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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
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
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

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
Importance of Genetic Diagnostics in Adult-Onset Focal Segmental Glomerulosclerosis.
Snoek R, Nguyen TQ, van der Zwaag B, van Zuilen AD, Kruis HME, van Gils-Verrij LA, Goldschmeding R, Knoers NVAM, Rookmaaker MB, van Eerde AM
Nephron 2019;142(4):351-358. Epub 2019 May 16 doi: 10.1159/000499937. PMID: 31096240Free 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
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
The development of proteinuria and focal-segmental glomerulosclerosis in recipients of pediatric donor kidneys.
Hayes JM, Steinmuller DR, Streem SB, Novick AC
Transplantation 1991 Nov;52(5):813-7. doi: 10.1097/00007890-199111000-00011. PMID: 1949166

Prognosis

Importance of Genetic Diagnostics in Adult-Onset Focal Segmental Glomerulosclerosis.
Snoek R, Nguyen TQ, van der Zwaag B, van Zuilen AD, Kruis HME, van Gils-Verrij LA, Goldschmeding R, Knoers NVAM, Rookmaaker MB, van Eerde AM
Nephron 2019;142(4):351-358. Epub 2019 May 16 doi: 10.1159/000499937. PMID: 31096240Free 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

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
MYH9 is a major-effect risk gene for focal segmental glomerulosclerosis.
Kopp JB, Smith MW, Nelson GW, Johnson RC, Freedman BI, Bowden DW, Oleksyk T, McKenzie LM, Kajiyama H, Ahuja TS, Berns JS, Briggs W, Cho ME, Dart RA, Kimmel PL, Korbet SM, Michel DM, Mokrzycki MH, Schelling JR, Simon E, Trachtman H, Vlahov D, Winkler CA
Nat Genet 2008 Oct;40(10):1175-84. Epub 2008 Sep 14 doi: 10.1038/ng.226. PMID: 18794856Free PMC Article
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

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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