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Monoclonal immunoglobulin deposition disease (MIDD) is a subtype of Monoclonal gammopathy of renal significance (MGRS) which causes a progressive decline in glomerular filtration rate (GFR) leading to eventual kidney failure. MIDD is characterized by the deposition of monoclonal immunoglobulin (MIg) light chains (LCDD), heavy chains (HCDD), or both in the mesangium and along the renal glomerular and tubular basement membranes. Effective treatment of MIDD necessitates the management of the underlying clonal plasma cell disorder. Once diagnosed, plasma cell directed therapy with a combination of daratumumab, cyclophosphamide, bortezomib, and dexamethasone (DARA-CYBOR-D) has shown promise in improving patient response rates and renal outcomes.
In this report, we present the novel treatment strategy of a 56-year-old male with an atypical presentation of MIDD coexisting with diabetic kidney disease. Although his primary renal disease was initially attributed to non-insulin dependent diabetes mellitus (NIDDM) due to clinical course, there was also a suspicion of myeloma-related involvement given his prior history of smoldering myeloma. Considering his chronic decline in kidney function, with as high as 9 g proteinuria and creatinine of 1.6-1.8 mg/dL, a renal biopsy was performed.
Outside Renal pathology was initially read as diabetic glomerulosclerosis with severe arteriosclerosis based on nodular glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Glomerular basement membranes were thickened, and the glomeruli showed mesangial expansion with an increase in mesangial matrix and a mild increase in mesangial cellularity. Biopsy was reviewed at our center for a second opinion (Figure 1). The nephropathology team identified linear staining for IgG and kappa light chains along the tubular and glomerular basement membranes via immunofluorescence (IF), indicative of HC + LCDD. Electron microscopy (EM) identified thickened glomerular basement membranes and the presence of hyaline-like material within some glomerular loops. Notably, there were no electron dense deposits in the glomerular mesangium or tubular basement membranes. Despite only presenting primarily with HC + LCDD features on IF, the patient was initiated on an 8-cycle regimen of DARA-CYBOR-D. The patient exhibited a positive hematological and renal response to treatment, with a reduction in monoclonal protein levels, GFR shift from 22 to 59 ml/min/BSA, and a significant drop in urine protein from 2.8 to 0.6 g. He is currently in complete remission from MIDD.
In conclusion, this case illustrates the efficacy of the DARA-CYBOR-D regimen in a patient with HC + LCDD, even when all the classical MIDD manifestations are not fully present. Our study highlights the importance of integrating patient history with pathology findings such as the detection of MIg in kidney biopsies via IF staining, despite only subtle deposits on EM. Integrating this information allows for the development of tailored treatment strategies for patients co-morbid with diabetic kidney disease and MIDD.