Genetic Testing for Glomerular Diseases
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Emily E. GroopmanDivision of Nephrology, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, New York

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Ali G. GharaviDivision of Nephrology, Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, New York and Institute for Genomic Medicine, Columbia University, Columbia University Vagelos College of Physicians and Surgeons New York, New York

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  • 1

    Kidney Disease: Improving Global Outcomes Glomerular Diseases Work Group: KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int 100: S1S276, 2021 10.1016/j.kint.2021.05.021

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  • 2

    Harada R, Hamasaki Y, Okuda Y, Hamada R, Ishikura K: Epidemiology of pediatric chronic kidney disease/kidney failure: Learning from registries and cohort studies. Pediatr Nephrol 37: 12151229, 2022 10.1007/s00467-021-05145-1 PubMed

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    • Search Google Scholar
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  • 3

    Groopman EE, Povysil G, Goldstein DB, Gharavi AG: Rare genetic causes of complex kidney and urological diseases. Nat Rev Nephrol 16: 641656, 2020 10.1038/s41581-020-0325-2 PubMed

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    • Search Google Scholar
    • Export Citation
  • 4

    Groopman EE, Rasouly HM, Gharavi AG: Genomic medicine for kidney disease. Nat Rev Nephrol 14: 83104, 2018 10.1038/nrneph.2017.167 PubMed

  • 5

    Connaughton DM, Hildebrandt F: Personalized medicine in chronic kidney disease by detection of monogenic mutations. Nephrol Dial Transplant 35: 390397, 2020 10.1093/ndt/gfz028 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6

    Skrunes R, Svarstad E, Reisaeter AV, Vikse BE: Familial clustering of ESKD in the Norwegian population. Clin J Am Soc Nephrol 9: 16921700, 2014 10.2215/CJN.01680214 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7

    Freedman BI, Soucie JM, McClellan WM: Family history of end-stage renal disease among incident dialysis patients. J Am Soc Nephrol 8: 19421945, 1997 PubMed

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    • Search Google Scholar
    • Export Citation
  • 8

    Freedman BI, Volkova NV, Satko SG, Krisher J, Jurkovitz C, Soucie JM, et al.: Population-based screening for family history of end-stage renal disease among incident dialysis patients. Am J Nephrol 25: 529535, 2005 10.1159/000088491 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9

    Shang N, Khan A, Polubriaginof F, Zanoni F, Mehl K, Fasel D, et al.: Medical records-based chronic kidney disease phenotype for clinical care and “big data” observational and genetic studies. NPJ Digit Med 4: 70, 2021 10.1038/s41746-021-00428-1 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10

    Wuttke M, Li Y, Li M, Sieber KB, Feitosa MF, Gorski M, et al.; Lifelines Cohort Study; V. A. Million Veteran Program: A catalog of genetic loci associated with kidney function from analyses of a million individuals. Nat Genet 51: 957972, 2019 10.1038/s41588-019-0407-x PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11

    Kopp JB, Anders HJ, Susztak K, Podestà MA, Remuzzi G, Hildebrandt F, et al.: Podocytopathies. Nat Rev Dis Primers 6: 68, 2020 10.1038/s41572-020-0196-7 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12

    Lemaire M, Noone D, Lapeyraque AL, Licht C, Frémeaux-Bacchi V: Inherited kidney complement diseases. Clin J Am Soc Nephrol 16: 942956, 2021 10.2215/CJN.11830720 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13

    Kiryluk K, Li Y, Scolari F, Sanna-Cherchi S, Choi M, Verbitsky M, et al.: Discovery of new risk loci for IgA nephropathy implicates genes involved in immunity against intestinal pathogens. Nat Genet 46: 11871196, 2014 10.1038/ng.3118 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14

    Lyons PA, Rayner TF, Trivedi S, Holle JU, Watts RA, Jayne DR, et al.: Genetically distinct subsets within ANCA-associated vasculitis. N Engl J Med 367: 214223, 2012 10.1056/NEJMoa1108735 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15

    Genovese G, Friedman DJ, Ross MD, Lecordier L, Uzureau P, Freedman BI, et al.: Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science 329: 841845, 2010

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16

    Tzur S, Rosset S, Shemer R, Yudkovsky G, Selig S, Tarekegn A, et al.: Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene. Hum Genet 128: 345350, 2010 10.1007/s00439-010-0861-0 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17

    Xie J, Liu L, Mladkova N, Li Y, Ren H, Wang W, et al.: The genetic architecture of membranous nephropathy and its potential to improve non-invasive diagnosis. Nat Commun 11: 1600, 2020 10.1038/s41467-020-15383-w PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18

    Stanescu HC, Arcos-Burgos M, Medlar A, Bockenhauer D, Kottgen A, Dragomirescu L, et al.: Risk HLA-DQA1 and PLA(2)R1 alleles in idiopathic membranous nephropathy. N Engl J Med 364: 616626, 2011 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19

    Jia X, Yamamura T, Gbadegesin R, McNulty MT, Song K, Nagano C, et al.; Research Consortium on Genetics of Childhood Idiopathic Nephrotic Syndrome in Japan; Korean Consortium of Hereditary Renal Diseases in Children; Midwest Pediatric Nephrology Consortium (Genetics of Nephrotic Syndrome Study Group); NEPHROVIR: Common risk variants in NPHS1 and TNFSF15 are associated with childhood steroid-sensitive nephrotic syndrome. Kidney Int 98: 13081322, 2020 10.1016/j.kint.2020.05.029 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20

    Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al.: Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17: 405424, 2015 10.1038/gim.2015.30

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21

    Katsanis SH, Katsanis N: Molecular genetic testing and the future of clinical genomics. Nat Rev Genet 14: 415426, 2013 10.1038/nrg3493 PubMed

  • 22

    Rehm HL: Disease-targeted sequencing: A cornerstone in the clinic. Nat Rev Genet 14: 295300, 2013 10.1038/nrg3463 PubMed

  • 23

    Petersen BS, Fredrich B, Hoeppner MP, Ellinghaus D, Franke A: Opportunities and challenges of whole-genome and -exome sequencing. BMC Genet 18: 14, 2017 10.1186/s12863-017-0479-5 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24

    South ST, Lee C, Lamb AN, Higgins AW, Kearney HM; Working Group for the American College of Medical Genetics and Genomics Laboratory Quality Assurance Committee: ACMG standards and guidelines for constitutional cytogenomic microarray analysis, including postnatal and prenatal applications: Revision 2013. Genet Med 15: 901909, 2013 10.1038/gim.2013.129

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25

    Sadowski CE, Lovric S, Ashraf S, Pabst WL, Gee HY, Kohl S, et al.; SRNS Study Group: A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. J Am Soc Nephrol 26: 12791289, 2015 10.1681/ASN.2014050489 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26

    Benson KA, Murray SL, Doyle R, Doyle B, Dorman AM, Sadlier D, et al.: Diagnostic utility of genetic testing in patients undergoing renal biopsy. Cold Spring Harb Mol Case Stud 6: a005462, 2020 10.1101/mcs.a005462 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27

    Mansilla MA, Sompallae RR, Nishimura CJ, Kwitek AE, Kimble MJ, Freese ME, et al.: Targeted broad-based genetic testing by next-generation sequencing informs diagnosis and facilitates management in patients with kidney diseases. Nephrol Dial Transplant 36: 295305, 2021 10.1093/ndt/gfz173 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28

    Ottlewski I, Münch J, Wagner T, Schönauer R, Bachmann A, Weimann A, et al.: Value of renal gene panel diagnostics in adults waiting for kidney transplantation due to undetermined end-stage renal disease. Kidney Int 96: 222230, 2019 10.1016/j.kint.2019.01.038 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29

    Mrug M, Bloom MS, Seto C, Malhotra M, Tabriziani H, Gauthier P, et al.: Genetic testing for chronic kidney diseases: Clinical utility and barriers perceived by nephrologists. Kidney Med 3: 10501056, 2021 10.1016/j.xkme.2021.08.006 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30

    Bleyer AJ, Westemeyer M, Xie J, Bloom MS, Brossart K, Eckel JJ, et al.: Genetic etiologies for chronic kidney disease revealed through next-generation renal gene panel. Am J Nephrol 53: 297306, 2022 10.1159/000522226 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31

    Jayasinghe K, Wu Y, Stark Z, Kerr PG, Mallett AJ, Gaff C, et al.: Cost-effectiveness of targeted exome analysis as a diagnostic test in glomerular diseases. Kidney Int Rep 6: 28502861, 2021 10.1016/j.ekir.2021.08.028 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32

    Shendure J, Balasubramanian S, Church GM, Gilbert W, Rogers J, Schloss JA, et al.: DNA sequencing at 40: Past, present and future. Nature 550: 345353, 2017 10.1038/nature24286 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33

    Logsdon GA, Vollger MR, Eichler EE: Long-read human genome sequencing and its applications. Nat Rev Genet 21: 597614, 2020 10.1038/s41576-020-0236-x PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 34

    Groopman EE, Marasa M, Cameron-Christie S, Petrovski S, Aggarwal VS, Milo-Rasouly H, et al.: Diagnostic utility of exome sequencing for kidney disease. N Engl J Med 380: 142151, 2019 10.1056/NEJMoa1806891 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 35

    Connaughton DM, Kennedy C, Shril S, Mann N, Murray SL, Williams PA, et al.: Monogenic causes of chronic kidney disease in adults. Kidney Int 95: 914928, 2019 10.1016/j.kint.2018.10.031 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 36

    Santín S, Bullich G, Tazón-Vega B, García-Maset R, Giménez I, Silva I, et al.: Clinical utility of genetic testing in children and adults with steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol 6: 11391148, 2011 10.2215/CJN.05260610 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 37

    Tan W, Lovric S, Ashraf S, Rao J, Schapiro D, Airik M, et al.: Analysis of 24 genes reveals a monogenic cause in 11.1% of cases with steroid-resistant nephrotic syndrome at a single center. Pediatr Nephrol 33: 305314, 2018 10.1007/s00467-017-3801-6 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38

    Warejko JK, Tan W, Daga A, Schapiro D, Lawson JA, Shril S, et al.: Whole exome sequencing of patients with steroid-resistant nephrotic syndrome. Clin J Am Soc Nephrol 13: 5362, 2018 10.2215/CJN.04120417 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 39

    Lata S, Marasa M, Li Y, Fasel DA, Groopman E, Jobanputra V, et al.: Whole-exome sequencing in adults with chronic kidney disease: A pilot study. Ann Intern Med 168: 100109, 2018 10.7326/M17-1319 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 40

    Mann N, Braun DA, Amann K, Tan W, Shril S, Connaughton DM, et al.: Whole-exome sequencing enables a precision medicine approach for kidney transplant recipients. J Am Soc Nephrol 30: 201215, 2019 10.1681/ASN.2018060575 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 41

    Hays T, Groopman EE, Gharavi AG: Genetic testing for kidney disease of unknown etiology. Kidney Int 98: 590600, 2020 10.1016/j.kint.2020.03.031 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 42

    Mele C, Lemaire M, Iatropoulos P, Piras R, Bresin E, Bettoni S, et al.: Characterization of a new DGKE intronic mutation in genetically unsolved cases of familial atypical hemolytic uremic syndrome. Clin J Am Soc Nephrol 10: 10111019, 2015 10.2215/CJN.08520814 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 43

    Carroll C, Hunley TE, Guo Y, Cortez D: A novel splice site mutation in SMARCAL1 results in aberrant exon definition in a child with Schimke immunoosseous dysplasia. Am J Med Genet A 167A: 22602264, 2015 10.1002/ajmg.a.37146 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 44

    King K, Flinter FA, Nihalani V, Green PM: Unusual deep intronic mutations in the COL4A5 gene cause X linked Alport syndrome. Hum Genet 111: 548554, 2002 10.1007/s00439-002-0830-3 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 45

    Murdock DR, Dai H, Burrage LC, Rosenfeld JA, Ketkar S, Müller MF, et al.; Undiagnosed Diseases Network: Transcriptome-directed analysis for Mendelian disease diagnosis overcomes limitations of conventional genomic testing. J Clin Invest 131: 141500, 2021 10.1172/JCI141500 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 46

    Stenton SL, Kremer LS, Kopajtich R, Ludwig C, Prokisch H: The diagnosis of inborn errors of metabolism by an integrative “multi-omics” approach: A perspective encompassing genomics, transcriptomics, and proteomics. J Inherit Metab Dis 43: 2535, 2020 10.1002/jimd.12130 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 47

    Trautmann A, Vivarelli M, Samuel S, Gipson D, Sinha A, Schaefer F, et al.; International Pediatric Nephrology Association: IPNA clinical practice recommendations for the diagnosis and management of children with steroid-resistant nephrotic syndrome. Pediatr Nephrol 35: 15291561, 2020 10.1007/s00467-020-04519-1 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 48

    Preston R, Stuart HM, Lennon R: Genetic testing in steroid-resistant nephrotic syndrome: Why, who, when and how? Pediatr Nephrol 34: 195210, 2019 10.1007/s00467-017-3838-6 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 49

    Savige J, Harraka P: Pathogenic variants in the genes affected in Alport syndrome (COL4A3-COL4A5) and their association with other kidney conditions: A review. Am J Kidney Dis 78: 857864, 2021 10.1053/j.ajkd.2021.04.017 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 50

    Kashtan CE, Ding J, Garosi G, Heidet L, Massella L, Nakanishi K, et al.: Alport syndrome: A unified classification of genetic disorders of collagen IV α345: A position paper of the Alport Syndrome Classification Working Group. Kidney Int 93: 10451051, 2018 10.1016/j.kint.2017.12.018 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 51

    Savige J, Lipska-Zietkiewicz BS, Watson E, Hertz JM, Deltas C, Mari F, et al.: Guidelines for genetic testing and management of Alport syndrome. Clin J Am Soc Nephrol 17: 143154, 2022 10.2215/CJN.04230321 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 52

    Gross O, Licht C, Anders HJ, Hoppe B, Beck B, Tönshoff B, et al.; Study Group Members of the Gesellschaft für Pädiatrische Nephrologie: Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy. Kidney Int 81: 494501, 2012 10.1038/ki.2011.407 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 53

    Savige J, Ariani F, Mari F, Bruttini M, Renieri A, Gross O, et al.: Expert consensus guidelines for the genetic diagnosis of Alport syndrome. Pediatr Nephrol 34: 11751189, 2019 10.1007/s00467-018-3985-4 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 54

    Bedin M, Boyer O, Servais A, Li Y, Villoing-Gaudé L, Tête MJ, et al.: Human C-terminal CUBN variants associate with chronic proteinuria and normal renal function. J Clin Invest 130: 335344, 2020 10.1172/JCI129937 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 55

    Beenken A, Barasch JM, Gharavi AG: Not all proteinuria is created equal. J Clin Invest 130: 7476, 2020 10.1172/JCI133250 PubMed

  • 56

    Watkins D, Rosenblatt DS: Inherited defects of cobalamin metabolism. Vitam Horm 119: 355376, 2022 10.1016/bs.vh.2022.01.010 PubMed

  • 57

    Daehn IS, Duffield JS: The glomerular filtration barrier: A structural target for novel kidney therapies. Nat Rev Drug Discov 20: 770788, 2021 10.1038/s41573-021-00242-0 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 58

    Tan W, Airik R: Primary coenzyme Q10 nephropathy, a potentially treatable form of steroid-resistant nephrotic syndrome. Pediatr Nephrol 36: 35153527, 2021 10.1007/s00467-020-04914-8 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 59

    Feng C, Wang Q, Wang J, Liu F, Shen H, Fu H, et al.: Coenzyme Q10 supplementation therapy for 2 children with proteinuria renal disease and ADCK4 mutation: Case reports and literature review. Medicine (Baltimore) 96: 8880, 2017 10.1097/MD.0000000000008880 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 60

    Stańczyk M, Bałasz-Chmielewska I, Lipska-Ziętkiewicz B, Tkaczyk M: CoQ10-related sustained remission of proteinuria in a child with COQ6 glomerulopathy-a case report. Pediatr Nephrol 33: 23832387, 2018 10.1007/s00467-018-4083-3 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 61

    Widmeier E, Airik M, Hugo H, Schapiro D, Wedel J, Ghosh CC, et al.: Treatment with 2,4-dihydroxybenzoic acid prevents FSGS progression and renal fibrosis in podocyte-specific Coq6 knockout mice. J Am Soc Nephrol 30: 393405, 2019 10.1681/ASN.2018060625 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 62

    Freyer C, Stranneheim H, Naess K, Mourier A, Felser A, Maffezzini C, et al.: Rescue of primary ubiquinone deficiency due to a novel COQ7 defect using 2,4-dihydroxybensoic acid. J Med Genet 52: 779783, 2015 10.1136/jmedgenet-2015-102986 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 63

    Kleiner G, Barca E, Ziosi M, Emmanuele V, Xu Y, Hidalgo-Gutierrez A, et al.: CoQ10 supplementation rescues nephrotic syndrome through normalization of H2S oxidation pathway. Biochim Biophys Acta Mol Basis Dis 1864: 37083722, 2018 10.1016/j.bbadis.2018.09.002 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 64

    Doimo M, Trevisson E, Airik R, Bergdoll M, Santos-Ocaña C, Hildebrandt F, et al.: Effect of vanillic acid on COQ6 mutants identified in patients with coenzyme Q10 deficiency. Biochim Biophys Acta 1842: 16, 2014 10.1016/j.bbadis.2013.10.007 PubMed

    • Crossref
    • Search Google Scholar
    • Export Citation

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