Help Plot a Different Future in C3G & PRIMARY IC-MPGN

C3G is considered a rare disease, with an estimated global incidence of 1 to 3 cases per million people.^1-3

The incidence of primary IC-MPGN (a subtype of IC-MPGN) is unknown, and it is also considered a rare disease.^3,4

1. ERKNET. C3 Glomerulonephritis & IC-MPGN. Available at: https://www.erknet.org/patients/your-kidney-disease/C3g-ic-mpgn/disease-information. Accessed August 2025.
2. Noris M & Remuzzi G. Nephrol Dial Transplant 2024;2:202-14.
3. Bomback AS, et al. Kidney Int Rep 2025;10:17-28.
4. Orphanet. Immunoglobulin-mediated membranoproliferative glomerulonephritis. Available at: https://www.orpha.net/en/disease/detail/329903. Accessed October 2025.

Diagnostic tools

Diagnosing patients with primary IC-MPGN or C3G is challenging, given their rarity and overlapping clinical presentations and histologic features – which makes these conditions difficult to distinguish from each other.¹

Reducing the burden

C3G & primary IC-MPGN are diseases that carry a high burden – not just a burden on patients, but on families and healthcare resources.^2,3

Treatments targeting disease drivers

A key barrier to optimal management of C3G & primary IC-MPGN is the need for more treatment options that target the pathologic mechanisms of these diseases.¹ Current guideline-endorsed therapeutic strategies focus primarily on supportive care and nonspecific immunosuppression.^1,

Understanding disease mechanisms

Despite advances in our understanding of IC-MPGN and C3G, a better understanding of the underlying pathophysiology is crucial to facilitating a personalized approach to the management of these complex glomerular diseases.¹

1. Bomback AS, et al. Kidney Int Rep 2025;10(1):17-28.
2. Feldman DL, et al. National Kidney Foundation. The Voice of the Patient report 2018. Available at: https://www.kidney.org/sites/default/files/C3G_EL-PFDD_VoP-Report_3-29-18.pdf. Accessed July 2025.
3. Rich C, et al. ISPOR Value in health 2024;27(11):S59.
4. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. Kidney Int 2021;100(4S):S1-276.

Improving quality of life

C3G & primary IC-MPGN have a substantial impact on quality of life, and on physical, social, and emotional wellbeing.¹

Controlling symptoms

Because symptoms worsen as the disease progresses, the constellation of symptoms, as well as the degree to which patients experience them, varies.¹ In one study, patients were asked to identify three symptoms that most negatively affect their daily lives. Fatigue, swelling (edema), and anxiety/depression were the three most commonly selected symptoms.¹

Modifying the underlying disease 

A key barrier in the management of primary IC-MPGN and C3G is the current lack of treatments that target the pathologic mechanisms of these diseases.²

Preventing or maximizing time before needing dialysis, or suffering kidney failure

Most patients who progress to kidney failure will need dialysis or kidney transplant, which are associated with significant risks and burdens.^3-7 Around half of patients progress to kidney failure within 10 years of diagnosis.⁵

Maximizing overall survival

Kidney transplant in patients with C3G or primary IC-MPGN is associated with a 76% greater risk of mortality vs other nephropathies.⁶ Five-year survival on dialysis is 59% for patients with primary IC-MPGN who have progressed to kidney failure.⁷

Reducing burden on healthcare systems

A real-world survey of 53 physicians providing data for 134 people living with primary IC-MPGN found the disease to be associated with substantial healthcare resource utilisation burden, emotional upset and disruption to patients’ lives.⁸

1. Feldman DL, et al. National Kidney Foundation. The Voice of the Patient report 2018. Available at: https://www.kidney.org/sites/default/files/C3G_EL-PFDD_VoP-Report_3-29-18.pdf. Accessed July 2025.
2. Bomback AS, et al. Kidney Int Rep 2025;10(1):17-28.
3. Heiderscheit AK, et al. Am J Med Genet C Semin Med Genet 2022;190:344-57.
4. Himmelfarb J, et al. Nat Rev Nephrol 2020;10:573-85.
5. Halfon M, et al. Kidney Int Rep. 2024;10(1):75-86.
6. O’Shaughnessy MM, et al. J Am Soc Nephrol 2017;28:632-44.
7. Wilson GJ, et al. BMC Nephrol 2019;20:417.
8. Rich C, et al. ISPOR Value in Health 2024; 27(11):S59.

A retrospective, multicenter observational cohort study in 35 nephrology departments (the GLOSEN group) enrolled 70 patients with C3G between 1995 and 2020 to evaluate the association between change in proteinuria levels over time, and kidney prognosis.¹

With a median follow-up of 42 months, investigators found that a 50% proteinuria reduction over time was significantly associated with a lower risk of kidney failure (hazard ratio 0.79; 95% confidence interval 0.56–0.97; P < 0.001). A doubling of proteinuria levels resulted in a 2.5-fold increase in risk of kidney failure.¹

Longitudinal change in proteinuria over time showed good discrimination and calibration, suggesting good clinical applicability. ¹

Another study of 225 patients with C3G or primary IC-MPGN evaluated the association between clinical and histologic variables, and a composite primary outcome of a 30% decline in estimated glomerular filtration rate (eGFR) or kidney failure.²

They found that a 50% reduction in proteinuria from baseline, to a value less than 1g/day was associated with a lower risk of the primary outcome (HR 0.35, 95% CI 0.12-0.97).²

Authors concluded that these results provide an evidence-based definition of proteinuria remission that can be used for patient care and in clinical trials.²

 A third study of longitudinal data from 371 patients with C3G or IC-MPGN, derived from the UK Registry of Rare Kidney Diseases (RaDaR), sought to understand the association between proteinuria changes and long-term kidney outcomes.³

They found that a 50% reduction in proteinuria from diagnosis to 12 months, and from 6-12 months, was associated with lower kidney failure risk than inferior reductions.³

Also, those with a UPCR under 100 mg/mmol at 12 months had a substantially lower risk of kidney failure (hazard ratio: 0.10; 95% confidence interval 0.03-0.30).³

1. Caravaca-Fontán F, et al. Nephrol Dial Transplant 2022;37:1270-80.
2. Ghaddar M, et al. Clin J Am Soc Nephrol 2025. 20(8):1119-1131.
3. Masoud S, et al. Kidney Int 2025. 108(3):455-469.