Renal Monoclonal Immunoglobulin Deposition Disease

Abstract

SummaryBackground and objectives To better define the clinical-pathologic spectrum and prognosis of monoclonal immunoglobulin deposition disease (MIDD), this study reports the largest series.Design, setting, participants, & measurements Characteristics of 64 MIDD patients who were seen at Mayo Clinic are provided.Results Of 64 patients with MIDD, 51 had light chain deposition disease, 7 had heavy chain deposition disease, and 6 had light and heavy chain deposition disease. The mean age at diagnosis was 56 years, and 23 patients (36%) were #50 years of age. Clinical evidence of dysproteinemia was present in 62 patients (97%), including multiple myeloma in 38 (59%). M-spike was detected on serum protein electrophoresis in 47 (73%). Serum free light chain ratio was abnormal in all 51 patients tested. Presentation included renal insufficiency, proteinuria, hematuria, and hypertension. Nodular mesangial sclerosis was seen in 39 patients (61%). During a median of 25 months of follow-up (range, 1-140) in 56 patients, 32 (57%) had stable/improved renal function, 2 (4%) had worsening renal function, and 22 (39%) progressed to ESRD. The mean renal and patient survivals were 64 and 90 months, respectively. The disease recurred in three of four patients who received a kidney transplant.Conclusions Patients with MIDD generally present at a younger age than those with light chain amyloidosis or light chain cast nephropathy. Serum free light chain ratio is abnormal in all MIDD patients, whereas only threequarters have abnormal serum protein electrophoresis. The prognosis for MIDD is improving compared with historical controls, likely reflecting earlier detection and improved therapies.

Rituximab–cyclophosphamide‐dexamethasone is highly effective in patients with monoclonal Ig deposit‐related glomerulopathy and indolent non‐Hodgkin lymphomas

“…Less commonly, iNHLs may also promote glomerulonephritis associated with monoclonal deposits [3,12,13], with extremely heterogeneous pathologic pattern as exemplified in our series.…”

“…To date, most published series on glomerulopathy with monoclonal Ig deposits have been based on pathologic patterns [3,6,[12][13][14][15]. Because of the wide heterogeneity of treatments in these series (e.g., no treatment, steroids only, rituximab, or combined chemotherapy), no firm recommendations for iNHL treatment are available.…”

A Patient with Abnormal Kidney Function and a Monoclonal Light Chain in the Urine

“…Similarly, 59% of 63 patients with monoclonal Ig deposition disease (MIDD) were reported to have myeloma in a large Italian series (4). In a different study, where the bone marrow plasma cells and end organ damage were assessed separately, again, 59% were found to have .10% plasma cells in the bone marrow, but only 20% had lytic lesions at the time of diagnosis (5). This correlated with a recent French series showing that only 20% met the definition of MM (6).…”

“…For example, in the glomerulus, MG can induce immunoglobulin derived (AIg) amyloidosis that includes AL amyloidosis, heavy-chain amyloidosis, and lightand heavy-chain amyloidosis (17). Other glomerular entities include MIDD, which is comprised of the variants light-chain deposition disease (LCDD), heavy-chain deposition disease, and light-and heavy-chain deposition disease named for the types of Ig deposits found in the kidney, and proliferative glomerulonephritidies, such as membranoproliferative GN and PGNMID (5,11). In the tubules, light-chain proximal tubulopathy (LCPT) with or without Fanconi syndrome and cast nephropathy are conditions associated with MG (18).…”

“…Monoclonal light chains are also capable of generating hydrogen peroxides, which activates the mitogen-activated protein kinase kinase kinase, known as apoptosis signal regulating kinase 1, causing apoptosis and NF k-light-chain enhancer of activated B cells (Nf-kB) via Src kinase resulting in fibrosis (20). Vascular involvement is common with amyloidosis and MIDD (5,21). The one issue with this classification is that overlap is common.…”