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 inflammation5,6
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
Hear From a Real Patient Living With C3G9
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Patient portrayal.
"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 prognosis3,5,6,10
Patients may present with low to heavy levels of proteinuria and hematuria
C3G can be acute, recurrent, or rapidly progressive
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
Accurate, confirmatory diagnosis of C3G requires a multistep process in collaboration with a pathologist, including urinalysis, serology, and biopsy.3
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 damage3,12-14
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
KDIGO guidelines ↗ recommend an in-depth study on the role of the complement system in C3G.17
The Burden of C3G
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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 adulthood3,18-20
Once diagnosed, patients rely on supportive care, steroids, other immunosuppressants, and lifestyle modifications to help slow the rate of progression to kidney failure17-19
Steroids can produce side effects that may need to be managed along with disease symptoms17
Hear From a Real Patient Living With C3G9
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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.