Abstract: TH-PO979
Clinical Course of a Patient Treated for Dense Deposit Disease (Monoclonal Protein Associated)
Session Information
- Glomerular Trainee Case Reports
November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Report
- 1500 Onco-Nephrology
Authors
- Borshchenko, Yevgeniy, NYU Winthrop, Mineola, New York, United States
- Moe, Win Win, NYU Winthrop, Mineola, New York, United States
- Nayyar, Kamal, NYU Winthrop, Mineola, New York, United States
- Tharian, Antonia, NYU Winthrop, Manhasset, New York, United States
- Drakakis, James, NYU Winthrop, Mineola, New York, United States
Introduction
Dense deposit disease (DDD), a subcategory of C3 glomerulopathy is a rare entity characterized by uncontrolled activation of the alternative pathway (AP) of the complement cascade. When diagnosed in the older population, there is often an accompanying monoclonal gammopathy of undetermined significance (MGUS). As the monoclonal protein may perturb AP regulation, treating with chemotherapy need be considered. We report a case of DDD (MGUS associated) first treated with bortezomib, later switched bortezomib plus cyclophosphamide and dexamethasone (CyBorD). As there was no histologic or serologic improvement, daratumumab was introduced with stability of kidney function.
Case Description
A 62 year old male was evaluated for a serum creatinine (Cr) of 1.3 mg/dL with urine protein of 3 g/g. There were low C3 and C4 levels. Urinalysis showed 3+ blood with 86 red blood cells. Serum immunofixation detected an IgG kappa monoclonal protein. Plasma cell count on bone marrow biopsy was 8%. Renal biopsy showed diffuse mesangial and segmental endocapillary proliferative glomerulonephritis with membranoproliferative features. Immunofluorescence had intense deposition of C3. Global, marked electron dense deposits were seen. As findings were consistent with DDD, bortezomib was initiated. After 3 months, this was held for observation. Cr then was 2.5 mg/dL with urine protein/creatinine of 4.5 g/g. Six months later, bortezomib was resumed but not effective. CyBorD followed, but Cr rose to 3.5 mg/dL. Second kidney biopsy revealed severe tubular atrophy and interstitial fibrosis. At this point, weekly daratumumab with bortezomib was started. After several months, renal function has not declined further and proteinuria reached nadir of 2.9 g/g.
Discussion
Monoclonal gammopathy has emerged as a potential driver of the complement dysregulation, known to characterize DDD. Although there have been several strategies reported, there is no standard approach to guide therapy. While chemotherapy is not used to treat MGUS, it is appropriate in cases whereby the monoclonal protein manifests as a form of C3 glomerulopathy (DDD). This case demonstrates various options which may be utilized to curtail renal morbidity. While bortezomib alone and CyBorD were not effective, our patient has achieved ongoing clinical and laboratory stability with daratumumab.