What is your diagnosis?

MPGN 1

Amyloidosis

Fibronectin glomerulopathy

Fibrillary glomerulonephritis

Dense deposit disease

Fibrillary glomerulonephritis (FGN) is a rare idiopathic disease characterized by the presence of randomly fibrillar glomerular deposits measuring10-20 nm in thickness(1). The deposits are usually composed of polyclonal IgG (i.e. with both kappa and lambda light chains), and C3(2), and patients generally lack evidence of dysproteinemia or other systemic disease(3-5). By contrast, immunotactoid glomerulopathy demonstrates larger (20-60 nm in diameter) microtubular deposits which have a central lumen, are often arranged in parallel bundles or stacks, are usually composed of monoclonal Ig, and are frequently associated with B cell neoplasia. Despite some clinical and pathologic overlap, most authors consider FGN and immunotactoid glomerulopathy to be distinct clinical-pathologic entities(3-5). As distinct from amyloidosis, the fibrillar deposits in FGN and immunotactoid glomerulopathy are Congo Red negative and are usually confined to the kidney, although rare cases associated with pulmonary(6, 7) or hepatic(8) deposits have been described.

FGN usually presents in the 6th decade and more commonly affects women and Caucasians(3, 5). Patients present with heavy proteinuria, often with the nephrotic syndrome. Renal insufficiency, hematuria, and hypertension are present in 50%, 70%, and 65% of patients, respectively. A positive SPEP or UPEP is present in only a minority of cases (15%)(5). Small numbers of patients have evidence of other immunologic or inflammatory disease, including vasculitis, lymphoproliferative disease, myeloproliferative disease, HCV infection, hepatitis, thyroiditis, rheumatoid arthritis, temporal arteritis, gout and bronchiectasis(5). The clinical course is variable but there is a high rate of progression to end-stage renal disease (50% within two years)(3, 5), despite the use of a variety of therapeutic strategies, including steroids, cytotoxic agents, and cyclosporine. No evidence-based recommendations for treatment are available, reflecting the rarity of this condition (0.6% of native kidney biopsy diagnoses at our center(5)). Recurrence in the renal allograft has been reported, providing evidence for a systemic pathogenetic factor(s), rather than a primary glomerular defect(9). 

Renal biopsy reveals a variety of patterns of glomerular injury associated with FGN. The most common is a membranoproliferative (“MPGN”) pattern of injury, as seen in the present case, where fibrillar deposits are present in the mesangium and peripheral capillary walls, with duplication of glomerular basement membranes and variable cellular interposition. Other patterns include predominantly mesangial deposition, membranous pattern (i.e. with subepithelial peripheral capillary wall deposits and basement membrane spike formation), diffuse endocapillary proliferative pattern, and diffuse global glomerulosclerosis(5). Crescents are seen most commonly with the diffuse endocapillary proliferative pattern (mean 25% of glomeruli)(5). The diffuse sclerosis, diffuse proliferative and “MPGN” patterns show more rapid progression to ESRD compared to mesangial and membranous patterns. By multivariate analysis, only serum creatinine at presentation and degree of interstitial fibrosis predicted worse outcomes.

The pathogenesis of FGN is unknown. The fibrils contain Ig and C3, suggesting polymerization of immune complexes. However, the putative antigen for these immune complexes is unknown. As noted above, some FGN patients have evidence of chronic immunologic or inflammatory disease which may be driving immune complex formation. One case report identified fibrillar deposits containing polyclonal Ig and C3 in the serum precipitate of a FGN patient, following storage of the serum at 4 degrees for several months(2). The authors proposed that a slow-forming cryoglobulin might be the underlying pathomechanism in their case of FGN. Others have noted an association between FGN and HCV infection(10), suggesting a possible overlap with cryoglobulinemic glomerulonephritis in some cases.   
       
References:

1.    Alpers CE, Rennke HG, Hopper J, Jr., Biava CG. Fibrillary glomerulonephritis: an entity with unusual immunofluorescence features. Kidney Int 1987; 31: 781-789.

2.    Yang GC, Nieto R, Stachura I, Gallo GR. Ultrastructural immunohistochemical localization of polyclonal IgG, C3, and amyloid P component on the congo red-negative amyloid-like fibrils of fibrillary glomerulopathy. Am J Pathol 1992; 141: 409-419.

3.    Fogo A, Qureshi N, Horn RG. Morphologic and clinical features of fibrillary glomerulonephritis versus immunotactoid glomerulopathy. Am J Kidney Dis 1993; 22: 367-377.

4.    Iskandar SS, Falk RJ, Jennette JC. Clinical and pathologic features of fibrillary glomerulonephritis. Kidney Int 1992; 42: 1401-1407.

5.    Rosenstock JL, Markowitz GS, Valeri AM, Sacchi G, et al. Fibrillary and immunotactoid glomerulonephritis: Distinct entities with different clinical and pathologic features. Kidney Int 2003; 63: 1450-1461.

6.    Calls Ginesta J, Torras A, Ricart MJ, Ramirez J, et al. Fibrillary glomerulonephritis and pulmonary hemorrhage in a patient with renal transplantation. Clin Nephrol 1995; 43: 180-183.

7.    Masson RG, Rennke HG, Gottlieb MN. Pulmonary hemorrhage in a patient with fibrillary glomerulonephritis. N Engl J Med 1992; 326: 36-39.

8.    Ozawa K, Yamabe H, Fukushi K, Osawa H, et al. Case report of amyloidosis-like glomerulopathy with hepatic involvement. Nephron 1991; 58: 347-350.

9.    Samaniego M, Nadasdy GM, Laszik Z, Nadasdy T. Outcome of renal transplantation in fibrillary glomerulonephritis. Clin Nephrol 2001; 55: 159-166.

10.    Markowitz GS, Cheng JT, Colvin RB, Trebbin WM, et al. Hepatitis C viral infection is associated with fibrillary glomerulonephritis and immunotactoid glomerulopathy. J Am Soc Nephrol 1998; 9: 2244-2252.