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. 2025 Apr 15;25(1):118.
doi: 10.1007/s10238-025-01646-7.

Monoclonal gammopathy of renal significance (MGRS): retrospective monocentric analysis of clinical outcomes and treatment strategies

Pasquale Esposito  1   2 , Lucia Macciò  3 , Antonia Cagnetta  3 , Francesca Costigliolo  3 , Emilio Venturelli  4 , Elisa Russo  4   3 , Marco Gallo  5 , Debora Soncini  5 , Francesca Viazzi  4   3 , Roberto Massimo Lemoli  3   5 , Michele Cea  6   7
Affiliations

Monoclonal gammopathy of renal significance (MGRS): retrospective monocentric analysis of clinical outcomes and treatment strategies

Pasquale Esposito et al. Clin Exp Med. .

Abstract

Monoclonal Gammopathy of Renal Significance (MGRS) is a group of rare disorders in which monoclonal proteins cause kidney damage. Due to its rarity, ongoing research is vital to refine diagnostics, enhance treatment, and improve outcomes. This retrospective study analyzed 34 patients with renal biopsy-proven MGRS-defining lesions. Patients were divided into two subgroups: kidney-limited AL amyloidosis (MGRS-A, 44%, n = 15) and other MGRS (MGRS-NA, 56%, n = 19). Key outcomes included progression-free survival and overall survival. Baseline characteristics such as histopathology, plasma cell percentage, kidney function, and proteinuria were documented alongside initial treatments, and hematologic and renal response. Distinct differences were observed between the two groups: MGRS-NA was primarily associated with glomerular lesions, while MGRS-A exhibited broader kidney involvement. Treatment varied: bortezomib for plasma cell-driven cases and rituximab for B-cell-related conditions. Anemia was the most common side effect (71%), associated with treatment intensity. Despite similar overall survival outcomes, MGRS-A followed a more aggressive course, with a shorter time from diagnosis to death (206 vs. 728 days). Renal and hematologic responses were comparable between the groups, although baseline factors such as hemoglobin and CRP levels were predictive of mortality. These findings underscore the need for more precise characterization and standardized criteria to optimize the management of MGRS.

Keywords: Amyloidosis; Anemia; Bone marrow plasma cells; Kidney; Monoclonal gammopathy of renal significance; Proteinuria.

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Conflict of interest statement

Declarations. Conflicts of interest: No conflicts of interest to disclose. Ethical approval statement: The study was conducted under all national and international ethical and legal recommendations, following approval by the local Ethics Review Committee, in accordance with the declaration of Helsinki. (Comitato Etico Territoriale, CER- Liguria: 515/2020). Informed consent was obtained from all participants prior to their inclusion in the study.

Figures

Fig. 1
Fig. 1
Comparisons between MGRS-NA and MGRS-A groups in term of prognosis. Kaplan-Meyer curves of the overall survival A, progression-free survival B and time to next treatment  C probability among MGRS-NA (blue line) or MGRS-A (red line) groups. Log-rank test is used to compute the p-value (Log-Rank test). MGRS (Monoclonal Gammopathy of Renal Significance), A (Amyloidosis), NA (Non-Amyloidosis)
Fig. 2
Fig. 2
Baseline clinical and laboratory parameters and mortality risk in MGRS patients. Forest plot based on Cox proportional Hazard analysis of the indicated variables for OS in our cohort. The hazard ratios (squares) are displayed with their corresponding confidence intervals (bars) and the p-values (after post hoc correction). Significance levels are clearly indicated by both the number and color (red and blue indicating statistically significant or not, respectively). The original p-value is shown next to each analyzed parameter. Abbreviations: OS (Overall Survival), stadPV (Pavia Renal Staging), prot_U (proteinuria), CRP (C-reactive protein), pcPCmid (Medullary Plasma Cell), LDH (Lactate Dehydrogenase), ISS (International Staging System), Hb (Hemoglobin), ECOG (Eastern Cooperative Oncology Group performance status), beta2m (β2 microglobulin)
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