A Tale of Two Chains: Light-Chain Proximal Tubulopathy and Amyloidosis

Introduction: MGRS and AL amyloidosis arise from abnormal monoclonal light chains or misfolded antibody fragments causing kidney disease via paraproteins, without meeting criteria for MM, WM, CLL, or lymphoma. MGRS is diagnosed by monoclonal immunoglobulin deposits on kidney biopsy, subcategorized by ultrastructure and organization. Paraprotein biochemical properties determine lesion type and location. Concurrent lesions are rare due to the clonal nature of these disorders. Case Description: A 74-year-old male with IgG kappa MGUS presented with kidney injury and nephrotic-range proteinuria. Serum creatinine rose from 1.0 to 1.77 mg/dL, albumin was 2.9 g/dL, κ/λ ratio increased from 8.68 to 14.12, M spike rose from 205 to 351 mg. Exam showed +1 edema and ecchymosis. Recommendations of a kidney bopsy revealed congested glomeruli, mesangial thickening, and hyalinization. Proximal tubules had eosinophilic crystalline material, with severe tubular atrophy and fibrosis. Congo red-positive material was in glomeruli and interstitium. Immunofluorescence detected IgG and Κ. Electron microscopy showed fibrils and rod-like crystals, confirming IgG-Κ AL amyloidosis and light chain proximal tubulopathy. Discussion: Mouse studies injected with Bence-Jones proteins from MGRS patients produced matching renal lesions, suggesting paraprotein properties drive lesion diversity. No case series has reported concurrent AL amyloidosis and LCPT. Said et al. reported 63% of 37 patients with AL amyloidosis and light chain deposition disease developed kidney failure, with 56% mortality over 16 months. Pathophysiology of concurrent AL and LCPT may involve light chain conformations or biclonal gammopathy. Clone-directed therapy outperforms immunosuppressive therapy for MGRS-related kidney diseases, preserving kidney function. This case highlights the complex spectrum of protein deposition in monoclonal gammopathies and the need for further research into clonal mechanisms.Proximal tubules showing crystalline structures