IgA nephropathy diagnostic study of choice
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IgA nephropathy has a heterogeneous unpredictable clinical course. However, nephritic syndrome with gross hematuria in a young male patient is the most common clinical presentation for IgA nephropathy. Classically, it follows an upper respiratory or gastrointestinal tract infection. The diagnosis of IgA nephropathy is not always obvious clinically; where only 30-40% of patients have such typical presentation. In comparison, another 30-40% of patients with IgA nephropathy remain asymptomatic and are only found to have microscopic hematuria.
Unlike poststreptococcal glomerulonephritis (PSGN), which is also a glomerular disease with similar clinical presentation, IgA nephropathy is called “synpharyngitic” because it typically becomes clinically evident within 2-3 days during the infectious episode vs. PSGN which becomes clinically evident a few weeks after a streptococcal infection.
Adult patients with IgA nephropathy have a less obvious course of disease. The most common presentation of IgA nephropathy among patients of older age groups is microscopic hematuria, proteinuria, and hypertension that might or might not be symptomatic. The presence and intensity of these signs and symptoms vary and may be present in isolation or in combination.
Only 10% of patients with IgA nephropathy present with nephrotic syndrome; usually these patients have pathological findings of minimal-change disease on biopsy. Finally, only 10% of the patients with IgA nephropathy present with renal failure at diagnosis.
Immunofluorescence microscopy is required for the diagnosis of IgA nephropathy. IgA nephropathy histopathological findings may vary among individuals and with disease progression. The histopathological hallmark of IgA nephropathy is the predominant presence of mesangial stains for IgA in comparison to the much less intense stains for IgG or C3. IgA1 deposits may be present anywhere along the mesangium, and even in the glomerular capillary wall.
IgA nephropathy may have any of the following 6 findings on light microscopy (in increasing order of severity):
- Normal appearing biopsy
- Focal mesangial hypercellularity
- Diffuse mesangial hypercellularity
- Focal proliferative glomerulonephritis (most common finding on diagnostic biopsy)
- Diffuse proliferative glomerulonephritis
- Chronic sclerosing glomerulonephritis
On electron microscopy, mesangial deposits are most commonly seen. However, depositions on capillary walls are possible; they herald worse prognosis.
The following variations may also be found; but they are not exclusive of IgA nephropathy:
- Segmental endocapillary proliferation
- Segmental Glomerulosclerosis and adhesions
- Tubular atrophy and interstitial fibrosis
- Glomerular crescent surrounding the glomerular tuft
Serum Galactose-Deficient IgA1 Levels
Although IgA1 levels are almost always elevated in patients with IgA nephropathy and seem to be a promising technique for diagnostic purposes, the sensitivity and specificity for lectin-based assays to determine galactose-deficient IgA1 levels are not yet sufficiently evaluated.
According to Moldoveanu et al., the sensitivity of serum IgA1 levels is 76.5% and the specificity is 94%, with an 88.6% positive predictive value and a 78.9% negative predictive value for the diagnosis of IgA nephropathy. They studied 153 patients in total and determined the upper normal limit to be 1076 U/ml for diagnosis. Of note, however, the study utilized a 90th percentile for statistical significance. Ultimately, renal biopsy is still considered the only diagnostic approach for IgA nephropathy.
Urinary Proteomic Analysis
Urinary proteomic analysis of samples using capillary electrophoresis coupled with mass spectrometry (CE-MS) allows to accurately evaluate up to urinary 2000 polypeptides using “total protein/peptide” different unique patterns, each corresponding to different pathology. CE-MS has been studied to provide a fast and accurate diagnosis of IgA nephropathy by utilizing specific polypeptide patterns in urinary samples of patients with IgA nephropathy.
When compared to urinary samples of 57 healthy subjects and 57 patients with membranous nephropathy, CE-MS showed a sensitivity of 100% and 77%, respectively, and a specificity of 90% and 100%, respectively. Urinary proteomic analysis may be a promising novel technique, but it requires further evaluation before it replaces a kidney biopsy for the diagnosis of IgA nephropathy.
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