Glomerular Diseases: Causes, Symptoms, Types, Diagnosis, Treatment

Glomerular Diseases: Causes, Symptoms, Types, Diagnosis, Treatment

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-MAIR-yoo-loh-neh-FRY-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-MAIR-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 end-stage renal disease (ESRD).

What Are the Kidneys and What Do They Do?

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 400 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.

Read more: Goodpasture Syndrome:: Causes, Symptoms, Diagnosis, Treatment

How Do Glomerular Diseases Interfere With Kidney Function?

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.

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.

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.

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. Researchers funded by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) are trying to discover why these deposits in the glomeruli are formed and whether dietary supplements of fish oil can inhibit IgA-induced inflammation and scarring in the kidney. A study is being conducted to compare the effectiveness of therapy involving daily fish oil supplements with that of a therapy involving prednisone, a drug that blocks the body's immune system. The study includes a placebo group. All three groups of patients in the study are receiving medication to control blood pressure. 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.

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 renal failure and sensory loss. Men with Alport syndrome usually first show evidence of renal insufficiency while in their twenties and reach ESRD 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.

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.

PSGN is most common in children between the ages of 3 and 7, although it can strike at any age, and it most often affects boys. It lasts only a brief time and usually allows the kidneys to recover. In a few cases, however, kidney damage may be permanent, requiring dialysis or transplantation to replace renal function.

Bacterial endocarditis, infection of the tissues inside the heart, is also associated with subsequent glomerular disease. Researchers are not sure whether the renal lesions that form after a heart infection are caused entirely by the immune response or whether some other disease mechanism contributes to kidney damage. Treating the heart infection is the most effective way of minimizing kidney damage. Chronic renal failure can result from endocarditis, but is not inevitable.

HIV, the virus that leads to AIDS, can also cause glomerular disease. Between 5 and 10 percent of people with HIV experience kidney failure, even before developing full-blown AIDS. HIV-associated nephropathy usually begins with heavy proteinuria and progresses rapidly (within a year of detection) to ESRD. Researchers are looking for therapies that can slow down or reverse this rapid deterioration of renal function, but some possible solutions involving immunosuppression are risky because of the patients' already compromised immune system.

Sclerotic diseases

Glomerulosclerosis is scarring (sclerosis) of the glomeruli. In several sclerotic conditions, a systemic disease like lupus or diabetes is responsible. Glomerulosclerosis is caused by the activation of glomerular cells to produce scar material. This may be stimulated by molecules called growth factors, which may be made by glomerular cells themselves or may be brought to the glomerulus by the circulating blood that enters the glomerular filter.

Diabetic nephropathy is the leading cause of ESRD in the United States. Kidney disease is one of several problems caused by elevated levels of blood glucose, the central feature of diabetes. In addition to scarring the kidney, elevated glucose levels appear to increase the speed of blood flow into the kidney, putting a strain on the filtering glomeruli and raising blood pressure.

Diabetic nephropathy usually takes many years to develop. People with diabetes can slow down damage to their kidneys by controlling their blood glucose through healthy eating with moderate protein intake, physical activity, and medications. People with diabetes should also be careful to keep their blood pressure at a level below 130/85 mm Hg, if possible. A class of blood pressure medications called angiotensin-converting enzyme (ACE) inhibitors is particularly effective at minimizing kidney damage and is now frequently prescribed to control blood pressure in patients with diabetes.

Focal segmental glomerulosclerosis (FSGS) describes scarring in scattered regions of the kidney, typically limited to one part of the glomerulus and to a minority of glomeruli in the affected region. FSGS may result from a systemic disorder or it may develop as an idiopathic kidney disease, without a known cause. Proteinuria is the most common symptom of FSGS, but, since proteinuria is associated with several other kidney conditions, the doctor cannot diagnose FSGS on the basis of proteinuria alone. Biopsy may confirm the presence of glomerular scarring if the tissue is taken from the affected section of the kidney. But finding the affected section is a matter of chance, especially early in the disease process, when lesions may be scattered.

Confirming a diagnosis of FSGS may require repeat kidney biopsies. Arriving at a diagnosis of idiopathic FSGS requires the identification of focal scarring and the elimination of possible systemic causes such as diabetes or an immune response to infection. Since idiopathic FSGS is, by definition, of unknown cause, it is difficult to treat. No universal remedy has been found, and most patients with FSGS progress to ESRD over 5 to 20 years. Some patients with an aggressive form of FSGS proceed to ESRD in 2 to 3 years. Treatments involving steroids or other immunosuppressive drugs appear to help some patients by decreasing proteinuria and improving kidney function. But these treatments are beneficial only to a minority of those in whom they are tried, and some patients experience even poorer kidney function as a result of therapy. ACE inhibitors may also be used in FSGS to decrease proteinuria. Treatment should focus on controlling blood pressure and blood cholesterol levels, factors that may contribute to kidney scarring.

Idiopathic nephrotic syndrome - minimal change disease

Minimal change disease (MCD) is the diagnosis given when a patient has the nephrotic syndrome and the kidney biopsy reveals little or no change to the structure of glomeruli or surrounding tissues when examined by a light microscope. Tiny drops of a fatty substance called a lipid may be present, but no scarring has taken place within the kidney. MCD may occur at any age, but it is most common in childhood. A small percentage of patients with idiopathic nephrotic syndrome do not respond to steroid therapy. For these patients, the doctor may recommend a low-sodium diet and prescribe a diuretic to control edema. The doctor may recommend the use of nonsteroidal anti-inflammatory drugs to reduce proteinuria. ACE inhibitors have also been used to reduce proteinuria in patients with steroid-resistant MCD. These patients may respond to larger doses of steroids, more prolonged use of steroids, or steroids in combination with immunosuppressant drugs, such as chlorambucil, cyclophosphamide, or cyclosporine.

What Are the Symptoms of Glomerular Disease?

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.

Glomerular Disease: Types list

The list of types of Glomerular Disease mentioned in various sources includes:

  • Glomerulonephritis
  • Glomerulosclerosis
  • Diabetic nephropathy, Lupus nephritis
  • Focal segmental glomerulosclerosis (FSGS)

How Is Glomerular Disease Diagnosed?

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 xray 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 under 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.

Treatment List for Glomerular Disease

The list of treatments mentioned in various sources for Glomerular Disease includes the following list. Always seek professional medical advice about any treatment or change in treatment plans.

Treatment depends on the underlying cause of the kidney disease

  • ACE inhibitors - for some subtypes
  • Plasmapheresis - for some subtypes related to immune problems
  • Blood pressure medications - if appropriate; some subtypes
  • Kidney dialysis - if kidneys fail
  • Kidney transplants - if kidneys fail

Treatment of glomerular disease is dependant upon the underlying cause of the kidney damage

The severity of the kidney damage, the age of the patient, and any other health problems that the patient might have. Treatments include:
  • Treatment of underlying cause - e.g., hypertension, diabetes, autoimmune diseases. This is very important in order to limit or slow the progression of renal disease
  • Avoidance of medications that may contribute to further renal damage - NSAID's, IV contrast
  • Smoking cessation - people who continue to smoke progress to end stage renal failure sooner
  • Close management of high blood pressure, whether it is a cause or result of renal disease
  • Use of ACE inhibitors - in patients both with and without proteinuria, has been shown to slow the progression of renal failure
  • Dietary management dependant upon the severity of renal impairment:
1. Protein restriction - may have a role in slowing the progress of renal failure, and is important to manage uremic symptoms in advanced failure, but needs to be managed carefully to avoid malnutrition

2. Salt and water restriction as necessary to manage fluid overload

3. Phosphate restriction
4. Potassium restriction as necessary

Management of chronic renal failure:

  • Erythropoietin agonists - for management of anaemia associated with chronic renal failure
  • Phosphate binders - for management of hyperphosphatemia in chronic renal failure
  • Calcium supplements - for hypocalcaemia
  • Calcitriol and other Vitamin D supplements - for hypocalcaemia and hyperparathyroidism associated with chronic renal failure
  • Sodium bicarbonate - for acid-base disturbance
  • Diuretics - may be used in situation of volume overload
  • Renal dialysis - used when there are manifestations of uraemia and the GFR is < 10mL/min
  • Haemodialysis
  • Peritoneal dialysis
  • Renal transplantation

What Are Renal Failure and End-Stage Renal Disease?

Renal failure is any acute or chronic loss of kidney function and is the term used when some kidney function remains. ESRD is total, or nearly total, and permanent kidney failure. Depending on the form of glomerular disease, renal function may be lost in a matter of days or weeks or may deteriorate slowly and gradually over the course of decades.

Acute renal failure

A few forms of glomerular disease cause very rapid deterioration of kidney function. For example, PSGN can cause severe symptoms (hematuria, proteinuria, edema) within 2 to 3 weeks after a sore throat or skin infection develops. The patient may temporarily require dialysis to replace renal function. This rapid loss of kidney function is called acute renal failure (ARF). Although ARF can be life-threatening while it lasts, kidney function usually returns after the cause of the kidney failure has been treated. In many patients, ARF is not associated with any permanent damage. However, some patients may recover from ARF and subsequently develop chronic renal failure (CRF).

Chronic renal failure

Most forms of glomerular disease develop gradually, often causing no symptoms for many years. CRF is the slow, gradual loss of kidney function. Some forms of CRF can be controlled or slowed down. For example, diabetic nephropathy can be delayed by tightly controlling blood glucose levels and using ACE inhibitors to reduce proteinuria and control blood pressure. But CRF cannot be cured. Partial loss of renal function means that some portion of the patient's nephrons have been scarred, and scarred nephrons cannot be repaired. In most cases, CRF leads to ESRD.

End-stage renal disease

To stay alive, a patient with ESRD must go on dialysis--hemodialysis or peritoneal dialysis-or receive a new kidney through transplantation. Patients with CRF who are approaching ESRD should learn as much about their treatment options as possible so they can make an informed decision when the time comes. With the help of dialysis or transplantation, many people continue to lead full, productive lives after reaching ESRD.