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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 m2 (interquartile range, 22-52 mL/min/1.73 m2). 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.

      Abbreviations and Acronyms:

      BM (bone marrow), CKD (chronic kidney disease), CLL (chronic lymphocytic leukemia), eGFR (estimated glomerular filtration rate), GN (glomerulonephritis), MGRS (monoclonal gammopathy of renal significance), MGUS (monoclonal gammopathy of undetermined significance), MIg (monoclonal immunoglobulin), MIDD (monoclonal immunoglobulin deposition disease), MIPG (monoclonal immunoglobulin (nonorganized) proliferative glomerulonephritis), MPGN (membranoproliferative glomerulonephritis), PGN (proliferative glomerulonephritis), PGNMID (proliferative glomerulonephritis with monoclonal IgG deposition), sFLCR (serum free light chain ratio), SIFE (serum immunofixation), SPEP (serum protein electrophoresis), UIFE (urine immunofixation), UPEP (urine protein electrophoresis)
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