Clinicopathologic Characteristics of Crystalglobulin-Induced Nephropathy: A Case Series.

in American journal of kidney diseases : the official journal of the National Kidney Foundation by Samih H Nasr, Satoru Kudose, Anthony M Valeri, Ali Kashkouli, Samar M Said, Dominick Santoriello, Glen S Markowitz, Lihong Bu, Lynn D Cornell, Adel Samad, Jahangir Ahmed, Sanjeev Sethi, Nelson Leung, Vivette D D'Agati

TLDR

  • The study looked at a rare condition called crystalglobulin-induced nephropathy (CIN) in people with intravascular (extracellular) monoclonal immunoglobulin (MIg) crystals visible by light (LM) and electron microscopy (EM). The study found that prompt initiation of clone-directed therapy, coupled with corticosteroids and plasmapheresis, may lead to recovery of kidney function. The study also suggests that IF performed on paraffin embedded kidney tissue is more sensitive than frozen tissue for demonstrating the crystal composition. Future research should focus on larger sample sizes and the development of more sensitive and specific diagnostic tools for CIN.

Abstract

Crystalglobulinemia is a rare syndrome characterized by intravascular crystallization of monoclonal immunoglobulins (MIgs). Data on kidney involvement are limited to case reports. This series characterizes the clinicopathologic spectrum of crystalglobulin-induced nephropathy (CIN). Case series. Nineteen CIN cases were identified from the nephropathology archives of Mayo Clinic and Columbia University. CIN was defined by intravascular (extracellular) MIg crystals visible by light (LM) and electron microscopy (EM). Among the cases, 68% were male and 65% were Caucasian (median age 56 years). Most patients presented with severe AKI (median creatinine 3.5 mg/dL), hematuria, and mild proteinuria (median 1.1 g). Common extrarenal manifestations were constitutional (67%), cutaneous (56%), and rheumatologic (50%). Fifty percent of cases had hypocomplementemia. The hematologic disorders were monoclonal gammopathy of renal significance (MGRS) (72%), lymphoma (17%), or myeloma (11%), with 65% of these disorders discovered concomitantly with CIN. All patients had MIg identified on SPEP/SIF (IgGκ in 65%). The sFLC ratio was outside the renal range in 40%, and bone marrow biopsy detected the responsible clone in 67%. On LM, crystals involved glomeruli (100%) and vessels (47%), often with an inflammatory reaction (89%) and fibrin (58%). All cases exhibited crystal substructures (mostly paracrystalline) by EM. Immunofluorescence (IF) on paraffin embedded tissue was more sensitive than frozen tissue (92% versus 47%) for demonstrating the crystal composition (IgGκ in 63%). Follow up (median 20 months) was available in 16 patients. Eighty-one percent received steroids, 44% plasmapheresis, 38% hemodialysis, and 69% chemotherapy. Ninety-percent of patients who received clone-directed therapy achieved kidney recovery vs. 20% of those who did not (p=0.017). Retrospective design, small sample size. CIN is a rare cause of nephropathy associated with lymphoplasmacytic disorders (mostly MGRS) and typically presents with severe AKI and extrarenal manifestations. Diagnosis often requires IF performed on paraffin embedded kidney tissue. Prompt initiation of clone-directed therapy, coupled with corticosteroids and plasmapheresis, may lead to recovery of kidney function.

Overview

  • The study aims to characterize the clinicopathologic spectrum of crystalglobulin-induced nephropathy (CIN) in patients with intravascular (extracellular) monoclonal immunoglobulin (MIg) crystals visible by light (LM) and electron microscopy (EM).
  • The study includes 19 cases of CIN identified from the nephropathology archives of Mayo Clinic and Columbia University. CIN was defined by intravascular MIg crystals visible by LM and EM. The study includes data on patient demographics, clinical presentation, extrarenal manifestations, hematologic disorders, and treatment outcomes.

Comparative Analysis & Findings

  • The study found that 68% of the cases were male and 65% were Caucasian, with a median age of 56 years. Most patients presented with severe AKI (median creatinine 3.5 mg/dL), hematuria, and mild proteinuria (median 1.1 g). Common extrarenal manifestations were constitutional (67%), cutaneous (56%), and rheumatologic (50%). Fifty percent of cases had hypocomplementemia. The hematologic disorders were monoclonal gammopathy of renal significance (MGRS) (72%), lymphoma (17%), or myeloma (11%), with 65% of these disorders discovered concomitantly with CIN. All patients had MIg identified on SPEP/SIF (IgGκ in 65%). The sFLC ratio was outside the renal range in 40%, and bone marrow biopsy detected the responsible clone in 67%. On LM, crystals involved glomeruli (100%) and vessels (47%), often with an inflammatory reaction (89%) and fibrin (58%). All cases exhibited crystal substructures (mostly paracrystalline) by EM. Immunofluorescence (IF) on paraffin embedded tissue was more sensitive than frozen tissue (92% versus 47%) for demonstrating the crystal composition (IgGκ in 63%). Follow-up (median 20 months) was available in 16 patients. Eighty-one percent received steroids, 44% plasmapheresis, 38% hemodialysis, and 69% chemotherapy. Ninety-percent of patients who received clone-directed therapy achieved kidney recovery vs. 20% of those who did not (p=0.017).

Implications and Future Directions

  • The study highlights the importance of prompt initiation of clone-directed therapy, coupled with corticosteroids and plasmapheresis, in the treatment of CIN. The study also suggests that IF performed on paraffin embedded kidney tissue is more sensitive than frozen tissue for demonstrating the crystal composition. Future research should focus on larger sample sizes and the development of more sensitive and specific diagnostic tools for CIN.
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