Immuotactoid glomerulopathy (fibrillary glomerulonephritis).

I mmunotactoid glomerulopathy first was described in 1977, when Rosenmann and Eliakim (1) reported an unusual glomerular lesion in a 45-yr-old woman who presented with the nephrotic syndrome and renal insufficiency. The electron microscopy was remarkable for organized electron-dense deposits in the form of randomly arranged fibrils that measured 10 nM in diameter. The deposits were associated with mesangial expansion and immune deposits of IgG, IgM, and C3 in a mesangial pattern. Congo red stain of the deposits was negative, and there was no clinical or serologic evidence of a systemic disease. They interpreted the deposits to be “amyloid-like” and speculated that they might represent a “preamyloid” state. In 1980, Schwartz and Lewis (2) reported a case of a 49-yr-old man who presented with the nephrotic syndrome and no evidence of systemic disease and had a similar renal lesion: Immune aggregates were associated with highly organized electron-dense deposits that were composed of microtubules that were arranged in parallel bundles. During 7 yr of follow-up, the patient progressed to renal failure but never demonstrated any clinical or serologic evidence of a systemic disease. To distinguish this lesion from other disorders that have glomerular immune deposits associated with highly organized microtubular or fibrillary structures, such as amyloidosis, cryoglobulinemia, paraproteinemias, and systemic lupus erythematosus (SLE), the term immunotactoid glomerulopathy (ITG) was coined, reflecting the composition (immuno-) and polymeric morphology (tactoid) of the glomerular deposits. In the past 25 yr, 200 cases of ITG have been reported (3–5). Various synonyms have been used to refer to the lesion that is described in these reports, including fibrillary glomerulonephritis (FGN), nonamyloidotic fibrillary glomerulopathy, amyloid-like glomerulopathy, and amyloid stain–negative microfibrillary glomerulopathy, but we believe that they all represent the same or a similar disease process (6–8). The unifying feature in all of the cases is the finding of highly organized ultrastructural deposits that seem to be composed of Ig and complement and are negative for amyloid by Congo red stain. Although there is increasing recognition of this lesion, ITG still is an uncommon glomerulopathy that accounts for 4% of renal biopsies that are done for the evaluation of nephrotic syndrome (3,4,6,9–12). The clinical diagnosis of ITG is based on a combination of pathologic, serologic, and clinical features and is applied only after the exclusion of diseases that are known to be associated with organized glomerular immune deposits, including amyloidosis, cryoglobulinemia, paraproteinemias, and SLE. Along with ITG, these disorders compose the family of histopathologic lesions that are referred to as the fibrillary glomerulopathies (Figure 1). The disorders that are included in this classification are defined histochemically. In this schema, ITG represents one of the nonamyloid, Ig-mediated fibrillary glomerulopathies of which there is a differential diagnosis with diseases, which must be excluded before the diagnosis of ITG is made. Many of the diseases that are associated with the fibrillary glomerulopathies have specific therapies and prognoses that differ significantly from that of ITG. As a result, it is critical that the clinician use a combined histologic, clinical, and serologic approach in reaching the correct diagnosis.