Tubulopatia proximal por cadeia leve kappa: revisão clínico-patológica, classificação ultraestrutural e implicações para a prática nefrológica

Light chain proximal tubulopathy (LCPT) represents a rare form of renal involvement in monoclonal gammopathies, defined by the endocytic uptake and cytoplasmic accumulation of nephrotoxic monoclonal light chains in proximal tubular epithelial cells. The classic form is crystalline and shows a marked predominance of kappa light chains; however, the current ultrastructural classification recognizes four variants: crystalline, fibrillary, amyloid, and lysosomal indigestion. This narrative review, intended for nephrologists, is based on a literature review. It addresses definition, history, etiology, pathogenesis, clinical presentation, investigation, light microscopy, immunofluorescence, electron microscopy, treatment, prognosis, and controversies. Etiopathogenesis includes glomerular filtration, megalin/cubilin-mediated endocytosis, resistance to lysosomal proteolysis, light-chain aggregation, lysosomal and mitochondrial dysfunction, oxidative stress, and loss of proximal reabsorptive capacity. Fanconi syndrome is prototypical but often incomplete; tubular proteinuria and kidney dysfunction are common. Electron microscopy is central to subclassification and may demonstrate crystals, nonamyloid fibrils, amyloid fibrils, or enlarged lysosomes containing indigestible material. Frozen-tissue immunofluorescence may be falsely negative, requiring pronase-digested paraffin immunofluorescence and, in selected cases, immunoelectron microscopy. Treatment combines replacement of tubular losses and management of bone-mineral complications with individualized clone-directed therapy according to renal progression, metabolic impact, clone type, comorbidities, and treatment risk. Early recognition is essential because baseline kidney function influences outcome and hematologic response does not invariably reverse established tubulointerstitial damage.