Glomerulonephritis

Glomerulonephritis

What are unmet needs in glomerulonephritis?

Glomerulonephritis is a subset of renal diseases where immune complexes damage various glomerular structures, such as the basement membrane, mesangium, or capillary endothelium. Such damage to the kidneys can lead to haematuria, proteinuria, azotaemia, and ultimately kidney failure. Timely identification and treatment of specific glomerular diseases, including immunoglobulin A (IgA) nephropathy, focal segmental glomerulosclerosis (FSGS), and lupus nephritis, represents a pressing unmet need. These diseases are clinically challenging to identify, treat, and manage, and approximately 91% of people with FSGS, 81% of people with IgA nephropathy, and 77% of lupus nephritis is not identified or managed properly.

How common is glomerulonephritis?

Glomerulonephritis constitutes 25–30% of all end-stage renal disease (ESRD) cases and affects males more than females, with a male-to-female ratio of 2:1. In the early stages of the disease, glomerulonephritis symptoms are often very mild or absent. Without timely identification and treatment, the disease progresses quickly, eventually leading to morbidity within weeks to months, making chronic glomerulonephritis the third most common cause of ESRD. Over the past decade, there has been a significant increase in FSGS, which is positively correlated with the increasing incidence of obesity and the aging population in developed countries. IgA nephropathy remains the most common form of glomerulonephritis globally, with membranous glomerulonephritis more prevalent in Western countries and mesangial proliferative glomerulonephritis more prevalent in many Asian countries.

What are the risk factors for glomerulonephritis?

Many pre-existing diseases and conditions are risk factors for developing glomerulonephritis. These include diabetes, cancer, HIV, hepatitis B and C, vasculitis and immune diseases (including lupus and Goodpasture syndrome). In addition to these diseases, lifestyle risk factors such as diet, smoking, and overuse of non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with glomerulonephritis.

How is glomerulonephritis treated?

Treatment outcome is highly dependent on timely intervention, and delays in treatment are likely to result in progression to chronic kidney disease (CKD) and ESRD. Primary glomerulonephritis is managed supportively and with specific disease-modifying therapy. Disease management revolves around immunosuppression; however, this will be influenced by factors such as histological diagnosis, disease severity, disease progression, and comorbidities. Available treatment options include angiotensin converting enzyme (ACE) inhibitors, antibiotics, high-dose corticosteroids, rituximab (a monoclonal antibody that causes the lysis of B lymphocytes), cytotoxic agents (cyclophosphamide and glucocorticoids in cases of post-streptococcal glomerulonephritis), and plasma exchange. In the instance of lupus nephritis, treatment with monoclonal antibodies has proven to be effective. Secondary glomerular diseases associated with a systemic disease are managed through treatment of the underlying cause.