Pathological characteristics of light chain crystalline podocytopathy

Samih H. Nasr, Satoru Kudose, Vincent Javaugue, Stéphanie Harel, Samar M. Said, Virginie Pascal, M. Barry Stokes, Julie A. Vrana, Surendra Dasari, Jason D. Theis, George A. Osuchukwu, Insara Jaffer Sathick, Arjun Das, Ali Kashkouli, Elliot J. Suchin, Yaakov Liss, Zalman Suldan, Jerome Verine, Bertrand Arnulf, Alexis TalbotSanjeev Sethi, Mohamad Zaidan, Jean Michel Goujon, Anthony M. Valeri, Ellen D. Mcphail, Christophe Sirac, Nelson Leung, Frank Bridoux, Vivette D. D'Agati

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)616-626
Number of pages11
JournalKidney international
Issue number3
StatePublished - Mar 2023


  • focal segmental glomerulosclerosis
  • light chain crystals
  • monoclonal gammopathy of renal significance
  • myeloma
  • podocytopathy

ASJC Scopus subject areas

  • Nephrology


Dive into the research topics of 'Pathological characteristics of light chain crystalline podocytopathy'. Together they form a unique fingerprint.

Cite this