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Abstract: SA-PO159

Clinicopathologic and Molecular Characteristics of Light Chain Crystalline Podocytopathy

Session Information

Category: Onconephrology

  • 1600 Onconephrology

Authors

  • Nasr, Samih H., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Kudose, Satoru, Columbia University, New York, New York, United States
  • Javaugue, Vincent, Universite de Poitiers, Poitiers, Nouvelle-Aquitaine, France
  • Said, Samar M., Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Harel, Stéphanie, Saint-Louis Hospital, Paris, France
  • Osuchukwu, George A., Victoria Kidney and Dialysis Associates, Victoria, Texas, United States
  • Das, Arjun, Nephrology Consultants of Northwest Ohio, Toledo, Ohio, United States
  • Suchin, Elliot J., Center for Kidney Care, Hainesport, New Jersey, United States
  • Leung, Nelson, Mayo Clinic Minnesota, Rochester, Minnesota, United States
  • Bridoux, Frank, Universite de Poitiers, Poitiers, Nouvelle-Aquitaine, France
  • D'Agati, Vivette D., Columbia University, New York, New York, United States
Background

Monoclonal immunoglobulin (MIg) light chain (LC) crystalline inclusions within podocytes is a rare finding usually seen in association with LC proximal tubulopathy (LCPT).

Methods

We describe the first clinicopathologic and molecular series on LC crystalline podocytopathy (LCCP) defined by the presence of extensive podocyte LC crystals.

Results

This multicenter cohort included 24 patients (63% male, 75% Caucasian, median age 57 yrs). Presentations included proteinuria (median 3.4 g/day, 56% albuminuria), CKD (median creatinine 2.1 mg/dl), hypertension (54%), nephrotic syndrome (29%), Fanconi syndrome (14%) and visual impairment from crystalline keratopathy (17%). The underlying hematologic condition was MGRS in 81% and symptomatic MM in 19%. The serum MIg was IgGκ in 86%, with urinary MIg detected in 94%, and abnormal serum FLC in all 19 tested (median ratio 12.6). Podocyte crystals were visible by light microscopy in 71%, with FSGS in 63% (including collapsing in 9 cases, NOS in 5 and tip in 1). All 20 cases studied by electron microscopy (EM) exhibited extensive podocyte crystals and 45% had diffuse effacement. Crystals were also present in proximal tubular cells (75%, indicating concurrent LCPT), distal tubular cells (33%), interstitial histiocytes (33%; crystal storing histiocytosis), endothelial cells (17%), mesangial cells (17%) and plasma cells (4%). Concurrent mild LC cast nephropathy was present in 7 cases, AL amyloidosis in 1, and LCDD in 1. While frozen-immunofluorescence (IF) failed to reveal the LC composition of crystals in 22 (91%) cases, this was successfully identified using paraffin-IF (14/20) or immunoEM (3/3) and was κ LC in 87%. The pathogenic LC variable gene segment determined by laser microdissection of glomeruli followed by mass spectrometry (n=3) or bone marrow plasma cell sequencing (n=2) was IGKV1-33 in 3 cases, IGKV1-39 in 1 and IGKV3-20 in 1. On follow up (median 30 months) in 23 patients, 19 received plasma-cell directed therapy. Outcomes were renal response in 40%, ESKD in 22% and death in 22%.

Conclusion

LCCP is a rare entity, mostly associated with IgGκ MGRS. Despite frequently concurrent LCPT and associations with IGKV1-33 & IGKV1-39, Fanconi syndrome is rare. Paraffin-IF and EM are needed to prevent misdiagnosis as FSGS.