2 (ORPHA:97566)
Non-amyloid fibrillary glomerulopathy (non-amyloid FGP) is a rare cause of glomerulonephritis (GN) characterized by glomerular accumulation of non-amyloid fibrils in the mesangium and the glomerular (and rarely tubular) basement membrane, that mainly presents with renal insufficiency, micro-hematuria and nephrotic range proteinuria. Non-amyloid FGP and immunotactoid glomerulopathy (ITG, see this term) are often grouped together as pathogenetically related diseases.
Epidemiology
Non-amyloid FGP is encountered in approximately 0.5 to 1.0% of native kidney biopsies. A peak of occurrence between the fifth and sixth decades of life is observed. Females are slightly more affected than men, and the disease mainly affects the Caucasian population.
Clinical description
The disease is characterized by subnephrotic or nephrotic range proteinuria, frequently associated with macro- or microscopic hematuria, hypertension and renal insufficiency. Patients present with edema, ascites, pleural effusion and an elevated risk of blood clots and infection.
Etiology
Non-amyloid FGP etiology is unknown. The disease is generally considered idiopathic but it may be associated with secondary causes such as a monoclonal (mainly immunoglobulin G4; IgG4) or oligoclonal (containing both IgG1 and IgG4) gammopathy, hepatitis B and C infections, autoimmune diseases and malignancies.
Diagnostic methods
The diagnosis of non-amyloid FGP is based on the biopsy specimen's absence of reactivity with Congo red and other agents typically used for the histochemical demonstration of amyloid tissues (i.e. Thioflavin T), as well as observation on light, fluorescence and electron microscopy. Crescents may be present, sometimes associated with crescentic fibrillary GN (FGN). Common histological patterns include those of a membranoproliferative GN, mesangial proliferative GN, diffuse proliferative GN with endocapillary exudation, sclerosing GN or membranous thickening of the capillary tufts. At the ultrastructural level, glomerular structures are infiltrated by amorphous acellular material composed of randomly arranged, non-branching fibrils, around twice the size of amyloid fibrils, and with no apparent lumen. Fibrillary deposits usually consist of polyclonal IgG and complement component 3. Granular electron-dense deposits may also be present and admixed among the accumulations of fibrils. Other laboratory features may include low serum albumin and an increase in creatinine and blood cholesterol.
Differential diagnosis
Differential diagnosis includes amyloidosis, ITG (see these terms) and the immune deposits seen in lupus nephritis (lupus membranous GN).
Management and treatment
Different therapeutic strategies have been reported for the disease, but treatment options are still not defined. The treatment of nephrotic syndrome is based on prednisone, alone in patients with preserved renal function, or associated with cyclophosphamide in cases with crescentic FGN. Clinical trial data demonstrated the association of rituximab with a decrease of proteinuria and a possible role of rituximab in preventing or slowing the progression of renal disease in patients with preserved renal function has been hypothesized.
Prognosis
Despite treatment, non-amyloid FGP prognosis remains poor, with progression to end-stage renal failure occurring within a few months to a few years in about half of patients. Fibril deposition may recur in transplanted allografts but the recurrent disease has a relatively benign course.

                            Last update: 
                            March 2016


                            - Expert reviewer(s): 
                            Dr Laure Hélène NOEL