IgG Kappa Monoclonal Gammopathy of Renal Significance (MGRS) Manifesting as Noncrystalline Light-Chain Proximal Tubulopathy (LCPT) with Fibrils

Introduction: LCPT is a rare manifestation of paraproteinemia (5% of MGRS cases). It can present with crystalline or non-crystalline deposition in the tubular epithelium and is more commonly associated with kappa light chain (KLC) predominance. Clinically, it presents with a variable degree of CKD, proteinuria, and/or Fanconi syndrome. Case Description: A 53 y/o male with IgG kappa MGUS (serum IgG 1.6 mg/dL, free KLC 13.5 mg/dL, kappa/lambda (K/L) 14.3, bone marrow with 7% plasma cells and no anemia, hypercalcemia, or bone lesions) was referred to nephrology due to eGFR of 68 mL/min. Clinical exam was unremarkable. Urinalysis showed trace blood and non-nephrotic proteinuria: 0.9 g/24h with a 0.3 g M-spike on UPEP. There was no Fanconi syndrome. All other serologies were negative. A renal biopsy was performed. Light microscopy showed diffuse, acute tubular injury with epithelial cell swelling, ballooning type vacuolization and granular cytoplasmic inclusions (Fig 1A). No definitive crystalloid structures, tubular necrosis, or tubulitis were identified. Frozen immunofluorescence (F-IF) showed a slight kappa predominance in tubular cell droplets compared to lambda (Fig 1B-C). Immunohistochemical (IHC) staining showed markedly increased staining with Kappa relative to Lambda in tubular epithelial cells (Fig 2A-B). Congo red was negative. EM showed fibrillar inclusions arranged in parallel arrays, ~10.2 nm (Fig 2C). The patient has been treated with daratumumab and bortezomib for six months with no evidence of disease progression and has sutained stable levels of KLC (5.8 mg/dL), with K/L 14.5. Discussion: This case represents a rarely reported variant of non-crystalline LCPT with fibrils and without significant renal dysfunction. KLC monoclonality was more evident in IHC than in F-IF staining. While paraffin IF (P-IF) is the standard for a diagnosis of LCPT, this case represents a variable technique that can be helpful in settings with limited access to P-IF technology.