INCIDENCE AND RISK FACTORS FOR MONOCLONAL GAMMOPATHY OF RENAL SIGNIFICANCE (MGRS) IN PATIENTS WITH MONOCLONAL GAMMOPATHY AND RENAL DISEASE

Introduction:

Both monoclonal gammopathy (MG) and chronic kidney disease (CKD) are common in the elderly population. Some patients with CKD also have MG, but the monoclonal protein is not the cause of the underlying kidney disease. Currently, there is limited knowledge about the clinical predictors of detecting an MGRS lesion on kidney biopsy. This study aims to determine the frequency of MGRS lesions in patients with MG undergoing kidney biopsy and to identify predictors that may increase the probability of finding such lesions.

Methods:

Retrospective study including all patients with monoclonal gammopathy who underwent a kidney biopsy between August/2017 and August/2024. Patients with overt lymphoplasmacytic malignancy or that had any myeloma-defining event were excluded. Multivariable logistic regression was used to analyze the odds ratios (OR) for developing MGRS. P < 0.05 was considered statistically significant. 

Results:

Kidney biopsies were performed on 168 patients with monoclonal gammopathy. Ten patients were excluded due to insufficient sample to establish a renal diagnosis. Of the eligible 158 patients, 67.1% male and their mean age was 67  11.9 years. Seventy-eight (49.4%) had an MGRS lesion. Mean serum creatinine was 2.82.3 mg/dL and mean proteinuria was 5.55.5 g/day; 31% of the patients had microhematuria. 

In the MGRS group, AL-amyloidosis was by far the most common finding (n=49, 62.8%). Monoclonal immunoglobulin deposition disease (MIDD) was the second most common lesion (n=16, 20.5%), followed by proliferative GN with monoclonal Ig deposition (n=8, 10.3%). Other lesions were light chain proximal tubulopathy (n=1), type 1 cryoglobulinemic GN (n=1), type 2 cryoglobulinemic GN (n=1), fibrillary GN (n=1) and membranous nephropathy with light chain–restricted deposits (n=1). In the non-MGRS group, diabetic nephropathy (n=29, 36.3%) was the most common finding, followed by chronic tubulointerstitial nephritis (n=10, 12.5%), membranous nephropathy (n=6, 7.5%) and FSGS (n=6, 7.5%). Additional lesions are summarized in Figure 1. 

Patients in the MGRS group had higher proteinuria at the time of kidney biopsy (6.6 ± 5 vs 4.3 ± 5.8 g/day) (p=0.005) and were more likely to be male (p=0.032). Presentation with nephrotic syndrome (p<0.001), proteinuria above 1.5 g/ day (p< 0.001) and an abnormal FLC ratio were associated with an increased likelihood of finding an MGRS lesion (p=0.046). Other clinical parameters such as age, presence of arterial hypertension, and hematuria were not associated with increased odds of finding an MGRS lesion. In the multivariate model, which considered age, sex, proteinuria, hematuria, serum creatinine, and abnormal FLC, the strongest predictors of finding an MGRS lesion were the presence of an abnormal FLC (OR 4.06; 95% CI 1.1 – 15.4) and higher proteinuria (OR 1.1; 95% CI 1.01 – 1.3).

Conclusions:

In patients with MG who undergo a kidney biopsy, the rate of finding an MGRS lesion was about 49%, with AL-amyloidosis and MIDD representing the majority of the cases. Higher proteinuria, namely greater than 1.5 g/day and an elevated free light chain ratio increase the likelihood of finding MGRS, and a kidney biopsy should be highly considered in these patients. 

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.