Abstract: SA-PO172
Rituximab Administration Unveils Monoclonal Gammopathy of Renal Significance (MGRS)
Session Information
- Onco-Nephrology: Clinical
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Onco-Nephrology
- 1500 Onco-Nephrology
Authors
- Sagiv, Itamar, Hadassah Hebrew University Medical Center, Jerusalem, Israel
- Meir, Karen, Hadassah Hebrew University Medical Center, Jerusalem, Israel
- Rubinger, Dvora, Hadassah Hebrew University Medical Center, Jerusalem, Israel
- Gatt, Moshe E., Hadassah Hebrew University Medical Center, Jerusalem, Israel
Introduction
Cryoglobulinemic renal disease occurs in the presence or the absence of serological markers. In this case type I cryogobulinemia-associated MGRS was diagnosed after rituximab (Rx) administration.
Case Description
A 52 yr old man was evaluated for moderate proteinuria with no extrarenal manifestations. Laboratory evaluation disclosed low C3 and increased antistreptolysin titer. Ramipril treatment did not affect urinary protein excretion.
On kidney biopsy, there were PAS positive proteinaceous thrombi obliterating capillary lumens in a focal segmental pattern.These findings were suggestive of cryoglobulinema. Immunofluorescence revealed intramembranous deposits positive for C3 and IgM κ chains (Figure1).
Cryocrit increased from traces to 2% (Table 1). Anti HCV antibodies, rheumatoid factor, ANA, ANCA were negative. No paraprotein was detected.
Treatment with Prednisone and subsequently with Rx had no effect. After Rx, the patient developed severe nephrotic syndrome and renal dysfunction. Cryocrit rose to 3% and IgM κ paraprotein appeared for the first time on immunofixation. A bone marrow biopsy showed 4-8% monoclonal plasma cells positive for IgM κ. Treatment with Bortezomib, Cyclophosphamide and Dexamethasone resulted in resolution of nephrotic syndrome and normalization of renal function.
Discussion
B cell suppression after Rx exposed the serum IgM/κ originating from a small clone of plasma cell and responsible for MGRS. A Bortezomib based protocol induced complete clinical and serological remission.
Table 1.Clinical course and response to treatment.
| Year | 2014 | 2015 | 2016 | 2017 | 2019 |
| Urinary protein excretion (mg/24 hr) | 945 | 1680 | 4600 | 11900 | 127 |
| Serum creatinine ( μmol/L) | 70 | 79 | 79 | 203 | 88 |
| Serum albumin (g/L) | 42 | 39 | 36 | 23 | 43 |
| Cryocrit | Trace | 1% | 2% | 3% | Trace |
| Free kappa/lambda (κ/λ) light chains ratio* | NA | 2.1 | 1.8 | 2.7 | 1.4 |
| IgM κ** | NA | Negative | Negative | Positive | Negative |
| Treatment | ACE Inhibitors | Prednisone | Rituximab | Bortezomide, Cyclophosphamide. Dexamethasone | ACE Inhibitors |
NA:not available; ACE: angiotensin converting enzyme *Normal range: 0.26-1.65; ** Immunofixation.
Figure 1.