Abstract 3992

Little is known about the rare entities of heavy and light chain amyloidosis (AHL) and heavy chain amyloidosis (AH). In this study, we report the renal and hematologic characteristics, pathology, and outcome of 17 patients with renal AH/AHL including 5 with AH (4 IgG and 1 IgA) and 12 with AHL (7 IgGλ, 3 IgAκ, 1 IgAλ, and 1 IgMλ), and compare them with 202 patients with renal AL amyloidosis (AL) diagnosed during the same time period. All cases were diagnosed by kidney biopsy that showed Congo red-positive deposits. Amyloid typing was done by laser microdissection and mass spectrometry (LMD/MS) (12 patients) or by immunofluorescence (5 patients). All patients with renal AH/AHL were Caucasians, with a M:F ratio of 2.4 and a median age at biopsy of 63 years. Compared with patients with renal AL, those with renal AH/AHL had less frequent concurrent cardiac involvement, higher likelihood of having circulating complete monoclonal Ig, lower sensitivity of fat pad biopsy and bone marrow biopsy for detecting amyloid, higher incidence of hematuria, and better patient survival. The hematologic and renal responses to chemotherapy were comparable to renal AL. In 42% of patients, AH/AHL could not have been diagnosed without LMD/MS. In conclusion, renal AH/AHL is an uncommon but under-recognized form of amyloidosis, and its diagnosis is greatly enhanced by the use of LMD/MS for amyloid typing. The accurate histological diagnosis of renal AH/AHL and distinction from AL may have important clinical and prognostic implications.

Table 1.

Demographics and hematologic characteristics

AH/AHLALp value
No. of patients 17 202  
Gender: Male/female 12/5 (71%/29%) 126/76 (62%/38%) 0.61 
Age, median (range) 63 (50–77) 62 (36–86) 0.73 
Additional organ involvement 8 (47%) 126 (62%) 0.3 
Cardiac involvement 3 (18%) 100 (50%) 0.01* 
% of plasma cells in bone marrow, median (IQR) 8 (5–15) 6 (5–10) 0.82 
    ≥30 plasma cells 4 (24%) 11/198 (6%) 0.02* 
Positive SPEP/SIF for paraprotein 15 (88%) 158/200 (79%) 0.53 
    Presence of whole monoclonal protein on SPEP 14 (82%) 108/200 (54%) 0.04* 
Positive UPEP/UIF for paraprotein 13/16 (81%) 158/189 (84%) 0.73 
    Presence of whole monoclonal protein on UPEP 10/16 (63%) 61/189 (32%) 0.03* 
Abnormal serum FLC ratio (<0.26 or >1.65) 9/12 (75%) 150/188 (80%) 0.71 
Markedly abnormal FLC ratio (< 0.125 or > 8) 5/12 (42%) 100/188 (53%) 0.55 
Positive bone marrow for amyloid 6/16 (38%) 135/183 (74%) 0.004* 
Positive fat pad biopsy for amyloid 2/14 (14%) 105/145 (72%) <0.001* 
AH/AHLALp value
No. of patients 17 202  
Gender: Male/female 12/5 (71%/29%) 126/76 (62%/38%) 0.61 
Age, median (range) 63 (50–77) 62 (36–86) 0.73 
Additional organ involvement 8 (47%) 126 (62%) 0.3 
Cardiac involvement 3 (18%) 100 (50%) 0.01* 
% of plasma cells in bone marrow, median (IQR) 8 (5–15) 6 (5–10) 0.82 
    ≥30 plasma cells 4 (24%) 11/198 (6%) 0.02* 
Positive SPEP/SIF for paraprotein 15 (88%) 158/200 (79%) 0.53 
    Presence of whole monoclonal protein on SPEP 14 (82%) 108/200 (54%) 0.04* 
Positive UPEP/UIF for paraprotein 13/16 (81%) 158/189 (84%) 0.73 
    Presence of whole monoclonal protein on UPEP 10/16 (63%) 61/189 (32%) 0.03* 
Abnormal serum FLC ratio (<0.26 or >1.65) 9/12 (75%) 150/188 (80%) 0.71 
Markedly abnormal FLC ratio (< 0.125 or > 8) 5/12 (42%) 100/188 (53%) 0.55 
Positive bone marrow for amyloid 6/16 (38%) 135/183 (74%) 0.004* 
Positive fat pad biopsy for amyloid 2/14 (14%) 105/145 (72%) <0.001* 

IQR, interquartile range.

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Table 2.

Renal characteristics at kidney biopsy

AH/AHLALp value
No. of patients 17 202  
24h urine protein in g, median (IQR) 5.1 (3.2–9.0) 6.0 (3.2–10.0) 0.9 
Full nephrotic syndrome 9/16 (56%) 132/197 (67%) 0.42 
Serum albumin in g/dl, median (IQR) 2.7 (2.2–3.3) 2.5 (1.9–2.9) 0.29 
% albuminuria on UPEP, median (IQR) 68 (61–72) 70 (60–76) 0.47 
Serum creatinine in mg/dl, median (IQR) 1.4 (1.1–2.1) 1.2 (0.9–1.8) 0.25 
Serum creatinine >1.2 mg/dl 10/16 (63%) 92/201 (46%) 0.3 
eGFR, median (IQR) 47 (27–67) 58 (36–75) 0.29 
Decreased eGFR 10/16 (63%) 103/201 (51%) 0.44 
Microscopic hematuria 9/16 (56%) 44/169 (26%) 0.02* 
AH/AHLALp value
No. of patients 17 202  
24h urine protein in g, median (IQR) 5.1 (3.2–9.0) 6.0 (3.2–10.0) 0.9 
Full nephrotic syndrome 9/16 (56%) 132/197 (67%) 0.42 
Serum albumin in g/dl, median (IQR) 2.7 (2.2–3.3) 2.5 (1.9–2.9) 0.29 
% albuminuria on UPEP, median (IQR) 68 (61–72) 70 (60–76) 0.47 
Serum creatinine in mg/dl, median (IQR) 1.4 (1.1–2.1) 1.2 (0.9–1.8) 0.25 
Serum creatinine >1.2 mg/dl 10/16 (63%) 92/201 (46%) 0.3 
eGFR, median (IQR) 47 (27–67) 58 (36–75) 0.29 
Decreased eGFR 10/16 (63%) 103/201 (51%) 0.44 
Microscopic hematuria 9/16 (56%) 44/169 (26%) 0.02* 

IQR, interquartile range.

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Disclosures:

No relevant conflicts of interest to declare.

Topics:
amyloidosis, kidney, primary amyloidosis, hypertension, biopsy, cardiovascular findings, creatinine tests, serum, free immunoglobulin light chain, monoclonal immunoglobulin, paraproteins

Author notes

*

Asterisk with author names denotes non-ASH members.

© 2012 by The American Society of Hematology
2012
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