The characteristics of seronegative and seropositive non-hepatitis-associated cryoglobulinemic glomerulonephritis

Vincent Javaugue, Anthony M. Valeri, Insara Jaffer Sathick, Samar M. Said, Sibel Erdogan Damgard, David L. Murray, Tyler Klobucher, Nicole K. Andeen, Sanjeev M Sethi, Fernando C. Fervenza, Nelson Leung, Samih H Nasr

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
JournalKidney international
StateAccepted/In press - 2022


  • cryoglobulinemic glomerulonephritis
  • kidney biopsy
  • MGRS
  • MPGN
  • serum cryoglobulin

ASJC Scopus subject areas

  • Nephrology


Dive into the research topics of 'The characteristics of seronegative and seropositive non-hepatitis-associated cryoglobulinemic glomerulonephritis'. Together they form a unique fingerprint.

Cite this