Immunofluorescence Patterns in IgA Nephropathy and Their Significance
Safia N Salaria, Michelle M Estrella, Lois J Arend. Johns Hopkins University, Baltimore, MD
Background: Immunoglobulin A nephropathy (IgAN), caused by glomerular IgA immune deposits, is the most common form of primary glomerulonephritis in the world. Prevalence of IgAN among racial groups, initial presentation, as well as progression of disease is highly variable. Diagnosis of IgAN relies on a combination of clinical history, light and electron microscopy, and direct immunofluorescence (IF) for immunoglobulins (Ig) and complements (C). Renal biopsy specimens are traditionally stained for IgA, IgM, IgG, C3, and C1q. Dominant or co-dominant IgA is considered diagnostic of IgAN, however, biopsies show a variety of IF patterns. The presence or absence of other Igs as well as complements may contribute to the pathology of IgAN.
Design: We reviewed IF staining in patients receiving an initial diagnosis of IgAN. We recorded Oxford classification scores as a measure of disease burden at the time of biopsy. This data was compared to the patient's demographics such as race, age, and gender; in addition, clinical parameters at the time of presentation were analyzed, including GFR and serum creatinine. Statistical significance was determined using T-test and Fisher's exact test.
Results: We identified 103 unique patients with a diagnosis of IgAN between 01/01/2000-09/24/2011. The median age of the patients was 35 years (3-82 years), 53% of the patients were male, 74% white, 13% black, 7% asian, 3% Hispanic, and 3% classified as other. Median creatinine at the time of diagnosis was 1.3 mg/dl (range 0.3-10.9). Mean GFR was 71 ml/min. The presence of C3 deposition in the biopsy correlated significantly with a higher mean GFR at diagnosis (73.2 with C3 vs 28.7 without C3; p 0.03), while C1q in the biopsy correlated with a lower GFR (40.7 with C1q vs 75.0 without C1q; p 0.01). Deposition of C1q was seen in 12% of the biopsies. There was no significant correlation between IgG and/or IgM deposition and GFR at diagnosis, but a trend toward higher GFR was seen with the presence of IgG or IgM alone as well as in combination. Comparing histologic scoring categories with Ig and C revealed a significant correlation between the presence of endocapillary proliferation and IgM deposition; in 78 biopsies with IgM deposits, 34 (44%) showed endothelial cell proliferation (E), versus 3 of 23 (13%; p 0.007) without IgM deposits with positive E score.
Conclusions: In conclusion, the presence of C1q deposition appears to correlate with lower renal function at the time of diagnosis of IgAN. Significantly, the presence of IgM was associated with more frequent endocapillary proliferation, a major risk factor for progressive renal failure in IgAN.
Category: Kidney (does not include tumors)
Wednesday, March 21, 2012 1:00 PM
Poster Session VI # 289, Wednesday Afternoon