A 55 year-old Chinese man presented to our center with three months history of proteinuria and bilateral eyelid edema form Aug. 15, 2017. This patient did not have any other significant comorbidities. His complete blood count was normal. Urinalysis showed microscopic hematuria with RBC 20–30/HP and proteinuria fluctuating between negative and microscale with 24 h urinary protein quantity (0.13 g/24 h).The biochemical test showed that kidney function and serum electrolytes were normal and total protein was obviously decreased along with hypoalbuminemia and normal immonoglobulin. The quantitative detection of immunoglobulin subclasses showed that Immunoglobulin A was significantly elevated, whereas Immunoglobulin G and Immunoglobulin M were both decreased. Urine kappa light chain was normal and urine lamda light chain was significantly increased (571 mg/L, normal range < 5.1 mg/L). In addition, serum free lamda light chain level was greatly elevated (8050 mg/L, normal range 5.71–26.3 mg/L), whereas serum free kappa light chain level was normal. M protein was detected by serum protein electrophoresis, and IgA-lamda-type monoclonal immunoglobulin band was identified by immunofixation electrophoresis. Furthermore, the bone marrow biopsy showed that his BMPC (bone marrow plasma cell) was 42.5%. The level of β2-Microglobulin was slightly raised. Based on the above, we believed that this patient had IgA-lamda-type multiple myeloma (D-S: stage I group A; ISS: stage II), even though bone lesions were not founded.
In order to clarify the cause of renal injury in this patient, we performed a renal biopsy on this patient in Nov. 21, 2017. Immunofluorescence microscopy showed that granular C3 deposited in the mesangial area (Fig. 1A). Kappa light chain staining was negative (Fig. 1B). Granular deposition of the lamda light chain was exhibited in the renal tubular epithelium (Fig. 1C). Under the light microscopy, glomerular mesangial cell hyperplasia was noted (Fig. 1D). Mild segmental hyperplasia of the stroma with a small amount of eosinophil deposition, granular degeneration of renal tubular epithelium and renal interstitium with small focal lymphocytes and monocytes infiltrating were also detected. Additionally, electron microscopy identified the dense deposits in the mesangial areas (Fig. 1E). Abnormal lysosomes in the cytoplasma of proximal tubular epithelial cells were also noted (Fig. 1F). He had marked hypocomplementemia with reductions in complement C3, but the complement C4 was normal. In addition, we found that the patient's C3 nephritic factor, complement factor H antibody, complement factor H concentration and vWF-cleaving protease (ADMAMTS13) activity were also normal.
Above all, this patient was diagnosed C3GN along with light chain tubular reabsorption resulted from multiple myeloma. The treatment effect of this patient was very good response with BD (Bortezomib plus dexamethasone) for 4 courses. In Apr. 19, 2018, this patient's disease had relapsed. Then, he was treated with one course of PAD (Bortezomib plus doxorubicin and dexamethasone) and BEAM (BCNU, etoposide, cytarabine and melphalan) pretreatment protocol along with the autologous stem cell transplantation in Jul. 11, 2019. He achieved a very good partial response again with stable renal function. The timeline of kidney function, proteinuria, C3, serum lamda light free chain and urine lamda light chain in relation to treatment was showed in Fig. 2 and Table 1. After that, this patient went to another hospital to accept the treatment. Unfortunately, this patient was dead of cardiovascular disease in May 13, 2020.
Table 1
The timeline of kidney function, 24 h UTP, C3, serum lamda light free chain and urine lamda light chain in relation to treatment.
| Time | Scr (mmol/L) | 24hUTP (g/24 h) | C3 (g/L) | Serum lamda light free chain (g/L) | Urine lamda light chain (g/L) |
| 2017.11.15 BD | 0.0606 | 0.13 | 0.047 | 8.05 | 0.517 |
| 2017.12.26 BD | 0.0541 | 0.09 | 0.058 | 5.05 | 0.005 |
| 2018.01.22 BD | 0.0563 | 0.14 | 0.632 | 3.11 | 0.005 |
| 2018.02.20 BD | 0.0581 | 0.16 | 0.661 | 1.55 | 0.005 |
| 2018.04.10 CTX | 0.0605 | 0.15 | 0.258 | 3.67 | 0.005 |
| 2018.06.19 PAD | 0.0668 | 0.16 | 0.189 | 3.71 | 0.005 |
| 2018.09.04 After autoHST | 0.0572 | 0.14 | 0.175 | 3.89 | 0.005 |
1Mobilization
BD: Bortezomib plus dexamethasone; CTX: Cyclophosphamide; PAD: Bortezomib plus doxorubicin and dexamethasone; autoHST: autologous stem cell transplantation. |