Background: Monoclonal gammopathy of renal significance (MGRS) is a term coined to describe patients with monoclonal gammopathy and concomitant renal pathology, typically due to immunoglobulin deposition or a fragment thereof, without evidence of an overt hematologic malignancy. Early identification of MGRS and treatment with chemotherapy can prevent progression to kidney failure. There is limited data on the characteristics of populations with concomitant monoclonal gammopathy of unknown significance (MGUS) and chronic kidney disease (CKD), and on the prevalence of diagnosed MGRS in this particular population. Methods: Through retrospective chart review, we identified 246 patients with ICD-9 or -10 codes denoting both MGUS and chronic kidney disease (CKD) between the years of 2000 and 2017. Patients with related overt malignancies such as multiple myeloma, Waldenstrom’s macroglobulinemia, and amyloidosis at onset were excluded, leaving 144 evaluable patients. Results: The median eGFR was 48 mL/min/1.73 m² at the time of MGUS diagnosis, and the median M-protein was 0.54 g/dL in patients with a quantifiable gammopathy. Conclusion: MGRS needs to be considered in patients with a monoclonal protein and chronic kidney disease. Renal biopsies are underutilized. Based on our findings, we propose a simple algorithm for workup of suspected MGRS. What is already known about this subject: Monoclonal gammopathy of renal significance (MGRS) is a disorder of deposition of monoclonal protein in the kidney without overt multiple myeloma or lymphoproliferative disorder, and can result in irreversible kidney failure. What this study adds: This study describes the characteristics of a population who harbors both a monoclonal protein and CKD, and identifies the prevalence of MGRS in this cohort. We postulate that MGRS is likely underreported due to a lack of kidney biopsies and propose a simple algorithm for the workup of MGRS. What impact this may have on practice or policy: This study may result in increased awareness of MGRS as a disease as well as an increased need for the pursuit of a renal biopsy in this particular at-risk population.