Abstract: TH-PO208

Recovery of Kidney Function Following Autologous Hematopoietic Stem Cell Transplant in a Patient with C3 Glomerulonephritis Associated with Monoclonal Gammopathy

Session Information

Category: Nephrology Education

  • 1302 Fellows and Residents Case Reports

Authors

  • Lepori, Nicola, Mayo Clinic, Rochester, Minnesota, United States
  • Cheungpasitporn, Wisit, Mayo Clinic, Rochester, Minnesota, United States
  • Sethi, Sanjeev, Mayo Clinic, Rochester, Minnesota, United States
  • Leung, Nelson, Mayo Clinic, Rochester, Minnesota, United States
  • Murray, David L., Mayo Clinic, Rochester, Minnesota, United States
  • Fervenza, Fernando C., Mayo Clinic, Rochester, Minnesota, United States
Background

C3 glomerulopathy is associated with presence of monoclonal immunoglobulin (MIg) in almost 60% of cases after 50 years of age. Overall renal prognosis is poor with frequent progression to ESRD.

Methods

A 55 y/o man was referred to our clinic for renal insufficiency (serum creatinine [sCr] from 1.0 to 2.7 mg/dl in the previous 16 months) with a recent episode of gross hematuria. Urinalysis showed hematuria with dysmorphic RBCs and 24h proteinuria was 643 mg. Serology tests showed elevated soluble membrane attack complex (sMAC) and CBb levels, with normal C3, C4, CH50. SPEP with immunofixation showed an Ig kappa M spike of 2.0 g/dL with kappa free light chains of 10.2 mg/dL. Kidney biopsy showed mesangial proliferative glomerulonephritis with bright C3 staining on IF (negative for all immunoglobulins), supporting a diagnosis of C3 glomerulonephritis (C3GN). A bone marrow biopsy revealed 5% to 10% kappa restricted plasma cells; diagnostic work up for multiple myeloma was negative. Patient was treated with 12 cycles of CyBorD based regimen; renal function significantly improved (Table), but after discontinuation of cyclophosphamide and dexamethasone, C3GN relapsed. VRD based regimen was ineffective to induce remission. Thus the patient subsequently underwent high-dose melphalan (HDM) followed by autologous hematopoietic stem cell transplant (ASCT). Three months following ASCT, sCr had fallen to 1.3 mg/dL with M-spike of 0.8 g/dL and kappa free light chains of 2.31 mg/dL

Conclusion

Recent evidences indicate that treatment direct against underlying monoclonal disorder improves renal survive in MIg-associated C3 GN. As we described in our case, ASCT may potentially be an emerging treatment option for patients with MIg-associated C3GN, especially in those with poor response to classical chemotherapy.

Laboratory testingPresentationCyBorD regimenMaintenance BortezomibVRD regimen3 months following ASCT
sCr (mg/dL)2.71.11.52.11.3
Hb (g/dL)9.8n/a12.510.512.2
24 h Urine Proteine (mg)643347n/a280224
Urinary RBC's (n/hpf)>10011-2021-3051-10011-20
M spike (g/dL)2.01.21.30.80.8
Kappa free light chain (0.33-2.63 mg/dL)10.22.923.443.362.31
Lambda free light chain (0.57-2.63 mg/dL)1.230.920.981.080.76
C3 (75-175 mg/dL)
C4 (14-40 mg/dL)
112
21
116
23
n/a
n/a
n/a
n/a
113
17