IgG nephropathy refers to a group of kidney conditions characterized by the involvement of Immunoglobulin G (IgG) antibodies. These are not a single disease, but a category of disorders where IgG antibodies contribute to kidney damage. This occurs when the immune system, specifically IgG, targets the kidneys, leading to various forms of kidney disease.
The Role of IgG and Kidney Function
Immunoglobulin G (IgG) is the most abundant type of antibody in the bloodstream, accounting for approximately 75% of serum antibodies in humans. These proteins are produced by plasma B cells as a part of the immune system’s defense against foreign invaders like bacteria and viruses. IgG antibodies neutralize pathogens and toxins, mark them for destruction by other immune cells, and activate immune responses, providing long-term immunity against infections previously encountered.
The kidneys are a pair of bean-shaped organs responsible for filtering waste products and excess fluids from the blood, maintaining the body’s fluid and electrolyte balance, and producing hormones. Blood enters the kidneys through the renal artery, where it is filtered by millions of tiny filtering units called glomeruli. These glomeruli allow waste and excess water to pass into the urine while retaining essential proteins and blood cells.
In certain circumstances, IgG antibodies can become problematic and lead to kidney damage. This occurs when IgG antibodies, alone or as part of immune complexes, are deposited within the glomeruli or other parts of the kidney. Such deposition can trigger inflammation and scarring, impairing the kidneys’ ability to filter blood effectively, leading to various kidney diseases.
Types of IgG-Mediated Kidney Disease
Immunoglobulin G4-related kidney disease (IgG4-RKD) is part of a broader systemic condition known as IgG4-related disease (IgG4-RD). IgG4-RKD most commonly presents as tubulointerstitial nephritis (IgG4-TIN), characterized by dense infiltration of IgG4-positive plasma cells and fibrosis within the kidney’s tubules and interstitium. It can also manifest as membranous glomerulopathy, where IgG4 antibodies deposit on the glomerular basement membrane, leading to protein leakage. Obstructive nephropathy can also occur due to IgG4-related retroperitoneal fibrosis, which can compress the urinary tract.
Other less common IgG-related glomerulonephritis types also involve IgG deposition. For instance, certain forms of lupus nephritis, an autoimmune disease, frequently involve IgG deposition in the kidneys, leading to inflammation and damage.
Recognizing the Signs and Getting a Diagnosis
IgG-mediated kidney diseases often do not cause noticeable symptoms in their early stages, sometimes for 10 years or more. When symptoms do appear, they can include cola- or tea-colored urine due to the presence of blood, which may be visible or only detectable through a urine test. Foamy urine, indicating protein leakage into the urine (proteinuria), is another common sign. Swelling in the hands, feet, and ankles, known as edema, can also occur, along with pain on one or both sides of the back below the ribs.
High blood pressure is a frequent complication as kidney damage impairs the organs’ ability to regulate blood pressure. Fatigue and general discomfort may also be present. If kidney function significantly declines, symptoms such as rashes, itchy skin, muscle cramps, upset stomach, vomiting, decreased appetite, a metallic taste in the mouth, and confusion may develop.
Diagnosis begins with initial screenings such as urine tests to detect protein and blood, and blood tests to assess kidney function, including creatinine levels and glomerular filtration rate (GFR). A definitive diagnosis and classification of the specific type of IgG-mediated kidney disease requires a kidney biopsy. During a biopsy, a small sample of kidney tissue is removed and examined under a microscope to identify characteristic immune deposits and structural changes. This examination helps determine the precise nature of the kidney damage and guides treatment strategies.
Managing the Condition
Managing IgG-mediated kidney conditions involves a multi-faceted approach tailored to the specific disease type and severity. A primary goal is to slow kidney damage progression and prevent or delay kidney failure. This includes strict blood pressure control, targeting less than 130/80 mmHg, often achieved with medications like ACE inhibitors or ARBs, which also help reduce protein in the urine.
Dietary modifications are recommended, such as reducing salt intake to help manage blood pressure and swelling. Lifestyle adjustments, including regular exercise and weight management, also contribute to overall kidney health. Specific medical treatments are necessary, particularly immunosuppressive therapies aimed at reducing the immune response damaging the kidneys.
Corticosteroids, such as prednisone, are a first-line treatment to reduce inflammation. For cases resistant to steroids or involving relapses, other immunosuppressive agents like rituximab, a B-cell depleting agent, are used. Cyclophosphamide is another immunosuppressant employed in more aggressive forms of the disease. Supportive care addresses complications like high cholesterol, with medications prescribed to lower lipid levels and reduce cardiovascular risk.
Outlook and Long-Term Care
The long-term outlook for individuals with IgG-mediated kidney diseases varies depending on the specific diagnosis, condition severity, and treatment response. Some individuals with milder forms may experience slow progression or remain stable for decades with minimal symptoms. Others, particularly those with significant proteinuria, reduced kidney function, or high blood pressure, face a higher risk of disease progression.
Ongoing monitoring is a cornerstone of long-term care, involving regular follow-up appointments with nephrologists. These appointments include periodic blood and urine tests to track kidney function, protein levels, and blood pressure. Adherence to prescribed treatment plans, including medications and lifestyle modifications, is important for managing the disease and preventing relapses.
Despite treatment, some individuals may experience a decline in kidney function over time, progressing to chronic kidney disease and, in severe cases, end-stage kidney disease (ESRD). For individuals who reach ESRD, options include dialysis, which artificially filters waste from the blood, or kidney transplantation. While transplantation can offer a new quality of life, the underlying IgG-mediated disease can sometimes recur in the transplanted kidney.