Glomerular Diseases

Many diseases affect kidney function by attacking the glomeruli, the tiny units within the kidney where blood is cleaned. Glomerular diseases include many conditions with a variety of genetic and environmental causes, but they fall into two major categories: * Glomerulonephritis (gloh-MEHR-yoo-loh-nef-RY-tis) describes the inflammation of the membrane tissue in the kidney that serves as a filter, separating wastes and extra fluid from the blood. * Glomerulosclerosis (gloh-MEHR-yoo-loh-skleh-ROH-sis) describes the scarring or hardening of the tiny blood vessels within the kidney. Although glomerulonephritis and glomerulosclerosis have different causes, they can both lead to kidney failure. The two kidneys are bean-shaped organs located near the middle of the back, just below the rib cage to the left and right of the spine. Each about the size of a fist, these organs act as sophisticated filters for the body. They process about 200 quarts of blood a day to sift out about 2 quarts of waste products and extra water that eventually leave the body as urine. Blood enters the kidneys through arteries that branch inside the kidneys into tiny clusters of looping blood vessels. Each cluster is called a glomerulus, which comes from the Greek word meaning filter. The plural form of the word is glomeruli. There are approximately 1 million glomeruli, or filters, in each kidney. The glomerulus is attached to the opening of a small fluid-collecting tube called a tubule. Blood is filtered in the glomerulus, and extra water and wastes pass into the tubule and become urine. Eventually, the urine drains from the kidneys into the bladder through larger tubes called ureters. Each glomerulus-and-tubule unit is called a nephron. Each kidney is composed of about 1 million nephrons. In healthy nephrons, the glomerular membrane that separates the blood vessel from the tubule allows waste products and extra water to pass into the tubule while keeping blood cells and protein in the bloodstream. Glomerular diseases damage the glomeruli, letting protein and sometimes red blood cells leak into the urine. Sometimes a glomerular disease also interferes with the clearance of waste products by the kidney, so they begin to build up in the blood. Furthermore, loss of blood proteins like albumin in the urine can result in a fall in their level in the bloodstream. In normal blood, albumin acts like a sponge, drawing extra fluid from the body into the bloodstream, where it remains until the kidneys remove it. But when albumin leaks into the urine, the blood loses its capacity to absorb extra fluid from the body. Fluid can accumulate outside the circulatory system in the face, hands, feet, or ankles and cause swelling. The signs and symptoms of glomerular disease include * proteinuria: large amounts of protein in the urine * hematuria: blood in the urine * reduced glomerular filtration rate: inefficient filtering of wastes from the blood * hypoproteinemia: low blood protein * edema: swelling in parts of the body One or more of these symptoms can be the first sign of kidney disease. But how would you know, for example, whether you have proteinuria? Before seeing a doctor, you may not. But some of these symptoms have signs, or visible manifestations: * Proteinuria may cause foamy urine. * Blood may cause the urine to be pink or cola-colored. * Edema may be obvious in hands and ankles, especially at the end of the day, or around the eyes when awakening in the morning, for example. Patients with glomerular disease have significant amounts of protein in the urine, which may be referred to as “nephrotic range” if levels are very high. Red blood cells in the urine are a frequent finding as well, particularly in some forms of glomerular disease. Urinalysis provides information about kidney damage by indicating levels of protein and red blood cells in the urine. Blood tests measure the levels of waste products such as creatinine and urea nitrogen to determine whether the filtering capacity of the kidneys is impaired. If these lab tests indicate kidney damage, the doctor may recommend ultrasound or an x ray to see whether the shape or size of the kidneys is abnormal. These tests are called renal imaging. But since glomerular disease causes problems at the cellular level, the doctor will probably also recommend a kidney biopsy—a procedure in which a needle is used to extract small pieces of tissue for examination with different types of microscopes, each of which shows a different aspect of the tissue. A biopsy may be helpful in confirming glomerular disease and identifying the cause. What causes glomerular disease? A number of different diseases can result in glomerular disease. It may be the direct result of an infection or a drug toxic to the kidneys, or it may result from a disease that affects the entire body, like diabetes or lupus. Many different kinds of diseases can cause swelling or scarring of the nephron or glomerulus. Sometimes glomerular disease is idiopathic, meaning that it occurs without an apparent associated disease. The categories presented below can overlap: that is, a disease might belong to two or more of the categories. For example, diabetic nephropathy is a form of glomerular disease that can be placed in two categories: systemic diseases, since diabetes itself is a systemic disease, and sclerotic diseases, because the specific damage done to the kidneys is associated with scarring. Autoimmune Diseases When the body’s immune system functions properly, it creates protein-like substances called antibodies and immunoglobulins to protect the body against invading organisms. In an autoimmune disease, the immune system creates autoantibodies, which are antibodies or immunoglobulins that attack the body itself. Autoimmune diseases may be systemic and affect many parts of the body, or they may affect only specific organs or regions. Systemic lupus erythematosus (SLE) affects many parts of the body: primarily the skin and joints, but also the kidneys. Because women are more likely to develop SLE than men, some researchers believe that a sex-linked genetic factor may play a part in making a person susceptible, although viral infection has also been implicated as a triggering factor. Lupus nephritis is the name given to the kidney disease caused by SLE, and it occurs when autoantibodies form or are deposited in the glomeruli, causing inflammation. Ultimately, the inflammation may create scars that keep the kidneys from functioning properly. Conventional treatment for lupus nephritis includes a combination of two drugs, cyclophosphamide, a cytotoxic agent that suppresses the immune system, and prednisolone, a corticosteroid used to reduce inflammation. A newer immunosuppressant, mychophenolate mofetil (MMF), has been used instead of cyclophosphamide. Preliminary studies indicate that MMF may be as effective as cyclophosphamide and has milder side effects. Goodpasture’s syndrome involves an autoantibody that specifically targets the kidneys and the lungs. Often, the first indication that patients have the autoantibody is when they cough up blood. But lung damage in Goodpasture’s syndrome is usually superficial compared with progressive and permanent damage to the kidneys. Goodpasture’s syndrome is a rare condition that affects mostly young men but also occurs in women, children, and older adults. Treatments include immunosuppressive drugs and a blood-cleaning therapy called plasmapheresis that removes the autoantibodies. IgA nephropathy is a form of glomerular disease that results when immunoglobulin A (IgA) forms deposits in the glomeruli, where it creates inflammation. IgA nephropathy was not recognized as a cause of glomerular disease until the late 1960s, when sophisticated biopsy techniques were developed that could identify IgA deposits in kidney tissue. The most common symptom of IgA nephropathy is blood in the urine, but it is often a silent disease that may go undetected for many years. The silent nature of the disease makes it difficult to determine how many people are in the early stages of IgA nephropathy, when specific medical tests are the only way to detect it. This disease is estimated to be the most common cause of primary glomerulonephritis—that is, glomerular disease not caused by a systemic disease like lupus or diabetes mellitus. It appears to affect men more than women. Although IgA nephropathy is found in all age groups, young people rarely display signs of kidney failure because the disease usually takes several years to progress to the stage where it causes detectable complications. No treatment is recommended for early or mild cases of IgA nephropathy when the patient has normal blood pressure and less than 1 gram of protein in a 24-hour urine output. When proteinuria exceeds 1 gram/day, treatment is aimed at protecting kidney function by reducing proteinuria and controlling blood pressure. Blood pressure medicines—angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin receptor blockers (ARBs)—that block a hormone called angiotensin are most effective at achieving those two goals simultaneously. Hereditary Nephritis—Alport Syndrome The primary indicator of Alport syndrome is a family history of chronic glomerular disease, although it may also involve hearing or vision impairment. This syndrome affects both men and women, but men are more likely to experience chronic kidney disease and sensory loss. Men with Alport syndrome usually first show evidence of renal insufficiency while in their twenties and reach total kidney failure by age 40. Women rarely have significant renal impairment, and hearing loss may be so slight that it can be detected only through testing with special equipment. Usually men can pass the disease only to their daughters. Women can transmit the disease to either their sons or their daughters. Treatment focuses on controlling blood pressure to maintain kidney function. Infection-related Glomerular Disease Glomerular disease sometimes develops rapidly after an infection in other parts of the body. Acute post-streptococcal glomerulonephritis (PSGN) can occur after an episode of strep throat or, in rare cases, impetigo (a skin infection). The Streptococcus bacteria do not attack the kidney directly, but an infection may stimulate the immune system to overproduce antibodies, which are circulated in the blood and finally deposited in the glomeruli, causing damage. PSGN can bring on sudden symptoms of swelling (edema), reduced urine output (oliguria), and blood in the urine (hematuria). Tests will show large amounts of protein in the urine and elevated levels of creatinine and urea nitrogen in the blood, thus indicating reduced kidney function. High blood pressure frequently accompanies reduced kidney function in this disease.