Glomerulopathy with Fibrils: An Exceptional Case of Deceit

Introduction: Diagnosis of renal amyloidosis relies heavily on Congo red stain positivity and non-branching fibrils averaging 8-10 nanometers in diameter on electron microscopy. A disease that it can resemble histologically is Fibrillary glomerulonephritis (FGN) as deposits are also comprised of non-branching fibrils ranging from 10 to 20 nanometers in diameter and typically Congo red negative. Recently, immunostaining for DNAJB9 has emerged as a sensitive and specific marker for FGN. Hence, distinguishing these two conditions histologically is usually not difficult. Difficulty may arise in rarely described cases of congophilic FGN, or in heavy and light chains amyloid (AL and AH). Case Description: 68 year old Caucasian male with long-standing juvenile rheumatoid arthritis (RA), other comorbidities including joint deformities, requiring joint replacements complicated by multiple infections who presented with worsening unexplained proteinuria (4 g/g) and chronic kidney disease (CKD) stage 2/3. The first kidney biopsy was small with widespread glomerulosclerosis, obliterative microvascular disease, cortical scarring and fibrils measuring 15 nanometers in diameter, Congo red negative, DNAJB9 negative, and monoclonal staining with IgG kappa. This was presumed to be an unusual FGN. Treated with supportive care, his proteinuria and SCr were stable for over a year before patient presented again with acute kidney injury (AKI), SCr 2.31 mg/dL and 10g microalbuminuria. Repeat biopsy again showed similar findings, staining for IgG1 kappa, DNAJB9 not repeated, but this time faint Congo red positivity was noted, raising possibility of amyloid. Immunostain revealed strong positivity for Amyloid A, further confirmed by mass spectrometry. Patient eventually progressed to renal failure on dialysis. Discussion: Diagnostic difficulties in this case include: Fibril diameter overlapping with the fibril diameter of FGN; weak to absent Congo red positivity; Presence of monoclonal IgG1 kappa staining, in the absence of serum M-protein or hematologic malignancy. Teaching points are: Overlap in fibril diameter can be seen between amyloidosis and FGN along with weak Congo red staining; Aberrant monoclonal immunofluorescence staining patterns can be seen in Amyloid A; Mass spectrometry should be attempted in ambiguous cases, provided sufficient tissue is available.