Monoclonal Gammopathy of Renal Significance: Diagnosis, Treatment and Prognosis. Experience in a Spanish Hospital Institution

Introduction: The term monoclonal gammopathy of renal significance (MGRS) consists of a clonal population of plasma cells or B lymphocytes that produces a nephrotoxic complete or partial immunoglobulin. MGRS constitute around 10% of monoclonal gammopathies of uncertain significance, and the prevalence among patients over 50, is about 0.32%.

Methods: This retrospective observational study included newly diagnosed MGRS patients, evaluated at 4 hospitals in the same institution between 01/01/2016 and 01/06/2024. The primary endpoint was to describe the types of MGRS diagnosed in our hospital complex. The secondary endpoints were to describe their clinical presentation, treatment, and prognosis. Hematological response was evaluated according to the response categories proposed for AL amyloidosis.

Results: This study includes 51 patients, 67% men. Twenty-one patients had AL amyloidosis, and 30 had other types of MGRS. Eighty-two percent of patients had renal biopsy. The median age at diagnosis was 66 years (interquartile range (IQR) 52 - 73). The median time between the first nephrology consultation and diagnosis was 68 days (IQR 8 - 284). In 69% of the cases, nephrology was the first medical appointment, and 33% of the patients did not have a consultation with Hematology before diagnosis. Table 1 describes clinical characteristics at diagnosis. At diagnosis, the median creatinine and glomerular filtration were 1.0 mg/dL (IQR 0.9 - 2.2) and 49 mL/min/m2 (IQR 31.0 - 84.0) respectively. The most frequent nephrological diagnosis was nephrotic syndrome (33%). Thirty-nine patients (76%) had detectable monoclonal immunoglobulin in serum or urine, and 19 (41%) had ≥10% monoclonal plasma cells in bone marrow. The most common MGRS was immunoglobulin-related amyloidosis (41%), followed by proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) (23%) and monoclonal immunoglobulin deposition disease (MIDD) (14%). Seventy percent of AL amyloidosis had extrarenal involvement. The median time between diagnosis and hematological treatment was 28 days (IQR 15 - 44). With a median follow-up of 30 months (IQR 7 - 50), 46 patients (90%) received hematological treatment and 10 (20%) received an autologous stem cell transplant (ASCT). The median duration of treatment was 3 months (IQR 1 - 7). The median number of induction cycles was 6 (IQR 3 - 6). The most frequent regimen was cyclophosphamide-bortezomib-dexamethasone (41%), followed by daratumumab-cyclophosphamide-bortezomib-dexamethasone (20%). Table 2 describes treatment regimens. Regarding hematological response, the overall response rate was 75%, and 64% of patients achieved ≥ very good partial response. Only one patient had a hematological relapse. Eleven patients (21%) required renal replacement therapy (RRT), and of them, seven (14%) required definitive RRT after a median time of 5 months (IQR 0 - 15) from diagnosis. One received a kidney transplant two years after diagnosis. Graphic 1 illustrates distribution according to the type of MGRS at diagnosis and the beginning of renal replacement therapy. Treatment of hemopathy was not required for reasons other than MGRS. Nine patients died. Five had AL amyloidosis, two had MIDD, and two had PGNMID. Seventy-eight percent of the deceased died from causes related to their disease.

Conclusion: Monoclonal gammopathy of renal significance is a rare entity, and population studies are scarce. This leads to limited consensus regarding the treatment and monitoring of this pathology. Real-life studies are necessary to understand our population and improve its management.

No relevant conflicts of interest to declare.

There have not been clinical trials in phase 3 designed for monoclonal gammopathies of renal significance apart from amyloidosis AL, therefore the treatment described is off-label.