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C3 glomerulonephritis

MedGen UID:
884569
Concept ID:
C4055342
Disease or Syndrome
Synonym: C3 GLOMERULOPATHY 3
 
Monarch Initiative: MONDO:0013892
OMIM®: 614809
Orphanet: ORPHA329931

Definition

C3 glomerulopathy-3 (C3G3) is an autosomal dominant kidney disease characterized by the onset of microscopic or macroscopic hematuria in the first 3 decades of life, followed by variable progression of renal disease. After age 30, about half of patients continue to have episodic hematuria while maintaining normal renal function, whereas the other half develop proteinuria and progressive renal failure or end-stage renal disease. In some cases, renal dysfunction may be triggered or exacerbated by an infectious disease, often an upper respiratory infection or pharyngitis. Some patients may also develop hypertension. Renal biopsy shows glomerular C3 deposition and mesangial proliferation with glomerulonephritis. Membranoproliferative glomerulonephritis (MPGN) may also be observed on renal biopsy. Males tend to have a more severe phenotype than females and are more likely to develop end-stage renal disease, often necessitating dialysis or renal transplant (summary by Athanasiou et al., 2011). For a general description and discussion of genetic heterogeneity of C3G, see C3G1 (609814). [from OMIM]

Additional description

From MedlinePlus Genetics
One of the two forms of C3 glomerulopathy, dense deposit disease, can also be associated with other conditions unrelated to kidney function. For example, people with dense deposit disease may have acquired partial lipodystrophy, a condition characterized by a lack of fatty (adipose) tissue under the skin in the upper part of the body. Additionally, some people with dense deposit disease develop a buildup of yellowish deposits called drusen in the light-sensitive tissue at the back of the eye (the retina). These deposits usually appear in childhood or adolescence and can cause vision problems later in life.

Researchers have identified two major forms of C3 glomerulopathy: dense deposit disease and C3 glomerulonephritis. Although the two disorders cause similar kidney problems, the features of dense deposit disease tend to appear earlier than those of C3 glomerulonephritis, usually in adolescence. However, the signs and symptoms of either disease may not begin until adulthood.

The kidney problems associated with C3 glomerulopathy tend to worsen over time. About half of affected individuals develop end-stage renal disease (ESRD) within 10 years after their diagnosis. ESRD is a life-threatening condition that prevents the kidneys from filtering fluids and waste products from the body effectively.

C3 glomerulopathy is a group of related conditions that cause the kidneys to malfunction. The major features of C3 glomerulopathy include high levels of protein in the urine (proteinuria), blood in the urine (hematuria), reduced amounts of urine, low levels of protein in the blood, and swelling in many areas of the body. Affected individuals may have particularly low levels of a protein called complement component 3 (or C3) in the blood.  https://medlineplus.gov/genetics/condition/c3-glomerulopathy

Clinical features

From HPO
Microscopic hematuria
MedGen UID:
65997
Concept ID:
C0239937
Finding
Microscopic hematuria detected by dipstick or microscopic examination of the urine.
Renal insufficiency
MedGen UID:
332529
Concept ID:
C1565489
Disease or Syndrome
A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism.
Stage 5 chronic kidney disease
MedGen UID:
384526
Concept ID:
C2316810
Disease or Syndrome
A degree of kidney failure severe enough to require dialysis or kidney transplantation for survival characterized by a severe reduction in glomerular filtration rate (less than 15 ml/min/1.73 m2) and other manifestations including increased serum creatinine.
Mesangial matrix expansion
MedGen UID:
766636
Concept ID:
C3553722
Finding
Increased mesangial extracellular material with interspace width of over 2 mesangial cell nuclei, in one or more peripheral mesangial areas.
Mesangial hypercellularity
MedGen UID:
924090
Concept ID:
C4281741
Cell or Molecular Dysfunction
Increased numbers of mesangial cells per glomerulus, defined as more than 3 nuclei fully surrounded by matrix in one or more mesangial areas, not including perihilar region, on a standard 3-micron-thick tissue section, best evaluated on periodic acid-Schiff (PAS) stain.
Thickening of glomerular capillary wall
MedGen UID:
927616
Concept ID:
C4293707
Finding
Widening of the wall of capillary blood vessels in the glomerulus. This feature may be produced by deposits and other changes affecting either subepithelial and subendothelial regions or the glomerular basement membrane itself.
Glomerular subendothelial electron-dense deposits
MedGen UID:
1370779
Concept ID:
C4476539
Anatomical Abnormality
Electron dense deposits at the glomerular basement membrane,
Glomerular C3 deposition
MedGen UID:
1375318
Concept ID:
C4476555
Finding
The presence of complement 3 deposits in the glomerulus.
Glomerulonephritis
MedGen UID:
6616
Concept ID:
C0017658
Disease or Syndrome
Inflammation of the renal glomeruli.

Professional guidelines

PubMed

Ahmad SB, Bomback AS
Adv Chronic Kidney Dis 2020 Mar;27(2):104-110. doi: 10.1053/j.ackd.2019.12.003. PMID: 32553242
Rudnicki M
Biomed Res Int 2017;2017:2180508. Epub 2017 May 9 doi: 10.1155/2017/2180508. PMID: 28573137Free PMC Article
Appel GB
Contrib Nephrol 2013;181:163-74. Epub 2013 May 8 doi: 10.1159/000348635. PMID: 23689578

Recent clinical studies

Etiology

Heiderscheit AK, Hauer JJ, Smith RJH
Am J Med Genet C Semin Med Genet 2022 Sep;190(3):344-357. Epub 2022 Jun 23 doi: 10.1002/ajmg.c.31986. PMID: 35734939Free PMC Article
Caravaca-Fontán F, Lucientes L, Cavero T, Praga M
Nephron 2020;144(6):272-280. Epub 2020 May 5 doi: 10.1159/000507254. PMID: 32369815
Kaartinen K, Safa A, Kotha S, Ratti G, Meri S
Semin Immunol 2019 Oct;45:101331. Epub 2019 Nov 9 doi: 10.1016/j.smim.2019.101331. PMID: 31711769
Smith RJH, Appel GB, Blom AM, Cook HT, D'Agati VD, Fakhouri F, Fremeaux-Bacchi V, Józsi M, Kavanagh D, Lambris JD, Noris M, Pickering MC, Remuzzi G, de Córdoba SR, Sethi S, Van der Vlag J, Zipfel PF, Nester CM
Nat Rev Nephrol 2019 Mar;15(3):129-143. doi: 10.1038/s41581-018-0107-2. PMID: 30692664Free PMC Article
Floege J, Amann K
Lancet 2016 May 14;387(10032):2036-48. Epub 2016 Feb 25 doi: 10.1016/S0140-6736(16)00272-5. PMID: 26921911

Diagnosis

Heiderscheit AK, Hauer JJ, Smith RJH
Am J Med Genet C Semin Med Genet 2022 Sep;190(3):344-357. Epub 2022 Jun 23 doi: 10.1002/ajmg.c.31986. PMID: 35734939Free PMC Article
Caravaca-Fontán F, Lucientes L, Cavero T, Praga M
Nephron 2020;144(6):272-280. Epub 2020 May 5 doi: 10.1159/000507254. PMID: 32369815
Schena FP, Esposito P, Rossini M
Int J Mol Sci 2020 Jan 14;21(2) doi: 10.3390/ijms21020525. PMID: 31947692Free PMC Article
Kaartinen K, Safa A, Kotha S, Ratti G, Meri S
Semin Immunol 2019 Oct;45:101331. Epub 2019 Nov 9 doi: 10.1016/j.smim.2019.101331. PMID: 31711769
Floege J, Amann K
Lancet 2016 May 14;387(10032):2036-48. Epub 2016 Feb 25 doi: 10.1016/S0140-6736(16)00272-5. PMID: 26921911

Therapy

Mehdi A, Taliercio JJ
Cleve Clin J Med 2023 May 24;90(6 suppl 1):e1-e4. doi: 10.3949/ccjm.90.e-s1.01. PMID: 37225259
Ahmad SB, Bomback AS
Adv Chronic Kidney Dis 2020 Mar;27(2):104-110. doi: 10.1053/j.ackd.2019.12.003. PMID: 32553242
Schena FP, Esposito P, Rossini M
Int J Mol Sci 2020 Jan 14;21(2) doi: 10.3390/ijms21020525. PMID: 31947692Free PMC Article
Ito N, Ohashi R, Nagata M
Clin Exp Nephrol 2017 Aug;21(4):541-551. Epub 2016 Nov 23 doi: 10.1007/s10157-016-1358-5. PMID: 27878657Free PMC Article
Servais A, Noël LH, Frémeaux-Bacchi V, Lesavre P
Contrib Nephrol 2013;181:185-93. Epub 2013 May 8 doi: 10.1159/000348654. PMID: 23689580

Prognosis

Mehdi A, Taliercio JJ
Cleve Clin J Med 2023 May 24;90(6 suppl 1):e1-e4. doi: 10.3949/ccjm.90.e-s1.01. PMID: 37225259
Ahmad SB, Bomback AS
Adv Chronic Kidney Dis 2020 Mar;27(2):104-110. doi: 10.1053/j.ackd.2019.12.003. PMID: 32553242
Caravaca-Fontán F, Lucientes L, Cavero T, Praga M
Nephron 2020;144(6):272-280. Epub 2020 May 5 doi: 10.1159/000507254. PMID: 32369815
Kaartinen K, Safa A, Kotha S, Ratti G, Meri S
Semin Immunol 2019 Oct;45:101331. Epub 2019 Nov 9 doi: 10.1016/j.smim.2019.101331. PMID: 31711769
Floege J, Amann K
Lancet 2016 May 14;387(10032):2036-48. Epub 2016 Feb 25 doi: 10.1016/S0140-6736(16)00272-5. PMID: 26921911

Clinical prediction guides

Schena FP, Esposito P, Rossini M
Int J Mol Sci 2020 Jan 14;21(2) doi: 10.3390/ijms21020525. PMID: 31947692Free PMC Article
Bomback AS, Santoriello D, Avasare RS, Regunathan-Shenk R, Canetta PA, Ahn W, Radhakrishnan J, Marasa M, Rosenstiel PE, Herlitz LC, Markowitz GS, D'Agati VD, Appel GB
Kidney Int 2018 Apr;93(4):977-985. Epub 2018 Jan 6 doi: 10.1016/j.kint.2017.10.022. PMID: 29310824
Ito N, Ohashi R, Nagata M
Clin Exp Nephrol 2017 Aug;21(4):541-551. Epub 2016 Nov 23 doi: 10.1007/s10157-016-1358-5. PMID: 27878657Free PMC Article
Nester CM, Smith RJ
Semin Immunol 2016 Jun;28(3):241-9. Epub 2016 Jul 9 doi: 10.1016/j.smim.2016.06.002. PMID: 27402056
Medjeral-Thomas NR, O'Shaughnessy MM, O'Regan JA, Traynor C, Flanagan M, Wong L, Teoh CW, Awan A, Waldron M, Cairns T, O'Kelly P, Dorman AM, Pickering MC, Conlon PJ, Cook HT
Clin J Am Soc Nephrol 2014 Jan;9(1):46-53. Epub 2013 Oct 31 doi: 10.2215/CJN.04700513. PMID: 24178974Free PMC Article

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