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Focal segmental glomerulosclerosis 4, susceptibility to(FSGS4)

MedGen UID:
390820
•Concept ID:
C2675525
•
Finding
Synonyms: END-STAGE RENAL DISEASE, NONDIABETIC, SUSCEPTIBILITY TO; FSGS4
 
Gene (location): APOL1 (22q12.3)
 
Monarch Initiative: MONDO:0012931
OMIM®: 612551

Definition

Focal segmental glomerulosclerosis (FSGS) is a pathologic entity associated clinically with proteinuria, the nephrotic syndrome (NPHS), and progressive loss of renal function. It is a common cause of end-stage renal disease (ESRD) (Meyrier, 2005). For a general phenotypic description and a discussion of genetic heterogeneity of focal segmental glomerulosclerosis and nephrotic syndrome, see FSGS1 (603278). [from OMIM]

Clinical features

From HPO
Focal segmental glomerulosclerosis
MedGen UID:
4904
•Concept ID:
C0017668
•
Disease or Syndrome
Segmental accumulation of scar tissue in individual (but not all) glomeruli.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature

Professional guidelines

PubMed

APOL1 risk genotype in European steroid-resistant nephrotic syndrome and/or focal segmental glomerulosclerosis patients of different African ancestries.
Gribouval O, Boyer O, Knebelmann B, Karras A, Dantal J, Fourrage C, Alibeu O, Hogan J, Dossier C, Tête MJ, Antignac C, Servais A
Nephrol Dial Transplant 2019 Nov 1;34(11):1885-1893. doi: 10.1093/ndt/gfy176. PMID: 29992269
Genotype-phenotype associations in WT1 glomerulopathy.
Lipska BS, Ranchin B, Iatropoulos P, Gellermann J, Melk A, Ozaltin F, Caridi G, Seeman T, Tory K, Jankauskiene A, Zurowska A, Szczepanska M, Wasilewska A, Harambat J, Trautmann A, Peco-Antic A, Borzecka H, Moczulska A, Saeed B, Bogdanovic R, Kalyoncu M, Simkova E, Erdogan O, Vrljicak K, Teixeira A, Azocar M, Schaefer F; PodoNet Consortium
Kidney Int 2014 May;85(5):1169-78. Epub 2014 Jan 8 doi: 10.1038/ki.2013.519. PMID: 24402088
The CTLA-4 +49GG genotype is associated with susceptibility for nephrotic kidney diseases.
Spink C, Stege G, Tenbrock K, Harendza S
Nephrol Dial Transplant 2013 Nov;28(11):2800-5. Epub 2013 Aug 23 doi: 10.1093/ndt/gft381. PMID: 23975748

Suggested Reading

PubMed

APOL1 risk variants, race, and progression of chronic kidney disease.
Parsa A, Kao WH, Xie D, Astor BC, Li M, Hsu CY, Feldman HI, Parekh RS, Kusek JW, Greene TH, Fink JC, Anderson AH, Choi MJ, Wright JT Jr, Lash JP, Freedman BI, Ojo A, Winkler CA, Raj DS, Kopp JB, He J, Jensvold NG, Tao K, Lipkowitz MS, Appel LJ; AASK Study Investigators; CRIC Study Investigators
N Engl J Med 2013 Dec 5;369(23):2183-96. Epub 2013 Nov 9 doi: 10.1056/NEJMoa1310345. PMID: 24206458Free PMC Article

Recent clinical studies

Etiology

Genetic Causes of Nephrotic Syndrome and Focal and Segmental Glomerulosclerosis.
Caparali EB, De Gregorio V, Barua M
Adv Kidney Dis Health 2024 Jul;31(4):309-316. doi: 10.1053/j.akdh.2024.04.001. PMID: 39084756
UBD modifies APOL1-induced kidney disease risk.
Zhang JY, Wang M, Tian L, Genovese G, Yan P, Wilson JG, Thadhani R, Mottl AK, Appel GB, Bick AG, Sampson MG, Alper SL, Friedman DJ, Pollak MR
Proc Natl Acad Sci U S A 2018 Mar 27;115(13):3446-3451. Epub 2018 Mar 12 doi: 10.1073/pnas.1716113115. PMID: 29531077Free PMC Article
Obesity-related kidney disease.
Snyder S, Turner GA, Turner A
Prim Care 2014 Dec;41(4):875-93. Epub 2014 Oct 3 doi: 10.1016/j.pop.2014.08.008. PMID: 25439539
Association of trypanolytic ApoL1 variants with kidney disease in African Americans.
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
Science 2010 Aug 13;329(5993):841-5. Epub 2010 Jul 15 doi: 10.1126/science.1193032. PMID: 20647424Free PMC Article
Genetic basis of nephrotic syndrome--review.
Obeidová H, Merta M, Reiterová J, Maixnerová D, Stekrová J, Rysavá R, Tesar V
Prague Med Rep 2006;107(1):5-16. PMID: 16752799

Diagnosis

Genetic Causes of Nephrotic Syndrome and Focal and Segmental Glomerulosclerosis.
Caparali EB, De Gregorio V, Barua M
Adv Kidney Dis Health 2024 Jul;31(4):309-316. doi: 10.1053/j.akdh.2024.04.001. PMID: 39084756
An Acidic Environment Induces APOL1-Associated Mitochondrial Fragmentation.
Li D, Snipes JA, Murea M, Molina AJA, Divers J, Freedman BI, Ma L, Petrovic S
Am J Nephrol 2020;51(9):695-704. Epub 2020 Aug 31 doi: 10.1159/000509989. PMID: 32866949Free PMC Article
TRPC6 Mutational Analysis in Iranian Children With Focal Segmental Glomerulosclerosis.
Gheissari A, Meamar R, Kheirollahi M, Rouigari M, Dehbashi M, Dehghani L, Abedini A
Iran J Kidney Dis 2018 Nov;12(6):341-349. PMID: 30595563
Genotype-phenotype associations in WT1 glomerulopathy.
Lipska BS, Ranchin B, Iatropoulos P, Gellermann J, Melk A, Ozaltin F, Caridi G, Seeman T, Tory K, Jankauskiene A, Zurowska A, Szczepanska M, Wasilewska A, Harambat J, Trautmann A, Peco-Antic A, Borzecka H, Moczulska A, Saeed B, Bogdanovic R, Kalyoncu M, Simkova E, Erdogan O, Vrljicak K, Teixeira A, Azocar M, Schaefer F; PodoNet Consortium
Kidney Int 2014 May;85(5):1169-78. Epub 2014 Jan 8 doi: 10.1038/ki.2013.519. PMID: 24402088
Thin basement membrane nephropathy.
Savige J, Rana K, Tonna S, Buzza M, Dagher H, Wang YY
Kidney Int 2003 Oct;64(4):1169-78. doi: 10.1046/j.1523-1755.2003.00234.x. PMID: 12969134

Therapy

Homozygous splicing mutation in NUP133 causes Galloway-Mowat syndrome.
Fujita A, Tsukaguchi H, Koshimizu E, Nakazato H, Itoh K, Kuraoka S, Komohara Y, Shiina M, Nakamura S, Kitajima M, Tsurusaki Y, Miyatake S, Ogata K, Iijima K, Matsumoto N, Miyake N
Ann Neurol 2018 Dec;84(6):814-828. doi: 10.1002/ana.25370. PMID: 30427554
Association of HLA-DR/DQ alleles and haplotypes with nephrotic syndrome.
Ramanathan AS, Senguttuvan P, Chinniah R, Vijayan M, Thirunavukkarasu M, Raju K, Mani D, Ravi PM, Rajendran P, Krishnan JI, Karuppiah B
Nephrology (Carlton) 2016 Sep;21(9):745-52. doi: 10.1111/nep.12669. PMID: 26566811
Galactose binds to focal segmental glomerulosclerosis permeability factor and inhibits its activity.
Savin VJ, McCarthy ET, Sharma R, Charba D, Sharma M
Transl Res 2008 Jun;151(6):288-92. Epub 2008 May 2 doi: 10.1016/j.trsl.2008.04.001. PMID: 18514139
The genetic basis of FSGS and steroid-resistant nephrosis.
Pollak MR
Semin Nephrol 2003 Mar;23(2):141-6. doi: 10.1053/snep.2003.50014. PMID: 12704574
Plasma and urinary endothelin-1 in focal segmental glomerulosclerosis.
Chen HC, Guh JY, Chang JM, Tsai JC, Hwang SJ, Lai YH
J Clin Lab Anal 2001;15(2):59-63. doi: 10.1002/jcla.2. PMID: 11291106Free PMC Article

Prognosis

An Update on Viral Infection-Associated Collapsing Glomerulopathy.
Fisher M, Ross M, DiFranza L, Reidy K
Adv Kidney Dis Health 2024 Jul;31(4):317-325. doi: 10.1053/j.akdh.2023.12.007. PMID: 39084757Free PMC Article
TRPC6 Mutational Analysis in Iranian Children With Focal Segmental Glomerulosclerosis.
Gheissari A, Meamar R, Kheirollahi M, Rouigari M, Dehbashi M, Dehghani L, Abedini A
Iran J Kidney Dis 2018 Nov;12(6):341-349. PMID: 30595563
Genotype-phenotype associations in WT1 glomerulopathy.
Lipska BS, Ranchin B, Iatropoulos P, Gellermann J, Melk A, Ozaltin F, Caridi G, Seeman T, Tory K, Jankauskiene A, Zurowska A, Szczepanska M, Wasilewska A, Harambat J, Trautmann A, Peco-Antic A, Borzecka H, Moczulska A, Saeed B, Bogdanovic R, Kalyoncu M, Simkova E, Erdogan O, Vrljicak K, Teixeira A, Azocar M, Schaefer F; PodoNet Consortium
Kidney Int 2014 May;85(5):1169-78. Epub 2014 Jan 8 doi: 10.1038/ki.2013.519. PMID: 24402088
Genetic basis of nephrotic syndrome--review.
Obeidová H, Merta M, Reiterová J, Maixnerová D, Stekrová J, Rysavá R, Tesar V
Prague Med Rep 2006;107(1):5-16. PMID: 16752799
Thin basement membrane nephropathy.
Savige J, Rana K, Tonna S, Buzza M, Dagher H, Wang YY
Kidney Int 2003 Oct;64(4):1169-78. doi: 10.1046/j.1523-1755.2003.00234.x. PMID: 12969134

Clinical prediction guides

An Update on Viral Infection-Associated Collapsing Glomerulopathy.
Fisher M, Ross M, DiFranza L, Reidy K
Adv Kidney Dis Health 2024 Jul;31(4):317-325. doi: 10.1053/j.akdh.2023.12.007. PMID: 39084757Free PMC Article
Novel Linkage Peaks Discovered for Diabetic Nephropathy in Individuals With Type 1 Diabetes.
Haukka J, Sandholm N, Valo E, Forsblom C, Harjutsalo V, Cole JB, McGurnaghan SJ, Colhoun HM, Groop PH; FinnDiane Study Group
Diabetes 2021 Apr;70(4):986-995. Epub 2021 Jan 7 doi: 10.2337/db20-0158. PMID: 33414249Free PMC Article
TRPC6 Mutational Analysis in Iranian Children With Focal Segmental Glomerulosclerosis.
Gheissari A, Meamar R, Kheirollahi M, Rouigari M, Dehbashi M, Dehghani L, Abedini A
Iran J Kidney Dis 2018 Nov;12(6):341-349. PMID: 30595563
NUP107 mutations in children with steroid-resistant nephrotic syndrome.
Park E, Ahn YH, Kang HG, Miyake N, Tsukaguchi H, Cheong HI
Nephrol Dial Transplant 2017 Jun 1;32(6):1013-1017. doi: 10.1093/ndt/gfw103. PMID: 27190346
The genetic basis of FSGS and steroid-resistant nephrosis.
Pollak MR
Semin Nephrol 2003 Mar;23(2):141-6. doi: 10.1053/snep.2003.50014. PMID: 12704574

Recent systematic reviews

The association between angiotensin-converting enzyme insertion/deletion gene variant and risk of focal segmental glomerulosclerosis: a systematic review and meta-analysis.
Zhou TB, Qin YH, Su LN, Lei FY, Huang WF, Zhao YJ, Pang YS, Yang KP
J Renin Angiotensin Aldosterone Syst 2011 Dec;12(4):624-33. Epub 2011 Jun 7 doi: 10.1177/1470320311410584. PMID: 21652690

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