Monoclonal immunoglobulin deposition disease (MIDD) is characterized by non-organized immunoglobulin-fragments along renal basement membranes with subsequent organ deterioration. Treatment is directed against the immunoglobulin-producing clone. We treated 18 MIDD patients with bortezomib-based regimens (12 received bortezomib-dexamethasone, 6 bortezomib-dexamethasone with cyclophosphamide). Eleven (61%) patients achieved a hematologic response, but only 6 (33.3%) reached to a complete (CR) or very good partial response (VGPR). Regarding renal outcomes 77.8 and 55.6% had ≥30 and ≥50% reduction of proteinuria, respectively, but 33.3% ended up in end-stage renal disease (ESRD). Among patients with CR or VGPR, median eGFR improvement was 7.7 ml/min/1.73 m and none progressed to ESRD, but no significant renal recovery was observed in patients achieving a partial response or less, with 50% progressing to dialysis. Pretreatment eGFR seems to influence renal prognosis. Bortezomib-based treatment is considered an effective approach in MIDD and reaching to a deep hematologic response (≥VGPR) conditionally controls further renal declining.