Hematologic characteristics of proliferative glomerulonephritides with nonorganized monoclonal immunoglobulin deposits.

Abstract

OBJECTIVE:

To study the hematologic characteristics of proliferative glomerulonephritides (GNs) from nonorganized glomerular monoclonal immunoglobulin (MIg) deposition (MIPG).

PATIENTS AND METHODS:

The pathology database at Mayo Clinic (Rochester, Minnesota) was used to find patients with MIPG who underwent a kidney biopsy between January 1, 2008, and December 31, 2013. Retrospective medical record review was conducted in the identified cohort (N=60).

RESULTS:

The median patient age was 56 years (interquartile range, 47-62 years) and the estimated glomerular filtration rate was 36 mL/min/1.73 m(2) (interquartile range, 22-52 mL/min/1.73 m(2)). Most patients had IgG MIg deposits (90%; 54 of 60) and a membranoproliferative pattern (48%; 29 of 60). A circulating nephropathic MIg was detected by serum immunofixation (SIFE(+)) in 20% (12 of 59) and by abnormal serum free light chain ratio (sFLCR(+)) in 21% (12 of 56). The subsets of SIFE(+) and sFLCR(+) incompletely overlapped. The nephropathic clone was found by bone marrow testing (BM(+)) in 25% (10 of 40; 6 plasma cell clones [5 IgG; 1 IgA], 3 chronic lymphocytic leukemia [all IgG], and 1 lymphoplasmacytic clone [IgM]). The clone detection rate was significantly higher in patients with SIFE(+) (P<.001) and in those with SIFE(+) and/or sFLCR(+) (P<.001). Patients with SIFE(+) and BM(+) frequently had IgG1-restricted MIg deposits on renal biopsy immunofluorescence (P=.005). Most BM(+) patients required flow cytometry and immunohistochemical analysis of the marrow specimen for accurate diagnosis.

CONCLUSION:

Undetectable circulating nephropathic MIg and pathologic clones characterize most MIPG. Immunoglobulin isotype may predict detectability of MIg and clone by currently available technology. Bone marrow evaluation, including flow cytometry and immunohistochemical analysis, should be performed for SIFE(+) and/or sFLCR(+). More sensitive clone-identifying techniques in the marrow and extramedullary tissue are needed when SIFE and sFLCR test negative.

• Authors: Gauri Bhutani, Samih H Nasr, Samar M Said, Sanjeev Sethi, Fernando C Fervenza, William G Morice, Paul J Kurtin, Francis K Buadi, David Dingli, Angela Dispenzieri, Morie A Gertz, Martha Q Lacy, Prashant Kapoor, Shaji Kumar, Robert A Kyle, S Vincent Rajkumar, Nelson Leung
• Journal: Mayo Clinic proceedings (Mayo Clin Proc) Vol. 90 Issue 5 Pg. 587-96 (May 2015) ISSN: 1942-5546 [Electronic] England
• PMID: 25939936 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Chemical References

• Immunoglobulin G

Topics

• Adult
• Aged
• Female
• Glomerulonephritis, Membranoproliferative (blood, metabolism)
• Humans
• Immunoglobulin G (metabolism)
• Male
• Middle Aged
• Retrospective Studies