Focal segmental glomerulosclerosis - Wikipedia, the free encyclopedia

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Focal segmental glomerulosclerosis

From Wikipedia, the free encyclopedia

Focal segmental
glomerulosclerosis (FSGS) is a
cause of nephrotic syndrome in
children and adolescents, as well
as an important cause of kidney

Focal segmental glomerulosclerosis

failure in adults.[1] It is also

known as "focal glomerular
sclerosis" or "focal nodular
glomerulosclerosis."[2] It accounts
for about a sixth of the cases of
nephrotic syndrome.[3] (Minimal
change disease (MCD) is by far
the most common cause of
nephrotic syndrome in children:
MCD and primary FSGS may

Light micrograph of focal segmental glomerulosclerosis, hilar variant. Kidney

biopsy. PAS stain.
Classification and external resources
ICD-10

N00
(http://apps.who.int/classifications/icd10/browse/2015/en#/N00)-N08
(http://apps.who.int/classifications/icd10/browse/2015/en#/N08)
(with .1 suffix)

ICD-9

581.1 (http://www.icd9data.com/getICD9Code.ashx?icd9=581.1)

OMIM

603278 (http://omim.org/entry/603278) 603965

(https://omim.org/entry/603965) 607832
(https://omim.org/entry/607832) 612551
(https://omim.org/entry/612551) 613237
(https://omim.org/entry/613237) 600995
(https://omim.org/entry/600995)

have a similar cause.[1])

Contents
1 Appearance
2 Classification
2.1 Pathologic
variants
3 Causes
4 Diagnosis
4.1 Symptoms and
signs
4.2 Tests
4.3 Differential
diagnosis
5 Treatment
6 Notable patients
7 See also
8 External links
9 References

MedlinePlus 000478
(http://www.nlm.nih.gov/medlineplus/ency/article/000478.htm)
eMedicine

med/2944 (http://www.emedicine.com/med/topic2944.htm)

MeSH

D005923 (https://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?
field=uid&term=D005923)

Appearance
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The individual components of the name refer to the appearance of the kidney tissue on biopsy: focalonly
some of the glomeruli are involved (as opposed to diffuse), segmentalonly part of each glomerulus is
involved (as opposed to global),[4] glomerulosclerosisrefers to scarring of the glomerulus (a part of the
nephron (the functional unit of the kidney)). The glomerulosclerosis is usually indicated by heavy PAS staining
and findings of IgM and C3 in sclerotic segment.[5]

Classification
Depending on the cause it is broadly classified as:
Primary, when no underlying cause is found; usually presents as nephrotic syndrome
Secondary, when an underlying cause is identified; usually presents with kidney failure and 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 heroin and pamidronate
Familial forms
Secondary to nephron loss and hyperfiltration, such as with chronic pyelonephritis and reflux,
morbid obesity, diabetes mellitus
There are many other classification schemes also.

Pathologic variants
Five mutually exclusive variants of focal segmental glomerulosclerosis
may be distinguished by the pathologic findings seen on renal biopsy:[6]
1.
2.
3.
4.
5.

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

Micrograph of the collapsing variant

of FSGS (collapsing glomerulopathy).
A collapsed glomerulus is seen at the
top, right-of-centre. PAS stain.
Kidney biopsy.

in most patients.[6] 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.[6]Collapsing variant is most common type of glomerulopathy caused by HIV infection.

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Causes
Some general secondary causes are listed below:
Glomerular hypertrophy/hyperfiltration
Unilateral renal agenesis
Massive obesity
Scarring due to previous injury
Focal proliferative glomerulonephritis
Vasculitis
Lupus
Toxins (pamidronate)
Human immunodeficiency virus-associated nephropathy
Heroin nephropathy[7]
There are currently several known genetic causes of the hereditary forms of FSGS.
Gene

OMIM

Description

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
FSGS1: 603278
ACTN4 (https://omim.org/entry/603278) 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.[8]
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
FSGS2: 603965
known to be activated by phospholipase C stimulation. There are at
TRPC6 (https://omim.org/entry/603965) least 6 mutations in this channel, located throughout the channel. At
least one of these mutations, P112Q, leads to increased intracellular
calcium influx. 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.[8]
Another gene that may be involved in hereditary forms of FSGS is
the gene known as CD2AP (CD2 associated protein) or CMS (Cas
binding protein with multiple SH3 domains). The protein expressed
by this gene is expressed in podocytes where it interacts with fyn
FSGS3: 607832
and synaptopodin. There is a report that a splicing mutation in this
CD2AP (https://omim.org/entry/607832) gene was found in two patients with HIV associated FSGS and this
led to altered protein translation. This has been theorized to result in
altered actin binding and, thus, alteration of the cytoskeletal
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podocyte architecture.[8]
In people of African descent, two common variants in APOL1 have
been associated with FSGS. It is believed that these variants arose
FSGS4: 612551
as a defensive mechanism against Trypanosoma brucei rhodesiense
APOL1 (https://omim.org/entry/612551) or some other sub-Saharan parasite despite conferring high
susceptibility to FSGS when inherited from both parents.[9]
Another gene associated with FSGS is INF2, which encodes a
member of the formin family of actin-regulating proteins. The
FSGS5: 613237
observation that alterations in this podocyte-expressed formin cause
INF2
(https://omim.org/entry/613237) FSGS emphasizes the importance of fine regulation of actin
polymerization in podocyte function.[10]
Mutations in the NPHS2 gene, which codes for the protein called
podocin,[11] can cause focal segmental glomerulosclerosis.[12] This
is a recessive form of FSGS.[13] An affected individual has two
SRN1: 600995
NPHS2 (https://omim.org/entry/600995) 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.
Some researchers found SuPAR as a cause of FSGS.

Diagnosis
Symptoms 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), hyperlipidemia
and hypertension (high blood pressure). In adults it may also present as kidney failure and proteinuria, without a
full-blown nephrotic syndrome.

Tests
Urinalysis
Blood tests cholesterol
Kidney biopsy

Differential diagnosis
Minimal change disease, especially in children
Several others

Treatment
Salt restriction and diuretics, such as furosemide, for edema.
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Antihypertensives (especially ACEIs) if the blood pressure is too high but not so for it, it has another
protective effect
Treat present hyperlipidemia (e.g. statins, fibrates; although fibrates are contraindicated in renal failure)
Aldosterone antagonist to decrease proteinuria and thus offer a degree of reno-protection
Angiotensin II receptor antagonist
rituximab
galactose
Pirfenidone
tacrolimus
Abatacept
Corticosteroids, such as prednisone based on the clinical judgment of physician (no broad
consensus/guideline)
Cytotoxics, such as cyclophosphamide may 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 plasma and replacing it
with donor plasma.
Vitamin E
Low-dose naltrexone cure FSGS on less than 6 months without side effects at cost of U$$ 300.00 year,
less than a dollar day.
Fish oil
Immunosuppressive drugs
If none of the above works, the patient will require dialysis with possibly later transplantation of a new
kidney that probably will be lost fast by FSGS due the FSGS agressor agent on the blood.

Notable patients
Former NBA basketball players Sean Elliott and Alonzo Mourning have both survived bouts with FSGS.
Mourning is an Ambassador to The NephCure Foundation (http://www.nephcure.org). Pro bodybuilder
Flex Wheeler was diagnosed with FSGS and had a kidney transplant. Former MLS player Clyde Simms
retired from professional soccer in 2014 due to FSGS.[14]
Gary Coleman American actor, known for his childhood role as Arnold Jackson in the American sitcom
Diff'rent Strokes.

See also
Glomerulonephritis
Nephrotic syndrome

External links
01 - FSGS cure on 4 months with cheap no side effects LDN (https://www.inspire.com/groups/nephroticsyndrome-and-fsgs/discussion/low-dose-naltrexone-ldn-6/)
02 - FSGS cure on 4 months with cheap no side effects LDN (https://www.inspire.com/groups/nephroticsyndrome-and-fsgs/discussion/low-dose-naltrexone-47/)
Wei C, El Hindi S, Li J, Fornoni A, Goes N, Sageshima J, Maiguel D, Karumanchi SA, Yap HK, Saleem
M, Zhang Q, Nikolic B, Chaudhuri A, Daftarian P, Salido E, Torres A, Salifu M, Sarwal MM, Schaefer F,
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Morath C, Schwenger V, Zeier M, Gupta V, Roth D, Rastaldi MP, Burke G, Ruiz P, Reiser J (July 2011).
"Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis"
(http://www.nature.com/nm/journal/v17/n8/abs/nm.2411.html). Nat Med 17 (8): 952960.
doi:10.1038/nm.2411 (https://dx.doi.org/10.1038%2Fnm.2411). PMID 21804539
(https://www.ncbi.nlm.nih.gov/pubmed/21804539).
NephCure Foundation (http://www.nephcure.org) Only organization solely committed to support research
seeking the cause of Nephrotic Syndrome and FSGS, improve treatment and find the cure.
Kidcomm (http://www.kidcomm.org) An online resource for parents dealing with childhood kidney
diseases (FSGS, Nephrotic Syndrome and others)
FSGS Research (http://www.fsgs.bwh.harvard.edu) A team of kidney doctors and scientists from Brigham
and Women's Hospital / Harvard Medical School working to learn more about the cause of FSGS and
Nephrotic Syndrome in children and adults, with an emphasis on the genetic basis of these diseases.
A general overview of Renal Pathology
(http://sites.google.com/site/medschoolnotesorg/pathology/kidney)
Tahzib M, Frank R, Gauthier B, Valderrama E, Trachtman H (October 1999). "Vitamin E treatment of
focal segmental glomerulosclerosis: results of an open-label study"
(http://link.springer.de/link/service/journals/00467/bibs/9013008/90130649.htm). Pediatr. Nephrol. 13
(8): 64952. doi:10.1007/s004670050674 (https://dx.doi.org/10.1007%2Fs004670050674).
PMID 10502120 (https://www.ncbi.nlm.nih.gov/pubmed/10502120).

References
1. Kumar V, Fausto N, Abbas A, ed. (2003). Robbins & Cotran Pathologic Basis of Disease (7th ed.). Saunders. pp. 9823.
ISBN 978-0-7216-0187-8.
2. "focal segmental glomerulosclerosis
(http://web.archive.org/web/20090616022448/http://www.mercksource.com/pp/us/cns/cns_hl_dorlands_split.jsp?
pg=/ppdocs/us/common/dorlands/dorland/four/000045124.htm)" at Dorland's Medical Dictionary
3. "Renal Pathology" (http://library.med.utah.edu/WebPath/RENAHTML/RENAL083.html). Retrieved 2008-11-25.
4. "Focal_segmental_glomerulosclerosis of the Kidney" (http://pathweb.uchc.edu/eAtlas/Code/1505.HTM). Retrieved
2008-11-25.
5. "Focal_segmental_glomerulosclerosis of the Kidney"
(http://sites.google.com/site/medschoolnotesorg/pathology/kidney). Retrieved 2009-11-20.
6. Thomas DB, Franceschini N, Hogan SL et al. (2006). "Clinical and pathologic characteristics of focal segmental
glomerulosclerosis pathologic variants". Kidney Int. 69 (5): 9206. doi:10.1038/sj.ki.5000160
(https://dx.doi.org/10.1038%2Fsj.ki.5000160). PMID 16518352 (https://www.ncbi.nlm.nih.gov/pubmed/16518352).
7. Burtis, C.A.; Ashwood, E.R. and Bruns, D.E. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 5th
Edition. Elsevier. pp1566
8. Mukerji N, Damodaran TV, Winn MP (2007). "TRPC6 and FSGS: The latest TRP channelopathy". Biochimica et
Biophysica Acta (BBA) - Molecular Basis of Disease 1772 (8): 85968. doi:10.1016/j.bbadis.2007.03.005
(https://dx.doi.org/10.1016%2Fj.bbadis.2007.03.005). PMID 17459670
(https://www.ncbi.nlm.nih.gov/pubmed/17459670).
9. Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, Bowden DW, Langefeld CD, Oleksyk TK,
Uscinski Knob AL, Bernhardy AJ, Hicks PJ, Nelson GW, Vanhollebeke B, Winkler CA, Kopp JB, Pays E, Pollak MR.
(Jul 2010). "Association of Trypanolytic ApoL1 Variants with Kidney Disease in African-Americans"
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980843). Science 329 (5993): 8415. doi:10.1126/science.1193032
(https://dx.doi.org/10.1126%2Fscience.1193032). PMC 2980843
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980843). PMID 20647424
(https://www.ncbi.nlm.nih.gov/pubmed/20647424).
https://en.wikipedia.org/wiki/Focal_segmental_glomerulosclerosis

Page 6 of 7

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6/28/15, 5:56

10. Brown EJ, Schlndorff JS, Becker DJ, Tsukaguchi H, Uscinski AL, Higgs HN, Henderson JM, Pollak MR. (Jan 2010).
"Mutations in the formin protein INF2 cause focal segmental glomerulosclerosis"
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980844). Nature Genetics 42 (1): 726. doi:10.1038/ng.505
(https://dx.doi.org/10.1038%2Fng.505). PMC 2980844 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2980844).
PMID 20023659 (https://www.ncbi.nlm.nih.gov/pubmed/20023659).
11. Tsukaguchi H, Sudhakar A, Le TC et al. (December 2002). "NPHS2 mutations in late-onset focal segmental
glomerulosclerosis: R229Q is a common disease-associated allele"
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC151634). J. Clin. Invest. 110 (11): 165966. doi:10.1172/JCI16242
(https://dx.doi.org/10.1172%2FJCI16242). PMC 151634 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC151634).
PMID 12464671 (https://www.ncbi.nlm.nih.gov/pubmed/12464671).
12. Franceschini N, North KE, Kopp JB, McKenzie L, Winkler C (February 2006). "NPHS2 gene, nephrotic syndrome and
focal segmental glomerulosclerosis: a HuGE review" (http://meta.wkhealth.com/pt/pt-core/templatejournal/lwwgateway/media/landingpage.htm?an=00125817-200602000-00001). Genet. Med. 8 (2): 6375.
doi:10.1097/01.gim.0000200947.09626.1c (https://dx.doi.org/10.1097%2F01.gim.0000200947.09626.1c).
PMID 16481888 (https://www.ncbi.nlm.nih.gov/pubmed/16481888).
13. Boute N, Gribouval O, Roselli S, Benessy F, Lee H, Fuchshuber A, Dahan K, Gubler M-C, Niaudet P, Antignac C (May
2000). "NPHS2, encoding the glomerular protein podocin, is mutated in autosomal recessive steroid-resistant nephrotic
syndrome". Nature Genetics 24 (4): 349354. doi:10.1038/74166 (https://dx.doi.org/10.1038%2F74166).
PMID 10742096 (https://www.ncbi.nlm.nih.gov/pubmed/10742096).
14. http://www.mlssoccer.com/news/article/2014/02/13/kidney-disease-forces-former-new-england-revolution-dc-unitedmidfielder-cly
[1]

1. {Mujtaba, 2015 #31}

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