Using immunostain for galactose-deficient IgA as a diagnostic tool

IgA nephropathy (IgAN) is common in medical kidney biopsy. The diagnosis of IgAN is usually straightforward with predominant glomerular mesangial staining with IgA along with clinical hematuria/acute nephritis. Problems arise when patients might have other causes for glomerular IgA deposition.

Cassol et al. investigated whether immunostaining for galactose-deficient IgA1 (GD-IgA1 or KM-55) can be used to differentiate between primary IgAN and others including secondary IgAN, infectious (staphylococcus)-related GN and incidental IgA deposition. They found GD-IgA1in all patients with IgAN and most patients in other category. Therefore GD-IgA1 immunostaining cannot reliably differentiate primary IgAN from other causes of dominant IgA glomerular deposition.

https://doi.org/10.1093/ndt/gfz152

Evaluation of the Oxford Classification of IgA Nephropathy: A Systematic Review and Meta-analysis

Oxford classification for IgA nephropathy was the result of rigorous methodology rather than relying purely on experts' opinion. Since its coming out in 2009 many validation studies followed. Lv et al. systematically reviewed and performed meta-analysis in 16 of
such studies with 3,896 patients included. Their findings confirmed the association of M (mesangial hypercellularity), S (segmental sclerosis) and T (tubular atrophy/interstitial fibrosis) with progression to renal failure. In addition, C (cellular/fibrocellular crescent) also had similar association (the Oxford did not include crescent in the classification/score. E (endocapillary proliferation) showed no association with renal failure but may indicate response to treatment by immunosuppressive agents.

IgA Nephropathy

IgA detected in glomerular mesangium by immunoflourescence

Wyatt and Julian had a review of IgA nephropathy (IgAN) in NEJM. The disease is now regarded as having autoimmune in origin. Abnormal immunoglobulin A molecule in the form of galactose-deficient IgA1 is the main etiology. The formation of immune complex between this molecule and anti-glycan antibody and deposition in the glomeruli are needed
for the pathogenesis. Then the immune complex activates mesangial cells in glomerulus to secrete more extracellular matrix and mediators such as angiotensin II responsible for glomerular injury.

Genetics play an important role in determining whether a person will have high level of galactose-deficient IgA1 and lack of protective genes. However, the high level of galactose-deficient IgA1 is not diagnostic of IgAN. Urine proteomics seems to have potential use as diagnostic tool in addition to renal biopsy.

The clinical outcome depends on amount of proteinuria, hypertension and pathologic findings. Oxford classification had been proven to have prognostic value, especially regarding tubular atrophy and interstitial fibrosis.

Currently there is no treatment targeting etiology of the disease. The principal treatment is ACE inhibitor or angiotensin II receptor blocker (ARB) to decrease blood pressure and proteinuria. Immunosuppressive drugs are reserved in patients with crescents in more than half of glomeruli in the biopsy and rapid deterioration in renal function.

Thrombotic microangiopathy in IgA nephropathy

Arteriosclerosis is a common finding in pathology of IgA nephropathy. Hypertension has been indicated as the cause of the arterial change. The chronic changes, ie. glomerulosclerosis, tubulointerstitial fibrosis, is implied as the cause of hypertension. However, prominent arteriosclerosis can be seen in biopsies with mild chronic changes.