Bergers Disease: IgA Nephropathy

Bergers Disease: IgA Nephropathy Sarah A. Poorman IgA nephropathy, or Bergers disease, is one of the most prevalent, primary, and chronic glomerular disease and an imperative cause of renal failure (Mayo Clinic, 2017). IgAN is one of the most common renal diseases present in todays world. It can occur at any age, perceiving first evidence of renal disease when people are in their teens to late 30s (Wyatt and Julian, 2013). It is twice more likely to appear in men than women, being the most common amongst Asian and Caucasian populations (Wyatt and Julian, 2013). Early stages of Bergers Disease may not have symptoms. It can be silent for years, sometimes even decades before a single symptom shows. The most common symptom witnessed is hematuria, or bloody urine (NIDDK, 2015). This is a definite sign of a damaged glomeruli. Usually, the tint of urine will become a hue of pink or resemble the color of tea or cola (National Kidney Foundation, 2016). Another common symptom to arise is albuminuria. This is when urine contains an overabundance or albumin. Albumin is a protein, typically found in the blood, which maintains fluid balance throughout the human body (Nephcure, 2016). Blood loses its capacity to absorb fluid from the body once albumin leaks into the urine. Due to the lost blood supply, low blood albumin levels will occur. Too much fluid will let to edema, or swelling, of various body parts. The most common body parts to experience edema are the legs, feet, and ankles, leaving the face and hands to be the least commonly affected (NIDDK, 2015). Foamy urine is a signal of albuminuria. The least common symptoms associated with IgAN are high blood pressure and high cholesterol levels (NIDDK, 2015). Glomerulus is a system of capillaries situated at the beginning of a nephron in the kidney (Wyatt and Julian, 2013). Its focal objective is to assist as the first phase of the filtration process of the blood, which is carried out by the nephron in the creation of urine (Mayo Clinic, 2017). IgA nephropathy, or IgAN, is considered an autoimmune disease that affects the glomeruli of the kidneys. Glomeruli are tiny filtering units where the blood is cleared. As the IgA deposits build up in the glomeruli, it causes the kidneys to leak blood and protein into the urine. Human IgA antibodies have two subclasses, IgA1 and IgA2, while IgA1 constitutes 85% of the total IgA in the circulation, starting in the bone marrow (Wyatt and Julian, 2013). Predominantly, these deposits consist of IgA, but they can also exhibit IgG and IgM antibodies by themselves or combined. As the IgA deposits build up in the glomeruli, it causes the kidneys to leak blood and protein into the urine. IgA in the glomerular deposits are exclusively of the IgA1 subclass and are in the polymeric form (Wyatt and Julian, 2013). IgA1 exhibits galactose deficiency in the O-linked glycans in the hinge region of the heavy chain (Suzuki et al, 2011). Going all the way back to basic chemistry, galactose, or Gal, is a monosaccharide sugar that is composed of the same element as glucose, but has a different arrangement of atoms (Maillard et al, 2015). The Fc receptor will blind the GD-IgA1 to create immune complexes that leads to the complement activation. The transcription of IgG and IgM trigger the pathways of complement activation, containing immune complexes (Maillard et al, 2015). Eventually, over time, the massive discharge of ctyokines, components of the ext racellular matrix, and oxidants that disrupt the function of the glomerular basement membrane will induce apoptosis (the product of TGF-B and IL-6) and glomerular scarring (Maillard et al, 2015). This creates the destruction of the kidneys which leads to the major development of end-stage renal disease. To put it simply, T cell-dependent activation of B Cells is initiated by APCs, which processes the antigen, and creates peptides to present, in MHC 11, to CD4+ T cells. This results in the production of T Helper cells. With the interaction of B and T cells, the expression of CD40L, a protein apart of the TNF (tumor necrosis factor) family, begins. Isotype switching of naà ¯ve B cells towards IgA1 and IgA2 producing plasma cells takes place. The B cells carry the antigens to the surface of the cell by Ig expression. They present this to MHC II, which aids in the recruitment of T cells. With the expression of CD40L and cytokines and signals from APCs will begin the regulation of production for IgA the IgA immunoglobulin will typically bind oneself to an antigen or infection found in the body. This will result in the activation of an immune response, which will find a way to rid the body of the infection. People with IgAN have an augmented blood result of IgA that signifies less galactose than what is considered normal. This galactose-deficient IgA, or GD-IgA1, in the blood, is recognized as foreign by the other antibodies circulating the blood. But, when an individual has IgAN, a flawed arrangement of IgA antibodies attach their selves to another IgA antibody, as an alternative of an infection or antigen, resulting in the creation of immune complexes. These immune complexes turn out to be jammed in the kidneys glomeruli, causing damage to the filters. Inflammation takes place, which causes blood and proteins to leak out of the kidneys and into the urine. Eventually, this will lead to end-stage renal disease (ESRD) and total kidney failure, resulting in death or the dire need of a kidney transplantation. Currently, there is no known cure for IgA nephropathy, with no ultimate way of knowing what path the ailment will take. Once the kidneys are scarred, they cannot be repaired. Therefore, the vital goal of IgA nephropathy treatment is to inhibit or delay the inevitable, end-stage renal disease. Some people experience complete remission and others live normal lives with low-grade blood or protein in their urine. Treatment with numerous of medications can slow the progress of the disease and help manage symptoms such as high blood pressure, protein in the urine, and swelling. Some of the medications that are currently being used to treat IgAN are as follows: 1) Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) which lowers blood pressure and reduces the amount of albumin in the urine. 2) Omega 3 Fatty acids, which aid in the reduction of inflammation throughout the body, in this case the glomeruli, leaving no harmful side effects. 3) Immunosuppressants such as corticosteroids medication (prednisone) will suppress the immune system response, allowing to protect kidney function. However, these can cause serious side effects such as high blood pressure and high blood sugar. 4) Statin therapy are cholesterol lowering medications that are known to help slow the damage to the kidneys. 5) Mycophenolate mofetil, or CellCept, has been successfully used in some pati ents who have had persistent protein in the urine, however, most studies so far have failed to show the benefit for using this medication. There are no sources in the current document.   Ã‚