Glomerular Disease: Symptoms, Diagnosis, and Treatment

Autoimmune disease occurs when the body's immune system creates antibodies that attack the body. Autoimmune disorders that affect the kidneys include:

Systemic lupus erythematosus (SLE). Lupus is a very complicated disease that affects women more than men, and often affects women of color. Lupus of the kidneys is called lupus nephritis. This is diagnosed with a kidney biopsy which helps classifying the severity of the disease. Severe lupus cases can result in kidney failure requiring dialysis or transplant. Mild to moderate cases can be treated using medications that suppress the immune system. Treatment is often tailored based off of an individual’s severity of disease. Recently, newer medications have been approved by FDA for lupus of the kidney.

IgA nephropathy. IgA nephropathy is a common glomerular disease caused by abnormal production of IgA protein. People with abnormal IgA develop antibodies to this protein which causes inflammation of the kidney.

IgA can vary from mild disease with tiny amounts of blood in the urine lifelong, to moderate disease with both blood and protein in the urine, to severe disease in which there is also loss of kidney function with eventual need for dialysis or transplantation. In rare cases, there may also be a rash, but most often IgA has no other symptoms and requires a urine test to diagnose. Diagnosis of IgA disease is done using a kidney biopsy.

Treatment of IgA nephropathy depends on disease severity: mild and some moderate disease is treated with particular blood pressure medications, while the treatment of moderate to severe disease often includes medications that suppress the immune system. Recently, newer medications have been approved by FDA for this particular disease.

ANCA Vasculitis. ANCA vasculitis is an auto-immune kidney disease that can also affect the lungs and blood vessels. The antibodies that are attacking the kidneys may also attack the sinuses, the lungs, the joints, or the skin, so the symptoms in an affected person could be a lingering sinus or respiratory infection, or a rash.

Diagnosis is through blood work and a kidney biopsy. Treatment depends on disease severity and involves using immunosuppressive medications. In some cases these diseases can result in complete kidney failure and a need for dialysis within weeks, so prompt diagnosis and aggressive treatment is needed to save as much of the kidney as possible.

Anti-glomerular basement membrane disease (anti-GBM, formerly known as Goodpasture). This is a lung-kidney disease where antibodies attack a specific protein found in the both the lungs and kidneys. Onset of the disease is short (weeks). Diagnosis is through kidney biopsy and involves immunosuppressive medications. Often plasmapheresis, a technique to remove abnormal anti-GBM proteins, is used to treat the disease. Often, patients can develop kidney damage or failure and require dialysis or transplant.

Membranoproliferative glomerulonephritis.This is broad spectrum of glomerular diseases that can be due to multiple causes. Diagnosis is done through a kidney biopsy which helps in classifying the cause. Treatment is based off the biopsy and can include medications that suppress the immune system. Examples of causes include certain types of blood cancers, Hepatitis C.

Infections in other areas of the body can lead to inflammation and perhaps even scarring in the kidneys. Infections that can lead to inflammation in the kidney include:

Post-infectious glomerulonephritis, in which antibodies fighting an infection also attack the kidneys. This usually occurs two to three weeks after the infection has resolved, usually in people who had strep throat, or sometimes a skin infection like impetigo, and in either case happens only to a minority of people who have these infections. Typical symptoms are dark urine with high amounts of blood cells and blood proteins in the urine, severe high blood pressure, and acute kidney injury. Children often appear very sick when they are diagnosed but usually heal very well. Adults often appear less sick than children but do not heal as well, and up to 50% will end up losing their kidney function over time, leading to a need for dialysis or transplantation.

Infectious glomerulonephritis. Similar to post-infectious glomerulonephritis, patients with this condition are fighting an infection, and their antibodies attack the kidneys. When the damage to the kidneys occurs while the infection is ongoing, we call this infectious glomerulonephritis. These patients are treated with powerful antibiotics to help them overcome the infection. Only once the infection is treated can their kidneys begin to heal. The most common cause is a bacterial infection of heart valves known as infective endocarditis. This condition is also found in patients who experience chronic infections of joint replacements and ventriculo-peritoneal shunts.

Viral infections, such as:

• HIV. When present at high amounts in the blood, HIV can infect the kidneys directly and cause focal and segmental glomerulosclerosis, often with high amounts of protein in the urine, very severe hypertension, and fairly quick loss of kidney function. HIV can also cause a more slowly progressive immune-complex glomerulonephririts, usually in people with HIV controlled so well that it is not detectable, and yet the virus is still able to activate the immune system enough to slowly attack the kidneys over a period of many years.
• Hepatitis B. Hepatitis B most often causes a membranous nephropathy, and is one of the “secondary" causes discussed below.
• Hepatitis C. Hepatitis C most often causes a membranoproliferative kidney disease, which we can treat in coordination with your liver doctor. Eradication of the hepatitis C virus often but not always makes the kidney disease resolve.

Diabetic kidney disease, or diabetic nephropathy, is the most common glomerular disease and is the most common cause of needing dialysis or kidney transplantation. High blood glucose from diabetes increases the speed of blood flow through the glomeruli, which makes the kidney filters work harder than they should, and leads to loss of excessive albumin and other blood proteins in the urine. Over time, the kidneys become scarred and lose function.

The best way to treat diabetic kidney disease is with early diagnosis and aggressive management. If not treated soon enough, it can lead the kidneys to fail a little bit more each year, leading to a need for dialysis or kidney transplantation.

Treatment for diabetic kidney disease is complex and includes:

• Changes in diet
• Insulin or other diabetes medications to control blood sugar
• Blood pressure medications that can slow progression of the disease
• A new class of medications, including canagliflozin, that lower blood sugar levels slightly, reduce the excess blood flow through the kidney filters, reduce the amount of protein in the urine, and slow the damage to the kidneys caused by diabetes.

This disease most often affects people with a family history of chronic kidney disease but can also affect patients with no family history.

There are three genes that can cause Alport's syndrome. Each of these genes creates a protein that helps form the kidney filter. The most commonly affected gene causes more severe symptoms in men than women. If the other two genes cause the condition, men and women are affected equally.

Medical treatment focuses on controlling blood pressure, but new treatments are being investigated. This severe illness frequently leads to a need for dialysis and transplantation.

A person affected by Alport's syndrome might pass the affected gene to their children, but this depends on which of the three genes is involved, the sex of the parent, and the sex of the child.

Nephrotic syndrome differs from most other glomerular diseases in that the kidneys may not be inflamed at all, but there is still a lot of protein entering the urine.

In nephrotic syndrome, the amount of protein in the urine can be very high. Your liver will struggle to create new proteins quickly enough, and protein levels in your blood will fall. Low levels of protein in the blood are accompanied by several symptoms and complications that can be severe including:

• Swelling of the legs, and in severe cases, swelling in the groin, back, abdomen, and face.
• Increased chance of infection due to the loss of antibodies and other proteins in the urine.
• Increased risk of blood clots, including deep vein thrombosis and pulmonary embolism, also due to loss of protein in the urine.
• Nutritional deficiency due to loss of protein in the urine.

Membranous nephropathy

Membranous nephropathy is either a primary disorder of the kidney (most often caused by an autoimmune disorder) or is connected to some other cause, such as medication, viral hepatitis, or adenocarcinoma. The first step after diagnosis is to determine the cause of your condition and to treat that cause.

If you have primary membranous nephropathy, your doctor may treat you with:

• Medication to reduce the amount of protein that enters your urine, such as ACE inhibitors.
• Steroids to reduce autoimmune attacks on your kidneys.
• Immune suppressing medications including certain type of chemotherapy.

Minimal change disease

Minimal change disease (MCD) is diagnosed using kidney biopsy. Using conventional microscopy, the kidney looks almost normal, hence the name “minimal change."

Despite the name, patients with minimal change disease typically experience severe symptoms of nephrotic syndrome, including severe swelling of the legs and other body parts. Sometimes minimal change disease is caused by a medication (such as a non-steroidal anti-inflammatory like ibuprofen, or lithium) or a lymphoma, but most of the time the cause is uncertain. Minimal change disease is the most common cause of nephrotic syndrome in children. Both children and adults with minimal change disease are initially treated with steroids.

Focal and Segmental Glomerulosclerosis (FSGS)

In the United States, FSGS is now the most common cause of nephrotic syndrome in adults. There are more possible causes of FSGS than any other nephrotic syndrome.

Determining the cause is an important step in the treatment process. Causes of FSGS include:

• Genetic.
• Recently more information about genetic causes of FSGS has been discovered.
• This is most commonly seen in children and in adults.
• Medication. In rare cases, some medications can cause FSGS.
• Hyperfiltration. Any time the kidneys filter at higher rates than usual, this is called hyperfiltration. This excess effort can cause kidney damage over time. The causes for this are numerous, and most common include renal dysplasia or hypoplasia, severe prematurity, severe obesity, sickle-cell nephropathy, congenital heart disease nephropathy, and sometimes people who had one kidney removed surgically for any reason.
• Viruses – HIV, parvovirus, COVID.
• Secondary – this is FSGS due to other disease of the kidney.

Treatments for FSGS include:

• Steroids
• Immune suppressive medications
• Blood pressure medications

FSGS can eventually lead to kidney failure requiring dialysis or transplant.