Seronegative type 1 cryoglobulinaemic glomerulonephritis with crystalline light-chain proximal tubulopathy: a case report

Type 1 cryoglobulinaemia is the rarest form of cryoglobulinaemia and an uncommon cause of kidney injury. It may result in a membranoproliferative glomerulonephritis and/or a crystalline light chain proximal tubulopathy due to pathogenic immunoglobulin deposition. Diagnosis is often challenging and prognosis can be poor. We report a case of a 52-year-old male with smouldering myeloma who presented with a rapidly progressive glomerulonephritis and a subacute length-dependent peripheral neuropathy. Despite negative serum cryoglobulins, kidney biopsy confirmed type 1 cryoglobulinaemia demonstrating monoclonal IgG3 kappa-associated membranoproliferative glomerulonephritis with concurrent crystalline light chain proximal tubulopathy. Initial management consisted of empirical methylprednisolone, plasmapheresis and cyclophosphamide. Following confirmation of monoclonal subtype, treatment was transitioned to clone-directed resulting in significant renal recovery. This case underscores the importance of early recognition and histopathological diagnosis, even in the context of negative serum cryoglobulins, and highlights the value of immunoglobulin subtyping to guide targeted therapy to improve outcomes.