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The Collagen IV Nephropathies

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Core Concepts in Parenchymal Kidney Disease

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Abstract

Inherited disorders of type IV collagen account for a significant percentage of patients with persistent hematuria. The two major forms of familial hematuria, Alport syndrome and thin basement membrane nephropathy, arise from mutations that affect a glomerular basement network composed of α(alpha)3, α(alpha)4, and α(alpha)5 type IV collagen chains. Patients with Alport syndrome exhibit a progressive nephropathy associated with sensorineural deafness and ocular anomalies, while the symptoms of thin basement membrane nephropathy are confined to the kidney and progressive nephropathy is unusual. Approximately 80 % of patients with Alport syndrome have X-linked disease due to mutations in COL4A5, which encodes the α(alpha)5(IV) chain. About 15 % have autosomal recessive disease due to mutations in both alleles of the COL4A3 or COL4A4 gene, which encode the α(alpha)3(IV) and α(alpha)4(IV) chains, respectively. Thin basement membrane nephropathy is typically an autosomal dominant disorder; heterozygous mutations in COL4A3 or COL4A4 are found in about 50 % of affected families. A less common form of familial hematuria, hereditary angiopathy associated with nephropathy, aneurysms, and muscle cramps (HANAC syndrome), is caused by mutations that affect another basement membrane type IV collagen network that consists of α(alpha)1(IV) and α(alpha)2(IV) chains. HANAC syndrome arises from mutations in the COL4A1 gene.

This chapter discusses the natural history of these disorders as well as what is known or hypothesized about the pathways from mutations to structural changes to clinical symptoms. Diagnostic approaches and therapy are also reviewed.

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References

  1. Antonovych TT, Deasy PF, Tina LU, D’Albora JB, Hollerman CE, Calcagno PL (1969) Hereditary nephritis: early clinical, functional and morphological studies. Pediatr Res 3:545–56

    Article  PubMed  CAS  Google Scholar 

  2. Gubler M, Levy M, Broyer M et al (1981) Alport’s syndrome: a report of 58 cases and a review of the literature. Am J Med 70:493–505

    Article  PubMed  CAS  Google Scholar 

  3. Jais JP, Knebelmann B, Giatras I et al (2003) X-linked Alport syndrome: natural history and genotype-phenotype correlations in girls and women belonging to 195 families: a “European Community Alport Syndrome Concerted Action” study. J Am Soc Nephrol 14:2603–10

    Article  PubMed  Google Scholar 

  4. Jais JP, Knebelmann B, Giatras I et al (2000) X-linked Alport syndrome: natural history in 195 families and genotype-phenotype correlations in males. J Am Soc Nephrol 11:649–57

    PubMed  CAS  Google Scholar 

  5. Rumpelt H-J (1980) Hereditary nephropathy (Alport syndrome): correlation of clinical data with glomerular basement membrane alterations. Clin Nephrol 13:203–7

    PubMed  CAS  Google Scholar 

  6. Feingold J, Bois E, Chompret A, Broyer M, Gubler MC, Grunfeld JP (1985) Genetic heterogeneity of Alport syndrome. Kidney Int 27:672–7

    Article  PubMed  CAS  Google Scholar 

  7. Hasstedt SJ, Atkin CL, San Juan AC (1986) Genetic heterogeneity among kindreds with Alport syndrome. Am J Hum Genet 38:940–53

    PubMed  CAS  Google Scholar 

  8. Renieri A, Meroni M, Sessa A et al (1994) Variability of clinical phenotype in a large Alport family with gly1143-ser change of collagen a5(IV) chain. Nephron 67:444–9

    Article  PubMed  CAS  Google Scholar 

  9. Grunfeld J-P, Noel LH, Hafez S, Droz D (1985) Renal prognosis in women with hereditary nephritis. Clin Nephrol 23:267–71

    PubMed  CAS  Google Scholar 

  10. Merchant SN, Burgess BJ, Adams JC et al (2004) Temporal bone histopathology in alport syndrome. Laryngoscope 114(9):1609–18

    Article  PubMed  Google Scholar 

  11. Perrin D, Jungers P, Grunfeld JP, Delons S, Noel LH, Zenatti C (1980) Perimacular changes in Alport’s syndrome. Clin Nephrol 13:163–7

    PubMed  CAS  Google Scholar 

  12. Colville DJ, Savige J (1997) Alport syndrome: a review of the ocular manifestations. Ophthalmic Genet 18:161–73

    Article  PubMed  CAS  Google Scholar 

  13. Colville D, Savige J, Morfis M et al (1997) Ocular manifestations of autosomal recessive Alport syndrome. Ophthalmic Genet 18:119–28

    Article  PubMed  CAS  Google Scholar 

  14. Nielsen CE (1978) Lenticonus anterior and Alport’s syndrome. Arch Ophthalmol 56:518–30

    CAS  Google Scholar 

  15. Arnott EJ, Crawfurd MDA, Toghill PJ (1966) Anterior lenticonus and Alport’s syndrome. Br J Ophthalmol 50:390–403

    Article  PubMed  CAS  Google Scholar 

  16. Brownell RD, Wolter JR (1964) Anterior lenticonus in familial hemorrhagic nephritis: demonstration of lens pathology. Arch Ophthalmol 71:481–3

    Article  PubMed  CAS  Google Scholar 

  17. Streeten BW, Robinson MR, Wallace R, Jones DB (1987) Lens capsule abnormalities in Alport’s syndrome. Arch Ophthalmol 105:1693–7

    Article  PubMed  CAS  Google Scholar 

  18. Polack BCP, Hogewind BL (1977) Macular lesions in Alport’s disease. Am J Ophthalmol 84:533–5

    Google Scholar 

  19. Sabates R, Krachmer JH, Weingeist TA (1983) Ocular findings in Alport’s syndrome. Ophthalmologica 186:204–10

    Article  PubMed  CAS  Google Scholar 

  20. Zylbermann R, Silverstone B-Z, Brandes E, Drukker A (1980) Retinal lesion in Alport’s syndrome. J Pediatr Ophthalmol 17:255–60

    CAS  Google Scholar 

  21. Govan JAA (1983) Ocular manifestations of Alport’s syndrome: a hereditary disorder of basement membranes. Br J Ophthalmol 67:493–503

    Article  PubMed  CAS  Google Scholar 

  22. Thompson SM, Deady JP, Willshaw HE, White RHR (1987) Ocular signs in Alport’s syndrome. Eye 1:146–53

    Article  PubMed  Google Scholar 

  23. Teekhasaenee C, Nimmanit S, Wutthiphan S et al (1991) Posterior polymorphous dystrophy and Alport syndrome. Ophthalmology 98:1207–15

    PubMed  CAS  Google Scholar 

  24. Rhys C, Snyers B, Pirson Y (1997) Recurrent corneal erosion associated with Alport’s syndrome. Kidney Int 52:208–11

    Article  PubMed  CAS  Google Scholar 

  25. Cochat P, Guibad P, Garcia Torres R, Roussel B, Guarner V, Larbre F (1988) Diffuse leiomyomatosis in Alport syndrome. J Pediatr 113:339–43

    Article  PubMed  CAS  Google Scholar 

  26. Garcia Torres R, Guarner V (1983) Leiomiomatosis del esofago, traqueo bronquial y genital asociada con nefropatia hereditaria tipo Alport: un nuevo syndrome. Rev Gastroenterol Mex 70:163–70

    Google Scholar 

  27. Garcia-Torres R, Cruz D, Orozco L, Heidet L, Gubler MC (2000) Alport syndrome and diffuse leiomyomatosis: clinical aspects, pathology, molecular biology and extracellular matrix studies. A synthesis. Nephrologie 21:9–12

    PubMed  CAS  Google Scholar 

  28. Vaicys C, Hunt CD, Heary RF (2000) Ruptured intracranial aneurysm in an adolescent with Alport’s syndrome—a new expression of type IV collagenopathy. Surg Neurol 54:68–72

    Article  PubMed  CAS  Google Scholar 

  29. Kashtan CE (2008) Alport syndrome and thin basement membrane nephropathy. In: Geary DF, Schaefer F (eds) Comprehensive pediatric nephrology. Mosby Elsevier, Philadelphia, PA, pp 229–37

    Chapter  Google Scholar 

  30. Kashtan CE, Segal Y, Flinter F, Makanjuola D, Gan JS, Watnick T (2010) Aortic abnormalities in males with Alport syndrome. Nephrol Dial Transplant 25:3554–60

    Article  PubMed  Google Scholar 

  31. Tayel S, Kurczynski TW, Levine M et al (1991) Marfanoid children: etiologic heterogeneity and cardiac findings. Am J Dis Child 145:90–3

    PubMed  CAS  Google Scholar 

  32. Bohrer N, Churg J, Gribetz D (1964) Glomerulonephritis in two sets of identical twins. Am J Med 36:787–94

    Article  PubMed  CAS  Google Scholar 

  33. Kinoshita Y, Morita T, Wada J et al (1969) Hereditary chronic nephritis (Alport) complicated by nephrotic syndrome. Acta Med Biol 17:101–17

    PubMed  CAS  Google Scholar 

  34. Hinglais N, Grunfeld J-P, Bois LE (1972) Characteristic ultrastructural lesion of the glomerular basement membrane in progressive hereditary nephritis (Alport’s syndrome). Lab Invest 27:473–87

    PubMed  CAS  Google Scholar 

  35. Spear GS, Slusser RJ (1972) Alport’s syndrome: emphasizing electron microscopic studies of the glomerulus. Am J Pathol 69:213–22

    PubMed  CAS  Google Scholar 

  36. Churg J, Sherman RL (1973) Pathologic characteristics of hereditary nephritis. Arch Pathol 95:374–9

    PubMed  CAS  Google Scholar 

  37. Rumpelt H-J (1987) Alport’s syndrome: specificity and pathogenesis of glomerular basement membrane alterations. Pediatr Nephrol 1:422–7

    Article  PubMed  CAS  Google Scholar 

  38. Yoshikawa N, White RHR, Cameron AH (1982) Familial hematuria: clinicopathological correlations. Clin Nephrol 17:172–82

    PubMed  CAS  Google Scholar 

  39. Spear GS (1974) Pathology of the kidney in Alport’s syndrome. Pathol Annu 9:93–138

    PubMed  CAS  Google Scholar 

  40. Hill GS, Jenis EH, Goodloe SG (1974) The nonspecificity of the ultrastructural alterations in hereditary nephritis. Lab Invest 31:516–32

    PubMed  CAS  Google Scholar 

  41. Cheong HI, Cho HY, Moon KC, Ha IS, Choi Y (2007) Pattern of double glomerulopathy in children. Pediatr Nephrol 22:521–7

    Article  PubMed  Google Scholar 

  42. Habib R, Gubler MC, Hinglais N et al (1982) Alport’s syndrome: experience at Hopital Necker. Kidney Int 21:S20–8

    Article  Google Scholar 

  43. Farboody GH, Valenzuela R, McCormack LJ, Kallaen R, Osborne DG (1979) Chronic hereditary nephritis: a clinicopathologic study of 23 new kindreds and review of the literature. Hum Pathol 10:655–68

    Article  PubMed  CAS  Google Scholar 

  44. Grunfeld J-P, Bois EP, Hinglais N (1973) Progressive and non-progressive hereditary nephritis. Kidney Int 4:216–28

    Article  PubMed  CAS  Google Scholar 

  45. Rogers PW, Kurtzman NA, Bunn SM, White MG (1973) Familial benign essential hematuria. Arch Intern Med 131:257–62

    Article  PubMed  CAS  Google Scholar 

  46. Yoshikawa N, Hashimoto H, Katayama Y, Yamada Y, Matsuo T (1984) The thin glomerular basement membrane in children with hematuria. J Pathol 142:253–7

    Article  PubMed  CAS  Google Scholar 

  47. Tina L, Jenis E, Jose P, Medani C, Papadopoulou Z, Calcagno P (1982) The glomerular basement membrane in benign familial hematuria. Clin Nephrol 17:1–4

    PubMed  CAS  Google Scholar 

  48. Nieuwhof CM, de Heer F, de Leeuw P, van Breda Vriesman PJ (1997) Thin GBM nephropathy: premature glomerular obsolescence is associated with hypertension and late onset renal failure. Kidney Int 51:1596–601

    Article  PubMed  CAS  Google Scholar 

  49. Voskarides K, Damianou L, Neocleous V et al (Nov 2007) COL4A3/COL4A4 mutations producing focal segmental glomerulosclerosis and renal failure in thin basement membrane nephropathy. J Am Soc Nephrol 18(11):3004–16

    Article  PubMed  CAS  Google Scholar 

  50. Kim KH, Kim Y, Gubler MC et al (1995) Structural-functional relationships in Alport syndrome. J Am Soc Nephrol 5:1659–68

    PubMed  CAS  Google Scholar 

  51. Hudson BG, Reeders ST, Tryggvason K (1993) Type IV Collagen: structure, gene organization, and role in human diseases. J Biol Chem 268:26033–6

    PubMed  CAS  Google Scholar 

  52. Hudson BG, Trygvasson K, Sundaramoorthy M, Neilson EG (2003) Alport’s syndrome, Goodpasture’s syndrome, and type IV collagen. N Engl J Med 348:2543–56

    Article  PubMed  CAS  Google Scholar 

  53. Tsilibary E, Charonis A (1986) The role of the main noncollagenous domain (NC1) in type IV collagen self-assembly. J Cell Biol 103:2467–73

    Article  PubMed  CAS  Google Scholar 

  54. Weber S, Engel J, Wiedemann H, Glanville RW, Timpl R (1984) Subunit structure and assembly of the globular domain of basement membrane collagen type IV. Eur J Biochem 139:401–10

    Article  PubMed  CAS  Google Scholar 

  55. Dolz R, Engel J, Kuhn K (1988) Folding of collagen IV. Eur J Biochem 178:357–66

    Article  PubMed  CAS  Google Scholar 

  56. Boutaud A, Borza DB, Bondar O et al (2000) Type IV collagen of the glomerular basement membrane: evidence that the chain specificity of network assembly is encoded by the noncollagenous NC1 domains. J Biol Chem 275:30716–24

    Article  PubMed  CAS  Google Scholar 

  57. Timpl R, Wiedemann H, van Delden V, Furthmayr H, Kuhn K (1981) A network model for the organization of type IV collagen molecules in basement membranes. Eur J Biochem 120:203–11

    Article  PubMed  CAS  Google Scholar 

  58. Yurchenco PD, Ruben GC (1988) Type IV collagen lateral associations in the EHS tumor matrix: comparison with amniotic and in vitro networks. Am J Pathol 132:278–91

    PubMed  CAS  Google Scholar 

  59. Aumailley M, Wiedemann H, Mann K, Timpl R (1989) Binding of nidogen and the laminin-nidogen complex to basement membrane collagen type IV. Eur J Biochem 184:241–8

    Article  PubMed  CAS  Google Scholar 

  60. Krishnamurti U, Chen Y, Michael A et al (1996) Integrin-mediated interactions between primary/T-SV40 immortalized human glomerular epithelial cells and type IV collagen. Lab Invest 74:650–7

    PubMed  CAS  Google Scholar 

  61. Boyd CD, Toth-Fejel S, Gadi IK et al (1988) The genes coding for human pro alpha 1(IV) and pro alpha 2(IV) collagen are both located at the end of the long arm of chromosome 13. Am J Hum Genet 42:309–14

    PubMed  CAS  Google Scholar 

  62. Mariyama M, Zheng K, Yang-Feng TL, Reeders ST (1992) Colocalization of the genes for the a3(IV) and a4(IV) chains of type IV collagen to chromosome 2 bands q35-q37. Genomics 13:809–13

    Article  PubMed  CAS  Google Scholar 

  63. Hostikka SL, Eddy RL, Byers MG, Hoyhtya M, Shows TB, Tryggvason K (1990) Identification of a distinct type IV collagen a chain with restricted kidney distribution and assignment of its gene to the locus of X chromosome-linked Alport syndrome. Proc Natl Acad Sci USA 87:1606–10

    Article  PubMed  CAS  Google Scholar 

  64. Myers JC, Jones TA, Pohjolainen E-R et al (1990) Molecular cloning of a5(IV) collagen and assignment of the gene to the region of the X chromosome containing the Alport syndrome locus. Am J Hum Genet 46:1024–33

    PubMed  CAS  Google Scholar 

  65. Sugimoto M, Oohashi T, Ninomiya Y (1994) The genes COL4A5 and COL4A6, coding for basement membrane collagen chains a5(IV) and a6(IV), are located head-to-head in close proximity on human chromosome Xq22 and COL4A6 is transcribed from two alternative promoters. Proc Natl Acad Sci USA 91:11679–83

    Article  PubMed  CAS  Google Scholar 

  66. Poschl E, Pollner R, Kuhn K (1988) The genes for the a1(IV) and a2(IV) chains of human basement membrane collagen type IV are arranged head-to-head and separated by a bidirectional promoter of unique structure. EMBO J 7:2687–95

    PubMed  CAS  Google Scholar 

  67. Momota R, Sugimoto M, Oohashi T, Kigasawa K, Yoshioka H, Ninomiya Y (1998) Two genes, COL4A3 and COL4A4 coding for the human a3(IV) and a4(IV) chains are arranged head-to-head on chromosome 2q36. FEBS Lett 424:11–6

    Article  PubMed  CAS  Google Scholar 

  68. Segal Y, Zhuang L, Rondeau E, Sraer JD, Zhou J (2001) Regulation of the paired type IV collagen genes COL4A5 and COL4A6. Role of the proximal promoter region. J Biol Chem 276(15):11791–7

    Article  PubMed  CAS  Google Scholar 

  69. Borza DB, Bondar O, Ninomiya Y et al (2001) The NC1 domain of collagen IV encodes a novel network composed of the alpha 1, alpha 2, alpha 5, and alpha 6 chains in smooth muscle basement membranes. J Biol Chem 276:28532–40

    Article  PubMed  CAS  Google Scholar 

  70. Seki T, Naito I, Oohashi T, Sado Y, Ninomiya Y (1998) Differential expression of type IV collagen isoforms, a5(IV) and a6(IV) chains, in basement membranes surrounding smooth muscle cells. Histochem Cell Biol 110:359–66

    Article  PubMed  CAS  Google Scholar 

  71. Butkowski RJ, Langeveld JPM, Weislander J, Hamilton J, Hudson BG (1987) Localization of the Goodpasture epitope to a novel chain of basement membrane collagen. J Biol Chem 262:7874–7

    PubMed  CAS  Google Scholar 

  72. Wieslander J, Barr JF, Butkowski R et al (1984) Goodpasture antigen of the glomerular basement membrane: localization to noncollagenous regions of type IV collagen. Proc Natl Acad Sci USA 81:3838–42

    Article  PubMed  CAS  Google Scholar 

  73. Saus J, Wieslander J, Langeveld JPM, Quinones S, Hudson BG (1988) Identification of the Goodpasture antigen as the a3(IV) chain of collagen IV. J Biol Chem 263:13374–80

    PubMed  CAS  Google Scholar 

  74. Kalluri R, Gunwar S, Reeders ST et al (1991) Goodpasture syndrome: localization of the epitope for the autoantibodies to the carboxyl-terminal region of the a3(IV) chain of basement membrane collagen. J Biol Chem 266:24018–24

    PubMed  CAS  Google Scholar 

  75. Hertz JM, Thomassen M, Storey H, Flinter F (2012) Clinical utility gene card for: Alport syndrome. Eur J Med Genet 20(6):e1–4

    Google Scholar 

  76. Barker DF, Pruchno CJ, Xiang X et al (1996) A mutation causing Alport syndrome with tardive hearing loss is common in the western United States. Am J Hum Genet 58:1157–65

    PubMed  CAS  Google Scholar 

  77. Bekheirnia MR, Reed B, Gregory MC et al (May 2010) Genotype-phenotype correlation in X-linked Alport syndrome. J Am Soc Nephrol 21(5):876–83

    Article  PubMed  CAS  Google Scholar 

  78. Antignac C, Heidet L (1996) Mutations in Alport syndrome associated with diffuse esophageal leiomyomatosis. Contrib Nephrol 117:172–82

    PubMed  CAS  Google Scholar 

  79. Antignac C, Zhou J, Sanak M et al (1992) Alport syndrome and diffuse leiomyomatosis: deletions in the 5' end of the COL4A5 gene. Kidney Int 42:1178–83

    Article  PubMed  CAS  Google Scholar 

  80. Zhou J, Mochizuki T, Smeets H et al (1993) Deletion of the paired a5(IV) and a6(IV) collagen genes in inherited smooth muscle tumors. Science 261:1167–9

    Article  PubMed  CAS  Google Scholar 

  81. Heidet L, Dahan K, Zhou J et al (1995) Deletions of both a5(IV) and a6(IV) collagen genes in Alport syndrome and in Alport syndrome associated with smooth muscle tumors. Hum Mol Genet 4:99–108

    PubMed  CAS  Google Scholar 

  82. Heidet L, Cohen-Solal L, Boye E et al (1997) Novel COL4A5/COL4A6 deletions and further characterization of the diffuse leiomyomatosis-Alport syndrome (DL-AS) locus define the DL critical region. Cytogenet Cell Genet 78:240–6

    Article  PubMed  CAS  Google Scholar 

  83. Segal Y, Peissel B, Renieri A et al (1999) LINE-1 elements at the sites of molecular rearrangements in Alport syndrome-diffuse leiomyomatosis. Am J Hum Genet 64:62–9

    Article  PubMed  CAS  Google Scholar 

  84. Heiskari N, Zhang X, Zhou J et al (1996) Identification of 17 mutations in ten exons in the COL4A5 collagen gene, but no mutations found in four exons in COL4A6: a study of 250 patients with hematuria and suspected of having Alport syndrome. J Am Soc Nephrol 7:702–9

    PubMed  CAS  Google Scholar 

  85. Jonsson JJ, Renieri A, Gallagher PG et al (1998) Alport syndrome, mental retardation, midface hypoplasia, and elliptocytosis: a new X linked contiguous gene deletion syndrome? J Med Genet 35:273–8

    Article  PubMed  CAS  Google Scholar 

  86. Piccini M, Vitelli F, Bruttini M et al (1998) FACL4, a new gene encoding long-chain acyl-CoA synthetase 4, is deleted in a family with Alport syndrome, elliptocytosis, and mental retardation. Genomics 47:350–8

    Article  PubMed  CAS  Google Scholar 

  87. Kobayashi T, Uchiyama M (Dec 2003) Characterization of assembly of recombinant type IV collagen alpha3, alpha4, and alpha5 chains in transfected cell strains. Kidney Int 64(6):1986–96

    Article  PubMed  CAS  Google Scholar 

  88. Piez KA (1984) Molecular and aggregate structures of the collagens. In: Piez KA, Reddi AH (eds) Extracellular matrix biochemistry. Elsevier, New York, NY, pp 1–39

    Google Scholar 

  89. Prockop DJ (1992) Mutations in collagen genes as a cause of connective-tissue diseases. N Engl J Med 326:540–6

    Article  PubMed  CAS  Google Scholar 

  90. Kuvaniemi H, Tromp G, Prockop DJ (1997) Mutations in fibrillar collagens (types I, II, III, and XI), fibril-associated collagen (type IV), and network-forming collagen (type X) cause a spectrum of diseases of bone, cartilage, and blood vessels. Hum Mutat 9:300–15

    Article  Google Scholar 

  91. Gross O, Netzer KO, Lambrecht R, Seibold S, Weber M (2002) Meta-analysis of genotype-phenotype correlation in X-linked Alport syndrome: impact on clinical counseling. Nephrol Dial Transplant 17:1218–27

    Article  PubMed  Google Scholar 

  92. van der Loop FTL, Heidet L, Timmer EDJ et al (2000) Autosomal dominant Alport syndrome caused by a COL4A3 splice site mutation. Kidney Int 58:1870–5

    Article  PubMed  Google Scholar 

  93. Ciccarese M, Casu D, Wong FK et al (2001) Identification of a new mutation in the a4(IV) collagen gene in a family with autosomal dominant Alport syndrome and hypercholesterolaemia. Nephrol Dial Transplant 16:2008–12

    Article  PubMed  CAS  Google Scholar 

  94. Longo I, Porcedda P, Mari F et al (2002) COL4A3/COL4A4 mutations: from familial hematuria to autosomal-dominant or recessive Alport syndrome. Kidney Int 61:1947–56

    Article  PubMed  CAS  Google Scholar 

  95. Guo C, Van Damme B, Vanrenterghem Y, Devriendt K, Cassiman J-J, Marynen P (1995) Severe Alport phenotype in a woman with two missense mutations in the same COL4A5 gene and preponderant inactivation of the X chromosome carrying the normal allele. J Clin Invest 95:1832–7

    Article  PubMed  CAS  Google Scholar 

  96. Vetrie D, Flinter F, Bobrow M, Harris A (1992) X inactivation patterns in females with Alport’s syndrome: a means of selecting against a deleterious gene? J Med Genet 29:663–6

    Article  PubMed  CAS  Google Scholar 

  97. Rheault MN, Kren SM, Thielen BK et al (Jun 2004) Mouse model of X-linked Alport syndrome. J Am Soc Nephrol 15(6):1466–74

    Article  PubMed  Google Scholar 

  98. Rheault MN, Kren SM, Hartich LA et al (Mar 2010) X-inactivation modifies disease severity in female carriers of murine X-linked Alport syndrome. Nephrol Dial Transplant 25(3):764–9

    Article  PubMed  CAS  Google Scholar 

  99. Mochizuki T, Lemmink HH, Mariyama M et al (1994) Identification of mutations in the a3(IV) and a4(IV) collagen genes in autosomal recessive Alport syndrome. Nat Genet 8:77–82

    Article  PubMed  CAS  Google Scholar 

  100. Ding J, Stitzel J, Berry P, Hawkins E, Kashtan C (1995) Autosomal recessive Alport syndrome: mutation in the COL4A3 gene in a woman with Alport syndrome and posttransplant antiglomerular basement membrane nephritis. J Am Soc Nephrol 5:1714–7

    PubMed  CAS  Google Scholar 

  101. Lemmink HH, Mochizuki T, van den Heuvel LPWJ et al (1994) Mutations in the type IV collagen a3 (COL4A3) gene in autosomal recessive Alport syndrome. Hum Mol Genet 3:1269–73

    Article  PubMed  CAS  Google Scholar 

  102. Jeraj K, Kim Y, Vernier RL, Fish AJ, Michael AF (1982) Absence of Goodpasture’s antigen in male patients with familial nephritis. Am J Kid Dis 2:626–9

    Google Scholar 

  103. Kashtan C, Fish AJ, Kleppel M, Yoshioka K, Michael AF (1986) Nephritogenic antigen determinants in epidermal and renal basement membranes of kindreds with Alport-type familial nephritis. J Clin Invest 78:1035–44

    Article  PubMed  CAS  Google Scholar 

  104. McCoy RC, Johnson HK, Stone WJ, Wilson CB (1982) Absence of nephritogenic GBM antigen(s) in some patients with hereditary nephritis. Kidney Int 21:642–52

    Article  PubMed  CAS  Google Scholar 

  105. Olson DL, Anand SK, Landing BH, Heuser E, Grushkin CM, Lieberman E (1980) Diagnosis of hereditary nephritis by failure of glomeruli to bind anti-glomerular basement membrane antibodies. J Pediatr 96:697–9

    Article  PubMed  CAS  Google Scholar 

  106. Savage COS, Pusey CD, Kershaw MJ et al (1986) The Goodpasture antigen in Alport’s syndrome: studies with a monoclonal antibody. Kidney Int 30:107–12

    Article  PubMed  CAS  Google Scholar 

  107. Kashtan CE, Kim Y (1992) Distribution of the a1 and a2 chains of collagen IV and of collagens V and VI in Alport syndrome. Kidney Int 42:115–26

    Article  PubMed  CAS  Google Scholar 

  108. Nakanishi K, Yoshikawa N, Iijima K et al (1994) Immunohistochemical study of a1–5 chains of type IV collagen in hereditary nephritis. Kidney Int 46:1413–21

    Article  PubMed  CAS  Google Scholar 

  109. Peissel B, Geng L, Kalluri R et al (1995) Comparative distribution of the a1(IV), a5(IV) and a6(IV) collagen chains in normal human adult and fetal tissues and in kidneys from X-linked Alport syndrome patients. J Clin Invest 96:1948–57

    Article  PubMed  CAS  Google Scholar 

  110. Ninomiya Y, Kagawa M, Iyama K et al (1995) Differential expression of two basement membrane collagen genes, COL4A6 and COL4A5, demonstrated by immunofluorescence staining using peptide-specific monoclonal antibodies. J Cell Biol 130:1219–29

    Article  PubMed  CAS  Google Scholar 

  111. Yoshioka K, Hino S, Takemura T et al (1994) Type IV Collagen a5 chain: normal distribution and abnormalities in X-linked Alport syndrome revealed by monoclonal antibody. Am J Pathol 144:986–96

    PubMed  CAS  Google Scholar 

  112. Cheong HI, Kashtan CE, Kim Y, Kleppel MM, Michael AF (1994) Immunohistologic studies of type IV collagen in anterior lens capsules of patients with Alport syndrome. Lab Invest 70:553–7

    PubMed  CAS  Google Scholar 

  113. Ohkubo S, Takeda H, Higashide T et al (Jun 2003) Immunohistochemical and molecular genetic evidence for type IV collagen alpha5 chain abnormality in the anterior lenticonus associated with Alport syndrome. Arch Ophthalmol 121(6):846–50

    Article  PubMed  CAS  Google Scholar 

  114. Gubler MC, Knebelmann B, Beziau A et al (1995) Autosomal recessive Alport syndrome: immunohistochemical study of type IV collagen chain distribution. Kidney Int 47:1142–7

    Article  PubMed  CAS  Google Scholar 

  115. Kuivaniemi H, Tromp G, Prockop DJ (1991) Mutations in collagen genes: causes of rare and some common diseases in humans. FASEB J 5:2052–60

    PubMed  CAS  Google Scholar 

  116. Gupta MC, Graham PL, Kramer JM (1997) Characterization of a1(IV) collagen mutations in Caenorhabditis elegans and the effects of a1 and a2(IV) mutations on type IV collagen distribution. J Cell Biol 137:1185–96

    Article  PubMed  CAS  Google Scholar 

  117. Kalluri R, Shield CF, Todd P, Hudson BG, Neilson EG (1997) Isoform switching of type IV collagen is developmentally arrested in X-linked Alport syndrome leading to increased susceptibility of renal basement membranes to endoproteolysis. J Clin Invest 99:2470–8

    Article  PubMed  CAS  Google Scholar 

  118. Miner JH, Sanes JR (1994) Collagen IV a3, a4 and a5 chains in rodent basal laminae: sequence, distribution, association with laminins, and developmental switches. J Cell Biol 127:879–91

    Article  PubMed  CAS  Google Scholar 

  119. Kim Y, Butkowski R, Burke B et al (1991) Differential expression of basement membrane collagen in membranous nephropathy. Am J Pathol 139:1381–8

    PubMed  CAS  Google Scholar 

  120. Harvey SJ, Zheng K, Sado Y et al (1998) Role of distinct type IV collagen networks in glomerular development and function. Kidney Int 54:1857–66

    Article  PubMed  CAS  Google Scholar 

  121. Kashtan CE, Kim Y, Lees GE, Thorner PS, Virtanen I, Miner JH (2001) Abnormal glomerular basement membrane laminins in murine, canine, and human Alport syndrome: aberrant laminin alpha2 deposition is species independent. J Am Soc Nephrol 12:252–60

    PubMed  CAS  Google Scholar 

  122. Abrahamson DR, Prettyman AC, Robert B, St John PL (Mar 2003) Laminin-1 reexpression in Alport mouse glomerular basement membranes. Kidney Int 63(3):826–34

    Article  PubMed  CAS  Google Scholar 

  123. Meehan DT, Delimont D, Cheung L et al (2009) Biomechanical strain causes maladaptive gene regulation, contributing to Alport glomerular disease. Kidney Int 76:968–76

    Article  PubMed  Google Scholar 

  124. Kashtan CE, Gubler MC, Sisson-Ross S, Mauer M (1998) Chronology of renal scarring in males with Alport syndrome. Pediatr Nephrol 12:269–74

    Article  PubMed  CAS  Google Scholar 

  125. Vinge L, Lees GE, Nielsen R, Kashtan CE, Bahr A, Christensen EI (Aug 2010) The effect of progressive glomerular disease on megalin-mediated endocytosis in the kidney. Nephrol Dial Transplant 25(8):2458–67

    Article  PubMed  CAS  Google Scholar 

  126. Sayers R, Kalluri R, Rodgers KD, Shield CF, Meehan DT, Cosgrove D (1999) Role for transforming growth factor-beta 1 in Alport renal disease progression. Kidney Int 56:1662–73

    Article  PubMed  CAS  Google Scholar 

  127. Cosgrove D, Rodgers K, Meehan D et al (2000) Integrin alpha1beta1 and transforming growth factor-beta 1 play distinct roles in Alport glomerular pathogenesis and serve as dual targets for metabolic therapy. Am J Pathol 157:1649–59

    Article  PubMed  CAS  Google Scholar 

  128. Rao VH, Lees GH, Kashtan CE et al (2003) Increased expression of MMP-2, MMP-9 (type IV collagenases/gelatinases), and MT1-MMP in canine X-linked Alport syndrome (XLAS). Kidney Int 63:1736–48

    Article  PubMed  CAS  Google Scholar 

  129. Zeisberg M, Bottiglio C, Kumar N et al (Dec 2003) Bone morphogenic protein-7 inhibits progression of chronic renal fibrosis associated with two genetic mouse models. Am J Physiol Renal Physiol 285(6):F1060–7

    PubMed  CAS  Google Scholar 

  130. Rodgers KD, Rao V, Meehan DT et al (Apr 2003) Monocytes may promote myofibroblast accumulation and apoptosis in Alport renal fibrosis. Kidney Int 63(4):1338–55

    Article  PubMed  CAS  Google Scholar 

  131. Gross O, Schulze-Lohoff E, Koepke ML et al (Jul 2004) Antifibrotic, nephroprotective potential of ACE inhibitor vs AT1 antagonist in a murine model of renal fibrosis. Nephrol Dial Transplant 19(7):1716–23

    Article  PubMed  CAS  Google Scholar 

  132. Gross O, Beirowski B, Koepke ML et al (Feb 2003) Preemptive ramipril therapy delays renal failure and reduces renal fibrosis in COL4A3-knockout mice with Alport syndrome. Kidney Int 63(2):438–46

    Article  PubMed  CAS  Google Scholar 

  133. Kagawa M, Kishiro Y, Naito I et al (1997) Epitope-defined monoclonal antibodies against type-IV collagen for diagnosis of Alport’s syndrome. Nephrol Dial Transplant 12:1238–41

    Article  PubMed  CAS  Google Scholar 

  134. Kashtan CE (1999) Alport syndrome: is diagnosis only skin deep? Kidney Int 55:1575–6

    Article  PubMed  CAS  Google Scholar 

  135. van der Loop FTL, Monnens LAH, Schroder CH et al (1999) Identification of COL4A5 defects in Alport syndrome by immunochemistry of skin. Kidney Int 55:1217–24

    Article  PubMed  Google Scholar 

  136. Turco AE, Rossetti S, Bresin E, Corra S (1995) Erroneous genetic risk assessment of Alport syndrome. Lancet 346:1237

    Article  PubMed  CAS  Google Scholar 

  137. Kashtan CE, McEnery PT, Tejani A, Stablein DM (1995) Renal allograft survival according to primary diagnosis: a report of the North American Pediatric Renal Transplant Cooperative Study. Pediatr Nephrol 9:679–84

    Article  PubMed  CAS  Google Scholar 

  138. van de Heuvel LPWJ, Schroder CH, Savage COS et al (1989) The development of anti-glomerular basement membrane nephritis in two children with Alport’s syndrome after renal transplantation: characterization of the antibody target. Pediatr Nephrol 3:406–13

    Article  Google Scholar 

  139. Peten E, Pirson Y, Cosyns J-P et al (1991) Outcome of thirty patients with Alport’s syndrome after renal transplantation. Transplantation 52:823–6

    Article  PubMed  CAS  Google Scholar 

  140. Gobel J, Olbricht CJ, Offner G et al (1992) Kidney transplantation in Alport’s syndrome: long-term outcome and allograft anti-GBM nephritis. Clin Nephrol 38:299–304

    PubMed  CAS  Google Scholar 

  141. Kashtan CE, Michael AF (1996) Perspectives in clinical nephrology: Alport syndrome. Kidney Int 50:1445–63

    Article  PubMed  CAS  Google Scholar 

  142. Hudson BG, Kalluri R, Gunwar S et al (1992) The pathogenesis of Alport syndrome involves type IV collagen molecules containing the a3(IV) chain: evidence from anti-GBM nephritis after renal transplantation. Kidney Int 42:179–87

    Article  PubMed  CAS  Google Scholar 

  143. Kashtan C, Butkowski R, Kleppel M, First M, Michael A (1990) Posttransplant anti-glomerular basement membrane nephritis in related Alport males with Alport syndrome. J Lab Clin Med 116:508–15

    PubMed  CAS  Google Scholar 

  144. Brainwood D, Kashtan C, Gubler MC, Turner AN (1998) Targets of alloantibodies in Alport anti-glomerular basement membrane disease after renal transplantation. Kidney Int 53:762–6

    Article  PubMed  CAS  Google Scholar 

  145. Pedchenko V, Bondar O, Fogo AB et al (2010) Molecular architecture of the Goodpasture autoantigen in anti-GBM nephritis. N Eng J Med 363:343–54

    Article  CAS  Google Scholar 

  146. Ding J, Zhou J, Tryggvason K, Kashtan CE (1994) COL4A5 deletions in three patients with Alport syndrome and posttransplant antiglomerular basement membrane nephritis. J Am Soc Nephrol 5:161–8

    PubMed  CAS  Google Scholar 

  147. Antignac C, Knebelmann B, Druout L et al (1994) Deletions in the COL4A5 collagen gene in X-linked Alport syndrome: characterization of the pathological transcripts in non-renal cells and correlation with disease expression. J Clin Invest 93:1195–207

    Article  PubMed  CAS  Google Scholar 

  148. Grodecki KM, Gains MJ, Baumal R, Osmond DH, Cotter B, Valli VE, Jacobs RM (1997) Treatment of X-linked hereditary nephritis in Samoyed dogs with angiotensin converting enzyme inhibitor. J Comp Pathol 117:209–25

    Article  PubMed  CAS  Google Scholar 

  149. Cohen EP, Lemann J (1996) In hereditary nephritis angiotensin-converting enzyme inhibition decreases proteinuria and may slow the rate of progression. Am J Kid Dis 27:199–203

    Article  PubMed  CAS  Google Scholar 

  150. Proesmans W, Knockaert H, Trouet D (2000) Enalapril in paediatric patients with Alport syndrome: 2 years’ experience. Eur J Pediatr 159:430–3

    Article  PubMed  CAS  Google Scholar 

  151. Adler L, Mathew R, Futterweit S et al (2002) Angiotensin converting enzyme inhibitor therapy in children with Alport syndrome: effect on urinary albumin, TGF-beta, and nitrite excretion. BMC Nephrol 3(1):2

    Article  PubMed  Google Scholar 

  152. Proesmans W, Van Dyck M (Mar 2004) Enalapril in children with Alport syndrome. Pediatr Nephrol 19(3):271–5

    Article  PubMed  Google Scholar 

  153. Gross O, Licht C, Anders H et al (2012) Early angiotensin-converting enzyme inhibition in Alport syndrome delays renal failure and improves life expectancy. Kidney Int 81(5):494–501

    Article  PubMed  CAS  Google Scholar 

  154. Callis L, Vila A, Nieto J, Fortuny G (1992) Effect of cyclosporin A on proteinuria in patients with Alport’s syndrome. Pediatr Nephrol 6:140–4

    Article  PubMed  CAS  Google Scholar 

  155. Callis L, Vila A, Carrera M, Nieto J (1999) Long-term effects of cyclosporine A in Alport’s syndrome. Kidney Int 55:1051–6

    Article  PubMed  CAS  Google Scholar 

  156. Charbit M, Dechaux M, Gagnadoux M, Grunfeld J, Niaudet P (2003) Cyclosporine A therapy in Alport syndrome. Pediatr Nephrol 22:57–63

    Article  Google Scholar 

  157. Massella L, Rizzoni G (2001) Cyclosporine treatment of young patients with Alport syndrome and proteinuria. J Am Soc Nephrol 12:116A

    Google Scholar 

  158. Chen D, Jefferson B, Harvey SJ et al (2003) Cyclosporine A slows the progressive renal disease of Alport syndrome (X-linked hereditary nephritis): results from a canine model. J Am Soc Nephrol 14:690–8

    Article  PubMed  CAS  Google Scholar 

  159. Heikkila P, Parpala T, Lukkarinen O, Weber M, Tryggvason K (1996) Adenovirus-mediated gene transfer into kidney glomeruli using an ex vivo and in vivo kidney perfusion system—first step towards gene therapy of Alport syndrome. Gene Ther 3:21–7

    PubMed  CAS  Google Scholar 

  160. Tryggvason K, Heikkila P, Pettersson E, Tibell A, Throner P (1997) Can Alport syndrome be treated by gene therapy? Kidney Int 52:1493–9

    Article  Google Scholar 

  161. Parpala-Sparman T, Lukkarinen O, Heikkila P, Tryggvason K (1999) A novel surgical organ perfusion method for effective ex vivo and in vivo gene transfer into renal glomerular cells. Urol Res 27:97–102

    Article  PubMed  CAS  Google Scholar 

  162. Harvey SJ, Zheng K, Jefferson B et al (2003) Transfer of the alpha 5(IV) collagen chain gene to smooth muscle restores in vivo expression of the alpha 6(IV) collagen chain in a canine model of Alport syndrome. Am J Pathol 162:873–5

    Article  PubMed  CAS  Google Scholar 

  163. Zeisberg M, Khurana M, Rao VH et al (Apr 2006) Stage-specific action of matrix metalloproteinases influences progressive hereditary kidney disease. PLoS Med 3(4):e100

    Article  PubMed  CAS  Google Scholar 

  164. Gross O, Koepke ML, Beirowski B, Schulze-Lohoff E, Segerer S, Weber M (2005) Nephroprotection by antifibrotic and anti-inflammatory effects of the vasopeptidase inhibitor AVE7688. Kidney Int 68:456–63

    Article  PubMed  CAS  Google Scholar 

  165. Koepke ML, Weber M, Schulze-Lohoff E, Beirowski B, Segerer S, Gross O (Apr 2007) Nephroprotective effect of the HMG-CoA-reductase inhibitor cerivastatin in a mouse model of progressive renal fibrosis in Alport syndrome. Nephrol Dial Transplant 22(4):1062–9

    Article  PubMed  CAS  Google Scholar 

  166. Ninichuk V, Gross O, Reichel C et al (2005) Delayed chemokine receptor 1 blockade prolongs survival in collagen 4A3-deficient mice with Alport disease. J Am Soc Nephrol 16:977–85

    Article  PubMed  CAS  Google Scholar 

  167. Sugimoto H, Mundel TM, Sund M, Xie L, Cosgrove D, Kalluri R (2006) Bone-marrow-derived stem cells repair basement membrane collagen defects and reverse genetic kidney disease. Proc Natl Acad Sci USA 103(19):7321–6

    Article  PubMed  CAS  Google Scholar 

  168. Prodromidi EI, Poulsom R, Jeffery R et al (Nov 2006) Bone marrow-derived cells contribute to podocyte regeneration and amelioration of renal disease in a mouse model of Alport syndrome. Stem Cells 24(11):2448–55

    Article  PubMed  CAS  Google Scholar 

  169. Ninichuk V, Gross O, Segerer S et al (Jul 2006) Multipotent mesenchymal stem cells reduce interstitial fibrosis but do not delay progression of chronic kidney disease in collagen4A3-deficient mice. Kidney Int 70(1):121–9

    Article  PubMed  CAS  Google Scholar 

  170. Lebleu V, Sugimoto H, Mundel TM et al (2009) Stem cell therapies benefit Alport Syndrome. J Am Soc Nephrol 20(11):2359–70

    Article  PubMed  CAS  Google Scholar 

  171. Katayama K, Kawano M, Naito I et al (Sep 2008) Irradiation prolongs survival of Alport mice. J Am Soc Nephrol 19(9):1692–700

    Article  PubMed  CAS  Google Scholar 

  172. Wuhl E, Trivelli A, Picca S et al (2009) Strict blood-pressure control and progression of renal failure in children. N Engl J Med 361(17):1639–50

    Article  PubMed  Google Scholar 

  173. Wuhl E, Mehls O, Schaefer F (Aug 2004) Antihypertensive and antiproteinuric efficacy of ramipril in children with chronic renal failure. Kidney Int 66(2):768–76

    Article  PubMed  Google Scholar 

  174. Trachtman H, Weiss R, Bennett B, Griefer I (1984) Isolated hematuria in children: indications for a renal biopsy. Kidney Int 25:94–9

    Article  PubMed  CAS  Google Scholar 

  175. Dische FE, Weston MJ, Parsons V (1985) Abnormally thin glomerular basement membranes associated with hematuria, proteinuria or renal failure in adults. Am J Nephrol 5:103–9

    Article  PubMed  CAS  Google Scholar 

  176. Tiebosch ATMG, Frederik PM, van Breda Vriesman PJC et al (1989) Thin-basement-membrane nephropathy in adults with persistent hematuria. N Engl J Med 320:14–8

    Article  PubMed  CAS  Google Scholar 

  177. van Paassen P, van Breda Vriesman PJ, van Rie H, Tervaert JW (Sep 2004) Signs and symptoms of thin basement membrane nephropathy: a prospective regional study on primary glomerular disease-The Limburg Renal Registry. Kidney Int 66(3):909–13

    Article  PubMed  Google Scholar 

  178. Vogler C, McAdams AJ, Homan SM (1987) Glomerular basement membrane and lamina densa in infants and children: an ultrastructural evaluation. Pediatr Pathol 7:527–34

    Article  PubMed  CAS  Google Scholar 

  179. Steffes MW, Barbosa J, Basgen JM, Sutherland DER, Najarian JS, Mauer SM (1983) Quantitative glomerular morphology of the normal human kidney. Kidney Int 49:82–6

    CAS  Google Scholar 

  180. Dische FE (1992) Measurement of glomerular basement membrane thickness and its application to the diagnosis of thin-membrane nephropathy. Arch Pathol Lab Med 116:43–9

    PubMed  CAS  Google Scholar 

  181. Schroder CH, Bontemps CM, Assmann KJM et al (1990) Renal biopsy and family studies in 65 children with isolated hematuria. Acta Paediatr Scand 79:630–6

    Article  PubMed  CAS  Google Scholar 

  182. Blumenthal SS, Fritsche C, Lemann J (1988) Establishing the diagnosis of benign familial hematuria: the importance of examining the urine sediment of family members. JAMA 259:2263–6

    Article  PubMed  CAS  Google Scholar 

  183. Lemmink HH, Nillesen WN, Mochizuki T et al (1996) Benign familial hematuria due to mutation of the type IV collagen a4 gene. J Clin Invest 98:1114–8

    Article  PubMed  CAS  Google Scholar 

  184. Badenas C, Praga M, Tazon B et al (2002) Mutations in the COL4A4 and COL4A3 genes cause familial benign hematuria. J Am Soc Nephrol 13:1248–54

    PubMed  CAS  Google Scholar 

  185. Buzza M, Dagher H, Wang YY et al (2003) Mutations in the COL4A4 gene in thin basement membrane disease. Kidney Int 63:447–53

    Article  PubMed  CAS  Google Scholar 

  186. Rana K, Wang YY, Buzza M et al (2005) The genetics of thin basement membrane nephropathy. Semin Nephrol 25:163–70

    Article  PubMed  CAS  Google Scholar 

  187. Piccini M, Casari G, Zhou J et al (1999) Evidence for genetic heterogeneity in benign familial hematuria. Am J Nephrol 19:464–7

    Article  PubMed  CAS  Google Scholar 

  188. Plaisier E, Gribouval O, Alamowitch S et al (2007) COL4A1 mutations and hereditary angiopathy, nephropathy, aneurysms, and muscle cramps. N Engl J Med 357(26):2687–95

    Article  PubMed  CAS  Google Scholar 

  189. Alamowitch S, Plaisier E, Favrole P et al (2009) Cerebrovascular disease related to COL4A1 mutations in HANAC syndrome. Neurology 73:1873–82

    Article  PubMed  CAS  Google Scholar 

  190. Plaisier E, Chen Z, Gekeler F et al (2010) Novel COL4A1 mutations associated with HANAC syndrome: a role for the triple helical CB3[IV] domain. Am J Med Genet A 152A:2550–5

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA

    Clifford E. Kashtan M.D.

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  1. Clifford E. Kashtan M.D.
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  1. Div. Nephrology & Hypertension, Mayo Clinic Dept. Internal Medicine, Rochester, Minnesota, USA

    Fernando C. Fervenza

  2. Renal Division, Brigham and Women's Hospital, Boston, Massachusetts, USA

    Julie Lin

  3. Mayo Clinic, Rochester, Minnesota, USA

    Sanjeev Sethi

  4. Renal Division, Brigham and Women's Hospital Harvard Medical School, Boston, Massachusetts, USA

    Ajay K. Singh

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Kashtan, C.E. (2014). The Collagen IV Nephropathies. In: Fervenza, F., Lin, J., Sethi, S., Singh, A. (eds) Core Concepts in Parenchymal Kidney Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8166-9_18

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