Navigating complement 3 glomerulopathy (C3G)

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Approximately 50% of patients with C3G progress to kidney failure within 10 years of diagnosis and require dialysis or transplant. C3G may reoccur almost immediately after kidney transplantation and contributes to allograft loss in approximately 50% of patients within 10 years.^1-3

Expert biopsy analysis with a renal pathologist is essential to confirmatory diagnosis and evaluating prognosis.^2-4

What is Complement 3 Glomerulopathy (C3G)?

C3G is an ultra-rare kidney disease that causes glomerular inflammation^5,6

Previously classified within MPGN, C3G was recently reclassified as its own disease state to better acknowledge the causative factors of the disease.⁷

Unlike CKD, patients with C3G often present as children and young adults, which can place a significant burden on their outlook for the future.⁸

~ Up to 50% of adult patients

progress to kidney failure within 10 years of diagnosis³

~ 70% of pediatric patients

progress to kidney failure within 10 years of diagnosis³

~ 50% of patients

who undergo kidney transplant for C3G experience allograft loss within 10 years due to disease recurrence³

Hear From a Real Patient Living With C3G⁹

"You can't plan for the future. You don't know where you'll be next year."⁹

— A real patient with C3G

Patients can be diagnosed with 1 of 2 subtypes of C3G: DDD or C3GN

DDD is usually associated with pediatric cases and may progress more quickly than C3GN.³

C3G can be heterogeneous in clinical presentation and prognosis^3,5,6,10

Patients may present with low to heavy levels of proteinuria and hematuria
C3G can be acute, recurrent, or rapidly progressive

Unresolved proteinuria and hematuria may be important indicators of C3G and should trigger expert biopsy analysis.³

A Multidisciplinary Approach Is Key to Help Accelerate the Differential Diagnosis of C3G vs Other Similarly Presenting Glomerulonephritis³

Collaborating with an expert renal pathologist as soon as C3G is suspected can help avoid delayed diagnosis^2-4

Accurate, confirmatory diagnosis of C3G requires a multistep process in collaboration with a pathologist, including urinalysis, serology, and biopsy.³

C3G Immunofluorescence — **IMMUNOFLUORESCENCE C3-DOMINANT STAINING: AT LEAST 2 ORDERS OF MAGNITUDE GREATER**

A biopsy is necessary for a pathologist to evaluate C3 accumulation, as well as glomerular inflammation and injury.^1,2,6

Using immunofluorescent analysis of biopsy staining, C3G can be identified by C3 accumulation seen as intense staining at least 2 orders of magnitude greater than any other immune component, with absence or low presence of immunoglobulin and components of the classical complement pathway.^2,3

_{^{Image credit: Martin B, Smith RJH. C3 Glomerulopathy. 2007 Jul 20 [Updated 2018 Apr 5]. In: Adam MP, Everman DB, Mirzaa GM, et al., editors.}}_^GeneReviews^®_{^{[Internet]. Seattle (WA): University of Washington, Seattle; 1993-2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1425/}}

Once diagnosis is confirmed, the latest ICD-10-CM codes should be used to categorize C3G¹¹

Clinical presentation of C3G can vary among patients, and accurate categorization of C3G diagnosis based on unique manifestation can help inform personalized care.^3,11

The latest ICD-10-CM codes recognize C3G and its subtypes with unique coding based on clinical presentation.¹¹ View codes here ↗.

Complement Overactivation Contributes to Disease Progression

In C3G, uncontrolled activation of the alternative complement pathway is the primary driver of disease and kidney damage^3,12-14

The alternative pathway is 1 of 3 pathways of the complement system, an innate component of the body's immune system.¹⁵

In C3G, uncontrolled activation of the alternative pathway results in the deposition of C3 fragments in the glomerular mesangium and along capillary walls. This disrupts kidney function and causes inflammation.^12,14,16

Diagram shows uncontrolled activation of the alternative pathway causes C3G.

KDIGO guidelines ↗ recommend an in-depth study on the role of the complement system in C3G.¹⁷

The Burden of C3G

“The fatigue is overwhelming. Living it, it becomes normal.” — Patient portrayal.

Patients living with C3G are at risk for rapid progression toward kidney failure—some even face the prospect of reaching kidney failure before adulthood^3,18-20
Once diagnosed, patients rely on supportive care, steroids, other immunosuppressants, and lifestyle modifications to help slow the rate of progression to kidney failure^17-19
Steroids can produce side effects that may need to be managed along with disease symptoms¹⁷

Hear From a Real Patient Living With C3G⁹

"The fatigue is overwhelming. Living it, it becomes normal."

"What's most difficult is knowing time is not on my side. I know that a healthy diet, exercise, and following doctor's orders will not stop the progression of this disease."

"You feel like you're going through it alone."

"We need a way to avoid a lifetime of dependence on a dialysis machine or a series of failed transplants."

Stay up to date

See the mechanism of disease (MOD) for C3G

View the MOD for C3G

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Novartis is committed to addressing unmet needs of people living with complement-mediated kidney diseases.

C3, complement 3; C3G, complement 3 glomerulopathy; C3GN, complement 3 glomerulonephritis; CKD, chronic kidney disease; DDD, dense deposit disease; GN, glomerulonephritis; ICD-10-CM, International Classification of Diseases, Tenth Revision, Clinical Modification; KDIGO, Kidney Disease Improving Global Outcomes; MPGN, membranoproliferative glomerulonephritis.

References: 1. C3 glomerulopathy: dense deposit disease and C3 glomerulonephritis. National Organization for Rare Disorders (NORD). Accessed September 24, 2022. https://rarediseases.org/rare-diseases/c3-glomerulopathy-dense-deposit-disease-and-c3-glomerulonephritis/ 2. Martin B, Smith RJH. C3 glomerulopathy. In: Adam MP, Mirzaa GM, Pagon RA, et al, eds. GeneReviews [Internet]. University of Washington; 2007. Updated April 5, 2018. Accessed July 28, 2022. https://www.ncbi.nlm.nih.gov/books/NBK1425/ 3. Smith RJH, Appel GB, Blom AM, et al. C3 glomerulopathy - understanding a rare complement-driven renal disease. Nat Rev Nephrol. 2019;15(3):129-143. 4. Hou J, Markowitz GS, Bomback AS, et al. Toward a working definition of C3 glomerulopathy: a rare renal disease. Int J Mol Sci. 2020;21(2):525. doi:10.3390/ijms21020525 5. Schena FP, Esposito P, Rossini M. A narrative review on C3 glomerulopathy: a rare renal disease. Int J Mol Sci. 2020;21(2):525. doi:10.3390/ijms21020525 6. Medjeral-Thomas NR, O’Shaughnessy MM, O’Regan JA, et al. C3 glomerulopathy: clinicopathologic features and predictors of outcome. Clin J Am Soc Nephrol. 2014;9(1):46-53. 7. Sethi S, De Vriese AS, Fervenza FC. Acute glomerulonephritis. Lancet. 2022;399(10335):1646-1663. 8. Gutierrez E, Praga M, Rivera F; Spanish Registry of Glomerulonephritis. Changes in the clinical presentation of immunoglobulin A nephropathy: data from the Spanish Registry of Glomerulonephritis. Nephrol Dial Transplant. 2018;33(3):472-477. 9. Feldman DL, Bomback A, Nester CN. Voice of the Patient: Report of Externally Led Patient-Focused Drug Development Meeting on Complement 3 Glomerulopathy (C3G). National Kidney Foundation; 2018. 10. Smith RJH, Alexander J, Barlow PN; Dense Deposit Disease Focus Group. New approaches to the treatment of dense deposit disease. J Am Soc Nephrol. 2007;18(9):2447-2456. 11. Centers for Disease Control and Prevention. ICD10 Coordination and Maintenance Committee Meeting Diagnosis Agenda. March 5-6, 2019, Part 2. Accessed April 11, 2023. https://www.cdc.gov/nchs/icd/icd10cm_maintenance.htm 12. Caravaca-Fontan F, Lucientes L, Cavero T, Praga M. Update on C3 glomerulopathy: a complement-mediated disease. Nephron. 2020;144(6):272-280. 13. Harris CL. Expanding horizons in complement drug discovery: challenges and emerging strategies. Semin Immunopathol. 2018;40(1):125-140. 14. Willows JW, Brown M, Sheerin NS. The role of complement in kidney disease. Clin Med (London). 2020;20(2):156-160. 15. Merle NS, Church SE, Fremeaux-Bacchi V, Roumenina LT. Complement system part I—molecular mechanisms of activation and regulation. Front Immunol. 2015;6:(262):1-30. doi:10.3389/fimmu.2015.00262 16. Merle NS, Noe R, Halbwachs-Mecarelli L, Fremeaux-Bachi V, Roumenina LT. Complement system part II: role in immunity. Front Immunol. 2015;6:(257):1-30. doi:10.3389/fimmu.2015.00257 17. Rovin BH, Adler SG, Barratt J, et al; Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int. 2021;100(suppl4):S1-S276. 18. Davison SN, Moss AH. Supportive care: meeting the needs of patients with advanced chronic kidney disease. Clin J Am Soc Nephrol. 2016;11(10):1879-1880. 19. Chronic kidney disease: MedlinePlus medical encyclopedia. MedlinePlus. Accessed June 6, 2023. https://medlineplus.gov/ency/article/000471.htm 20. Kirpalani A, Jawa N, Smoyer WE, Licht C; Midwest Pediatric Nephrology Consortium. Long-term outcomes of C3 glomerulopathy and immune-complex membranoproliferative glomerulonephritis in children. Kidney Int Rep. 2020;5(12):2313-2324.

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What is Complement 3 Glomerulopathy (C3G)?

C3G is an ultra-rare kidney disease that causes glomerular inflammation5,6

~ Up to 50% of adult patients

~ 70% of pediatric patients

~ 50% of patients

Hear From a Real Patient Living With C3G9

Patient portrayal.

Patients can be diagnosed with 1 of 2 subtypes of C3G: DDD or C3GN

C3G can be heterogeneous in clinical presentation and prognosis3,5,6,10

A Multidisciplinary Approach Is Key to Help Accelerate the Differential Diagnosis of C3G vs Other Similarly Presenting Glomerulonephritis3

Collaborating with an expert renal pathologist as soon as C3G is suspected can help avoid delayed diagnosis2-4

IMMUNOFLUORESCENCE C3-DOMINANT STAINING: AT LEAST 2 ORDERS OF MAGNITUDE GREATER

Once diagnosis is confirmed, the latest ICD-10-CM codes should be used to categorize C3G11

Complement Overactivation Contributes to Disease Progression

In C3G, uncontrolled activation of the alternative complement pathway is the primary driver of disease and kidney damage3,12-14

KDIGO guidelines ↗ recommend an in-depth study on the role of the complement system in C3G.17

The Burden of C3G

Patient portrayal.

Hear From a Real Patient Living With C3G9

Stay up to date

See the mechanism of disease (MOD) for C3G

C3G is an ultra-rare kidney disease that causes glomerular inflammation^5,6

Hear From a Real Patient Living With C3G⁹

C3G can be heterogeneous in clinical presentation and prognosis^3,5,6,10

A Multidisciplinary Approach Is Key to Help Accelerate the Differential Diagnosis of C3G vs Other Similarly Presenting Glomerulonephritis³

Collaborating with an expert renal pathologist as soon as C3G is suspected can help avoid delayed diagnosis^2-4

Once diagnosis is confirmed, the latest ICD-10-CM codes should be used to categorize C3G¹¹

In C3G, uncontrolled activation of the alternative complement pathway is the primary driver of disease and kidney damage^3,12-14

KDIGO guidelines ↗ recommend an in-depth study on the role of the complement system in C3G.¹⁷

Hear From a Real Patient Living With C3G⁹