Monoclonal Immunoglobulin-Associated Renal Lesions in Patients with Newly Diagnosed Multiple Myeloma: A Report from a Single Center

Figures & data

Table 1 Baseline Clinical Characteristics of Patients with Renal Involvement

Parameters	Patients without Kidney Biopsy	Patients with Kidney Biopsy	p
Number of patients	200	56
Male/female	124/76	35/21	0.946
Age (y)	60±12	55±11	0.003
Hemoglobin (g/L)	91.0 (40.0, 168.0)	94.3 (70.0, 162.0)	0.03
Serum creatinine (μmol/L)	182.5 (31.0, 2361.0)	182.5 (31.0, 1294.1)	0.729
eGFR (mL/min/1.73 m^2)	30.54 (1.69, 118.23)	30.35 (2.5, 114.68)	0.842
Calcium (mmol/L)	2.3 (1.7, 3.9)	2.3 (1.8, 3.5)	0.06
Heavy chain type
IgG (%)	83 (41.5%)	13 (23.2%)	0.012
IgA (%)	37 (18.5%)	8 (14.3%)	0.464
IgM (%)	0	1 (1.8%)	0.219
IgD (%)	2 (1%)	0	1.0
None (%)	78 (39%)	34 (60.7%)	0.004
Light chain type
κ (%)	89 (44.5%)	19 (33.9%)	0.157
λ (%)	111 (55.5%)	37 (66.1%)	0.157
Proteinuria (%)	76 (38%)	22 (39%)	0.861
Microscopic hematuria (%)	62 (31%)	16 (29%)	0.691

Table 2 Kidney Biopsy Findings of Monoclonal Immunoglobulin-Associated Renal Lesions in 51 NDMM Patients

Pathological Diagnosis	Number of Patients (%)	Light Chain Isotype (κ/λ)
Pure MCN	25 (49%)	7/18
MCN concurrent with amyloidosis	2 (4%)	0/2
MCN concurrent with LCDD	4 (8%)	3/1
Pure LCDD	5 (10%)	3/2
Pure amyloidosis	9 (17%)	1/8
Light and heavy chain deposition disease	2 (4%)	2 (IgGκ)/0
LCPT	1 (2%)	1/0
C3 glomerulopathy concurrent with LCPT	1 (2%)	0/1
Fibrillary glomerulonephritis	2 (4%)	1/1

Abbreviations: NDMM, newly diagnosed multiple myeloma; MCN, myeloma cast nephropathy; LCDD, light chain deposition disease; light and heavy chain deposition disease; LCPT, light chain proximal tubulopathy; C3, complement factor 3.

Figure 1 A patient with light chain cast nephropathy and light chain amyloidosis. (A) showed κ light chain was negative on the arteriolar wall and protein cast (×200); (B) showed λ light chain was positive on the arteriolar wall and strong positive on the protein cast (×200); (C) showed Congo-red positive amyloid on the arteriolar/artery wall and weak positive in the glomeruli (×400); (D) showed PAS-negative protein casts in tubular lumen (arrow, ×200, periodic acid-Schiff staining); (E) showed cell infiltration around the protein casts (arrow, ×200, hematoxylin and eosin staining); (F) showed non-branch fibrils in the subepithelial area of glomeruli (×40,000).

Table 3 Pathological Characteristics of Monoclonal Immunoglobulin-Associated Renal Lesions at Diagnosis

Parameters	Pure MCN	MCN + Other Pathologies	Non-MCN
Number of patients	25	6	20
Median number of casts per ×200 fields	9.5 (4.6–31)	8.4 (4.1–13.8)	0
Acute tubular injury	2 (0–4)	2.5 (2–3)	1 (1–4)
Tubular atrophy	1 (0–4)	0 (0–1)	0 (0–4)
Interstitial fibrosis	2 (0–4)	2 (2, 2)	1 (0, 3)
Interstitial inflammation	2 (0–4)	2.5 (2–3)	1 (0–3)
Interstitial edema	15 (60%)	1 (17%)	3 (15%)

Abbreviation: MCN, myeloma cast nephropathy.

Table 4 Clinical Characteristics of Patients with Kidney Biopsy-Proven Monoclonal Immunoglobulin-Associated Renal Lesions at Diagnosis

Parameters	Pure MCN	MCN + Other Pathologies	Non-MCN	p
Number of patients	25	6	20
Male/female	14/11	4/2	14/6	0.664
Age (y)	52±10	55±6	56±13	0.682
Hemoglobin (g/L)	83.0 (70.0–119.0)	90.5 (81.0–133.0)	114.5 (80.0–162.0)	0.006^a
Serum albumin (g/L)	42.6 (32.2–51.4)	40.0 (35.4–46.9)	26.3 (15–50.1)	0.002^a
Hypoalbuminemia	0	0	11 (55%)	<0.001^a, b
Serum creatinine (μmol/L)	606.9 (92.4–1294.1)	325.3 (147.5–815.6)	135.1 (31.0–946.0)	0.002^a
eGFR (mL/min/1.73 m^2)	9.7 (2.5–62.0)	17.8 (6.6–44.5)	55.2 (5.5–114.68)	0.001^a
24-h urine output
Anuria	2 (8%)	0	0	0.162
Oliguria	8 (32%)	2 (33%)	4 (20%)	0.631
24-h urine protein (g/d)	3.8 (0–23.5)	5.61 (2.2–9.1)	5.2 (0–18.7)	0.428
Nephrotic-range proteinuria	13 (52%)	3 (50%)	12 (60%)	0.924
Nephrotic syndrome	0	0	8 (40%)	<0.001^a, b
Albumin in urine protein (%)	23.0 (1.0–70.5)	17.0 (2.3–31.6)	73.6 (4.6–85.5)	0.012^a
Urine protein composition category
<10% albumin	6/15 (40%)	2/3 (67%)	1/12 (8%)	0.054
10%-50%	3/15 (20%)	1/3 (33%)	0	0.181
>50% albumin	6/15 (40%)	0	11/12 (92%)	0.002^a, b
Microscopic hematuria	3 (12%)	0	13 (48%)	<0.001^a, b
Requiring hemodialysis	14 (56%)	3 (50%)	2 (10%)	0.004^a
Heavy chain type in serum
IgG	2/24 (8%)	1/6 (17%)	7/20 (35%)	0.071
IgA	2/24 (8%)	0	4/20 (20%)	0.46
IgM	0	0	1/20 (5%)	0.52
None	20/24 (84%)	5/6 (83%)	8/20 (40%)	<0.006^a
Light chain type in urine
κ	7/24 (29%)	3/6 (50%)	4/20 (20%)	0.41
λ	17/24 (71%)	3/6 (50%)	12/20 (60%)	0.55
None	0	0	4/20 (20%)	0.055
Bone lesions	7 (28%)	3 (50%)	3 (15%)	0.208
Plasma cells on bone marrow smear (%)	33.5 (10.0, 79.5)	17.0 (11.5, 84.5)	15.8 (10.0, 32.5)	0.013^a

Notes: ^aPure MCN vs non-MCN, p < 0.05; ^bMCN + other pathologies vs non-MCN, p < 0.05.

Abbreviations: MCN, myeloma cast nephropathy; eGFR, estimated glomerular filtration rate; ESRD, end-stage renal disease.

Table 5 Treatment and Outcomes

Characteristic	Pure MCN	MCN + Other Pathologies	Non-MCN	P
Number of patients	22	5	18
Median duration of follow up, (months)	14 (3–91)	50 (2–58)	25 (2–109)	0.187
Supportive therapy	22	5	4	<0.001^a, b
Chemotherapy
Proteasome inhibitors included	17 (77%)	4 (80%)	10 (56%)	0.353
Other chemotherapy (VAD/MPT)	3/2 (23%)	1/0 (20%)	1/1 (11%)	0.549
Proteasome inhibitors included + HDM/ASCT	0	0	6 (33%)	0.006^a
Renal outcomes, number (%)
Improved/stable	11 (50%)	2 (40%)	13 (72%)	0.290
Worsening	0	1 (20%)	3 (17%)	0.114
ESRD	11 (50%)	2 (40%)	2 (11%)	0.021^a
Death, number (%)	11 (50%)	1 (20%)	5 (28%)	0.275

Notes: ^aPure MCN vs non-MCN, p < 0.05; ^bMCN + other pathologies vs non-MCN, p < 0.05.

Abbreviations: HDM/ASCT, autologous peripheral blood stem cell transplantation; VAD, vinorelbine, pirarubicin and dexamethasone; MPT, melphalan, prednisone and thalidomide; ESRD, end-stage renal disease.

Table 6 Prognostic Factors Associated with Renal Survival

Parameters	Univariate Analysis		Multivariate Analysis
	HR (95% CI)	p	HR (95% CI)	p
Age	0.98 (0.95–1.02)	0.37	0.997 (0.96–1.04)	0.890
Male	2.13 (0.92–4.94)	0.78	1.81 (0.79–4.11)	0.159
Serum creatinine	1.002 (1.002–1.003)	<0.001	–	–
HDM/ASCT	0.20 (0.27–1.52)	0.12	–	–
Number of myeloma casts	1.09 (1.03–1.15)	0.002	1.08 (1.08–1.15)	0.012
Plasma cells on bone marrow smear (%)	1.01 (0.99, 1.03)	0.062	–	–
Acute tubular injury	2.27 (0.96–5.40)	0.063	–	–
Tubular atrophy	1.60 (0.94–2.7)	0.082	–	–
Interstitial fibrosis	1.08 (0.61–1.93)	0.79	–	–
Anemia	1.91 (0.83–4.42)	0.131	–	–

Note: Multivariate hazard ratio model: age, male gender and number of myeloma casts.

Abbreviation: HDM/ASCT, autologous peripheral blood stem cell transplantation.

Figure 2 (A) shows renal survival of patients divided according to renal histology. The median renal survival was 6.9 months in the pure MCN group and was not reached in the non-MCN and MCN + other pathologies groups. Log rank p = 0.0093. (pure MCN vs MCN + other pathologies, p = 0.3993; pure MCN vs non-MCN, p = 0.0021; MCN + other pathologies vs non- MCN, p = 0.2163); (B) shows overall survival of patients divided according to renal histology. The median overall survival was 8.7 months in the pure MCN group and was not reached in the non-MCN and MCN + other pathologies groups. Log rank p = 0.0418 (pure MCN vs MCN + other pathologies, p = 0.124; pure MCN vs non-MCN, p = 0.0298; MCN + other pathologies vs non- MCN, p = 0.800).

Table 7 Prognostic Factors Associated with Overall Survival

Parameters	Univariate Analysis		Multivariate Analysis
	HR (95% CI)	p	HR (95% CI)	p
Age	0.75 (0.29–1.98)	0.6	1.02 (0.96–1.08)	0.479
Male	2.89 (1.07–7.76)	0.04	3.64 (1.28–10.34)	0.015
Serum creatinine	1.001 (1.000–1.003)	0.04	–	–
HDM/ASCT	0.26 (0.34–1.95)	0.2	–	–
Number of myeloma casts	1.09 (1.02–1.16)	0.02	1.17 (1.07–1.29)	0.001
Plasma cells on bone marrow smear (%)	1.02 (0.99, 1.04)	0.084	–	–
Acute tubular injury	1.78 (0.67–4.75)	0.248	–	–
Tubular atrophy	3.5 (1.19–10.27)	0.023	–	–
Interstitial fibrosis	1.35 (0.75–2.43)	0.311	–	–
Anemia	1.009 (0.50–2.05)	0.981	–	–

Note: Multivariate hazard ratio model: age, male gender and number of myeloma casts.

Abbreviation: HDM/ASCT, autologous peripheral blood stem cell transplantation.