Congophilic Fibrillary Glomerulonephritis

A Case Series

Mariam P Alexander, Surendra Dasari, Julie A. Vrana, Julie Riopel, Anthony M. Valeri, Glen S. Markowitz, Aviv Hever, Vanesa Bijol, Christopher P. Larsen, Lynn D. Cornell, Mary E. Fidler, Samar M. Said, Sanjeev M Sethi, Loren Paola Herrera Hernandez, Joseph Peter Grande, Stephen B. Erickson, Fernando Custodio Fervenza, Nelson Leung, Paul J. Kurtin, Samih H. Nasr

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Rationale & Objective: Congo Red positivity with birefringence under polarized light has traditionally permitted classification of organized glomerular deposits as from amyloid or nonamyloid diseases. The absence of congophilia has been used to differentiate fibrillary glomerulonephritis (GN) from amyloidosis. We describe a series of fibrillary GN cases in which the deposits are Congo Red–positive (congophilic fibrillary GN) and discuss the role of DNAJB9 in distinguishing congophilic fibrillary GN from amyloidosis. Study Design: Case series. Setting & Participants: Analysis of the clinicopathologic characteristics of 18 cases of congophilic fibrillary GN. Mass spectrometry was performed and compared with 24 cases of Congo Red–negative fibrillary GN, 145 cases of amyloidosis, and 12 apparently healthy individuals. DNAJB9 immunohistochemistry was obtained for a subset of cases. Results: The proteomic signature of amyloid was not detected using mass spectrometry among cases of congophilic fibrillary GN. DNAJB9, a recently discovered proteomic marker for fibrillary GN, was detected using mass spectrometry in all cases of fibrillary GN regardless of congophilia and was absent in cases of amyloidosis and in healthy individuals. DNAJB9 immunohistochemistry confirmed the mass spectrometry findings. The congophilic fibrillary GN cases included 11 men and 7 women with a mean age at diagnosis of 65 years. Concomitant monoclonal gammopathy, hepatitis C virus infection, malignancy, or autoimmune disease was present in 35%, 22%, 17%, and 11% of patients, respectively. No patient had evidence of extrarenal amyloidosis. Patients presented with proteinuria (100%), nephrotic syndrome (47%), hematuria (78%), and chronic kidney disease (83%). After a mean follow-up of 23 months, 31% of patients progressed to end-stage kidney disease and the remaining 69% had persistently reduced kidney function. Limitations: Retrospective nature. Blinded pathology evaluations were not performed. Conclusions: The congophilic properties of organized fibrillary deposits should not be solely relied on in differentiating fibrillary GN from renal amyloidosis. Mass spectrometry and DNAJB9 immunohistochemistry can be useful in making this distinction.

Original languageEnglish (US)
JournalAmerican Journal of Kidney Diseases
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Glomerulonephritis
Amyloidosis
Mass Spectrometry
Congo
Immunohistochemistry
Proteomics
Birefringence
Kidney
Congo Red
Paraproteinemias
Amyloid Plaques
Nephrotic Syndrome
Hematuria
Virus Diseases
Chronic Renal Insufficiency
Proteinuria
Amyloid
Hepacivirus
Autoimmune Diseases
Chronic Kidney Failure

Keywords

  • AL amyloidosis
  • amyloid
  • biomarker
  • Congo Red
  • congophilic
  • DNAJB9
  • fibrillary deposits
  • fibrillary glomerulonephritis
  • immunohistochemistry
  • kidney biopsy
  • laser microdissection
  • mass spectrometry
  • misdiagnosis
  • proteomics
  • renal pathology

ASJC Scopus subject areas

  • Nephrology

Cite this

Congophilic Fibrillary Glomerulonephritis : A Case Series. / Alexander, Mariam P; Dasari, Surendra; Vrana, Julie A.; Riopel, Julie; Valeri, Anthony M.; Markowitz, Glen S.; Hever, Aviv; Bijol, Vanesa; Larsen, Christopher P.; Cornell, Lynn D.; Fidler, Mary E.; Said, Samar M.; Sethi, Sanjeev M; Herrera Hernandez, Loren Paola; Grande, Joseph Peter; Erickson, Stephen B.; Fervenza, Fernando Custodio; Leung, Nelson; Kurtin, Paul J.; Nasr, Samih H.

In: American Journal of Kidney Diseases, 01.01.2018.

Research output: Contribution to journalArticle

Alexander, MP, Dasari, S, Vrana, JA, Riopel, J, Valeri, AM, Markowitz, GS, Hever, A, Bijol, V, Larsen, CP, Cornell, LD, Fidler, ME, Said, SM, Sethi, SM, Herrera Hernandez, LP, Grande, JP, Erickson, SB, Fervenza, FC, Leung, N, Kurtin, PJ & Nasr, SH 2018, 'Congophilic Fibrillary Glomerulonephritis: A Case Series', American Journal of Kidney Diseases. https://doi.org/10.1053/j.ajkd.2018.03.017
Alexander, Mariam P ; Dasari, Surendra ; Vrana, Julie A. ; Riopel, Julie ; Valeri, Anthony M. ; Markowitz, Glen S. ; Hever, Aviv ; Bijol, Vanesa ; Larsen, Christopher P. ; Cornell, Lynn D. ; Fidler, Mary E. ; Said, Samar M. ; Sethi, Sanjeev M ; Herrera Hernandez, Loren Paola ; Grande, Joseph Peter ; Erickson, Stephen B. ; Fervenza, Fernando Custodio ; Leung, Nelson ; Kurtin, Paul J. ; Nasr, Samih H. / Congophilic Fibrillary Glomerulonephritis : A Case Series. In: American Journal of Kidney Diseases. 2018.
@article{9003a61b5b394a568a1080c205e03a10,
title = "Congophilic Fibrillary Glomerulonephritis: A Case Series",
abstract = "Rationale & Objective: Congo Red positivity with birefringence under polarized light has traditionally permitted classification of organized glomerular deposits as from amyloid or nonamyloid diseases. The absence of congophilia has been used to differentiate fibrillary glomerulonephritis (GN) from amyloidosis. We describe a series of fibrillary GN cases in which the deposits are Congo Red–positive (congophilic fibrillary GN) and discuss the role of DNAJB9 in distinguishing congophilic fibrillary GN from amyloidosis. Study Design: Case series. Setting & Participants: Analysis of the clinicopathologic characteristics of 18 cases of congophilic fibrillary GN. Mass spectrometry was performed and compared with 24 cases of Congo Red–negative fibrillary GN, 145 cases of amyloidosis, and 12 apparently healthy individuals. DNAJB9 immunohistochemistry was obtained for a subset of cases. Results: The proteomic signature of amyloid was not detected using mass spectrometry among cases of congophilic fibrillary GN. DNAJB9, a recently discovered proteomic marker for fibrillary GN, was detected using mass spectrometry in all cases of fibrillary GN regardless of congophilia and was absent in cases of amyloidosis and in healthy individuals. DNAJB9 immunohistochemistry confirmed the mass spectrometry findings. The congophilic fibrillary GN cases included 11 men and 7 women with a mean age at diagnosis of 65 years. Concomitant monoclonal gammopathy, hepatitis C virus infection, malignancy, or autoimmune disease was present in 35{\%}, 22{\%}, 17{\%}, and 11{\%} of patients, respectively. No patient had evidence of extrarenal amyloidosis. Patients presented with proteinuria (100{\%}), nephrotic syndrome (47{\%}), hematuria (78{\%}), and chronic kidney disease (83{\%}). After a mean follow-up of 23 months, 31{\%} of patients progressed to end-stage kidney disease and the remaining 69{\%} had persistently reduced kidney function. Limitations: Retrospective nature. Blinded pathology evaluations were not performed. Conclusions: The congophilic properties of organized fibrillary deposits should not be solely relied on in differentiating fibrillary GN from renal amyloidosis. Mass spectrometry and DNAJB9 immunohistochemistry can be useful in making this distinction.",
keywords = "AL amyloidosis, amyloid, biomarker, Congo Red, congophilic, DNAJB9, fibrillary deposits, fibrillary glomerulonephritis, immunohistochemistry, kidney biopsy, laser microdissection, mass spectrometry, misdiagnosis, proteomics, renal pathology",
author = "Alexander, {Mariam P} and Surendra Dasari and Vrana, {Julie A.} and Julie Riopel and Valeri, {Anthony M.} and Markowitz, {Glen S.} and Aviv Hever and Vanesa Bijol and Larsen, {Christopher P.} and Cornell, {Lynn D.} and Fidler, {Mary E.} and Said, {Samar M.} and Sethi, {Sanjeev M} and {Herrera Hernandez}, {Loren Paola} and Grande, {Joseph Peter} and Erickson, {Stephen B.} and Fervenza, {Fernando Custodio} and Nelson Leung and Kurtin, {Paul J.} and Nasr, {Samih H.}",
year = "2018",
month = "1",
day = "1",
doi = "10.1053/j.ajkd.2018.03.017",
language = "English (US)",
journal = "American Journal of Kidney Diseases",
issn = "0272-6386",
publisher = "W.B. Saunders Ltd",

}

TY - JOUR

T1 - Congophilic Fibrillary Glomerulonephritis

T2 - A Case Series

AU - Alexander, Mariam P

AU - Dasari, Surendra

AU - Vrana, Julie A.

AU - Riopel, Julie

AU - Valeri, Anthony M.

AU - Markowitz, Glen S.

AU - Hever, Aviv

AU - Bijol, Vanesa

AU - Larsen, Christopher P.

AU - Cornell, Lynn D.

AU - Fidler, Mary E.

AU - Said, Samar M.

AU - Sethi, Sanjeev M

AU - Herrera Hernandez, Loren Paola

AU - Grande, Joseph Peter

AU - Erickson, Stephen B.

AU - Fervenza, Fernando Custodio

AU - Leung, Nelson

AU - Kurtin, Paul J.

AU - Nasr, Samih H.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Rationale & Objective: Congo Red positivity with birefringence under polarized light has traditionally permitted classification of organized glomerular deposits as from amyloid or nonamyloid diseases. The absence of congophilia has been used to differentiate fibrillary glomerulonephritis (GN) from amyloidosis. We describe a series of fibrillary GN cases in which the deposits are Congo Red–positive (congophilic fibrillary GN) and discuss the role of DNAJB9 in distinguishing congophilic fibrillary GN from amyloidosis. Study Design: Case series. Setting & Participants: Analysis of the clinicopathologic characteristics of 18 cases of congophilic fibrillary GN. Mass spectrometry was performed and compared with 24 cases of Congo Red–negative fibrillary GN, 145 cases of amyloidosis, and 12 apparently healthy individuals. DNAJB9 immunohistochemistry was obtained for a subset of cases. Results: The proteomic signature of amyloid was not detected using mass spectrometry among cases of congophilic fibrillary GN. DNAJB9, a recently discovered proteomic marker for fibrillary GN, was detected using mass spectrometry in all cases of fibrillary GN regardless of congophilia and was absent in cases of amyloidosis and in healthy individuals. DNAJB9 immunohistochemistry confirmed the mass spectrometry findings. The congophilic fibrillary GN cases included 11 men and 7 women with a mean age at diagnosis of 65 years. Concomitant monoclonal gammopathy, hepatitis C virus infection, malignancy, or autoimmune disease was present in 35%, 22%, 17%, and 11% of patients, respectively. No patient had evidence of extrarenal amyloidosis. Patients presented with proteinuria (100%), nephrotic syndrome (47%), hematuria (78%), and chronic kidney disease (83%). After a mean follow-up of 23 months, 31% of patients progressed to end-stage kidney disease and the remaining 69% had persistently reduced kidney function. Limitations: Retrospective nature. Blinded pathology evaluations were not performed. Conclusions: The congophilic properties of organized fibrillary deposits should not be solely relied on in differentiating fibrillary GN from renal amyloidosis. Mass spectrometry and DNAJB9 immunohistochemistry can be useful in making this distinction.

AB - Rationale & Objective: Congo Red positivity with birefringence under polarized light has traditionally permitted classification of organized glomerular deposits as from amyloid or nonamyloid diseases. The absence of congophilia has been used to differentiate fibrillary glomerulonephritis (GN) from amyloidosis. We describe a series of fibrillary GN cases in which the deposits are Congo Red–positive (congophilic fibrillary GN) and discuss the role of DNAJB9 in distinguishing congophilic fibrillary GN from amyloidosis. Study Design: Case series. Setting & Participants: Analysis of the clinicopathologic characteristics of 18 cases of congophilic fibrillary GN. Mass spectrometry was performed and compared with 24 cases of Congo Red–negative fibrillary GN, 145 cases of amyloidosis, and 12 apparently healthy individuals. DNAJB9 immunohistochemistry was obtained for a subset of cases. Results: The proteomic signature of amyloid was not detected using mass spectrometry among cases of congophilic fibrillary GN. DNAJB9, a recently discovered proteomic marker for fibrillary GN, was detected using mass spectrometry in all cases of fibrillary GN regardless of congophilia and was absent in cases of amyloidosis and in healthy individuals. DNAJB9 immunohistochemistry confirmed the mass spectrometry findings. The congophilic fibrillary GN cases included 11 men and 7 women with a mean age at diagnosis of 65 years. Concomitant monoclonal gammopathy, hepatitis C virus infection, malignancy, or autoimmune disease was present in 35%, 22%, 17%, and 11% of patients, respectively. No patient had evidence of extrarenal amyloidosis. Patients presented with proteinuria (100%), nephrotic syndrome (47%), hematuria (78%), and chronic kidney disease (83%). After a mean follow-up of 23 months, 31% of patients progressed to end-stage kidney disease and the remaining 69% had persistently reduced kidney function. Limitations: Retrospective nature. Blinded pathology evaluations were not performed. Conclusions: The congophilic properties of organized fibrillary deposits should not be solely relied on in differentiating fibrillary GN from renal amyloidosis. Mass spectrometry and DNAJB9 immunohistochemistry can be useful in making this distinction.

KW - AL amyloidosis

KW - amyloid

KW - biomarker

KW - Congo Red

KW - congophilic

KW - DNAJB9

KW - fibrillary deposits

KW - fibrillary glomerulonephritis

KW - immunohistochemistry

KW - kidney biopsy

KW - laser microdissection

KW - mass spectrometry

KW - misdiagnosis

KW - proteomics

KW - renal pathology

UR - http://www.scopus.com/inward/record.url?scp=85047823705&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047823705&partnerID=8YFLogxK

U2 - 10.1053/j.ajkd.2018.03.017

DO - 10.1053/j.ajkd.2018.03.017

M3 - Article

JO - American Journal of Kidney Diseases

JF - American Journal of Kidney Diseases

SN - 0272-6386

ER -