There are a variety of causes of end stage renal disease (ESRD) in teenagers and adults. Immunoglobulin-A (IgA) nephropathy could be a cause of end stage renal disease (ESRD) in around 25% of cases. There are five types of immunoglobulins in our body for protection against microorganisms and IgA provides defence at mucous membranes. Colostrum and breast milk are rich sources of IgA and protect us during infancy through breast-feeding. However, later in life, chronic mucosal inflammation (inflammation of respiratory, oral, or gastrointestinal mucous membranes) may lead to IgA-nephropathy (IgAN). Viral (including HIV), bacterial, yeast and parasitic infections have been found to be associated with IgAN. Environmental and food antigens have also been implicated in IgAN as these may mimic molecular structure of microbial antigens and lead to excessive IgA production, aggregation and breakdown of mucosal barrier. Patients affected by IgAN may present with hematuria (blood in urine) and/or proteinuria (protein in urine) with or without rise in serum creatinine. The most common initial symptom in children is microscopic hematuria. Some adults may present with acute or chronic renal failure.
IgA nephropathy is a common nephropathy, which could be detected on renal (kidney) biopsy evaluation through light and fluorescence microscopy. However, electron microscopic study of renal biopsy acts as a diagnostic adjunct as the location of immune complexes in the renal glomerulus could be pronounced on electron micrographs. Figures 1 and 2 are the electron micrographs from a proven case of IgAN, illustrating mesangial deposits of IgA.
Figure-1: Electron micrograph of an area of glomerulus of a case of IgAN showing electron dense deposits (D) in the mesangial (Mes) area. Glomerular basement membrane (GBM), capillary lumen (CL), podocyte or epithelial cell (EpC) and urinary space (US) are also exhibited; Original Magnification 4600x.
Figure-2: Electron micrograph of an area of glomerulus of a case of IgAN showing electron dense deposits (D) in the mesangial (Mes) area. Glomerular basement membrane (GBM), capillary lumen (CL), podocyte or epithelial cell (EpC) and urinary space (US) are also exhibited; Original Magnification 6000x.
The pathology of IgAN may be variable depending on underlying cause. Mesangioproliferative glomerulonephritis is the most common pattern in many renal biopsies; however, glomeruli may appear normal on light microscopy in some of the cases. Renal biopsies in a few cases may also show crescent formation in occasional glomeruli. Diagnosis of IgA nephropathy is established by direct immunofluorescence technique on renal biopsies and the pattern may be dominant or co-dominant for IgA staining. The incidence of ESRD has been found to be high in patients presenting with >1g/day proteinuria with increased level of serum creatinine as compared to those having proteinuria <1g/day with increased level of serum creatinine. Pathogenesis of IgAN is very complex. A variety of underlying diseases including hepato-biliary disease can be associated with IgA nephropathy. Defective detection and clearance by liver of polymeric immune complexes of IgA (IgA1) due to abnormal galactosylation of O-linked glycans is probably the major cause of IgAN in addition to loss of mucosal barrier and chronic mucosal inflammation. Recurrent tonsillitis may also lead to IgA nephropathy and tonsillectomy may be helpful in these cases to remove the mucosal foci of infection. Optimal treatment of tonsillitis and other oromucosal infections with antibiotics along with conventional treatment of IgAN would be helpful to put brakes on the progression of IgA nephropathy. Patients with acute or chronic renal failure due to advanced stage of IgAN may need hemodialysis or renal transplantation. Use of anti-oxidants and fish oil as food supplements in some cases of IgA nephropathy have been found beneficial.
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