An 86-year-old female patient was referred from a local clinic due to uncontrolled generalized edema. The patient’s significant medical history included 7 years of diabetes and hypertension, both managed with medication. She reported the use of diuretics prescribed at a private clinic for a month without achieving control of her edema. One month prior, her serum creatinine level was 1.07 mg/dL and her estimated glomerular filtration rate was 47 mL/min/1.73m². She appeared to be in good health except for presenting with grade 4 edema in both legs. Upon admission, her serum creatinine had risen to 2.36 mg/dL (Table 1). Initially, her albumin/globulin (A/G) ratio showed a reversal at 0.89. Serum electrophoresis did not show a monoclonal peak with increases in alpha 1/2 and beta 2 fractions (Fig. 1A). Serum immuno-fixation electrophoresis also showed a normal immune typing pattern. Her serum cryoglobulin was negative. Autoimmune tests were negative for anti-GBM antibody (Ab), anti-proteinase 3 Ab, and anti-myeloperoxidase Ab. Despite treating the edema with diuretics, there was no improvement. Renal ultrasound and computed tomography revealed decreased sizes of both kidneys with echogenicity consistent with renal parenchymal diseases (Fig. 1C). Kidney biopsy was delayed due to the patient’s advanced age, existing diabetic kidney disease, and aspirin use. However, as there was no response to steroid treatment and RPGN was clinically suspected, a kidney biopsy was eventually performed. The kidney biopsy revealed type I CG combined with diabetic nephropathy that was consistent with membranoproliferative glomerulonephritis characterized by increased mesangial matrix and cellularity having lobular accentuation and hyaline intraluminal thrombi (Fig. 1D). Immunofluorescence microscopy showed intraluminal staining for Ig lambda (Fig. 1E), but not kappa (not shown). There also was intraluminal staining for C1q and a predominance of IgM (Figs. 1F, G, respectively). Electron microscopy revealed that some tubular basement membranes were thickened and multilayered. The interstitium exhibited edema and infiltration by inflammatory cells (Figs. 1H, I). Bone marrow biopsy demonstrated no evidence of monoclonal hematologic disease (Fig. 1J). Since initiating continuous renal replacement therapy (CRRT) due to her rapid deterioration of renal function with metabolic acidosis and oliguria, the patient’s condition continued to worsen throughout her admission.

Despite treatment with CRRT, plasmapheresis, and pulse methylprednisolone, her renal function, hematologic anomalies, and systemic condition deteriorated further (Fig. 1B). This report was approved from the Institutional Review Board of the Catholic University of Korea, Seoul St. Mary's Hospital (No.KC23ZASI0826). Written informed consent was obtained from the patient for the publication of this report including all clinical images.

For MGRS-related diseases, clone-directed therapy such as bortezomib and ofatumumab, which were not prescribed in this patient, would have resulted in better outcomes than high-dose prednisolone treatment [6]. In this report, we diagnosed MGRS with type 1 CG presenting with intractable edema, a reversed serum A/G ratio, and a full-fledged nephrotic syndrome, which led to renal failure and ultimately the patient’s death. Recognizing MGRS is crucial for managing end-organ damage and improving patient survival, potentially leading to better treatments with fewer adverse effects, even in very old patients [1]. Early diagnosis is key to successfully treating RPGN, including MGRS. However, this can be particularly challenging in the elderly, especially for those with hypertension and diabetes as these patients often present with typical or minimal clinical symptoms [7]. The diagnosis may be challenging because the hallmark of cryoglobulinemia is the detection of cryoglobulins in the serum. However, cases of CG without serological evidence of cryoglobulins are often diagnosed by anatomopathological findings in renal biopsy [8].

In conclusion, our case report emphasizes the importance of considering MGRS as a potential cause of RPGN in elderly patients, even if they have underlying renal diseases. It underscores the significance of conducting a kidney biopsy to accurately determine the cause of kidney injury, thereby facilitating proper and timely treatment.