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


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.


CONCLUSIONS
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.
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN.
Gauri
G
Bhutani
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Samih H
SH
Nasr
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Samar M
SM
Said
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Sanjeev
S
Sethi
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN.
Fernando C
FC
Fervenza
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
William G
WG
Morice
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
Paul J
PJ
Kurtin
Division of Hematology, Mayo Clinic, Rochester, MN.
Francis K
FK
Buadi
Division of Hematology, Mayo Clinic, Rochester, MN.
David
D
Dingli
Division of Hematology, Mayo Clinic, Rochester, MN.
Angela
A
Dispenzieri
Division of Hematology, Mayo Clinic, Rochester, MN.
Morie A
MA
Gertz
Division of Hematology, Mayo Clinic, Rochester, MN.
Martha Q
MQ
Lacy
Division of Hematology, Mayo Clinic, Rochester, MN.
Prashant
P
Kapoor
Division of Hematology, Mayo Clinic, Rochester, MN.
Shaji
S
Kumar
Division of Hematology, Mayo Clinic, Rochester, MN.
Robert A
RA
Kyle
Division of Hematology, Mayo Clinic, Rochester, MN.
S Vincent
SV
Rajkumar
Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN; Division of Hematology, Mayo Clinic, Rochester, MN. Electronic address: leung.nelson@mayo.edu.
Nelson
N
Leung
D000328:Adult; D000368:Aged; D005260:Female; D015432:Glomerulonephritis, Membranoproliferative / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
D007074:Immunoglobulin G