To better define their clinicopathologic features and outcome, we report the largest single center series of 67 cases biopsied from 1980 to 2001, including 61 FGN and 6 IT. FGN was defined by glomerular immune deposition of
Congo red-negative randomly oriented fibrils of < 30 nm (mean, 20.1 +/- 0.4 nm). IT was defined by glomerular deposition of hollow, stacked microtubules of > or = 30 nm (mean, 38.2 +/- 5.7 nm).
RESULTS: FGN comprised 0.6% of total native kidney biopsies and IT was tenfold more rare (0.06%). Deposits in FGN were
immunoglobulin G (
IgG) dominant and polyclonal in 96%.
IgG subtype analysis in 19 FGN cases showed monotypic deposits in four (two
IgG1 and two
IgG4) and oligotypic deposits in 15 (all combined
IgG1 and
IgG4). In IT, deposits were
IgG dominant in 83% and monoclonal in 67% (three
IgG1 kappa and one
IgG1 lambda). FGN patients were a mean age of 57 years, 92% were Caucasian, and 39% were male. At biopsy, FGN patients had the following clinical characteristics (mean, range):
creatinine 3.1 mg/dL (0.5 to 14),
proteinuria 6.5 g/day (0.8 to 25), 60% microhematuria, and 59%
hypertension. Histologic patterns of FGN were diverse, including diffuse proliferative
glomerulonephritis (DPGN) (nine cases),
membranoproliferative glomerulonephritis (MPGN) (27 cases), mesangial proliferative/sclerosing (MES) (13),
membranous glomerulonephritis (MGN) (four), and diffuse sclerosing (DS) (eight). The more proliferative (MPGN and DPGN) and sclerosing (DS) forms presented with a higher
creatinine and greater
proteinuria compared to MES and MGN. Median time to
end-stage renal disease (
ESRD) was 24.4 months for FGN and mean time to
ESRD varied by histologic subtype: DS 7 months, DPGN 20 months, MPGN 44 months, compared to MES 80 months and MGN 87 months. There was no statistically significant effect of immunosuppressive therapy (given to 36% of FGN patients). By Cox regression (hazard ratio, confidence interval, P value), independent predictors of progression to
ESRD were
creatinine at biopsy [2.05 (1.55 to 2.72) P < 0.001] and severity of interstitial
fibrosis [2.01 (1.05 to 3.85) P = 0.034]. Although IT had similar presentation, histologic patterns, and outcome compared to FGN, it had a greater association with
monoclonal gammopathy (P = 0.014), underlying lymphoproliferative disease (P = 0.020), and hypocomplementemia (P = 0.032).
CONCLUSION: FGN is an idiopathic condition characterized by polyclonal immune deposits with restricted gamma isotypes. Most patients present with significant
renal insufficiency and have a poor outcome despite immunosuppressive therapy, and outcome correlates with histologic subtype. By contrast, IT often contains monoclonal
IgG deposits and has a significant association with underlying dysproteinemia and hypocomplementemia. Differentiation of FGN from the much more rare entity IT appears justified on immunopathologic, ultrastructural, and clinical grounds.