C4 glomerulopathy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Ali Poyan Mehr, M.D. [2] Associate Editor(s)-in-Chief: Olufunmilola Olubukola M.D.[3] Norina Usman, M.B.B.S[4]
Synonyms and keywords: glomerulonephritis; C4 glomerulonephritis; dense deposit disease
Overview
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Ali Poyan Mehr, M.D. [2]; Associate Editor(s)-in-Chief: Olufunmilola Olubukola M.D.[3]
Overview
Complement system activation includes three pathways â the classical pathway, alternate pathway, and lectin pathway. C4d is a split product of C4 glomerulopathy, which itself results by overactivation of the lectin pathway. C4 glomerulopathy is further categorized into dense deposit disease and C4 glomerulonephritis.
Historical Perspective
There is limited information about the historical perspective of C4 glomerulopathy.
Classification
C4 glomerulopathy may be classified based on complement deposition into dense deposit disease and C4 glomerulonephritis.
Pathophysiology
It is thought that C4 glomerulopathy is the result of the activation of immune complex glomerulonephritis or lectin pathway of the complement.
Differential Diagnosis
C4 glomerulopathy must be differentiated from other diseases that cause proteinuria, hematuria, and peripheral edema, such as IgA nephropathy, membranous nephropathy, focal segmental glomerulus /minimal change disease, membranoproliferative glomerulonephritis, and lupus nephritis.
Causes
C4 glomerulopathy may be caused by mutation of complement factor,anti-factor H, anti-factor B, or C4 nephritic factor.
Risk Factors
There are no established risk factors for C4 glomerulopathy.
Screening
There is insufficient information to recommend routine screening for C4 glomerulopathy.
Epidemiology and Demographics
There is not much information available about the incidence and prevalence.
Natural History, Complications, and Prognosis
If left untreated, C4 glomerulopathy may progress to develop renal failure.
Diagnosis
History and Symptoms
The most common symptoms of C4 glomerulopathy include hematuria, proteinuria, and hypertension.
Physical Examination
Physical examination of patients with C4 glomerulopathy is usually remarkable for high blood pressure, peripheral edema, pale skin, and periorbital edema.
Laboratory Findings
Laboratory findings consistent with the diagnosis of C4 glomerulopathy include abnormal urinalysis, abnormal BUN: Creatinine ratio, and abnormal serum C3 and C4 levels
Imaging Studies
There are no other imaging findings associated with C4 glomerulopathy.
Other Diagnostic Studies
A kidney biopsy may be helpful in the diagnosis of C4 glomerulopathy. Findings diagnostic of C4 glomerulopathy include glomerular capillary walls thickening, large subendothelial osmiophilic dense deposits, and ribbonlike material on the glomerular basement membrane.
Treatment
Medical Therapy
The mainstay of treatment for C4 glomerulopathy is antihypertensive and lipid-lowering drugs.
Surgery
Surgical intervention is not recommended for the management of C4 glomerulopathy.
Prevention
There are no established measures for the primary or secondary prevention of C4 glomerulopathy.
References
Historical Perspective
There is limited information about the historical perspective of C4 glomerulopathy.
Classification
C4 glomerulopathy may be classified based on complement deposition into Dense Deposit Disease (DDD) and C4 Glomerulonephritis (C4GN).
Pathophysiology
It is thought that C4 glomerulopathy is the result of the activation of immune complex glomerulonephritis or lectin pathway of the complement.
Causes
C4 glomerulopathy may be caused by mutation of complement factor,anti-factor H, anti-factor B, or C4 nephritic factor.
Differentiating C4 glomerulopathy from other Diseases
C4 glomerulopathy must be differentiated from other diseases that cause proteinuria, hematuria, and peripheral edema, such as IgA nephropathy, membranous nephropathy, focal segmental glomerulus /minimal change disease, membranoproliferative glomerulonephritis, and lupus nephritis.
Epidemiology and Demographics
There is not much information available about the incidence and prevalence.
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Ali Poyan Mehr, M.D. [2]; Associate Editor(s)-in-Chief: Olufunmilola Olubukola M.D.[3]
Overview
There is not much information available about the incidence and prevalence.
Epidemiology and Demographics
Prevalence
There is not much information available about the prevalence of the disease.
Incidence
There is not much information available about the incidence of the disease.
Age
Patients of all age groups may develop C4 glomerulopathy.
Gender
C4 glomerulopathy affects men and women equally.
Race
There is no racial predilection to C4 glomerulopathy.
Geographic Distribution
C4 glomerulopathy can affect both developed or underdeveloped countries equally.
References
Risk factors
There are no established risk factors for C4 glomerulopathy.
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Ali Poyan Mehr, M.D. [2]; Associate Editor(s)-in-Chief: Olufunmilola Olubukola M.D.[3]
Overview
There are no established risk factors for C4 glomerulopathy.
Risk Factors
There are no established risk factors for C4 glomerulopathy.
References
Screening
There is insufficient information to recommend routine screening for C4 glomerulopathy.
Natural History, Complications and Prognosis
If left untreated, C4 glomerulopathy may progress to develop renal failure.
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Ali Poyan Mehr, M.D. [2]; Associate Editor(s)-in-Chief: Olufunmilola Olubukola M.D.[3]
Overview
If left untreated, C4 glomerulopathy may progress to develop renal failure.
Natural History, Complications, and Prognosis
Natural History
The symptoms of C4 glomerulopathy usually start with symptoms such as proteinuria, hematuria, edema, renal insufficiency hypocomplementemia, and hypertension[1].
Complications
Common complications of C4 glomerulopathy include[2][3]:
- Renal failure
Prognosis
Depending on the extent of the disease at the time of diagnosis, the prognosis may vary. However, the prognosis is generally regarded as poor[4].
References
- â Appel GB, Cook HT, Hageman G, Jennette JC, Kashgarian M, Kirschfink M; et al. (2005). “Membranoproliferative glomerulonephritis type II (dense deposit disease): an update”. J Am Soc Nephrol. 16 (5): 1392â403. doi:10.1681/ASN.2005010078. PMIDÂ 15800116.
- â Garam N, ProhĂĄszka Z, SzilĂĄgyi Ă, Aigner C, Schmidt A, Gaggl M; et al. (2019). “C4 nephritic factor in patients with immune-complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy”. Orphanet J Rare Dis. 14 (1): 247. doi:10.1186/s13023-019-1237-8. PMCÂ 6839100 Check
|pmc=value (help). PMID 31703608. - â Ali, Arshad; Schlanger, Lynn; Nasr, Samih H.; Sethi, Sanjeev; Gorbatkin, Steven M. (2016). “Proliferative C4 Dense Deposit Disease, Acute Thrombotic Microangiopathy, a Monoclonal Gammopathy, and Acute Kidney Failure”. American Journal of Kidney Diseases. 67 (3): 479â482. doi:10.1053/j.ajkd.2015.10.020. ISSN 0272-6386.
- â Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K; et al. (1993). “GeneReviewsÂź”. PMIDÂ 20301598.
Diagnosis
Diagnosis
History and Symptoms | Physical Examination | Laboratory Findings | X ray | CT | MRI | Echocardiography or Ultrasound | Other Imaging Studies | Other Diagnostic Studies
Treatment
Treatment
Surgery | Medical therapy | Primary Prevention | Secondary Prevention | Cost-Effectiveness of Therapy | Future or Investigational Therapies
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