- Focal segmental glomerulosclerosis
Name = Focal segmental glomerulosclerosis
ICD10 = N00-N08 (with .1 suffix)
ICD9 = ICD9|581.1
OMIM = 603278
OMIM_mult = OMIM2|603965 OMIM2|607832
eMedicineSubj = med
eMedicineTopic = 2944
MeshID = D005923
Focal segmental glomerulosclerosis is a cause of
nephrotic syndromein children and adolescents, as well as an important cause of kidney failurein adults.cite book | author = Kumar V, Fausto N, Abbas A (editors) | title = Robbins & Cotran Pathologic Basis of Disease | edition = 7th | pages= pp. 982-3 | publisher = Saunders | year = 2003 | isbn= 978-0-721-60187-8 ] Minimal change disease(MCD) is by far the most common cause of nephrotic syndrome in children: MCD and primary FSGS may have a similar cause.
The individual components of the name refer to the appearance of the kidney tissue on
biopsy: "focal" - only some of the glomeruli are involved (as opposed to diffuse), "segmental" - only part of an entire glomerulus is involved (as opposed to global), "glomerulosclerosis" - refers to scarring of the glomerulus(a part of the nephron(the functional unit of the kidney))
Depending on the cause it is broadly classified as
*Primary, when no underlying cause is found; usually presents as
*Secondary, when an underlying cause is identified; usually presents with
kidney failureand proteinuria. This is actually a heterogeneous group including numerous causes such as
**Infections such as
HIV(known as HIV-Associated Nephropathy)
**Toxins and drugs such as
nephronloss and hyperfiltration, such as with chronic pyelonephritisand reflux, morbid obesity, diabetes mellitus
There are many other classification schemes also.
Five mutually exclusive variants of focal segmental glomerulosclerosis may be distinguished by the pathologic findings seen on renal biopsy:cite journal |author=Thomas DB, Franceschini N, Hogan SL, "et al" |title=Clinical and pathologic characteristics of focal segmental glomerulosclerosis pathologic variants |journal=Kidney Int. |volume=69 |issue=5 |pages=920–6 |year=2006 |pmid=16518352 |doi=10.1038/sj.ki.5000160 |url=]
# Collapsing variant
# Glomerular tip lesion variant
# Cellular variant
# Perihilar variant
# Not otherwise specified (NOS) variant. Recognition of these variants may have prognostic value in individuals with primary focal segmental glomerulosclerosis (i.e. where no underlying cause is identified). The collapsing variant is associated with higher rate of progression to
end-stage renal disease, whereas glomerular tip lesion variant has low rate of progression to end-stage renal disease in most patients. Cellular variant shows similar clinical presentation to collapsing and glomerular tip variant but has intermediate outcomes between these two variants. However, because collapsing and glomerular tip variant show overlapping pathologic features with cellular variant, this intermediate difference in clinical outcomes may reflect sampling bias in cases of cellular focal segmental glomerulosclerosis (i.e. unsampled collapsing variant or glomerular tip variant). The prognostic significance of perihilar and NOS variants has not yet been determined. The NOS variant is the most common subtype.
There are currently several known genetic causes of the hereditary forms of FSGS.
* The first gene involved with this disorder is
ACTN4, which encodes alpha-actinin 4. This protein crosslinks bundles of actin filaments and is present in the podocyte. Mutations in this protein associated with FSGS result in increased affinity for actin binding, formation of intracellular aggregates, and decreased protein half-life. While it is unclear how these effects might lead to FSGS there are a number of theories. Firstly, protein aggregation may have a toxic effect on the podocyte. Secondly, decreased protein half-life or increased affinity for actin binding may alter actin polymerization and thereby affect the podocytes cytoskeletal architecture.cite journal |author=Mukerji N, Damodaran TV, Winn MP |title=TRPC6 and FSGS: The latest TRP channelopathy |journal= |volume= |issue= |pages= |year=2007 |pmid=17459670 |doi=10.1016/j.bbadis.2007.03.005 |url]
* A second gene associated with FSGS is
TRPC6, which encodes a member of the canonical family of TRP channels. This family of ion channels conduct cations in a largely non-selective manner. As with ACTN4, TRPC6 is expressed in podocytes. While TRP channels can be activated through a variety of methods, TRPC6 is known to be activated by phospholipase Cstimulation. There are at least 6 mutations in this channel, located throughout the channel. At least one of these mutations, P112Q, leads to increased intracellular calcium. It is unclear how this might lead to FSGS, though it has been proposed that it may result in alteration of podocyte dynamics or podocytopenia.
* Another gene known to be involved in hereditary forms of FSGS is the p130(Cas) ligand. The mouse homologue of this protein, CD2, is located in podocytes where it interacts with fyn and
synaptopodin. Mutations in this gene associated with FSGS occur at splice sites and lead to altered protein translation. This has been theorized to result in altered actin binding and, thus, alteration of the cytoskeletal podocyte architecture.
*Mutations in the NPHS2 gene, which codes for the protein called podocin, cause a recessive form of FSGS. An affected individual has two mutant copies of the NPHS2 gene, in contrast to ACTN4 and TRPC6 mediated forms of disease, which are dominant and require only one mutant copy of the gene. NPHS2-mediated FSGS is resistant to treatment with steroids.
ymptoms and signs
In children and some adults, FSGS presents as a
nephrotic syndrome(which is characterized by edema(associated with weight gain), hypoalbuminemia(low serum albumin (a protein) in the blood), hyperlipidemiaand hypertension(high blood pressure)). In adults it may also present as kidney failureand proteinuria, without a full-blown nephrotic syndrome.
blood tests- cholesterol
Minimal change disease, especially in children
* Salt restriction and
diuretics(water pills), such as furosemide, for edema
Antihypertensives(especially ACEIs) - if the blood pressure is too high
* treat present
hyperlipidemia(e.g. statins, fibrates)
Aldosterone antagonistto decrease proteinuria and thus offer a degree of reno-protection
Corticosteroids, such as prednisone- based on the clinical judgment of physician(no broad consensus/guideline)
Cytotoxics, such as cyclophosphamidemay be used to induce remission in patients presenting with FSGS refractory to corticosteroids, or in patients who do not tolerate steroids.
Plasmapheresis- blood cleansing using a machine to remove the patient's blood plasmaand replacing it with donor plasma.
*None - sometimes none of the above works and the patient will required
dialysiswith possibly later transplantation of a new kidney.
* [http://www.nephcure.org NephCure Foundation] Only organization solely committed to support research seeking the cause of Nephrotic Syndrome and FSGS, improve treatment and find the cure.
* [http://www.kidcomm.org Kidcomm] An online resource for parents dealing with childhood kidney diseases (FSGS, Nephrotic Syndrome and others)
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