Building a better knowledge of anti-GBM disease
Anti-glomerular basement membrane disease (anti-GBM), also known as Goodpasture’s disease, is an ultra-rare disease of the kidney affecting around 1.6 people per million annually (1). We spoke with Mårten Segelmark, Professor of Nephrology at Lund University in Sweden, who shared his experience in studying this disease, its associated challenges, as well as the importance of a faster diagnosis, and how we can achieve this.
Prof Segelmark, can you tell us what is Anti-GBM?
Anti-GBM, is a form of glomerulonephritis (GNN), a set of inflammatory conditions of the kidneys, and is one of the leading causes for kidney disease. It is an acute and very severe inflammatory disease characterized by the development of IgG-antibodies that attack a specific part of the kidney called the glomerular basement membrane (GBM), they can also attack a similar structure in the lungs.
How long have you studied this specific disease for?
I started doing research in anti-GBM disease already when I was a medical student in 1982, more than 40 years ago.
How severe is this rare condition?
Anti-GBM is an acute condition. This means that a previously functioning kidney can get destroyed within a few weeks. Only if treatment is instituted early, there is a chance of salvaging their function. Damage often extends to the lungs where patients can experience bleeding, which can be life-threatening. In one out of six patients, anti-GBM can become fatal during the acute phase, while the majority of patients end up on dialysis (2,3). Kidney transplantation is not possible in the acute phase, but it becomes a possible option for many after around a year. Only one in three anti-GBM patients will have a preserved renal function after six months with current standard of care (4).
How can the worst outcomes be prevented, and what are the main challenges in treating anti-GBM patients?
Given the severity of its acute phase, the autoimmune reaction needs to be counteracted and stopped as quickly as possible if we want to limit the damage to the organs. And here is where we have the biggest challenge: patients with anti-GBM disease are seldom correctly identified in the early stage of the acute phase, and often misdiagnosed. This causes dangerous delays in the initiation of the correct treatment. What we observe in clinical practice is that by the time anti-GBM patients are correctly identified, often the damage to kidneys (and lungs) is already advanced and sometimes irreparable, and these patients end up needing dialysis. In worst cases, the effects of the diseases are fatal.
Why is anti-GBM so hard to identify?
The cause of this problem is two-fold: the ultra-rare nature of this condition and the wide variety of symptoms associated with glomerulonephritis, the family of conditions anti-GBM is part of. Its rarity has the dire side effect that many physicians, particularly those not specialized in nephrology, are either not aware of the condition, or don’t include it among the potential causes during the diagnosis phase. Secondly, patients with glomerulonephritis, including anti-GBM, usually experience quite diffuse symptoms in the initial stages that are not always easy to identify. When the symptoms become apparent, the damage of the organ is often in an advanced state. This is a serious problem in a condition where time is a commodity these patients cannot afford.
What can be done to tackle this latency in the proper identification of anti-GBM patients, and to make sure the autoimmune reaction is counteract as quickly as possible?
Screening tests for markers of kidney dysfunction, such as urine dipstick tests and blood tests for serum creatine levels, are cheap and available for all family doctors and at all hospitals. Such tests should be ordered for all patients with diffuse symptoms, even if there is no direct suspicion of renal disease. In the case these tests result positive, it becomes necessary to take appropriate actions as early as possible. There is a need for better knowledge about renal diseases, especially rare ones, within the medical community.
- Henderson R et al. Nephrology Dialysis Transplantation 2018. (33) 2: 196-202.
- McAdoo S et al. Anti-GBM disease. Clin J Am Soc Nephrol 2017. 12: 1162–1172.
- Cohort of 13 studies (661 patients in anti-GBM 1993-2017) Treating anti-GBM disease with imlifidase Mårten Segelmark, Professor OF Nephrology
- Kluth et al. J Am Soc Nephrol. 1999 Nov;10(11):2446-53 and Hellmark et al. J Autoimmun. 2014 Feb-Mar;48-49:108-12