Kidney Week

Abstract: TH-OR50

Immunotactoid Glomerulopathy: A Rare Entity with Monoclonal and Polyclonal Variants

Session Information

• Pathology of Kidney Diseases: Novel Mechanisms and Clinical Correlations
  October 22, 2020 | Location: Simulive
  Abstract Time: 05:00 PM - 07:00 PM

Category: Pathology and Lab Medicine

• 1602 Pathology and Lab Medicine: Clinical

Authors

• Nasr, Samih H., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Samih H. Nasr, MD



After graduating from Damascus University (Syria), Dr. Nasr completed his pathology residency and nephropathology fellowship at Columbia University, New York. He then served on the faculty at McGill University and Columbia University. He is currently a professor of laboratory medicine and pathology and a co-director of the Renal Biopsy Laboratory at Mayo Clinic, Rochester. He has published over 185 manuscripts, focusing on paraprotein-related kidney diseases and glomerular diseases with organized deposits.

• Kudose, Satoru, Columbia University Medical Center, New York, New York, United States

Satoru Kudose,

• Said, Samar M., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Samar M. Said,

• Santoriello, Dominick, Columbia University Medical Center, New York, New York, United States

Dominick Santoriello,

• Sethi, Sanjeev, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Sanjeev Sethi,

• Fidler, Mary E., Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Mary E. Fidler,

• Leung, Nelson, Mayo Foundation for Medical Education and Research, Rochester, Minnesota, United States

Nelson Leung,

• D'Agati, Vivette D., Columbia University Medical Center, New York, New York, United States

Vivette D. D'Agati,

• Markowitz, Glen S., Columbia University Medical Center, New York, New York, United States

Glen S. Markowitz,

Background

Immunotactoid glomerulopathy (ITG) is a rare disease currently classified as an MGRS lesion for which our understanding is limited.

Methods

73 patients with ITG were identified by retrospective review of all native renal biopsies received at two large renal pathology laboratories from 1993-2019.

Results

ITG biopsy incidence was 0.04%. Median age at diagnosis was 61 years, 86% were Caucasian, and there was no gender predilection. Patients presented with proteinuria (median 6.6 g/day, 58% with full nephrotic syndrome), hematuria (86%), and renal insufficiency (median creatinine 1.6 mg/dl). Hematologic disorders were present in 66%, including lymphoma in 41% (mainly CLL) and plasma cell dyscrasia in 26% (most commonly MGRS). 14% had underlying autoimmune disease and 33% had hypocomplementemia. Light microscopy revealed endocapillary proliferative (35%), membranoproliferative (29%) and membranous (29%) patterns. Immunohistochemical staining for DNAJB9 was negative on all cases tested. Electron microscopy showed microtubular deposits with diameter of 14-60 nm, hollow cores, frequent parallel alignment, and a predominant distribution outside of the lamina densa of the GBM. Immunofluorescence revealed IgG-dominant staining which was light chain restricted and IgG subclass restricted in 67% of cases (most commonly IgG-κ), indicating monoclonal composition. This finding was used to distinguish monoclonal ITG from polyclonal ITG. As compared to polyclonal ITG, monoclonal ITG had a higher incidence of lymphoma (53% vs. 11%), multiple myeloma (8% vs. 0), and MGRS (22% vs. 0). On follow up (median 47 months), 31% had complete remission, 11% partial remission, 35% persistent renal dysfunction, and 24% progressed to ESRD. The median survival (not reaching ESRD or death) was 123 months. Monoclonal ITG was more commonly treated with clone-directed therapy, which was associated with more frequent remission and less frequent ESRD compared to polyclonal ITG. ITG recurred within 10 months in 3 of 5 patients who received kidney transplants.

Conclusion

ITG is an extremely rare disease. Based on our observations, we propose that ITG should be subclassified as two overlapping but distinct entities – monoclonal ITG and polyclonal ITG. Prognosis is good if the underlying hematologic condition is treated.