A 78-Year-Old Man with Anasarca and Chronic Kidney Disease

Answer: C

MGRS is a heterogeneous group of pathologic renal conditions attributed to a clonal plasma cell disorder. MGRS does not meet the criteria for overt MM or a B-cell lymphoproliferative disorder, and the hematologic component of the disorder is generally consistent with MGUS (Table). However, there is a need to distinguish MGRS from MGUS and unrelated renal abnormalities, as the clonal protein in MGRS plays a direct role in kidney damage and requires treatment of the underlying clone.

There are two main categories of renal disorders associated with monoclonal gammopathies.1 The first group of renal disorders requires the secretion of large amounts of all or part of the monoclonal immunoglobulin (MIg). This is typically illustrated by the massive precipitation of light chain (LC) in the lumen of distal tubules, which characterizes LC-cast nephropathy (this the most common cause of acute kidney injury in MM). The other group is renal diseases associated with low-grade lymphoproliferative disorders. In this setting, structural peculiarities of the MIg, particularly the variable domain and not the rate of production, are the main determinants of renal lesions. For this reason, the spectrum of renal diseases in MGRS is extensive. Kidney disorders that are caused by the interaction of MIgs or their components may meet criteria for the diagnosis of MGRS. These include well-established entities such as AL amyloidosis and more recently described pathology, particularly proliferative glomerulonephritis with MIg deposits and C3 glomerulopathy with monoclonal gammopathy.

When should we suspect MGRS? Patients with a nonmalignant or premalignant monoclonal gammopathy (e.g., MGUS, smoldering MM, smoldering Waldenström macroglobulinemia, or monoclonal B-cell lymphocytosis) who present with unexplained kidney function impairment and/or proteinuria.²

Kidney biopsy is indicated in most cases to determine the exact lesion associated with MGRS and to evaluate its severity. Diagnosis requires integration of morphologic alterations by light microscopy, immunofluorescence (IF), electron microscopy, and immunoelectron microscopy, and in some cases by IF staining for Ig isotypes. Factors associated with MGRS included proteinuria of at least 1.5 g/day, hematuria, and abnormal serum-free LC ratio.²

Since patients with MGRS do not meet diagnostic criteria for MM or a lymphoproliferative disorder, clinicians have previously been reluctant to treat these patients with chemotherapy.³ Therapy is tailored based on characteristics of monoclonal gammopathy, particularly its isotype, and whether it corresponds to an overt lymphoid and/or plasmacytic disorder.

Early recognition of MGRS is crucial, and our understanding of the spectrum of MGRS is evolving. MGRS is also very likely to progress to MM. To date, no strategy is available to inhibit MIg tissue deposition or to remove the already deposited material.³ Suppression of MIg secretion by chemotherapy often improves outcomes, thus preserving kidney function. The choice of chemotherapeutic agents should consider the patient’s renal metabolism and potential renal and extrarenal toxicity.2

Sorry, that was not the preferred response.