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 endothelium¹. Such damage to the kidneys can lead to haematuria, proteinuria, azotaemia and ultimately kidney failure¹. Timely identification and treatment of specific glomerular diseases, including IgA nephropathy, focal segmental glomerulosclerosis (FSGS) and lupus nephritis, represents a highly pressing unmet need². These specific 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 people with lupus nephritis are not identified or managed properly³.

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^{1, 3}. In the early stages of the disease, glomerulonephritis symptoms are often very mild or absent⁴. 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 ESRD³. In 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^3,5,6. 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 countries³.

What are the risk factors for glomerulonephritis?

Many pre-existing diseases and conditions are risk factors for developing glomerulonephritis. These include diabetes, cancer, human immunodeficiency virus (HIV), hepatitis B and C, vasculitis and immune diseases (including lupus and Goodpasture syndrome)^7,8. 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^7,8.

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 ESRD⁹. 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 comorbidities10. 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^9,10. 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^9,10.

References

1. Trachtman H, Herlitz LC, Lerma E V., Hogan JJ. Glomerulonephritis. Glomerulonephritis. 2021;1–888.
2. Spherix Global Insights. Nephrologists Point to Profound Unmet Need for New Agents to Treat Glomerular Diseases Such as IgA Nephropathy, Focal Segmental Glomerulosclerosis (FSGS), and Lupus Nephritis. 2021. https://www.prnewswire.com/news-releases/nephrologists-point-to-profound-unmet-need-for-new-agents-to-treat-glomerular-diseases-such-as-iga-nephropathy-focal-segmental-glomerulosclerosis-fsgs-and-lupus-nephritis-301120738.html. Accessed 17 December 2021.
3. Woo KT, Chan CM, Chin YM, Choong HL, Tan HK, Foo M, et al. Global evolutionary trend of the prevalence of primary glomerulonephritis over the past three decades. Nephron - Clin Pract. 2010;116(4). doi:10.1159/000319594.
4. Stahl RAK, Hoxha E. Glomerulonephritis. Dtsch Med Wochenschr. 2016;141(13):960–968.
5. Ng JKC, Li PKT. Chronic kidney disease epidemic: How do we deal with it? Nephrology. 2018;23:116–120.
6. Noris M, Remuzzi G. Glomerular Diseases Dependent on Complement Activation, Including Atypical Hemolytic Uremic Syndrome, Membranoproliferative Glomerulonephritis, and C3 Glomerulopathy: Core Curriculum 2015. Am J Kidney Dis. 2015;66(2):359–375.
7. Neale EP, Middleton J, Lambert K. Barriers and enablers to detection and management of chronic kidney disease in primary healthcare: A systematic review. BMC Nephrol. 2020;21(1):1–17.
8. Shlipak MG, Tummalapalli SL, Boulware LE, Grams ME, Ix JH, Jha V, et al. The case for early identification and intervention of chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2021;99(1):34–47.
9. Kimmel M. [Infections-associated Glomerulonephritis]. Dtsch Med Wochenschr. 2020;145(4):240–247.
10. Couser WG. Pathogenesis and treatment of glomerulonephritis-an update. J Bras Nefrol. 2016;38(1):107–122.