chain amyloidosis (LCDD+AL), with or without light chain cast nephropathy (LCCN). Our LCDD+AL cohort consisted of 37 patients (54% females, median age 70 years (range 40-86)). All cases showed Congo red-positive amyloid deposits staining for one light chain isotype on immunofluorescence (62% lambda), and LCDD with diffuse linear staining of glomerular and tubular basement membranes for one light chain isotype (97% same isotype as the amyloidogenic light chain) and ultrastructural non-fibrillar punctate deposits. Twelve of 37 cases (about 1/3 of patients) had concomitant LCCN of same light chain isotype. Proteomic analysis of amyloid and/or LCDD deposits in eight revealed a single light chain variable domain mutable subgroup in all cases (including three with separate microdissections of LCDD and amyloid light chain deposits). Clinical data on 21 patients showed proteinuria (100%), hematuria (75%), kidney insufficiency and nephrotic syndrome (55%). Extra-kidney involvement was present in 43% of the patients. Multiple myeloma occurred in 68% (about 2/3) of these patients; none had lymphoma. On follow up (median 16 months), 63% developed kidney failure and 56% died. The median kidney and patient survivals were 12 and 32 months, respectively. LCDD+AL mainly affected patients 60 years of age or older. Thus, LCDD+AL could be caused by two pathological light chains produced by subclones stemming from one immunoglobulin light chain lambda or kappa rearrangement, with a distinct mutated complementary determining region.
AB - The type of monoclonal light chain nephropathy is thought to be largely a function of the structural and physiochemical properties of light chains; hence most affected patients have only one light chain kidney disease type. Here, we report the first series of kidney light chain deposition disease (LCDD) concomitant with light chain amyloidosis (LCDD+AL), with or without light chain cast nephropathy (LCCN). Our LCDD+AL cohort consisted of 37 patients (54% females, median age 70 years (range 40-86)). All cases showed Congo red-positive amyloid deposits staining for one light chain isotype on immunofluorescence (62% lambda), and LCDD with diffuse linear staining of glomerular and tubular basement membranes for one light chain isotype (97% same isotype as the amyloidogenic light chain) and ultrastructural non-fibrillar punctate deposits. Twelve of 37 cases (about 1/3 of patients) had concomitant LCCN of same light chain isotype. Proteomic analysis of amyloid and/or LCDD deposits in eight revealed a single light chain variable domain mutable subgroup in all cases (including three with separate microdissections of LCDD and amyloid light chain deposits). Clinical data on 21 patients showed proteinuria (100%), hematuria (75%), kidney insufficiency and nephrotic syndrome (55%). Extra-kidney involvement was present in 43% of the patients. Multiple myeloma occurred in 68% (about 2/3) of these patients; none had lymphoma. On follow up (median 16 months), 63% developed kidney failure and 56% died. The median kidney and patient survivals were 12 and 32 months, respectively. LCDD+AL mainly affected patients 60 years of age or older. Thus, LCDD+AL could be caused by two pathological light chains produced by subclones stemming from one immunoglobulin light chain lambda or kappa rearrangement, with a distinct mutated complementary determining region.
KW - AL amyloidosis
KW - MGRS
KW - light chain cast nephropathy
KW - light chain deposition disease
KW - monoclonal gammopathy
KW - multiple myeloma
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UR - http://www.scopus.com/inward/citedby.url?scp=85120774557&partnerID=8YFLogxK
U2 - 10.1016/j.kint.2021.10.019
DO - 10.1016/j.kint.2021.10.019
M3 - Article
C2 - 34767832
AN - SCOPUS:85120774557
SN - 0085-2538
VL - 101
SP - 152
EP - 163
JO - Kidney International
JF - Kidney International
IS - 1
ER -