TY - JOUR
T1 - The characteristics of seronegative and seropositive non-hepatitis-associated cryoglobulinemic glomerulonephritis
AU - Javaugue, Vincent
AU - Valeri, Anthony M.
AU - Jaffer Sathick, Insara
AU - Said, Samar M.
AU - Erdogan Damgard, Sibel
AU - Murray, David L.
AU - Klobucher, Tyler
AU - Andeen, Nicole K.
AU - Sethi, Sanjeev
AU - Fervenza, Fernando C.
AU - Leung, Nelson
AU - Nasr, Samih H.
N1 - Funding Information:
This work was supported by a grant from Fondation Française pour la Recherche Contre le Myélome et les Gammapathies (FFRMG). The authors thank the patients reported in the study, as well as all physicians and staff who participated in their care. We are grateful to Jon Charlesworth, Lisa Cummins, and the Microscopy and Cell Analysis Core at Mayo Clinic for performing additional ultrastructural analyses for the purpose of this study. We are grateful to Dr. Donald Houghton, Oregon Health & Science University, for providing electron microscopy images in one case. We also thank Pr. Frank Bridoux (University of Poitiers) for helpful discussions.
Publisher Copyright:
© 2022 International Society of Nephrology
PY - 2022/8
Y1 - 2022/8
N2 - The clinicopathologic characteristics and long-term outcome of non-hepatitis-associated cryoglobulinemic glomerulonephritis (CryoGN) are not well-defined and cases with undetectable serum cryoglobulin (seronegative CryoGN) have not been investigated. To resolve this, we retrospectively identified 81 patients with biopsy-proven non-hepatitis CryoGN, including 22 with seronegative CryoGN. The median age was 61 years and 76% presented with nephritic syndrome. A hematologic condition was found in 89% of patients, including monoclonal gammopathy of renal significance (65%) and symptomatic lymphoproliferative disorder (35%). In the seropositive group, 56% had type II, 29% type I, and 8% type III cryoglobulin. Extrarenal manifestations, mostly of skin, were present in 64% and were significantly less common in seronegative CryoGN. Glomerular deposits by immunofluorescence were IgM dominant (84%) and polytypic (70%) in the seropositive group, whereas 52% of seronegative cases had monotypic deposits (i.e., type I cryoglobulin). Ultrastructurally, the deposits were organized in 77% of cases. Substructure appearance significantly differed according to the type of CryoGN, forming most commonly short cylindrical structures in type II and other organized substructures in type I CryoGN. Most patients were treated with clone-directed therapy. On follow up (median 33 months), 77% had partial or complete remission, 10% reached kidney failure and 14% died. Predictors of kidney failure on univariate analysis were AKIN stage 3, positive rheumatoid factor and biclonal gammopathy at diagnosis. We conclude that most CryoGN cases (types I and II) are due to a hematologic condition and are associated with favorable outcome after clone-directed therapy. Seronegative CryoGN accounts for about a quarter of cases and is mostly a kidney-limited disease. Thus, further investigations are needed to unravel the pathophysiology of seronegative CryoGN.
AB - The clinicopathologic characteristics and long-term outcome of non-hepatitis-associated cryoglobulinemic glomerulonephritis (CryoGN) are not well-defined and cases with undetectable serum cryoglobulin (seronegative CryoGN) have not been investigated. To resolve this, we retrospectively identified 81 patients with biopsy-proven non-hepatitis CryoGN, including 22 with seronegative CryoGN. The median age was 61 years and 76% presented with nephritic syndrome. A hematologic condition was found in 89% of patients, including monoclonal gammopathy of renal significance (65%) and symptomatic lymphoproliferative disorder (35%). In the seropositive group, 56% had type II, 29% type I, and 8% type III cryoglobulin. Extrarenal manifestations, mostly of skin, were present in 64% and were significantly less common in seronegative CryoGN. Glomerular deposits by immunofluorescence were IgM dominant (84%) and polytypic (70%) in the seropositive group, whereas 52% of seronegative cases had monotypic deposits (i.e., type I cryoglobulin). Ultrastructurally, the deposits were organized in 77% of cases. Substructure appearance significantly differed according to the type of CryoGN, forming most commonly short cylindrical structures in type II and other organized substructures in type I CryoGN. Most patients were treated with clone-directed therapy. On follow up (median 33 months), 77% had partial or complete remission, 10% reached kidney failure and 14% died. Predictors of kidney failure on univariate analysis were AKIN stage 3, positive rheumatoid factor and biclonal gammopathy at diagnosis. We conclude that most CryoGN cases (types I and II) are due to a hematologic condition and are associated with favorable outcome after clone-directed therapy. Seronegative CryoGN accounts for about a quarter of cases and is mostly a kidney-limited disease. Thus, further investigations are needed to unravel the pathophysiology of seronegative CryoGN.
KW - MGRS
KW - MPGN
KW - cryoglobulinemic glomerulonephritis
KW - kidney biopsy
KW - serum cryoglobulin
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U2 - 10.1016/j.kint.2022.03.030
DO - 10.1016/j.kint.2022.03.030
M3 - Article
C2 - 35513122
AN - SCOPUS:85130407703
SN - 0085-2538
VL - 102
SP - 382
EP - 394
JO - Kidney International
JF - Kidney International
IS - 2
ER -