Light Chain Proximal Tubulopathy: Clinical and Pathologic Characteristics in the Modern Treatment Era

Abstract

Light chain proximal tubulopathy (LCPT) is characterized by cytoplasmic inclusions of monoclonal LC within proximal tubular cells. The significance of crystalline versus noncrystalline LCPT and the effect of modern therapies are unknown. We reported the clinical-pathologic features of 40 crystalline and six noncrystalline LCPT patients diagnosed between 2000 and 2014. All crystalline LCPTs were κ-restricted and displayed acute tubular injury. One-third of noncrystalline LCPT patients displayed λ-restriction or acute tubular injury. Only crystalline LCPT frequently required antigen retrieval to demonstrate monoclonal LC by immunofluorescence. In five of 38 patients, crystals were not detectable by light microscopy, but they were visible by electron microscopy. Hematolymphoid neoplasms, known before biopsy in only 15% of patients, included 21 monoclonal gammopathies of renal significance; 15 multiple myelomas; seven smoldering multiple myelomas; and three other neoplasms. Biopsy indications included Fanconi syndrome (38%; all with crystalline LCPT), renal insufficiency (83%), and proteinuria (98%). Follow-up was available for 30 (75%) patients with crystalline LCPT and all six patients with noncrystalline LCPT, of whom 11 underwent stem cell transplant, 16 received chemotherapy only, and nine were untreated. Complete or very good partial hematologic remissions occurred in six of 22 treated crystalline LCPT patients. By multivariable analysis, the only independent predictor of final eGFR was initial eGFR, highlighting the importance of early detection. All patients with crystalline LCPT treated with stem cell transplant had stable or improved kidney function, indicating the effectiveness of aggressive therapy in selected patients.

Proximal Tubulopathy With Fibrillary Inclusions: A Rare Manifestation of Lymphoma-Associated Monoclonal Gammopathy of Renal Significance (MGRS)

“…The inclusions, composed of light chains in the proximal tubular cytoplasm with light chain proximal tubulopathy, are generally crystalline and most exhibit a rhombic shape, but other shapes have been reported. 2 A few reports have addressed light chain proximal tubulopathy with noncrystalline structures, but these have often been shown to be diffuse and patchy. 3 These structural differences are considered to be due to differences in protease reactivity or proteolytic enzymes found in the lysosome.…”

“…Early diagnosis of light chain proximal tubulopathy is important because those who have undergone chemotherapy have an improvement in kidney prognosis, and having a high estimated glomerular filtration rate before treatment is a positive factor for kidney prognosis. 2 However, in cases of kidney involvement with blood disorders, thrombocytopenia is often present, and kidney biopsy is generally not performed. However, it is also often the case that the treatment strategy is decided based on kidney pathologic findings, as in the present case, and thus open kidney biopsy should also be actively considered.…”

“…Light chain proximal tubulopathy was rarer (5%). 2 Light chain proximal tubulopathy occurs when inclusions composed of light chains accumulate in the proximal tubular cytoplasm. The light chains cause an indigestion in the lysosome, resulting in lysosome abnormalities or proximal tubular dysfunction.…”

Recurrent Light Chain Proximal Tubulopathy in a Kidney Allograft

“…1,2 It is part of a larger spectrum of lesions secondary to dysproteinemias known as immunoglobulin-related crystalline nephropathies. In the native kidney, light chain proximal tubulopathy accounts for approximately 0.5% to 5% of kidney diseases associated with paraproteinemia.…”

“…In the native kidney, light chain proximal tubulopathy accounts for approximately 0.5% to 5% of kidney diseases associated with paraproteinemia. 2,3 The prognosis of light chain proximal tubulopathy is difficult to predict and in part is likely related to the hematologic response of the dysproteinemia. Cases of light chain proximal tubulopathy are rare; there are only a few studies in native kidneys and even fewer of light chain proximal tubulopathy in the kidney transplant.…”