Kidney failure as an unusual initial presentation of biclonal gammopathy ( IgD multiple myeloma associated with light chain disease ) – A case report

Introduction. Immunoglobulin D (IgD) myeloma is a rare disease, about 2% of all myelomas, even rarer when accompanied with another multiple myeloma in biclonal gammopathy. We presented a case of biclonal gammopathy – associated manifestation of IgD myeloma and light chain disease in a patient who initially had renal failure. Case report. 37-year-old male approximately one month before hospitalization began to feel malaise and fatigue along with decreased urination. Laboratory analysis revealed azotemia. A dialysis catheter was placed and hemodialysis started. The patient was then admitted to our hospital for further tests and during admission, objective examination revealed pronounced paleness with hepatosplenomegaly and hypertension (170/95 mmHg). Laboratory analysis showed erythrocyte sedimentation rate 122 mm/h, expressed anemic syndrome (Hb 71 g/L) and renal failure dialysis rank: creatinine 1,408 mol/L, urea31.7 mmol/L. There was two M components in serum protein electrophoresis: IgD lambda and free light chain lambda. Proteinuria was nephrotic rank (5.4 g/24 h), whose electrophoresis revealed 2 M components – massive in 2 fraction of 71%; 7% in the discrete fraction, beta 2M /serum 110 mg / L, in urine 1.8 mg/L – extremely high; IgL kappa / lambda index 1 : 13 (reference value ratio 2 : 1). The findings pointed to double myeloma disease: IgD myeloma and Bence Jones lambda myeloma. Bone biopsy confirmed IgD myeloma lambda 100% infiltration medulla predominantly plasmablasts. The treatment continued with hemodialysis 3 times per week with chemotherapy protocol bortezomib, doxorubicin, dexamethasone. After 4 cycles of chemotherapy, there was a decrease of IgD, – light chains, reduction in proteinuria (1.03 g/24 h), so hemodialysis was reduced to once per week. Six months after treatment initiation the patient underwent autologous bone marrow transplantation. In a 2-year follow-up period double myeloma disease showed complete remission. Conclusion. The presented rare form of double myeloma disease with initial renal insufficiency underscores the importance of careful observation and teamwork that can alter the course of this serious disease.

fraction of 71%; 7% in the discrete fraction, beta 2M /serum 110 mg / L, in urine 1.8 mg/L -extremely high; IgL kappa / lambda index 1 : 13 (reference value ratio 2 : 1).The findings pointed to double myeloma disease: IgD myeloma and Bence Jones lambda myeloma.Bone biopsy confirmed IgD myeloma lambda 100% infiltration medulla predominantly plasmablasts.The treatment continued with hemodialysis 3 times per week with chemotherapy protocol bortezomib, doxorubicin, dexamethasone.After 4 cycles of chemotherapy, there was a decrease of IgD, -light chains, reduction in proteinuria (1.03 g/24 h), so hemodialysis was reduced to once per week.Six months after treatment initiation the patient underwent autologous bone marrow transplantation.In a 2-year follow-up period double myeloma disease showed complete remission.Conclusion.The presented rare form of double myeloma disease with initial renal insufficiency underscores the importance of careful observation and teamwork that can alter the course of this serious disease.

Introduction
Multiple myeloma is a plasma-proliferative disease characterized by uncontrolled proliferation of a pathologic plasma cell clone, and its incidence is about 10% of all malignancies 1 .Tissue damage in multiple myeloma are complex, but essentially is the immunobiological activity of monoclonal immunoglobulin (Ig).Every abnormal clone of plasma cells normally secretes one monoclonal immunoglobulin, which indicates the type of myeloma (IgG, IgA, IgM, IgD, IgE-kappa and lambda).Joint appearance of two malignant clones, named biclonal gammopathy, is as rare as about 1% 2 .One of the rarest multiple myelomas is IgD myeloma (2%), so its appearance in biclonal gammopathy is also extremely rare.IgD myeloma is often accompanied by complications such as the occurrence of renal failure, thus the treatment and survival of these patients is very uncertain 3 .We reported a patient with IgD myeloma associated with light chain disease with the initial manifestation as renal failure.

Case report
Approximately one month before hospitalization, a 37-year-old male began to feel malaise and fatigue along with decreased urination.Laboratory analysis revealed azotemia, so a dialysis catheter was placed and hemodialysis started.The patient was then hospitalized for further tests and during admission objective examination, pronounced paleness with hepatosplenomegaly, and hypertension (170/95 mmHg) were noted.Laboratory analysis showed erythrocyte sedimentation rate 122 mm/h, expressed anemic syndrome (Hb 71g/L) and renal failure dialysis rank: creatinine 1,408 mol /L, urea 31.7 mmol /L were presented.There was two M components in serum protein electrophoresis: IgD lambda and free light chain lambda.Proteinuria was nephrotic rank (5.4 g/24 h), whose electrophoresis revealed 2M components -massive in 2 fraction of 71%, and 7% in the discrete fraction, serum beta 2M 110 mg/L, in urine 1.8 mg/L -extremely high; IgL kappa / lambda index 1:13 (reference value ratio 2 : 1).The findings pointed to double myeloma disease: IgD myeloma and Bence Jones lambda myeloma (Figures 1a and b).
X-ray indicated osteolytic changes in craniograph and the pelvis (Figure 3).
The treatment continued with hemodialysis 3 times per week with the chemotherapy protocol: bortezomib, doxorubicin, dexamethasone.After 4 cycles of chemotherapy, a re- Six months after initiation of the treatment the patient underwent autologous bone marrow transplantation.In a 2year follow-up period double myeloma disease showed complete remission.

Discussion
Biclonal gammopathy in which the occurrence of IgD myeloma is associated with other myeloma such as in this case of light chain disease is very rare, occurring in about 4% of biclonal gammopathies 3 .However, the very appearance of IgD myeloma is rare which is confirmed by many authors [1][2][3] .Among them is an interesting study by Kyle et al. 4 who examined 1,027 patients with multiple myeloma and found IgD myeloma with the incidence of 1% 4 .IgD myeloma has an extremely unfavorable course and serious complications, with median survival of about 12 months 3,5,6 .
In the presented patient there was a combined occurrence of IgD myeloma and Light Chain disease, where the initial manifestation was oliguria with a consequent azotemia of dialysis rank and anemic syndrome.Describing a group of 16 patients with IgD myeloma, Lin et al. 5 observed that renal failure occurs in about 75% of cases.Among other complications, the most common are related to the gastrointestinal tract (38%), bone pain (56%), and loss of body weight (25%).
Renal failure in multiple myeloma can be acute or chronic which is much more frequent.Changes in tubules are dominant while glomeruli and intersticium are affected to a lesser extent 7 .Renal impairment in multiple myeloma occurs due to different mechanisms -tubule damage caused by immunobiological activity of malignant clones and deposition of immunoglobulin light chains with obstruction of tubules and the consequent development of tubulointerstitial nephritis.The development of renal lesion is effected by hyperviscosity, infection, hypercalcemia, hyperuricemia, medication and many other factors.Therefore, patients with multiple myeloma and renal failure have many reasons for unfavorable course of treatment and shorter survival 8,9 .The cases such as the one described by Tharp et al. 10 of a patient with IgD myeloma survival longer than 9 years are rare.They concluded that the survival of IgD kappa myeloma is somewhat better compared to the lambda type.
In patients with acute renal failure (which is more often the case with Light Chain disease as in the presented patient) the favorable results are achieved by removing the light chains either by therapeutic plasma exchange or hemodiafiltration along with chemotherapy application protocol 11 .
According to Hutchison et al. 12 the high cut-off hemodialysis is the method of reducing the influence of the concentration of light chains and contributes to recovery of renal function.In recent years, modern protocols and new drugs (thalidomide, bortezomib) significantly improve survival, both through use in treatment as well as induction agents in bone marrow stem cell transplantation 13,14 .
The presented patient received modern treatment protocol (bortezomib, doxorubicin, dexamethasone) and after 4 cycles of chemotherapy, bone biopsy demonstrated a significant reduction of malignant cells.Infiltration of bone marrow in the presented patient initially was 100% mainly plasmablasts, while after 4 cycles of chemotherapy infiltration was 40% plasmacytes.Along with chemotherapy, the patient underwent hemodialysis 3 times a week, with gradual reduction to once per week after the establishment of diuresis.
By analyzing 75 patients with IgD myeloma Kim et al. 15 concluded that in the group that was transplanted after induction therapy, the average survival was 30 months while for patients treated with conventional therapy, the average survival was 16,4 months.The presented patient, 6 months after initiation of the treatment underwent autologous bone marrow transplantation and after a 2-year follow-up period double myeloma disease showed complete remission.

Conclusion
The presented rare form of double myeloma disease with initial manifestation of renal insufficiency underscores the importance of careful observation and team work which can alter the course of this serious disease.

Fig. 1 -
Fig. 1 -Immunofixation (IF) of the serum and urine.a) IF in the serum shows homogenious fraction to immunoglobulin (IgD) and IgL lambda antibodies (red arrows).IF of the urine confirmed a fraction which belongs to IgD and a fraction of free light chain (FLC) lambda -possible dimmers or tetramers molecules (blue arrows); b) Urine protein electrophoresis confirmed the existence of 2 homogeneous fractions: IgD and FLC lambda.G,A,M -antibody to class Ig.; IgK -antibody on light chain Ig kappa type; IgL -antibody on light chain Ig lambda type; FLC-k -Free kapa; FLC-l -free lambda; S -serum.