A 73-year-old Caucasian male with a past medical history of hypertension presented to the hospital for progressive lower extremity edema and shortness of breath. Laboratory work showed a worsening of creatinine at 3.1 mg/dL, an increase from 1.1 mg/dL 1 month ago. Twenty-four-hour urine quantification showed nephrotic range proteinuria with 26 g of urine protein, urine albumin to creatinine ratio of 11 791, and serum albumin of 1.8 g/dL. Workup included normal echocardiogram and HbA1c of 5.8. Autoimmune workup with ANA, anti-dsDNA, anti-proteinase 3 antibody (c-ANCA), and anti-myeloperoxidase antibody (p-ANCA) were all negative. He had normal serum C3 and C4 complement levels. HIV screen, hepatitis B surface antigen, and anti-hepatitis C virus antibody were negative. The patient was thoroughly questioned about bisphosphonate use, recent viral illnesses (cytomegalovirus), or recent blood-tinged coughing and prior tuberculosis exposure, all of which were unremarkable according to the patient.
Serum protein electrophoresis showed 2 immunoglobulin G Kappa monoclonal bands (0.2 g/dL and 0.3 g/dL) confirmed with immunofluorescence. Serum free light chain ratio was elevated at 10.96, serum kappa light chain levels were elevated at 521 mg/L, and serum lambda light chains were elevated at 47.6 mg/L. The patient underwent a kidney biopsy and the results showed an acute tubular epithelial cell injury with focal sclerotic glomeruli and mild mesangial hypercellularity (Figure 1). Immunofluorescence on frozen tissue was negative for staining and electron microscopy was negative for immune deposits but showed 40% podocyte effacement (Figure 2). Despite a normal kidney biopsy, a bone marrow biopsy was performed 3 weeks later to investigate the elevated serum free light chain ratio and showed 10% plasmacytosis. Over the course of 2 months, the patient's kidney function continued to deteriorate. Despite tubular injury justifying worsening renal function, there was still questions of tubular injury causing such massive proteinuria, in addition to the concern that an immunofluorescence paraffin technique had not been performed on the initial biopsy, which can be sensitive to certain light chain tubulopathies.
As a result, a repeat kidney biopsy was performed showing acute severe tubular injury with collapsing type focal sclerotic glomeruli, electron microscopy demonstrating 90% podocyte effacement, and immunofluorescence with paraffin technique positive for kappa light chain and lambda light chain (kappa greater than lambda). As a result, the diagnosis of focal segmental glomerulosclerosis secondary to monoclonal gammopathy of renal significance (MGRS) was made. Given the patient's positive result for kappa light chain on immunofluorescence, APOL1 gene testing was not performed given the high likelihood of MGRS. The patient was subsequently started on a CyBorD chemotherapy regimen, and after 6 cycles, the patient's outpatient laboratory creatinine level was improved to 1.4 mg/dL. Additionally, there was improvement of proteinuria with urine albumin to creatinine ratio decreasing to 7456 and serum albumin improving to 2.9 g/dL.