Epidemiological Characteristics and Clinical Outcomes of Patients with Monoclonal Gammopathy of Renal Significance (MGRS) Diagnosed in a Large Safety-Net Hospital in the US

Monoclonal gammopathy of renal significance (MGRS) refers to renal disorders caused by a monoclonal immunoglobulin (MIg) including AL amyloidosis and other entities. The epidemiology of MGRS is largely unknown particularly in diverse populations.

We aimed to evaluate the epidemiologic and clinical characteristics of patients with MGRS. We retrospectively reviewed all renal biopsies performed between 2009 and 2022 at Boston Medical Center (BMC), the largest safety net hospital in the New England area of Massachusetts, and evaluated the clinical characteristics of patients with MGRS. Patients with a known diagnosis of myeloma cast nephropathy or those who were referred to the BMC amyloidosis center due to concern for AL or ATTR amyloidosis were excluded.

Out of 1896 patients who underwent renal biopsy, MGRS was diagnosed in 70 (3.7%) patients. The MGRS cohort was comprised of 44% non-Hispanic white patients, 27% non-Hispanic Black (NHB) patients, 15% Hispanic patients, and 4% Asian patients. Gender was similarly distributed between MGRS and non MGRS patients (approx. 44% female in each group), but MGRS patients were older (mean age 65 vs 52, p<0.05) and more frequently white (44% vs. 30%, p<0.05). The most frequent type of MGRS was AL amyloidosis (30%), followed by monoclonal immunoglobulin deposition disease (MIDD, 17%), proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID, 15%), light chain tubulopathy (10%), other (9%- includes fibrillary glomerulonephritis) and C3 glomerulonephritis (7%). Four patients (6%) were diagnosed with MGRS after renal transplantation. These biopsies were performed in the setting of worsening renal disease without a known prior diagnosis of MGRS.

Only 54% of MGRS patients had a detectable monoclonal immunoglobulin in the serum or the urine. Of the 31 individuals with AL amyloidosis, seven patients (53%) had a detectable M-protein. Six patients had an IgG lambda MIg, one had an IgA lambda MIg and two had light chain disease. In the MIDD subgroup (n=12), three patients had a kappa M-protein (one IgM, one IgA, one IgG). One individual had Lambda FLC only (LCDD) MIg. Among patients with PGNMID (n=5), two had an IgG lambda MIg. The remaining three patients had IgG kappa MIg, IgA kappa MIg and IgM kappa MIg, respectively.

Creatinine level, 24 hour protein and age varied among MGRS subtypes but differences were not statistically significant. However, individuals with fibrillary glomerulonephritis tended to have the highest creatinine level (median 4.18 +/- 1.6) and the highest 24 hour urine protein excretion (6.5g +/-3) at presentation. MGRS patients had an average Charlson Comorbidity Index (CCI) of 5.6. Non-Hispanic Black patients had significantly higher CCI scores than non-Hispanic white patients (6.7 vs. 4.5, p<0.05). Patients with AL amyloidosis, MIDD and PGNMID received either Daratumumab or Bortezomib based regimens. Seventy-five percent of patients with AL amyloidosis and 50% of patients with MIDD achieved at least hematologic very good partial response. A total of 16 patients progressed to HD (hemodialysis). This included 4 out of the 31 patients (13%) with AL amyloidosis, 2 out of the 12 patients with MIDD (17%), and 5 out of the 11 patients with PGNMID (45%).

In conclusion, in this diverse population, patients with MGRS patients were more likely to be older, when compared to patients without MGRS, and more often, non-Hispanic White. AL amyloidosis was the most frequent subtype of MGRS followed by MIDD and PGNMID. MGRS appears to be associated with high CCI scores especially in non-Hispanic Black patients. High baseline creatinine level is associated with progression to HD. Given the association of high CCI with mortality and the association of higher creatinine levels at diagnosis with progression to HD, early identification and management of comorbidities appear essential for MGRS patients, especially those of non-Hispanic Black ethnicity. Larger epidemiologic studies are needed to confirm these data.