Analysis of clinical and pathological manifestations of light chain proximal tubulopathy / 中华肾脏病杂志

ABSTRACT

Objective To investigate the clinical and pathological characteristics of light chain proximal tubulopathy (LCPT).Methods Nine patients with LCPT diagnosed by renal biopsy in Peking University First Hospital from January 1,2011 to September 30,2016 were enrolled,and their clinical findings and pathological features were reviewed.Immunofluorescence (IF) of light chains (κ,λ) on paraffin sections after protease digestion and immunogold labeling of light chains (κ,λ) on ultrathin sections were performed in some cases.Results The main clinical manifestation of the nine patients was proteinuria of small molecules,with acute or chronic renal insufficiency,and six of them led to partial or complete Fanconi syndrome (FS).The hematologic diseases included 3 cases of multiple myeloma and 6 cases of monoclonal gammopathy of renal significance (MGRS).Pathological examination of renal biopsy showed two typescrystalline and noncrystalline LCPT.Seven cases of crystalline LCPT were stained for κ light chain,the proximal tubular epithelial cytoplasm exhibited fine granular vacuolation,with needle-shaped crystals and clear clefts by light microscopy,the intracytoplasmic inclusions of various shapes including rhomboidal,rectangular and rod-shaped crystals were identified by electron microscopy.Two cases of noncrystalline LCPT were stained for λ light chain,the prominent argyrophilic granules in cytoplasm of proximal tubular epithelia were observed by light microscopy,and intracytoplasmic large and irregular shaped phagolysosomes were found by electron microscopy,cast nephropathy were coexisted in these 2 cases,the additional light chain deposition disease were confirmed in one of them by electron microscopy and IF.All cases had monotypic staining of light chains in cytoplasm of proximal tubules by IF on frozen tissue and paraffin sections after protease digestion,with the latter method being more sensitive than the routine IF.The immunogold labeling showed specific monotypic labeling of κ and λ light chain on intracytoplasmic crystals and phagolysosomes respectively by immunoelectron microscopy.Conclusions LCPT is a rarely reported entity that manifested as acquired Fanconi syndrome and dysfunction of proximal tubules clinically.Pathologically it is divided into two typescrystalline and noncrystalline LCPT,with more prevalent of κ light chain related crystalline type,noncrystalline LCPT is mostly λ type,and is easily coexisted with cast nephropathy.The IF and immunoelectron microscopy of light chains(κ,λ) and ultrastructural examination by electron microscopy are important methods for the diagnosis of LCPT.