Pathological characteristics of light chain crystalline podocytopathy Journal Article
| Authors: | Nasr, S. H.; Kudose, S.; Javaugue, V.; Harel, S.; Said, S. M.; Pascal, V.; Stokes, M. B.; Vrana, J. A.; Dasari, S.; Theis, J. D.; Osuchukwu, G. A.; Sathick, I. J.; Das, A.; Kashkouli, A.; Suchin, E. J.; Liss, Y.; Suldan, Z.; Verine, J.; Arnulf, B.; Talbot, A.; Sethi, S.; Zaidan, M.; Goujon, J. M.; Valeri, A. M.; McPhail, E. D.; Sirac, C.; Leung, N.; Bridoux, F.; D'Agati, V. D. |
| Article Title: | Pathological characteristics of light chain crystalline podocytopathy |
| Abstract: | Monoclonal immunoglobulin light chain (LC) crystalline inclusions within podocytes are rare, poorly characterized entities. To provide more insight, we now present the first clinicopathologic series of LC crystalline podocytopathy (LCCP) encompassing 25 patients (68% male, median age 56 years). Most (80%) patients presented with proteinuria and chronic kidney disease, with nephrotic syndrome in 28%. Crystalline keratopathy and Fanconi syndrome were present in 22% and 10%, respectively. The hematologic condition was monoclonal gammopathy of renal significance (MGRS) in 55% and multiple myeloma in 45%. The serum monoclonal immunoglobulin was IgG κappa in 86%. Histologically, 60% exhibited focal segmental glomerulosclerosis (FSGS), often collapsing. Ultrastructurally, podocyte LC crystals were numerous with variable effacement of foot processes. Crystals were also present in proximal tubular cells as light chain proximal tubulopathy (LCPT) in 80% and in interstitial histiocytes in 36%. Significantly, frozen-section immunofluorescence failed to reveal the LC composition of crystals in 88%, requiring paraffin-immunofluorescence or immunohistochemistry, with identification of kappa LC in 87%. The LC variable region gene segment, determined by mass spectrometry of glomeruli or bone marrow plasma cell sequencing, was IGKV1-33 in four and IGKV3-20 in one. Among 21 patients who received anti-plasma cell-directed chemotherapy, 50% achieved a kidney response, which depended on a deep hematologic response. After a median follow-up of 36 months, 26% progressed to kidney failure and 17% died. The mean kidney failure-free survival was 57.6 months and was worse in those with FSGS. In sum, LCCP is rare, mostly associates with IgG κappa MGRS, and frequently has concurrent LCPT, although Fanconi syndrome is uncommon. Paraffin-immunofluorescence and electron microscopy are essential to prevent misdiagnosis as primary FSGS since kidney survival depends on early diagnosis and subsequent clone-directed therapy. © 2022 International Society of Nephrology |
| Keywords: | immunohistochemistry; adult; clinical article; controlled study; human tissue; treatment response; aged; middle aged; human cell; lenalidomide; clinical feature; histopathology; microscopy; follow up; mass spectrometry; electron microscopy; bortezomib; infection; multiple myeloma; peripheral neuropathy; cohort analysis; cyclophosphamide; dexamethasone; autologous stem cell transplantation; kidney failure; survival time; prednisolone; plasma cell; immunoglobulin variable region; bone marrow cell; histiocyte; molecular biology; blood clotting disorder; immunoglobulin kappa chain; immunoglobulin blood level; monoclonal immunoglobulinemia; frozen section; disease exacerbation; proteinuria; cyclosporine; chronic kidney failure; nephrotic syndrome; myeloma; clinical outcome; cell ultrastructure; fanconi renotubular syndrome; podocyte; paraprotein; glomerulus; human; male; female; article; focal segmental glomerulosclerosis; immunofluorescence assay; kidney tubule disorder; keratopathy; focal glomerulosclerosis; myeloma cast nephropathy; light chain crystals; monoclonal gammopathy of renal significance; podocytopathy; crystalline keratopathy; kidney interstitium cell; light chain crystalline podocytopathy; proximal tubule cell |
| Journal Title: | Kidney International |
| Volume: | 103 |
| Issue: | 3 |
| ISSN: | 0085-2538 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2023-03-01 |
| Start Page: | 616 |
| End Page: | 626 |
| Language: | English |
| DOI: | 10.1016/j.kint.2022.11.026 |
| PUBMED: | 36581019 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 March 2023 -- Source: Scopus |
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