Navigating the complexities of glomerular disease—C3G and IC-MPGN: an HCP perspective
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As a nephrology nurse practitioner with nearly a decade of experience, Katerina Jones has the privilege of caring for patients with a wide range of kidney disorders. Among the most complex and challenging conditions she has encountered are the glomerular diseases, particularly C3 glomerulopathy (C3G) and immune complex membranoproliferative glomerulonephritis (IC-MPGN). From the frontline, Katerina shares insights from her perspective as a healthcare professional guiding individuals through diagnosis and beyond
Written by Nicola Miller
Interview with Katerina Jones, nephrology nurse practitioner, Metrolina Nephrology Associates
C3 glomerulopathy (C3G) and immune complex membranoproliferative glomerulonephritis (IC-MPGN) are two sub-types of glomerulopathies that fall under the umbrella of glomerular diseases in particular membranoproliferative glomerulonephritis (MPGNs).
At the heart of these glomerular diseases lies the complement system1, a complicated network of proteins arranged in three pathways that converge on the complement protein C3. In both C3G and IC-MPGN, the complement system is overactive. This overactivation leads to excessive deposition of breakdown products of C3. This abnormal accumulation of C3 breakdown products leads to inflammation and abnormal cell proliferation that disrupts kidney function, eventually leading to kidney damage. IC-MPGN may occur secondary to other factors (eg, infection, autoimmune diseases, malignancy); IC-MPGN without a known secondary cause is classified as “primary.” The defining differentiator between C3G and IC-MPGN is the presence and intensity of immunoglobulin deposits as seen on histology of biopsied tissue.
[See box at end for definitions]
The diagnostic journey for these diseases often begins with the presence of protein in the urine (proteinuria), a hallmark symptom that prompts further investigation. As a nurse practitioner, Katerina takes a comprehensive approach, delving into the patient’s detailed medical history, conducting a thorough physical examination, and ordering a battery of laboratory tests. This meticulous process helps to identify potential underlying causes and to rule out other causes of glomerulonephritis. Patient history and bloodwork are immensely helpful and play a crucial role in this diagnostic process; a kidney biopsy and evaluation of the kidney tissues by a pathologist are necessary to establish the official diagnosis. By examining a small sample of kidney tissue, a pathologist can determine the specific histological pattern and the presence or absence of the characteristic C3 and/or immunoglobulin deposits and provide Katerina and her team with the information needed to determine what type of glomerulonephritis the patient is experiencing.
Once a diagnosis is established, the management of C3G and IC-MPGN varies depending on the stage of the disease. In the case of secondary IC-MPGN, treating the underlying condition (eg, infection, autoimmune diseases, malignancy) often produces improvements in the kidneys.
In contrast, treatments for primary IC-MPGN and C3G aim to reduce the symptoms of complement overactivation. Medications to control blood pressure and limit inflammation (ie, steroids and other immunosuppressants) are common therapies for people with C3G or IC-MPGN. Unfortunately, the efficacy of any of the available treatments is variable, and the risks associated with long-term immunosuppression must be carefully weighed. There remains no approved targeted therapy for either C3G or IC-MPGN. Katerina explains,
“Navigating these treatment decisions is a constant challenge, as we strive to find the right balance between managing the disease and minimising the impact on our patients’ overall health and well-being. It’s a delicate process, and one that requires a deep understanding of the nuances of these conditions and a willingness to collaborate with our patients, their families, and the broader healthcare team to strike the right balance.”
Katerina explains that the risk of progression to end-stage kidney disease is quite high for C3G, with the 10-year risk estimated to be ~70% in paediatric patients and 30-50% in adults.1 This is due to the underlying dysfunction in the alternative complement pathway, which can be difficult to effectively manage with current treatment options. Additionally, the recurrence rate of C3G or primary IC-MPGN after kidney transplantation can be up to 89% 2-9, posing significant challenges for long-term disease management. Katerina explains that at times this can feel like a “fight to buy time.” She further expands that, “while some treatments in clinical trials are showing promise, they are not yet available to our patients,” expressing the critical need for continued research and the development of more effective, targeted treatments.
Over and above the lack of treatment options, perhaps one of the most challenging aspects of caring for individuals with C3G and IC-MPGN is the emotional toll it can take. These are rare and complex conditions, and the uncertainty surrounding their prognosis and the effectiveness of available treatments can be overwhelming for patients and their loved ones. As a nurse practitioner, Katerina has learned the importance of creating a safe and supportive environment where patients feel empowered to express their fears, frustrations and grief.
“It’s not uncommon for individuals to experience a range of emotions, from anger at the unfairness of their situation to a profound sense of loss and uncertainty about their future.”
To address these emotional needs, Katerina encourages patients to connect with support groups, both in-person and online. “These communities can provide a valuable outlet for sharing experiences, exchanging information and finding solace in the shared understanding of those who have walked a similar path.”
Additionally, Katerina’s practice makes it a priority to regularly assess patients’ mental health, screening for signs of depression and anxiety, and connecting them with mental health professionals when necessary. The emotional burden of living with a chronic, potentially life-threatening condition cannot be overstated, and addressing these needs is just as crucial as managing the physical aspects of the disease.
As Katerina reflects on her experiences in the field of nephrology, she recounts the remarkable resilience and strength of the individuals she’s had the privilege of caring for. Despite the challenges they face, many of her patients have demonstrated an unwavering determination to navigate the complexities of their conditions and maintain a sense of hope and optimism. It’s this spirit of resilience that inspires Katerina to continue her pursuit of knowledge and to advocate for the advancement of research and treatment options for glomerular diseases.
Katerina explained, “I’m heartened by the growing attention and investment in this field, as new therapies and clinical trials offer the promise of improved outcomes and a brighter future for those affected by these rare and debilitating conditions. In the end, my role as a nephrology nurse practitioner is not just about managing the clinical aspects of these diseases; it’s about fostering a deep connection with my patients, empowering them to navigate the complexities of their care and providing the emotional support they need.” This is a “privilege” and a responsibility that Katerina takes on with the utmost care and dedication, striving to make a meaningful difference in the lives of those entrusted to her care.
What is the complement pathway?
The complement pathway is part of the body’s immune system—a series of reactions that involve proteins in the blood that help destroy unwanted or invading cells and control our inflammatory responses.
What is proteinuria?
The presence of a high level of protein in an individual’s urine.
What are the glomeruli?
Glomeruli are a network of tiny blood vessels that filter waste and remove extra fluid from your blood. They are often referred to as the ‘cleaning units’ of the kidneys. When the glomeruli are unable to function as required this is referred to by the umbrella term of glomerular disease. The causation of this and the appearance of the glomerulus on biopsy examination determines the subcategory of glomerular disease, ie. C3G or IC-MPGN.
What are immune complex depositions?
Immune complex depositions are the accumulation of immune complexes in the body’s tissue. Immune complexes are formed by the binding of antibodies and antigens. This can lead to severe inflammatory responses.
References:
[1] Smith RJH, et al. Nat Rev Nephrol. 2019;15(3):129-143.
[2] Caravaca-Fontán F, et al. Nephrol Dial Transplant. 2023;38(1):222-235.
[3] Frangou E, et al. Nephrol Dial Transplant. 2019;34(10):1780-1788.
[4] Medjeral-Thomas NR, et al. Clin J Am Soc Nephrol. 2014;9(1):46-53.
[5] Patry C, et al. Pediatr Nephrol. 2024;39(12):3569-3580.
[6] Regunathan-Shenk R, et al. Am J Kidney Dis. 2019;73(3):316-323.
[7] Servais A, et al. Kidney Int. 2012;82(4):454-464.
[8] Tarragón B, et al. Clin J Am Soc Nephrol. 2024;19(8):1005-1015.
[9] Zand L, et al. J Am Soc Nephrol. 2014;25(5):1110-1117.
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