Cryofibrinogen-Associated Glomerulonephritis.

ABSTRACT

Cryofibrinogen is an under-recognized cryoprotein. Cryofibrinogen is a cryoprecipitate that develops following plasma refrigeration, but does not occur in cold serum. People with cryofibrinogenemia may be asymptomatic, but this cryoprotein can be associated with thromboembolic disease, particularly affecting the skin. Kidney manifestations are relatively uncommon, but are likely underestimated. We describe clinical features and kidney biopsy results in 2 patients with cryofibrinogen-related kidney disease. Both patients presented with proteinuria and hematuria. One had significant cutaneous ulcers and palpable purpura. Kidney biopsy in both cases showed membranoproliferative glomerulonephritis with no immunoglobulin deposition. Weak segmental capillary wall fibrinogen staining was noted in glomeruli. Immunofluorescence studies following pronase digestion failed to reveal masked immunoglobulin deposits. Ultrastructural studies were distinctive and characterized by organized deposits of large-bore with multilayered tubular structures and fine fibrillary structures in a matrix. To confirm the composition of deposits, we extracted the cryoprecipitate from plasma of a patient and performed ultrastructural studies, which showed identical ultrastructural characteristics to those seen on the kidney biopsy. We also performed proteomic analysis of the cryoprecipitate that confirmed the presence of fibrinogen. Subsequent laboratory evaluation was positive for cryofibrinogen in both patients on multiple occasions. Appropriate therapy was instituted in both patients, which included prednisone, immunosuppressive therapy, and avoidance of cold exposure. In summary, we present clinical, kidney biopsy, and laboratory findings and the treatment and follow-up of cryofibrinogen-associated glomerulonephritis. Awareness of this entity will result in accurate diagnoses, appropriate investigation, and treatment.