Clinicopathologic Significance of Predominant Lambda Light Chain Deposition in IgA Nephropathy

CureGN Consortium

doi:10.1016/j.ekir.2022.08.003

Clinicopathologic Significance of Predominant Lambda Light Chain Deposition in IgA Nephropathy

CureGN Consortium

Research output: Contribution to journal › Article › peer-review

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Abstract

Introduction: IgA nephropathy (IgAN) differs from other glomerular diseases by the frequently predominant lambda over kappa light chain deposition. Using the Cure Glomerulonephropathy (CureGN) IgAN cohort, we aimed to determine whether predominant lambda chain deposition is associated with worse clinical outcomes or histopathologic markers of more active disease. Methods: Patients were categorized based on the intensity of light chain staining. The lambda dominant (LD) group was defined by a difference in intensity score of lambda minus kappa ≥ 1+ and the kappa-lambda codominant (KL) group by a difference < 1+. We compared the clinical course of patients in each category from the time of kidney biopsy and time of enrollment into CureGN to the time of remission (proteinuria < 0.3 g/g), 50% reduction in estimated glomerular filtration rate (eGFR), or progression to end-stage kidney disease (ESKD). We also analyzed differences in histopathologic characteristics between the 2 groups. Results: Among 440 patients, we found no significant differences between groups in baseline clinical characteristics nor in rates of remission, 50% reduction in eGFR, or progression to ESKD. Patients in the LD group had a modestly greater frequency of IgG staining ≥ 1+. The biopsy results of 234 patients reviewed by CureGN pathologists revealed a greater frequency of endocapillary hypercellularity (51.1% vs. 36.3%, P = 0.04) in the LD group, but no other significant difference in histopathologic features. Conclusion: In IgAN, we found an association between lambda predominance and increased endocapillary hypercellularity, but no association with clinical outcomes.

Original language	English (US)
Pages (from-to)	2462-2473
Number of pages	12
Journal	Kidney International Reports
Volume	7
Issue number	11
DOIs	https://doi.org/10.1016/j.ekir.2022.08.003
State	Published - Nov 2022

Bibliographical note

Funding Information:
This research was presented in part as an abstract at the American Society of Nephrology's 2021 Annual Meeting. This research was supported by the National Institutes of Health's National Center for Advancing Translational Sciences, grant UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health's National Center for Advancing Translational Sciences. We acknowledge the efforts of all CureGN participants and staff. We appreciate the input received from the CureGN publications committee. Funding for the CureGN Consortium is provided by U24DK100845 (formerly UM1DK100845), U01DK100846 (formerly UM1DK100846), U01DK100876 (formerly UM1DK100876), U01DK100866 (formerly UM1DK100866), and U01DK100867 (formerly UM1DK100867) from the National Institute of Diabetes and Digestive and Kidney Diseases. Patient recruitment is supported by NephCure Kidney International. Dates of funding for the first phase of CureGN were September 16, 2013, to May 31, 2019. All authors declared no competing interests.

Publisher Copyright:
© 2022 International Society of Nephrology

Keywords

IgA nephropathy
MEST score
glomerular disease
immunoglobulin light chains

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ekir.2022.08.003

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@article{c5c7b124b81149b5a7ca5e8d7b346cb8,

title = "Clinicopathologic Significance of Predominant Lambda Light Chain Deposition in IgA Nephropathy",

abstract = "Introduction: IgA nephropathy (IgAN) differs from other glomerular diseases by the frequently predominant lambda over kappa light chain deposition. Using the Cure Glomerulonephropathy (CureGN) IgAN cohort, we aimed to determine whether predominant lambda chain deposition is associated with worse clinical outcomes or histopathologic markers of more active disease. Methods: Patients were categorized based on the intensity of light chain staining. The lambda dominant (LD) group was defined by a difference in intensity score of lambda minus kappa ≥ 1+ and the kappa-lambda codominant (KL) group by a difference < 1+. We compared the clinical course of patients in each category from the time of kidney biopsy and time of enrollment into CureGN to the time of remission (proteinuria < 0.3 g/g), 50% reduction in estimated glomerular filtration rate (eGFR), or progression to end-stage kidney disease (ESKD). We also analyzed differences in histopathologic characteristics between the 2 groups. Results: Among 440 patients, we found no significant differences between groups in baseline clinical characteristics nor in rates of remission, 50% reduction in eGFR, or progression to ESKD. Patients in the LD group had a modestly greater frequency of IgG staining ≥ 1+. The biopsy results of 234 patients reviewed by CureGN pathologists revealed a greater frequency of endocapillary hypercellularity (51.1% vs. 36.3%, P = 0.04) in the LD group, but no other significant difference in histopathologic features. Conclusion: In IgAN, we found an association between lambda predominance and increased endocapillary hypercellularity, but no association with clinical outcomes.",

keywords = "IgA nephropathy, MEST score, glomerular disease, immunoglobulin light chains",

author = "{CureGN Consortium} and Prasanth Ravipati and Freese, {Rebecca L.} and Virginie Royal and Lihong Bu and Pietro Canetta and Debbie Gipson and Mahmood Kallash and Krzysztof Kiryluk and Cynthia Nast and Reich, {Heather N.} and Rheault, {Michelle N.} and Manish Saha and Nachman, {Patrick H.}",

note = "Funding Information: This research was presented in part as an abstract at the American Society of Nephrology's 2021 Annual Meeting. This research was supported by the National Institutes of Health's National Center for Advancing Translational Sciences, grant UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health's National Center for Advancing Translational Sciences. We acknowledge the efforts of all CureGN participants and staff. We appreciate the input received from the CureGN publications committee. Funding for the CureGN Consortium is provided by U24DK100845 (formerly UM1DK100845), U01DK100846 (formerly UM1DK100846), U01DK100876 (formerly UM1DK100876), U01DK100866 (formerly UM1DK100866), and U01DK100867 (formerly UM1DK100867) from the National Institute of Diabetes and Digestive and Kidney Diseases. Patient recruitment is supported by NephCure Kidney International. Dates of funding for the first phase of CureGN were September 16, 2013, to May 31, 2019. All authors declared no competing interests. Publisher Copyright: {\textcopyright} 2022 International Society of Nephrology",

year = "2022",

month = nov,

doi = "10.1016/j.ekir.2022.08.003",

language = "English (US)",

volume = "7",

pages = "2462--2473",

journal = "Kidney International Reports",

issn = "2468-0249",

publisher = "Elsevier Inc.",

number = "11",

}

TY - JOUR

T1 - Clinicopathologic Significance of Predominant Lambda Light Chain Deposition in IgA Nephropathy

AU - CureGN Consortium

AU - Ravipati, Prasanth

AU - Freese, Rebecca L.

AU - Royal, Virginie

AU - Bu, Lihong

AU - Canetta, Pietro

AU - Gipson, Debbie

AU - Kallash, Mahmood

AU - Kiryluk, Krzysztof

AU - Nast, Cynthia

AU - Reich, Heather N.

AU - Rheault, Michelle N.

AU - Saha, Manish

AU - Nachman, Patrick H.

N1 - Funding Information: This research was presented in part as an abstract at the American Society of Nephrology's 2021 Annual Meeting. This research was supported by the National Institutes of Health's National Center for Advancing Translational Sciences, grant UL1TR002494. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health's National Center for Advancing Translational Sciences. We acknowledge the efforts of all CureGN participants and staff. We appreciate the input received from the CureGN publications committee. Funding for the CureGN Consortium is provided by U24DK100845 (formerly UM1DK100845), U01DK100846 (formerly UM1DK100846), U01DK100876 (formerly UM1DK100876), U01DK100866 (formerly UM1DK100866), and U01DK100867 (formerly UM1DK100867) from the National Institute of Diabetes and Digestive and Kidney Diseases. Patient recruitment is supported by NephCure Kidney International. Dates of funding for the first phase of CureGN were September 16, 2013, to May 31, 2019. All authors declared no competing interests. Publisher Copyright: © 2022 International Society of Nephrology

PY - 2022/11

Y1 - 2022/11

N2 - Introduction: IgA nephropathy (IgAN) differs from other glomerular diseases by the frequently predominant lambda over kappa light chain deposition. Using the Cure Glomerulonephropathy (CureGN) IgAN cohort, we aimed to determine whether predominant lambda chain deposition is associated with worse clinical outcomes or histopathologic markers of more active disease. Methods: Patients were categorized based on the intensity of light chain staining. The lambda dominant (LD) group was defined by a difference in intensity score of lambda minus kappa ≥ 1+ and the kappa-lambda codominant (KL) group by a difference < 1+. We compared the clinical course of patients in each category from the time of kidney biopsy and time of enrollment into CureGN to the time of remission (proteinuria < 0.3 g/g), 50% reduction in estimated glomerular filtration rate (eGFR), or progression to end-stage kidney disease (ESKD). We also analyzed differences in histopathologic characteristics between the 2 groups. Results: Among 440 patients, we found no significant differences between groups in baseline clinical characteristics nor in rates of remission, 50% reduction in eGFR, or progression to ESKD. Patients in the LD group had a modestly greater frequency of IgG staining ≥ 1+. The biopsy results of 234 patients reviewed by CureGN pathologists revealed a greater frequency of endocapillary hypercellularity (51.1% vs. 36.3%, P = 0.04) in the LD group, but no other significant difference in histopathologic features. Conclusion: In IgAN, we found an association between lambda predominance and increased endocapillary hypercellularity, but no association with clinical outcomes.

AB - Introduction: IgA nephropathy (IgAN) differs from other glomerular diseases by the frequently predominant lambda over kappa light chain deposition. Using the Cure Glomerulonephropathy (CureGN) IgAN cohort, we aimed to determine whether predominant lambda chain deposition is associated with worse clinical outcomes or histopathologic markers of more active disease. Methods: Patients were categorized based on the intensity of light chain staining. The lambda dominant (LD) group was defined by a difference in intensity score of lambda minus kappa ≥ 1+ and the kappa-lambda codominant (KL) group by a difference < 1+. We compared the clinical course of patients in each category from the time of kidney biopsy and time of enrollment into CureGN to the time of remission (proteinuria < 0.3 g/g), 50% reduction in estimated glomerular filtration rate (eGFR), or progression to end-stage kidney disease (ESKD). We also analyzed differences in histopathologic characteristics between the 2 groups. Results: Among 440 patients, we found no significant differences between groups in baseline clinical characteristics nor in rates of remission, 50% reduction in eGFR, or progression to ESKD. Patients in the LD group had a modestly greater frequency of IgG staining ≥ 1+. The biopsy results of 234 patients reviewed by CureGN pathologists revealed a greater frequency of endocapillary hypercellularity (51.1% vs. 36.3%, P = 0.04) in the LD group, but no other significant difference in histopathologic features. Conclusion: In IgAN, we found an association between lambda predominance and increased endocapillary hypercellularity, but no association with clinical outcomes.

KW - IgA nephropathy

KW - MEST score

KW - glomerular disease

KW - immunoglobulin light chains

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UR - http://www.scopus.com/inward/citedby.url?scp=85138210593&partnerID=8YFLogxK

U2 - 10.1016/j.ekir.2022.08.003

DO - 10.1016/j.ekir.2022.08.003

M3 - Article

C2 - 36531879

AN - SCOPUS:85138210593

SN - 2468-0249

VL - 7

SP - 2462

EP - 2473

JO - Kidney International Reports

JF - Kidney International Reports

IS - 11

ER -

Clinicopathologic Significance of Predominant Lambda Light Chain Deposition in IgA Nephropathy

Abstract

Bibliographical note

Keywords

UN SDGs

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