NORD gratefully acknowledges Greg Cichon, MD candidate, Creighton School of Medicine and Khalid Bashir, MD, Assistant Professor of Nephrology, Creighton School of Medicine, for the preparation of this report.
Summary
Immunotactoid glomerulopathy is a rare kidney disease of the glomerulus, the site where blood and waste are filtered from the body. Microtubule proteins plug the glomerulus, causing damage. It can cause blood and protein in the urine (hematuria and proteinuria, respectively), which makes urine look red or foamy. Other symptoms include decreased kidney function (renal insufficiency), swelling in the legs or feet and high blood pressure (hypertension). It is diagnosed with a kidney biopsy. While the exact cause is unknown, it is most often found in patients with chronic lymphocytic leukemia (CLL), B cell lymphomas and multiple myeloma. It has also been diagnosed in patients with a history of hepatitis C virus (HCV) infection. Treatment is typically aimed at the associated diseases since no treatments have been demonstrated to be effective for immunotactoid glomerulopathy yet. 40-50% of patients with immunotactoid glomerulopathy will progress to end stage renal disease within two to six years, depending on the severity. These patients will eventually need a kidney transplant and dialysis. The disease may return even after a kidney transplant, but it is usually less severe.
Introduction
Immunotactoid glomerulopathy and fibrillary glomerulonephritis, a similar but slightly more common condition, are two forms of non-amyloid fibrillary glomerular deposition diseases. Microtubules and antibodies (immunoglobulins) plug the glomerulus, the body’s filter in the kidneys. Under normal conditions, the glomerulus filters the blood to form urine and keeps the antibodies to help fight infections and microtubules to maintain cell structure. The word “immunotactoid” refers to these rod-like structures (“-tactoid”) produced by the immune system (“immuno”). “Glomerulopathy” refers to the abnormal buildup of these proteins, which causes swelling and eventually irreversible kidney damage. Scientists do not fully understand why these antibodies begin depositing in the glomerulus, but most that suspect certain underlying diseases play a role. Over time, the damaged filters spill proteins into the urine and eventually lose their ability to filter blood altogether.
The most common symptoms of immunotactoid glomerulopathy include:
The causes of immunotactoid glomerulopathy are still unknown and are being researched. Microtubules build up in the glomerulus, often in patients with an underlying disease such as cancer (particularly leukemia, lymphoma and multiple myeloma) or a previous hepatitis C viral infection.
Adults with a history of leukemia, lymphoma, multiple myeloma or another monoclonal gammopathy are most at risk for immunotactoid glomerulopathy. Some evidence also shows an association between a previous hepatitis C viral infection and immunotactoid glomerulopathy. However, many cases have no identifiable underlying disease and the cause is unknown.
A diagnosis is made from a kidney biopsy to look at the microtubules under an electron microscope and immunofluorescence microscope. Routine lab tests may detect the blood and protein in the urine, but a biopsy is the only way to determine which proteins are affecting the glomerulus.
Clinical Testing and Work-up
Abnormal results from routine blood and urine tests are the first line of evidence for kidney damage. Kidney function tests can then detect the level of kidney damage. After a kidney biopsy confirms the diagnosis of immunotactoid glomerulopathy, a physician will likely order more blood tests and imaging. These tests are important to find any underlying cancer, hepatitis or autoimmune disease which may be associated with the glomerulonephritis. In some patients, finding and treating the underlying condition can decrease the severity of the kidney disease. When an underlying condition is not found, treatment focuses on controlling the hypertension, protein in the urine and progression of the kidney disease.
Treatment
There is currently no approved therapy to treat immunotactoid glomerulopathy with unknown cause. Many therapies have been unsuccessful including steroids, plasmapheresis, cyclophosphamide and cyclosporine. Clinicians will likely focus instead on controlling the symptoms of hypertension, proteinuria and kidney insufficiency. If an underlying condition is present (see Affected Populations), clinicians will instead focus on treating the underlying condition, which may improve symptoms of immunotactoid glomerulopathy.
Patients who progress to end-stage renal disease will likely need kidney transplants and/or dialysis, although immunotactoid glomerulopathy can recur after a kidney transplant.
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