Introduction:
MGRS comprises a diverse group of kidney diseases caused by monoclonal immunoglobulins or their components. The clinical presentation is highly variable, featuring different combinations of proteinuria, hematuria, renal dysfunction, and hypertension. Both the type of monoclonal protein involved and the associated hematological disorder can vary widely. This study sought to characterize the spectrum of MGRS lesions and identify clinical indicators that might point to specific underlying disorders.
Methods:
A retrospective analysis was conducted on all patients diagnosed with MGRS between August 2017 and August 2024. Patients with MGRS lesions associated with cast nephropathy were excluded. SPSS® was used for statistical analysis, considering p ≤ 0.05 as statistically significant.
Results:
Seventy-eight patients were diagnosed with MGRS through biopsy. The group consisted of 59% men, with an average age of 67±13 years. The majority (n=74) had a previous diagnosis of monoclonal gammopathy of undetermined significance, while the remaining patients were diagnosed with indolent myeloma (n=2) and smoldering Waldenström macroglobulinemia (n=2). Only 57% of the patients showed an abnormal serum free light chain ratio. Mean serum creatinine was 2.5±2.3 mg/dL, and mean proteinuria was 6.6±5.0 g/day. AL amyloidosis was the most common diagnosis (n=49, 62.8%), followed by monoclonal immunoglobulin deposition disease (MIDD) (n=16, 20.5%) and proliferative glomerulonephritis with monoclonal Ig deposition (PGNMID) (n=8, 10.3%).
In the AL amyloidosis group, the involved monoclonal gammopathy was more frequently a lambda light chain producer (p<0.001); these patients, at the time of renal biopsy, presented with higher proteinuria (8.2±5.3 vs 4.2±3.3 g/day; p<0.001) but were less likely to have hematuria (p=0.002). No differences were found in age, hypertension, and serum creatinine.
In the MIDD group, only one case of heavy chain deposition disease (IgG1) was observed, while the remaining cases were due to light chain deposition. The kappa light chain was significantly more prevalent (p=0.001). Patients in this group presented with higher serum creatinine (3.9±2.2 vs 2.2±2.2 mg/dL, p=0.005) and lower proteinuria (3.7±3.2 vs 7.4±5.1 g/day) compared to other MGRS patients. No significant differences were found regarding age, hypertension, or hematuria.
PGNMID patients most commonly had IgG and kappa light chain deposits. Kappa light chains were significantly more prevalent in PGNMID compared to other MGRS cases (p=0.009). In 2 patients, pronase digestion was necessary to identify the involved clone. In 1 patient, it was not possible to identify the monoclonal protein, but immunofluorescence demonstrated glomerular-restricted deposits of IgG3 and kappa. Compared to other MGRS patients, those with PGNMID were generally older (73±6 vs 66±13 years, p=0.022) and more likely to have hematuria (p=0.002) at the time of renal biopsy. No significant differences were found in sex, hypertension, serum creatinine, or proteinuria.
Conclusions:
In patients with suspected MGRS, AL-amyloidosis was the most common lesion, followed by MIDD and PGNMID. The type of free light chain produced by the monoclonal gammopathy, the magnitude of proteinuria, and the presence of hematuria can provide valuable clues to the underlying MGRS lesion.
I have no potential conflict of interest to disclose.
I did not use generative AI and AI-assisted technologies in the writing process.