Crystalline versus non-crystalline light-chain proximal tubulopathy: a case series

Light-chain proximal tubulopathy (LCPT) represents a rare paraprotein-associated kidney disorder resulting from the intracellular accumulation of monoclonal free light chains within proximal tubular epithelial cells, and manifests as either crystalline or non-crystalline inclusions. Crystalline LCPT is most frequently observed in IgG-κ multiple myeloma. Conversely, IgD-λ multiple myeloma typically presents as the non-crystalline variant. The histopathological findings, clinical correlations, and therapeutic outcomes differ substantially between these two entities. This study comparatively analyzed two LCPT cases and summarized the clinicopathological characteristics, diagnostic strategies and treatment outcomes of different LCPT subtypes. The 55-year-old male patient with IgG-κ multiple myeloma presented with renal insufficiency, and renal biopsy confirmed crystalline LCPT. Typical crystalline structures in proximal tubular epithelial cells and κ light chain deposition were verified by light, electron and immunoelectron microscopy. The patient achieved favorable hematologic and renal prognosis after bortezomib-based chemotherapy combined with autologous hematopoietic stem-cell transplantation (ASCT). The 64-year-old male patient with IgD-λ multiple myeloma suffered from progressive renal failure. Biopsy revealed non-crystalline LCPT characterized by non-crystalline lysosomal lesions with concurrent light-chain cast nephropathy, characterized by non-crystalline lysosomal lesions and λ light chain accumulation. He received multiple cycles of bortezomib-based chemotherapy without ASCT and finally died of multiple organ failure. Literature review indicates that LCPT morphological phenotypes are closely correlated with light chain subtypes. IgD-λ-related non-crystalline LCPT is rarer, more aggressive, and prone to severe renal impairment. In conclusion, for patients with unexplained proximal tubular dysfunction and monoclonal gammopathy, early precise diagnosis relying on ultrastructural examination and light chain immunohistochemical detection is critical. Bortezomib combined with ASCT is the optimal treatment for LCPT to achieve hematologic remission and preserve renal function, while close attention is required for high-risk IgD-λ non-crystalline LCPT.