Glomeruli are the tiny filters in the kidney that clean the blood. Glomerular disease is an umbrella term that includes many conditions that damage the glomeruli. When glomeruli are damaged protein leaks into the urine. Over time, the damage can lead to kidney failure.

Abnormal antibodies are the source of damage for several glomerular diseases.

The PIONEER study is enrolling participants with the following glomerular diseases:

IgA nephropathy (IgAN)

• IgAN is a disease where defective IgA antibodies build up and form clumps inside the glomeruli. The antibody buildup causes kidney damage over time. Signs of disease activity or damage can include blood and/or protein measured in the urine.
• IgAN is typically diagnosed by kidney biopsy where clumps of IgA and IgG antibodies are visible under the microscope.
• The most common age at diagnosis is between 10 and 40 years old.
• Symptoms can include blood in the urine, foamy urine, and swelling of the arms or legs.

IgAN with vasculitis (IgAVN)

• Formerly known as Henoch Schönlein Purpura (or HSP), IgAVN is a disease of the blood vessels and kidneys.
• Similar to IgAN above, the IgA proteins damage the filters inside the kidneys (glomeruli).
• In addition, the antibodies also cause inflammation in blood vessels which can lead to skin rash (purpura), abdominal pain, poor blood flow to the intestines, or inflammation in the joints.
• When affecting the kidneys, blood and protein may be visible in urine. High blood pressure and swelling might also occur.

• Primary membranous nephropathy (pMN): In most people with pMN, the immune system makes antibodies (anti-PLA2R antibodies) against the glomerulus filter cells allowing high levels of protein to pass through the filter.
• If the protein loss is high, it can cause low protein levels in the blood (called albumin) leading to swelling in the body (edema).
• pMN is typically diagnosed based on a combination of blood tests, urine tests, and kidney biopsy.
• The antibodies cause the leaking of proteins and if they remain for a long period of time, they damage the kidney filters leading to kidney failure.

• Nephrotic syndrome (MCD and FSGS): Nephrotic syndrome is a family of diseases where the glomeruli leak large amounts of protein into the urine. The extensive protein loss into the urine lowers the protein levels (called albumin) in the blood leading to swelling in many parts of the body.
• A kidney biopsy is typically performed to determine the cause of nephrotic syndrome. Two common findings on biopsy include a specific pattern of scarring (aka Focal Segmental Glomerulosclerosis or FSGS) or little change under the microscope (aka Minimal Change Disease or MCD).
• The most common treatment for MCD and FSGS is steroids taken for weeks to months until the protein levels in the urine return to normal.

• In some people, the protein loss in the urine and swelling returns after treatment, called a relapse. When relapse occurs, multiple treatment courses may be needed to keep the disease under control (or in remission).
• Recently, an antibody that attaches to the kidney filter (called anti-nephrin) was discovered in the blood of some people with MCD or FSGS. Testing for the anti-nephrin antibody is currently only available in research studies. Studies so far suggest that anti-nephrin antibody levels are increased when nephrotic syndrome is active (relapsing) and decrease when it is under control (in remission), but research is still needed to better understand if and how these antibodies are causing nephrotic syndrome in MCD or FSGS.